第22回
日本臨床口腔病理学会 総会・学術大会

The 22nd Annual Meeting of the Japanese Society of Oral Pathology
大会長

谷口 邦久（福岡歯科大学生体構造学講座病態構造学分野 教授）
President Dr. KUNIHISA TANIGUCHI D.D.S., Ph.D.

第5回
アジア口腔病理学会

The 5th Meeting of Asian Society of Oral and Maxillofacial Pathology
大会長 高田 隆（広島大学大学院医歯薬学総合研究科創生医科学専攻
先進医療開発科学講座口腔顎顔面病理病態学研究室 教授）
President Dr. TAKASHI TAKATA D.D.S., Ph.D.

プログラム・抄録集
Program・Abstracts

2011

テーマ

福岡

飛躍する口腔病理学

Themes Hopping, Jumping,………Oral Pathologist

2011年8月24日（水）・25日（木）August 24-25, 2011 Fukuoka Japan
九州大学医学部百年講堂
Centennial Hall Kyushu University School of Medicine（役員会等：2011年8月23日（火））(Executive committe : August 23, 2011)

大扉

目

次

Contents
ごあいさつ…………………………………………………………………… 3
Greeting
日本臨床口腔病理学会総会・学術大会の記録・予定…………………… 6
Annual Meeting of JSOP
ご案内とお願い……………………………………………………………… 7
Information
学会行事案内………………………………………………………………… 10
Event Information
学会周辺案内図／学会会場案内図………………………………………… 11
Location Map / Floor Map
座長一覧……………………………………………………………………… 13
List of Chairs
学会日程表…………………………………………………………………… 14
Schedule
プログラム…………………………………………………………………… 19
Program
講演抄録……………………………………………………………………… 33
Abstracts
一般演題（口演）Ⅰ・症例検討Ⅰ Oral PresentationⅠ・Case StudyⅠ … 35
特別講演

Special Lecture ………………… 45

ランチョン・セミナーⅠ

Luncheon SeminarⅠ ………… 49

ASOMP Session…………………………………… 53

一般演題（口演）Ⅱ

Oral PresentationⅡ …………… 81

研修プログラム

Training Program ……………… 87

ランチョン・セミナーⅡ

Luncheon SeminarⅡ ………… 99

症例検討Ⅱ

Case StudyⅡ ………………… 103

公開シンポジウム

Public Symposium…………… 109

一般演題（示説）

Poster Presentation ………… 117

協賛企業一覧……………………………………………………………… 185
List of Sponsors

目次Greeting

ごあいさつ

Greeting

第22回日本臨床口腔病理学会 総会・学術大会
The 22nd Annual Meeting of the Japanese Society of Oral Pathology
大会長

谷

口

邦

久

（福岡歯科大学生体構造学講座病態構造学分野 教授）
President Dr. KUNIHISA TANIGUCHI D.D.S., Ph.D.

はじめに，この度の東日本大震災に被災されました方々に衷心よりお見舞いとお悔やみを申し上げます。
心中をお察し申し上げますとともに，一日も早い復興をお祈り致します。
さて，第22回NPO法人日本臨床口腔病理学会総会・学術集会は2011年８月23日（火）〜25日（木）に福岡歯科大学主催で，福岡市の九州大学医学部百年講堂において開催されます。今大会は第５回アジア口腔病理学会との同時併催となります。本学会は2003年に初めて日本（淡路）でアジア諸国の研究者とシンポジウムを開催して以来の日本での開催となりますし，福岡での開催は第４回大会以来18年ぶりとなります。
福岡市は九州におけるアジアの玄関口として，歴史的にもアジア諸国と多くの交流があります。この地
でアジアの先生方が一同に会して研究発表し，親交を深めることは大変喜ばしい限りです。
日本では超高齢化社会を迎え，疾病の構造も医療も大きく変化しており，口腔疾患と全身との関わりを深く理解する口腔病理学者の育成や歯学・医学の知識を統合し，臨床と口腔病理との関係をより密にして口腔病変の幅広い病理診断，口腔疾患の予防に真に活躍することが求められていると思います。
本学会が，口腔病理学を探究するベテランと若手研究者，アジアの研究者が一体となり，学術研究交流を深め，口腔病理学が未来に向け飛躍する場になればと念じております。多数のご参加を心よりお願いする次第です。
First, we would like to mourn the disaster of Japan Earthquake 2011. We hope for a swift recovery fromthe loss endured during the tragedy.
From August 23 to 25, 2011, the 22nd Annual Meeting of the Japanese Society of Oral Pathology will beheld at Cenennila Hall, Kyushu University, School of Medicine, which is in charge of Fukuoka Dental
College. As a collaboration, The 5th Meeting of Asian Society of Oral and Maxillofacial Pathology will beheld concurrently.
Fukuoka City, by tradition, has always welcomed delegates from various Asian countries. We are happy
to host the above events in Fukuoka and make academic and personal communications between
delegates stronger. The Meeting of Asian Society of Oral and Maxillofacial Pathology was held at the
Awaji Island (ﬁrst time in Japan) in 2003, and shall be hosted by Japan (Fukuoka) again this year. The
Meeting of the Japanese Society of Oral Pathology is being held for the 2nd time in Fukuoka after 18
years since 1993.
Japan has an ever-increasing, super-ageing society, and consequently disease patterns and the medicalcare processes have been changing drastically. Oral pathologists, who treat oral diseases considering thewhole body, are expected to integrate both dental and medical knowledge, make diagnosis of oral
lesions, and, discuss them in view of the overall health; thus contributing to the disease prevention andpromotion of general healthcare.
We expect and hope that many delegates (both pathologists and clinicians) would come together, makepresentations of the results of pathological cases and researches, leading to exchange of information
between delegates.
We eagerly look forward to seeing you in Fukuoka.
33Greeting

Greeting

The 5th Meeting of Asian Society of Oral and Maxillofacial Pathology

Gao YanPresident of ASOMP
Former Chair of Chinese Society of Oral Pathology
Professor of Department of Oral Pathology
Peking University School of Stomatology

Dear Colleagues and Friends,
Almost 2 years have passed since the fourth meeting of Asian Society of Oral and Maxillofacial
Pathology (ASOMP), which was held in Beijing, China in November 2009. Fifth ASOMP meeting as apart of 22nd JSOP meeting in Fukuoka on August 24 and 25, 2011 will be held in the afternoon ofAugust 24. Here, I would like to express my very warm welcome to your participation.
The Scientific Committee of 5th ASOMP has been working hard to develop an interesting andstimulating program, cover a wide range of disciplines and interests in the ﬁeld of oral and maxillofacial
histopathology. At the meeting you will meet some Asia's authorities in the ﬁeld of oral and maxillofacial
pathology. Advanced knowledge, techniques and new approaches in the research will be presented.
Besides, you will also make new friends in the meeting. There are much beautiful scenery worth
watching and much delicious food waiting for you to enjoy. You can also experience Japanese culture
and customs. Your participation will contribute to success of the meeting greatly. Sincerely wish theconference a great success.

44Greeting

Greeting

The 5th Meeting of Asian Society of Oral and Maxillofacial Pathology

Takashi Takata
Chair of Organizing Committee
President of JSOP, President-elect of ASOMP and IAOP

It is my great honor and pleasure to host 5th Meeting of Asian Society of Oral and Maxillofacial
Pathology (ASOMP) in conjunction with 22nd Annual meeting of Japanese Society of Oral Pathology(JSOP) in Fukuoka on August 23-25, 2011.
ASOMP is still at the stage of dawn and we need to develop our association under the mutual
understanding and collaboration among Asian countries. For this purpose, we have to cultivate humanresources and facilitate our research activities in the ﬁeld of oral pathology in Asia.
In this meeting, we plan a keynote lecture and two symposia. Professor Yamaguchi, an internationallyrecognized authority on bone pathobiology, will give up-to-date information about bisphosphonaterelated osteomyelitis of jaw. At educational symposium on education of Oral Pathology, Professor
Tilakaratne, IAOP councilor, Professor Chiang, president of Taiwan Academy of Oral Pathology, andProfessor Zain, a leading oral pathologist in Southeast Asia, will make some proposal toward educational
standardization and mutual accreditation of oral pathologist in Asia. To share current information andencourage each other, seven active oral pathologists will present their current research achievement at
the symposium of Frontier Research of Oral Pathology in Asia.
We believe that you will have exciting time and renew friendship at the meeting. On behalf of theorganizing committee, I deeply appreciate your participation in 5th ASOP Meeting.

55Annual Meeting of JSOP日本臨床口腔病理学会総会・学術大会の記録・予定−Annual Meeting of JSOP−

6

6

回

年

会

期

主催校

1

1990

7/4,5

第5回IAOP会議と共催

東

2

1991

8/22,23愛知学院大学歯学部

名古屋

亀山洋一郎

3

1992

8/27,28

明海大学歯学部

東

京

内海

順夫

4

1993

8/26,27

福岡歯科大学

福

岡

北村

勝也

5

1994

8/4,5

昭和大学歯学部

東

京

吉木

周作

6

1995

8/29,30

北海道大学歯学部

札

幌

雨宮

璋

7

1996

8/22,23

松本歯科大学

塩

尻

枝

重夫

8

1997

8/21,22長崎大学歯学部

長

崎

岡邊

治男

9

1998

9/11,12広島大学歯学部

広

島

二階

宏昌

10

1999

8/26,27

日本大学松戸歯学部

松

戸

山本

浩嗣

11

2000

8/25,26

鶴見大学歯学部

横

浜

菅原

信一

鹿児島

北野

元生

東

高木

実

12

2001

8/23,24

鹿児島大学歯学部

132002

8/23,24東京医科歯科大学大学院歯学総合研究科

14

2003

8/21-23大阪大学大学院歯学研究科

15

2004

8/5-7

16

2005

17

開催地
京

京

大会長
石木

哲夫

淡路島

伊集院直邦

日本大学歯学部

東

京

茂呂

周

8/24-26

岩手医科大学歯学部

盛

岡

佐藤

方信

2006

8/17-19

日本歯科大学新潟生命歯学部

新

潟

片桐

正隆

18

2007

8/9-11

朝日大学歯学部

岐

阜

竹内

宏

19

2008

8/9-11

東京歯科大学

東

京

下野

正基

20

2009

7/29-31北海道医療大学歯学部

札

幌

賀来

亨

21

2010

7/30-8/1

大阪歯科大学

枚

方

田中

昭男

22

2011

8/23-25

福岡歯科大学

福

岡

谷口

邦久

23

2012

Information

ご 案 内 と お 願 い−Information−

１．総合受付 Registration
九州大学医学部百年講堂1Fロビーにて８月24日（水），８月25日（木）午前8：15より受付を開始致します。
当日参加される方は，当日受付にて参加費10,000円，懇親会費8,000円（希望者のみ）をお支払い下さい。
その後，抄録集とネームカードをお受け取り下さい。
演者・共同演者は，日本臨床口腔病理学会会員，あるいはアジア口腔病理学会会員に限ります。
未入会の方は参加登録と共に，いずれかの学会事務局にて入会手続きをお願い致します。
※ご注意・ネームカード（参加証）を着用していない方の入場はお断りいたします。
・ランチョンセミナーは，会場（中ホール）でお弁当をお受け取り下さい。
但し人数に限りがありますのでご了承下さい。

On-site registration
Registration desk in the lobby on the 1st floor, Centennial Hall, Kyushu University, School of
Medicine
24, August（Wed）：8:15 〜
25, August（Thu）：8:15 〜
Please bring the printed conﬁrmation form to registration desk for overseas participants. You should
pay preregistration fee of JPN 8,000. The participant who has the confirmation form after preregistration period or who does not have conﬁrmation form should pay on-site registration fee of JPN
10,000. (See the following table.)
On-site Registration fee
GeneralJPN 10,000

Student

JPN 5,000

Reception fee

JPN 8,000

２．会場 Meeting Place
総合受付
Registration Desk

九州大学医学部百年講堂1F
交流ロビー
the lobby on the 1st ﬂoor, Centennial Hall Kyushu University School of Medicine

A会場
Meeting Place A〃

メインホールMain hall

B会場
Meeting Place B

〃

中ホール１
Medium hall 1

C会場
Meeting Place C

〃

中ホール３
Medium hall 3

クローク
Cloak

〃

交流ロビー
Lobby

7

7

Information

懇親会
Reception〃

中ホール１＋中ホール２
Medium hall 1 & 2

３．発表される先生方へ Informaton for presenters●口演発表（A会場）について

Oral Presentation

1）一般演題（口演）は口演８分，質疑応答２分とさせていただきます。ただし，症例検討につきましては口演10分，質疑応答５分とさせていただきます。口演スライドのテキストやキャプション部は，英語表記でお願いします。
2）発表の30分前までに交流ホールのスライド受付までお越しください。講演データの取り込みを行います。液晶ディスプレイで試写確認の上，PCオペレーターへデータをご提出ください。
3）講演データはメディアにてご持参ください。Windows FormatのCD-RあるいはUSBフラッシュメモ
リーをご準備ください。Macintosh版でのご提出，会場でのWindows版への変換はできませんのでご留意ください。CD-Rをご利用の場合は汎用に再生できるよう，ファイナライズを行ってください。
4）会場で使用するPCのOSはWindows Vistaです。
5）Windows版Power Point2003，2007，2010など当該OSで作動するものでファイルを作成してください。Windowsに標準搭載されているフォントのみ使用可能です。これ以外のフォントを使用した場
合，文字・段落のずれ，文字化け，表示されない等のトラブルが発生する可能性があります。
6）Power Pointのスライドの枚数に制限はありませんが，制限時間内に発表が終了するようにしてください。
7）事故に備えて，バックアップのCD-RあるいはUSBフラッシュメモリーをご用意ください。
8）保存ファイル名は発表者の「演題番号氏名.ppt」としてください。 （例）1A-01 福岡太郎.ppt

9）動画はWindows Media Playerで再生可能な形式としてください。動画を使用する場合はリンク切れにご注意ください。メディアにコピーした後，作成したPC以外のPCで動作確認を行ってください。
なお，動画ファイルには必ず拡張子（.aviなど）を付けてください。
10）PCをご持参の場合は，専用ACアダプターをご持参ください。ディスプレイ外部出力はD-SUB15ピ
ンにてご用意致します。接続コネクタが必要な場合はご持参ください。

●示説（ポスターについて） Poster presentation
1）ポスターパネルサイズは１演題につき縦210cm，横90cmです。
2）ポスターの貼付・撤去の日時は以下の通りです。
貼付

８月24日（水）9:00〜11:00

撤去

８月25日（木）15:00〜

3）演題番号は合同開催事務局にて準備・掲示いたします。
題名・所属・氏名については各発表者にてご用意ください。
4）討論時間は8月24日（水）17:30〜18:00です。
5）ポスターのテキストやキャプション部は，英語表記でお願いします。

Poster registration time:

24, August（Wed）, 9:00 〜 11:00*Please get a ribbon for presenter and clipping tools at registration desk.
*Make sure that your poster is exhibited at the right place according your poster number.（Check
your poster number.）88

Information

Poster discussion time:

24, August（Wed）, 17:30 〜 18:00*Poster presenter（with ribbon-wearing）should stand beside your poster and be ready for thequestions from visitors.
Tips for making poster

Poster removal time:

25, August（Thu）, 15:00 〜Notes:
1. All the items above should be completed.
2. Each letter of your family name should be in capital.
For example:Taro HIROSHIMA, Haruki MURAKAMI
3. The poster should be 210cm in height and 90cm in width.
4. The content should be in English.

４．座長の先生へ Information for chairs1）担当セクション開始予定時間の15分前までに次座長席にお着きください。
2）発表時間および質疑応答時間は以下の通りです。定時進行にご協力をお願い致します。
・口演発表の発表時間は８分，討論時間は２分間です。
・症例検討の発表時間は10分，討論時間は５分間です。
Please sit at the next chair seat before 15 minutes of your charged session and direct your session
according to the schedule.

５．総会 JSOP general meeting
日本臨床口腔病理学会総会
日時：平成23年８月24日（水）13：00〜13：30
会場：九州大学医学部百年講堂

A会場（メインホール）

24, August（Wed）, 13：00〜13：30
Meeting Place A : Main Hall, Centennial Hall, Kyushu University, School of Medicine

６．懇親会

Reception

招待客，一般会員，理事，評議員合同の懇親会を開催致します。
日時：平成23年８月24日（水）18：00〜20：00
会場：九州大学医学部百年講堂

中ホール１＋中ホール２

会費：会員・非会員 8,000円
大学院生

8,000円

学部学生

無料（※但し学生証提示。大学院生は対象となりません。）

Time: 24, August（Wed）, 18:00 〜 20:00
Place: medium hall 1 & 2, Centennial Hall, Kyushu University School of Medicine
On-site Reception fee: general member and non-member JPN 8,000
Post graduate student
JPN 8,000
Under graduate student
Free（*show student ID）
皆様のご参加をお待ち申し上げます。
99

Event Information

学 会 行 事 案 内−Event Information−
８月23日（火）九州大学医学部百年講堂にて第22回日本臨床口腔病理学会 総会・学術大会，第５回アジア
口腔病理学会の各種学会行事が開催されます。各行事の日程につきましては，以下の表をご確認ください。

8月23日（火）九州大学医学部百年講堂
行事名

10

10

時

間

会

アジア留学生病理実習

10:00〜16:30

会議室２

編集委員会

14:00〜15:00

会議室１

会則検討委員会

15:00〜16:00

中ホール１

教育委員会

15:00〜16:00

中ホール１

医療業務委員会

15:00〜16:00

中ホール１

研究委員会

15:00〜16:00

中ホール１

企画委員会

15:00〜16:00

中ホール１

広報・渉外委員会

15:00〜16:00

中ホール１

国際交流委員会

15:00〜16:00

中ホール１

常任委員会

16:15〜18:00

会議室１

役員会・理事会

18:00〜20:00

中ホール１

若手の集い

18:30〜20:30

会議室２

場

Location Map

学 会 周 辺 案 内 図−Location Map−

会場交通案内九州大学医学部百年講堂
【空路】
福岡空港→
（地下鉄空港線）→「中洲川端駅」、貝塚方面へ乗換→（地下鉄箱崎線）→「馬出九大病院前駅」【JR】「JR博多駅」→（地下鉄空港線）→「中洲川端駅」、貝塚方面へ乗換→（地下鉄箱崎線）→「馬出九大病院前駅」「JR博多駅」→「JR吉塚駅」で下車【西鉄】「西鉄福岡駅」→（地下鉄）→「馬出九大病院前駅」で下車【高速バス】
天神バスセンター下車→（地下鉄）→「馬出九大病院前駅」で下車

Venue &
AccessCentennial Hall Kyushu University School of Medicine【Route】
Fukuoka Airport → (Subway Kuko Line) → Nakasu-Kawabata Station →(Transfer Subway Kaizuka Line) → Maidashi-Kyudaibyoinmae Station →Hospital Campus

1111Floor Map

学会会場案内図（九州大学医学部百年講堂）−Floor Map (Centennial Hall Kyushu University School of Medicine)−【中ホール1】【Medium Hall 1】
B会場
Meeting Place B
ランチョンセミナー
Luncheon Semminar
懇親会
Reception
ステージ
Stage

中庭
GardenEV

中ホール3
Medium Hall 3

中ホール1
Medium Hall 1
中ホール2
Medium Hall 2
交流ロビー
Lobby

交流ホール
Hall

Restroom
女子 男子
便所 便所

大ホール
Large Hall

【メインホール】【Main Hall】

受付
Registration Desk
交流ロビー
Lobby

A会場
Meeting Place A

カフェテリアCafeteria【中ホール3】【Medium Hall 3】

１階
1F

C会場（ポスター会場）
Meeting Place C（Poster Exhibition Place）【会議室2】【Conference Room 2】
アジア控室
Waiting Room for ASOMPASOMP打ち合わせ

Restroom

男子便所

会議室2
Conference Room 2
会議室1
EV
Conference Room 1

会議室3
Conference Room 3

女子便所【会議室3】【Conference Room 3】
本部
Headquarters

2階
2F

12

12

List of Chairs

座 長 一 覧−List of Chairs−◆一般演題（口演）Ⅰ ＜A会場：メインホール＞ 8月24日（水）9：10〜 9：50
井上孝（東京歯科大学）
9：55〜10：55
朔敬（新潟大学）◆特別講演 ＜A会場：メインホール＞ 8月24日（水）11：00〜12：00 谷口 邦久（福岡歯科大学）◆ランチョンセミナーⅠ ＜B会場：中ホール1＞ 8月24日（水）12：10〜13：00 斎藤 一郎（鶴見大学歯学部 教授・病院長）◆ASOMP Session ＜24, August 2011, Main hall in Centennial Hall＞
Keynote lecture
13：30〜14：30 Takashi Takata（Hiroshima University）
Educational Symposium
14：30〜15：30 Sam-Pyo Hong
（Seoul National University）
Hatsuhiko Maeda （Aichigakuin University）
ASOMP Scientiﬁc Session 15：40〜17：25 Takashi Saku
（Niigata University）
Eun-Cheol Kim（Kyung Hee University）
Kazuo Komiyama （Nihon University）
Yu Chen（Sichuan University）
Akio Tanaka
Kuo-Wei Chang（Osaka Dental University）（National Yang Ming University）◆一般演題（口演）Ⅱ ＜A会場：メインホール＞ 8月25日（木）9：00〜 9：30
工藤 保誠（広島大学大学院医歯薬学総合研究科口腔顎顔面病理病態学）◆研修プログラム ＜A会場：メインホール＞ 8月25日（木）10：00〜12：00 清島保（九州大学大学院歯学研究院 口腔顎顔面病態学講座 口腔顎顔面病態病理学分野）
岡村 和彦（福岡歯科大学生体構造学講座病態構造学分野）◆ランチョンセミナーⅡ ＜B会場：中ホール1＞ 8月25日（木）12：10〜13：00 仙波伊知郎（鹿児島大学大学院医歯学総合研究科口腔病理解析学分野）◆一般演題（口演）Ⅲ ＜A会場：メインホール＞ 8月25日（木）13：30〜14：30 進藤 正信（北海道大学歯学研究科 口腔病態学講座）◆公開シンポジウム
14：30〜16：30＜A会場：メインホール＞ 8月25日（木）田中 陽一（東京歯科大学）
関根 浄治（島根大学）

13

13

Schedule

日程−Schedule−

学会日程表/第１日目：８月24日（水）A会場（メインホール）

B会場
C会場
会議室2
（中ホール1）（中ホール3）（アジア控室）

会議室3

会議室3
（本部）
８：50
９：10

開会のご挨拶
一般演題（口演）
Ⅰ
座長：井上
孝

９：50
９：55 症例検討Ⅰ
座長：朔

11：00

12：00

敬

13：30

ポスター・展示

特別講演「頭頚部骨軟部腫瘍および腫瘍類似病変の病理」
九州大学大学院医学研究院 形態機
能病理 九州大学病院病理部
小田 義直

12：10

13：00

ポスター貼付
9:00〜11:00

ASOMP
打ち合わせ

ランチョン
セミナーⅠ
総会

日本臨床口腔病理学会

13:30 ‒ 17:25
ASOMP Session

14：00 13:30-14:30

Keynote lecture
Histopathological characteristics
of bisphosphonate-related
osteomyelitis (osteonecrosis) of jaw
Akira Yamaguchi

15：00 14:30-15:30

Educational Symposium：
Education of oral pathology in Asia,
toward educational standardizationand mutual accreditation of oral
pathologist in Asia

16：00 15:40-17:25

ASOMP Scientiﬁc Session：
Frontier research of oral pathology
in Asia

17：00
17：25
18：00

14

14

ポスター討論17:30〜18:00
18:00〜20:00
懇親会(中ホール1+2)

Schedule

学会日程表/第２日目：８月25日（木）A会場（メインホール）

B会場
C会場
会議室2
（中ホール1）（中ホール3）（アジア控室）

会議室3

会議室3
（本部）

９：00

一般演題（口演）Ⅱ
座長：工藤保誠
９：35 「口腔病理基本画像アトラス」
小宮山先生
10：00

ポスター・展示

研修プログラム「口腔病理医の剖検」

11：00

12：00
12：10

ランチョン
セミナーⅡ

13：00
13：20
14：00

症例検討Ⅱ
座長：進藤

正信

14：20
14：30

公開シンポジウム「口腔がんに挑む細胞診−口腔病
15：00 理医と開業歯科医の連携を目指して−」ポスター撤去15:00〜

16：00
16：30

閉会のご挨拶

15

15

Schedule

Schedule/The ﬁrst day August 24
Meeting Place A(Main Hall)

８：50
９：10

Meeting Place B Meeting Place C Conference Room 2
Conference Room 3(Medium Hall 1) (Medium Hall 3) (Waiting Room)
Conference
Room3(Headquarters)

Opening Address
Oral PresentationⅠ

9:00〜11:00
Posterregistration

９：50
９：55 Case StudyⅠ

11：00

Special Lecture

PosterPresentation

12：00
12：10

13：00
13：30

ASOMP
Meeting

Luncheon
SeminarⅠ
JSOP general meeting
13:30 ‒ 17:25
ASOMP Session

14：00 13:30-14:30

Keynote lecture
Histopathological characteristics
of bisphosphonate-related
osteomyelitis (osteonecrosis) of jaw
Akira Yamaguchi

15：00 14:30-15:30

Educational Symposium：
Education of oral pathology in Asia,
toward educational standardizationand mutual accreditation of oral
pathologist in Asia

16：00 15:40-17:25

ASOMP Scientiﬁc Session：
Frontier research of oral pathology
in Asia

17：00
17：25
18：00

16

16

17:30〜18:00
Poster Discussion
18:00〜20:00
Reception(Medium Hall 1&2)

Schedule

Schedule/The second day August 25
Meeting Place A(Main Hall)

Meeting Place B Meeting Place C Conference Room 2
Conference Room 3(Medium Hall 1) (Medium Hall 3) (Waiting Room)
Conference
Room3(Headquarters)

９：00
９：35

10：00

Oral PresentationⅡ
Presentation「The Basic Oral Pathology
Atras」

PosterPresentation

Training Program

11：00

12：00
12：10

Luncheon
SeminarⅡ

13：00
13：20

Case StudyⅡ

14：00
14：20
14：30

Public Symposium

15：00

Poster removal
15:00〜

16：00
16：30

Closing Address

17

17

プログラムProgram19

Program

開会のご挨拶

A会場（メインホール）8月24日（水）8：50〜9：00

Opening Address

Meeting Place A (Main Hall) August 24

一般演題（口演）Ⅰ・症例検討Ⅰ

8:50〜9:00

A会場（メインホール）8月24日（水）Oral PresentationⅠ・Case StudyⅠ

Meeting Place A (Main Hall) August 24

9：10〜9：50
Chair：Takashi Inoue (Tokyo Dental College)
1A-01

Bizarre parosteal osteochondromatous proliferation of the maxilla; A case report
Department of Stomatology and Oral Surgery, Graduate School of Medicine, Gunma University
Aiko Nobusawa …36

1A-02

Intraoral polypoid lesions during the course of GVHD
Clinical Laboratory, Osaka University Dental Hospital
Yu Usami …37

1A-03 Hemophagocytosis-induced Par-2 expression regulates cytoskeletal rearrangement andcell growth of oral squamous cell carcinoma
Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences
Al-eryani Kamal …38
1A-04

A case of adenoid cystic carcinoma partially-observed growth of myoepithelial cells
Department of Clinical Pathophysiology, Tokyo Dental College
Kei Nakajima …39

Case StudyⅠ

9：55〜10：55

Chair：Takashi Saku (Niigata University)
1A-05

A case of the tumor in the left inferolateral margin of the tongue
Department of Pathology, Hyogo College of Medicine, Hyogo college of Medicine
Koji Yamanegi …40

1A-06

Soft tissue tumour of the lower lip
Laboratory of Oral Pathology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University
Hiroko Wada …41

1A-07

Maxillary tumor
Department of Oral pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Naoki Katase …42

1A-08

Tumor of mandible
Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences
Manabu Yamazaki …43

20

20

Program

特別講演A会場（メインホール）8月24日（水）11：00〜12：00

Special Lecture

Meeting Place A (Main Hall) August 24

11:00〜12:00

Chair：Kunihisa Taniguhi (Fukuoka Dental College)

Pathology of bone and soft tissue tumor and tumor-like lesions in head and neck
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University
Yoshinao Oda …47

ランチョンセミナー
Luncheon Seminar

ランチョンセミナーⅠ
Luncheon Seminar Ⅰ

B会場（中ホール1）8月24日（水）12：10〜13：00
Meeting Place B (Medium Hall 1) August 24 12:10〜13:00

Chair：Ichiro Saito (Department of Pathology, Tsurumi University School of Dental Medicine)

Diagnosis and treatment for Sjögrenʼs syndrome and the similar diseases
Professor and Chairman, Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic
and Surgical Sciences, Faculty of Dental Science, Kyushu University
Seiji Nakamura …51

ASOMP Session

24, August 2011, Main hall in Centennial Hall

Keynote lecture

13:30-14:30

Chair : Takashi Takata (Hiroshima University)

Histopathological characteristics of bisphosphonate-related osteomyelitis (osteonecrosis)
of jaw
Akira Yamaguchi (Tokyo Medical and Dental University) …55

Educational Symposium:

14:30-15:30

Education of oral pathology in Asia, toward educational standardization and mutual
accreditation of oral pathologist in Asia
Chair：Sam-Pyo Hong (Seoul National University)
Hatsuhiko Maeda (Aichigakuin University)

Introduction
Hatsuhiko Maeda (Aichigakuin University) …57

Oral Pathology in Asia; where are we?
Tilakaratne WM (University of Peradeniya) …59

21

21

Program

Current status of education for the oral pathologist in Taiwan
Chun-Pin Chiang (National Taiwan University) …61

Oral Pathology Specialty Training in Asia ‒ ensuring quality standards through strong
partnerships
Rosnah Zain (University of Malaya) …63

Panel discussion

ASOMP Scientiﬁc Session:

15:40-17:25

Frontier research of oral pathology in Asia
Chair： Takashi Saku (Niigata Unicersity)
Eun- Cheol Kim (Kyung Hee University)

A new insights into tumor endothelial cell
Kyoko Hida (Hokkaido University) …67

MicroRNA alterations in oral carcinoma - a linkage to hypoxia regulation
Kuo-Wei Chang (National Yang Ming University) …69
Chair：Kazuo Komiyama (Nihon University)
Yu Chen (Sichuan University)

Identiﬁcation of novel invasion related molecules in oral cancer
Yasusei Kudo (Hiroshima University) …71

The role of Cripto-1 in the tumorigenesis and progression of oral squamous cell
carcinoma
Seong-Doo Hong (Seoul National University) …73
Chair：Akio Tanaka (Osaka Dental University)
Kuo-Wei Chang (National Yang Ming University)

Wnt-1/beta-catenin signaling and WIF-1 deficiency are important events in salivary
gland adenoid cystic carcinoma progression
Yu Chen (Sichuan University) …75

Study on different cryopreservations and hepatogenic differentiation of human dental
pulp stem cells
Yuk-Kwan Chen (Kaohsiung Medical University) …77

Gender-based molecular pathogenesis of Sjögren's syndrome
Naozumi Ishimaru (Tokushima University) …79

22

22

Program

一般演題（口演）Ⅱ

A会場（メインホール）8月25日（木）Oral PresentationⅡ

Meeting Place A (Main Hall) August 25

9：00〜9：30
Chair：Yasusei Kudo (Hiroshima University)
2A-01 Genomic proﬁle of oral squamous cell carcinoma by oligonucleotide-array comparative
genomic hybridization
Department of Dentistry and Oral Maxillofacial Surgery, Oita University
Shunichi Yoshioka …82
2A-02

The role of thrombospondin-1 (TSP1) in invasion of oral cancer
Department of "Oral Pathology", Graduate School of Medical and Dental Science, Tokyo Medical and Dental University
Samir Kumar Pal …83

2A-03

The diﬀerential diagnosis and histopathogenesis of thyroglossal duct cyst: a comparative
immunohistochemical study
Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction,
Graduate School of Medical and Dental Sciences, Niigata University
Henry Ademola Adeola …84

Presentation

9:35〜9:50

Chair：Takashi Takata (Hiroshima University)

The Basic Oral Pathology Atlas
The Board of Education of the Japanese Society of Oral Pathologists The database subcommittee of “The Basic Oral Pantology Atlas”
Kazuo Komiyama …85

研修プログラム
Training Program

A会場（メインホール）8月25日（木）10：00〜12：00

Meeting Place A (Main Hall) August 25 10:00〜12:00

Chair：Tamotsu Kiyoshima (Kyushu University)
Kazuhiko Okamura (Fukuoka Dental College)

Autopsy by oral pathologists

Presentation of Autopsy Cases
・An autopsy case of hemorrhagic shock by ruptured of gastroesophageal varix
Department of Oral Pathology, Division of Oral Pathogenesis and Disease Control, Asahi University School of Dentistry
Michiko Ehara, et al. …89

23

23

Program

・An autopsy case of osteosarcoma occurred in the maxillary sinus after radiotherapy
to malignant lymphoma
Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Science
Hanako Suzuki …90

・Toxoplasma encephalitis presenting clinically as a suspected relapse of malignant
lymphoma involving the central nervous system: an autopsy case
Division of Oral Pathology, Department of Biosciences, Science of Health Improvement, Kyushu Dental College
Ayataka Ishikawa, et al. …93

Summary
The knowledge of pathological autopsy report
Department of Pathology, Saitama Cancer Center
Toshiyuki Izumo …97

ランチョンセミナー
Luncheon Seminar

ランチョンセミナーⅡ

B会場（中ホール1）8月25日（木）12：10〜13：00

Luncheon Seminar Ⅱ

Meeting Place B (Medium Hall 1) August 25 12:10〜13:00

chair： Ichiro Semba (Kagoshima University)
Yoshiaki Kamikawa …100

症例検討Ⅱ

A会場（メインホール）8月25日（木）Case StudyⅡ

Meeting Place A (Main Hall) August 25

13：20〜14：20
chair：Masanobu Shindo (Hokkaido University)
2A-04

A case of parotid gland tumor
Department of Diagnostic Pathology, Fujita Health University, School of Medicine
Makoto Urano …104

2A-05

A case of palatal tumor
Department of Pathology, Nihon University School of Dentistry
Naoyuki Matsumoto …105

2A-06

Palatal tumor
Center of Oral Clinical Examination, Hiroshima University Hospital
Ikuko Ogawa …106

24

24

Program

2A-07

A case of odontogenic tumor
Department of Oral Pathology, Asahi University School of Dentistry
Motohiko Nagayama …107

公開シンポジウム

A会場（メインホール）8月25日（木）14：30〜16：30

Public Symposium

Meeting Place A (Main Hall) August 25 14:30〜16:30

Organizer：Yoichi Tanaka (Tokyo Dental College Ichikawa General Hospital)
Joji Sekine (Shimane University Faculty of Medicine)

Our approach to early detection of oral cancer using smear cytology
by general practitioners in collaboration with oral pathologists

基調講演
Keynote lecture

Tokyo Dental College Ichikawa General Hospital
Yoichi Tanaka

Clinical application of cytology
Shimane University Faculty of Medicine
Hiraoki Ishibashi, et al. …112

Mass screening of oral cancer
Nihon University School of Dentistry at Matsudo
Kayo Kuyam …113

Advantage and disadvantage of oral cytology
Faculty of Medicine, Oita University
Naomi Yada …114

Oral cancer detecting system Ichikawa network
Ichikawa Dental Association
Katsuhiro Takakura …115

一般演題（示説）
Poster Presentation

ポスター討論C会場（中ホール3）8月24日（水）Meeting Place C (Medium Hall 3) August 24

17：30〜18：00

Poster Discussion

P-01 Immunohistochemical localization of Notch signaling molecules in ameloblastomas
Department of Oral Pathology, School of Dentistry, Aichi Gakuin University
Katsutoshi Kubo, et al. …118

25

25

Program

P-02 Immunohistochemical observation of Notch signaling in a case of calcifying cystic
odontogenic tumor
Hard Tissue Pathology Unit, Matsumoto Dental University Graduate School of Oral Medicine
Toshiyuki Kawakami, et al. …119
P-03

Differential expression of Notch receptors and their ligands in calcifying epithelial
odontogenic tumors
Department of Oral Pathology, Oral Medicine & Periodontology, Faculty of Dentistry, University of Malaya
Chong Huat Siar, et al. …120

P-04

Co-expression of BMP-2 and -7 in the epithelium of calcifying epithelial odontogenic tumor
with selective BMP-7 expression in amyloid materials
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Hidetsugu Tsujigiwa …121

P-05

Ameloblastic carcinoma of the maxilla.
Department of Oral Pathology, Graduate School of Dentistry, Aichi Gakuin University
Anuudari Erkhembaatar …122

P-06

Ameloblastoma, - a case report and treatment conditions in Laos.
Department of Oral Surgery, Faculty of Dentistry, University of Health Sciences, Lao P.D.R
Souksavanh Vongsa …123

P-07

Clinicopathological study in keratocystic odontogenic tumors
Second Department of oral and maxillofacial Surgery, Osaka Dental University
Katsuko Horii …124

P-08

Fate of epithelial cell rests of Malassez on MNU-induced rat molar regions
Department of Pathology 2, Kansai Medical University
Ayako Kimura …125

P-09 Histopathological analysis of the precancerous lesion using 4NQO-induced rat tongue
carcinogenesis experimental model
Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Kagoshima University
Yoshitaka Oyazato …126
P-10

Cytokeratin expression in oral epithelial hyperplasia
Department of Oral Pathology, Matsumoto Dental University
Takanaga Ochiai …127

P-11

Laser light-mediated topical photodynamic therapy for oral precancers
Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University
Hung-pin Lin …128

P-12

A role of Trk family in oral cancer
Deapartment of Molecular Pathology, Nara Medical University
Tomonori Sasahira …129

26

26

Program

P-13

New methods to identify resistant genes for chemotherapy
Department of Oral Pathology & Biology, Hokkaido University Graduate School of Dental Medicine
Tetsuya Kitamura …130

P-14

Investigation into Notch-1 expression and its role in oral squamous cell carcinoma.
Department of Pathology and Experimental Medicine/Oral and Maxillofacial Surgery, Graduate School of Life Sciences, Kumamoto University
Ryoji Yoshida …131

P-15

MUC1 expression in squamous cell carcinoma of the tongue
Department of Dentistry, Oral and Maxillofacial Surgery, Jichi Medical University
Yoshinori Jinbu …132

P-16

CXCR-4 overexpression increases the cell proliferation and invasion via MAPK/ERK
signaling in oral cancer cells.
Department of Oral Pathology, School of Dentistry, Seoul National University
Ji soo Hong …133

P-17

Intraductal papilloma with peri-luminal extension of the minor salivary gland: a new disease
entity by clinicopathological analysis of 82 cases
Division of Oral Pathology Department of Tissue Regeneration and Reconstruction,
Graduate School of Medical and Dental Sciences, Niigata University
Jun Cheng …134

P-18

miR-146a expression is associated with the oncogenicity of oral carcinoma
Institute of Oral Biology, National Yang-Ming University
Shu-chun Lin …135

P-19

Nuclear Survivin expression is well correlated with tumor progression of head and neck cancer
Department of Oral & Maxillofacial Pathobiology, Graduate School of Biomedical Sciences, Hiroshima University
Intan suraiya Merican Aljunid merican …136

P-20

Proteomic proﬁle of VX2 induced rabbit OSCC (early- and late- stage) ‒ preliminary report
Departments of Oral Pathology, School of Dentistry, Kaohsiung Medical University
Li-min Lin …137

P-21 Immunohistochemical study of cytokeratin-13, -17 and p53 in epithelial dysplasia and carcinomaof the tongue
Department of Pathology, School of Life Dentistry at Niigata, The Nippon Dental University
Yasuo Okada …138
P-22

Roles of N-cadherin in head and neck squamous cell carcinoma
Department of Oral & Maxillofacial Pathobiology, Graduate School of Biomedical Sciences, Hiroshima University
Phuong thao Thi Nguyen …139

P-23 Comparison of expression proﬁles of MMP2 and MMP9 in primary and metastatic OSCCs
in relation to CD68 positive macrophage distribution
Department of Pathology, Nihon University School of Dentisry
Daisuke Omagari …14027

27

Program

P-24

Signiﬁcance of podoplanin expression in oral precancerous and cancerous lesions
Research Group in Oral Pathology, Meikai University Graduate School of Dentistry
Harumi Inoue …141

P-25

Expression of pyruvate kinase isozymes in oral squamous cell carcinoma
Department of Molecular Pathology, Nara Medical University
Miyako Kurihara …142

P-26 Relationship between the expressions of PD-L1 and tumor-inﬁltrating lymphocytes in oral
squamous cell carcinoma
Department of Oral Pathology, School of Dentistry, Seoul National University
Young-ah Cho …143
P-27

Ni2+ ion inhibited the secretion of IL-8 by oral squamous cell carcinoma cells (OSCCs)
Department of Partial Denture Prosthodontics, Nihon University School of Dentistry
Shigeki Endo …144

P-28 Comparative characterization of tumor endothelial cells isolated from highly and low
metastatic tumors
Dept. Vascular Biology, Hokkaido Univ.Grad.Sch.Dent.Med.
Noritaka Ohga, et al. …145
P-29

Expression of PTHrP in mucoepidermoid carcinoma
Department of Oral Pathology & Biology, Hokkaido University Graduate School of Dental Medicine
Kyosuke Nagamine …146

P-30

Application of salivary gland tumors using triple-immunostaining method
Department of Oral Pathology, Osaka Dental University
Masahiro Wato …147

P-31

High-grade transformation in adenoid cystic carcinoma: report of three cases withhistological study
Japanese Foundation for Cancer Research, The Cancer Institute, Division of Pathology
Yukiko Sato …148

P-32

A case of metachronous carcinoma ex pleomorphic adenoma arising from the buccal
minor salivary gland and the contralateral parotid gland
Department of Oral Pathology and Bone Metabolism, Unit of Basic Medical Sciences,
Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences
Shuichi Fujita …149

P-33

Mucepidermoid carcinoma of the salivary glands: three unusual examples
Department of Pathology and Research, Sakai Municipal Hospital
Hiroshi Harada …150

P-34

Mucoepidermoid carcinoma of the sublingual gland with mandibular invasion: a case report
Division of Oral and Maxillofacial Reconstructive Surgery, Department of Oral and Maxillofacial Surgery, Kyushu Dental College
Shoko Tsuruoka …151

28

28

Program

P-35 Endoglin expression in oral hemangioma −A comparative study with expression ofendothelial markers and angiogenic factors−
Department of Pathology, Nihon University School of DentistryMotomi Tsuchiya …152
P-36

A case of leiomyoma arising in the lingual edge
Department of Diagnostic Pathology, Kobe University Graduate School of medicine
Chihoko Hirai …153

P-37

A case of myxoid tumor of the lower lip
Department of Oral Pathology, School of Dentistry, Aichi Gakuin University
Yoshihiko Sugita …154

P-38 Immunohistochemical study of carcinoma cuniculatum-subtype of oral squamous cell
carcinoma
Nihon University Graduate School of Dentistry at Matsudo, Department of Oral Pathology
Yan Sun …155P-39

A case of large cell neuroendocrine carcinoma of the tongue
Pathology Division of Clinical Laboratory, National Center for Global Health and Medicine
Shigeo Kawai …156

P-40 Pilomatricoma with extensive ossification mimicking a salivary stone in a panoramic
photograph: a case report
Division of Oral and Maxillofacial Reconstructive Surgery, Department of Oral and Maxillofacial Surgery, Kyushu Dental College
Hiroyasu Kiyomiya …157
P-41

Mast cell and myoﬁbroblast in denture-related ﬁbrous hyperplasia
Department of Partial Denture Prosthodontics, Nihon University School of Dentistry
Misa Kiuchi …158

P-42

A case of maxillary gingival ulcer in relation to the Antirheumatic drug (MTX)
Department of Pathology, School of Life Dentistry at Niigata, The Nippon Dental University
Yoriaki Kanri …159

P-43

A case of primary oral sporadic-Burkkitt's lymphoma in an adult female
Division of Pathology, Department of Diagnostic & Therapeutic Sciences, Meikai University School of Dentistry
Kentaro Kikuchi …160

P-44

Areca nut extract reduces the phagocytic function of human peripheral blood mononuclear cells
Institute of Oral Biology, Dental Department, School of Dentistry, National Yang-Ming University
Lien-yu Chang …161

P-45

Expression of hBD-2 and inﬁltration of T lymphocytes in chronic hyperplastic candidiasis
Department of Oral Pathology, School of Dentistry, Seoul National University
So-young Choi …162

29

29

Program

P-46

miR-214 acts as a repressor of adenovirus proliferation by inactivating E1A
Department of Oral Pathology & Biology, Hokkaido University Graduate School of Dental Medicine
Aya Matsuda …163

P-47

Adenovirus E4orf6/7 activates ASPP1 that induces apoptosis
Department of Oral Pathology and Biology, Graduate School of Dental Medicine, Hokkaido University
Alam Towﬁk

P-48

Mohammad …164

Immunohistochemical expression of HSP27 in the mouse periodontal tissues due toorthodontic mechanical stress
Hard Tissue Pathology Unit, Matsumoto Dental University Graduate School of Oral Medicine
Rina Muraoka …165

P-49

Promoting eﬀect of mechanical stress to transplanted bone marrow-derived cell migration
into periodontal tissues
Department of Oral Physiology, Matsumoto Dental University School of Dentistry
Mihoko Tomida …166

P-50

Strawberry gingivitis as the ﬁrst presenting sign of Wegener's granulomatosis: Report of a case
Department of Oral Pathology, Matsumoto Dental University School of Dentistry
Keisuke Nakano …167

P-51

Notch signaling proteins in primary and recurrent chondrosarcoma of the jaw: A case report
Formerly Unit of Stomatology, Cancer Research Centre, Institute for Medical Research
Kok Han Ng …168

P-52

Low level laser therapy at acupuncture points in temporomandibular joint disorderCollege of Oral Medicine, Chung Shan Medical University
Yu-feng Huang …169

P-53

A comparative study of seven devices used for oral squamous cell sampling
Department of Oral Medicine, Oral and Maxillofacial Surgery, Tokyo Dental College
Hiroaki Ikawa …170

P-54

The current state of the Oral Cancer Detecting system ICHIKAWA Network (OCDSIN)
Oral Cancer Center, Tokyo Dental College, Tokyo Dental College
Kazumichi Sato …171

P-55

Usefulness of Oral Exfoliative Cytology as a Follow-up Examination for Leukoplakia
Department of Oral Medicine, Oral and Maxillofacial Surgery, Tokyo Dental College
Shuichi Nishikubo …172

P-56

Oral exfoliative cytology is useful in diagnosing early cancer; report of two cases
Department of Oral Medicine, Oral and Maxillofacial surgery, Tokyo Dental College
Yoshifumi Yoshida …17330

30

Program

P-57 Histone deacetylases (HDACs) inhibitor, Trichostatin A, induces G2/M phase arrest andapoptosis in oral squamous carcinoma YD-10B cells
Department of Pathology, School of Dentistry, Chosun University
Sang-Gun Ahn, et al. …174
P-58

Inhibition of autophagy enhances apicidin-induced apoptosis in human oral squamous
carcinoma cells
Department of Pathology, School of Dentistry, Chosun University
Jung-Hoon Yoon, et al. …175

P-59

In vitro and in vivo photodynamic therapy using pheophorbide A induces apoptosis inmouse oral cancer AT-84 cells
Department of Pathology, School of Dentistry, Chosun University
Jung-Hoon Yoon, et al. …176

P-60

Eﬀect of Dentin Sialoprotein on Proliferation, Migration and Diﬀerentiation in Human Dental
Pulp Cells
Department of Maxillofacial Tissue Regeneration, School of Dentistry and Institute of Oral Biology, Kyung Hee University
Eun-Cheol Kim …177

P-61

The Role of SIRT1 on Angiogenic and Odontogenic Potential in Human Dental Pulp Cells
Department of Animal Biotechnology, College of Animal Biosciences & Technology, Konkuk Unversity
Jong-Jin Kim …178

P-62 A case of acinic cell carcinoma arising in the lower lip
Department of Clinical Pathophysiology, Tokyo Dental College
Kazuhiko Hashimoto, et al. …179
P-63

Eﬃcacy of ﬁne needle biopsy in the diagnosis of oral and maxillofacial lesions
Division of Oral Medicine, Department of Oral and Maxillofacial Surgery, Shimane University Hospital
Yoshihiko Kaneda, et al. …180

P-64

Eﬀect of surgical instruments on cytological features
Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine
Katsumi Hideshima, et al. …181

P-65

Our cytological approach to oral lesions
Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine
Katsumi Hideshima, et al. …182

P-66

Feasibility of cytological examination of oral and maxillofacial lesions
Division of Oral Medicine, Department of Oral and Maxillofacial Surgery, Shimane University Hospital
Mayumi Ueno, et al. …183

P-67

Oral cancer detection by mass screening using smear cytology in Shimane prefecture
Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine
Masaaki Watanabe, et al. …184

31

31

講演抄録
Abstracts

33

一般演題（口演）
Ⅰ・症例検討Ⅰ
Oral PresentationⅠ ・Case StudyⅠ35

1A-01上顎前歯部に発生したBizarre parosteal osteochondromatous
proliferationの１例

Bizarre parosteal osteochondromatous proliferation of the maxilla; A case report
信澤 愛子1,2，根岸 明秀1，佐野 孝昭2，小山 徹也2，横尾 聡1
Aiko Nobusawa1,2, Akihide Negishi1, Takaaki Sano2, Tetsunari Oyama2 andSatoshi Yokoo1
1

群馬大学大学院医学系研究科 顎口腔科学分野
群馬大学大学院医学系研究科 病理診断学分野
1
Department of Stomatology and Oral Surgery, Graduate School of Medicine, Gunma University
2
Department of Diagnostic Pathology, Graduate School of Medicine, Gunma University
2【緒言】傍骨性骨軟骨異形増生（Bizarre parosteal osteochondromatous proliferation：BPOP）は，稀な反応性の傍骨性良性病変である。好発部位は手足の小管骨とされ，頭頸部領域では極めて稀である。今回わ
れわれは，上顎前歯部に発生し，再発を繰り返した既往のあるBPOPを経験したので報告する。
【症例および経過】患者は45歳女性。3 年前より上顎前歯部唇側にエプーリス様病変を認め，近医歯科にて3 回にわたり切除を行うも再発を繰り返した。 2 回目の切除後に，矯正治療も開始していた。 2 か月前の再発後，急速な増大を示し唇側方向に加え口蓋側方向にも病変が認められ，悪性腫瘍も疑われたため精査加療目的に当院歯科口腔外科を受診した。初診時，病変は唇側および口蓋側に認められた。唇側は有茎性で大きさ15×14×7mm，口蓋側は丘状に隆起し大きさ20×12×7mmで，いずれも骨様硬を呈した。歯間離開は認めないものの，正中部歯間乳頭を通じて連続している状態であった。CT所見では，病変相当部に不透過像を認めた。唇側部の生検にて骨芽細胞腫が疑われ，全身麻酔下にて周囲健常組織を含めた上顎部分切除術を施行した。切除標本の病変表層は軟骨で覆われており，不規則な成熟を示しながら内部へ向かって石灰化し放射状の骨梁を形成する病理組織学的所見であった。軟骨は富細胞性であり，その軟骨細胞の核は腫大しており大小不同・二核細胞などの異型を示していた。また，石灰化部位の骨梁はヘマトキ
シリンに濃染し，いわゆる blue-bone を呈していた。さらに，骨髄腔との連続を伴わないX線画像所見からBPOPと診断した。術後約 6 か月の現在，病変の再発は認めていない。
【結語】本病変は，急速な増大や局所再発傾向，細胞異型などの悪性を疑う臨床所見や組織学的所見を示す特異な病態である。頭頸部領域での報告は 3 例であり，極めて稀と考えられるため，骨肉腫や骨軟骨肉腫などの悪性腫瘍との鑑別を含めた診断・治療が重要である。
Bizarre parosteal osteochondromatous proliferation (BPOP) is a rare tumorous lesion of the bone, deﬁned
in 1983. BPOP usually occurs in the small tubular bones of the hands and the feets, sometimes confusedwith other benign or malignant lesions. BPOP grows rapidly and often recurs, and histologically it shows
hypercellular cartilage with bizarre chondrocytes and immature bony trabeculae. We report a case of
BPOP in the anterior maxilla of an adult woman. Only 3 cases have been reported in the head and neckregion; in the skull, maxilla and zygoma. BPOP in the head and neck region is still rare.

3636

1A-02

慢性GVHDの経過中に生じた口腔内腫瘤性病変
Intraoral polypoid lesions during the course of GVHD

宇佐美 悠1,2，竹信 俊彦3，岸野 万伸4，佐藤 淳4，石田 健4，小川 裕三4，
豊澤 悟4，福田 康夫1
Yu Usami1,2, Toshihiko Takenobu3, Mitunobu Kishino4, Sunao Sato4, Ken Ishida4,
Yuzo Ogawa4, Satoru Toyosawa4 and Yasuo Fukuda1
1

大阪大学歯学部附属病院 検査部
神戸市医療センター中央市民病院 病理診断科
3
神戸市医療センター中央市民病院 歯科口腔外科
4大阪大学大学院歯学研究科 口腔病理学教室
1
Clinical Laboratory, Osaka University Dental Hospital2
Department of Clinical Pathology, Kobe City Medical Center General Hospital3
Department of Oral and Maxillofacial Surgery, Kobe City Medical Center General Hospital
4
Department of Oral Pathology, Osaka University Graduate School of Dentistry2

近年，白血病といった造血器悪性腫瘍や造血器疾患に対し，骨髄移植が盛んに行われるようになり，免疫抑制状態に伴う感染予防目的の歯科的介入や，骨髄移植の合併症であるGVHDの治療，診断に歯科医が介入する機会が増えた。GVHDはレシピエントに定着したドナー由来のリンパ球がレシピエント組織を攻撃する事により，全身に様々な症状を生じる移植合併症であり，特に口腔病変は慢性GVHDのほとんどの症
例で認められ，扁平苔癬様粘膜病変，口腔乾燥の出現を特徴とする。一方で，GVHDを予防ないし軽減を目的として使用されるシクロスポリンA（CyA）は歯肉肥大を引き起こす代表的な薬物として知られている。我々は造血器腫瘍に対し，骨髄移植を施行され，慢性GVHDとともに出現したCyA投与患者の口腔内多発腫瘤性病変３例を経験した。腫瘤はいずれも表層に潰瘍形成を認め，血管増生，炎症性肉芽組織を主体として線維化を伴うpolypoidな病変で，病理組織学的にはpyogenic granulomaあるいはgranulation
tissueと診断された。慢性GVHDの口腔内病変として腫瘤形成性病変の報告は稀であり，GVHDによる病変か，CyAの副作用による病変か不明な点が多い。若干の考察を加え，報告する。
GVHD is a major complication of allogeneic bone marrow transplantation (BMT). It occur in both acuteand chronic forms, resulting from immunocompetent donor T cell that react against host cell antigens.
The most common oral manifestations of GVHD include lichenoid changes, mucosal atrophy andulcerations. On the other hand, Cyclosporine A (CyA), which is administered for preventing GVHD, isknown to induce gingival overgrowth. We have studied three cases of multiple oral polypoid lesions,diagnosed as pyogenic granuloma, that occurred in BMT recipients who were receiving CyA for GVHD.
We report these three rare manifestation with consideration of the pathogenesis.

37

37

1A-03

Hemophagocytosis-induced Par-2 expression regulates cytoskeletal
rearrangement and cell growth of oral squamous cell carcinoma
Al-eryani Kamal1,2, Satoshi Maruyama3, Manabu Yamazaki1, Masayuki Tsuneki1, Cheng Jun1
and Takashi Saku1,3
1

Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences
Department of Oral Pathology, Sana'a University Faculty of Dentistry, Sana'a, Yemen
3
Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital2

Background and Purpose: Protease-activated receptor-2 (PAR-2), a G-protein-coupled receptor, that iscleaved and activated by trypsin, tryptase, or synthetic peptides mimicking their cleavage part, has beenshown to be involved in cellular proliferation of many kinds of cancer. We have found the expression ofPAR-2 in association with hemorrhage due to intraepithelial blood vessel collapse in oral carcinoma in-situ
and squamous cell carcinoma (SCC), and these findings motivated us to study roles of PAR-2 in oral SCC
cell proliferation. Materials and Methods: To approve this hypothesis, the PAR-2 expression was
immunohistochemically investigated in formalin-fixed paraffin sections of oral SCC surgical specimens.
ZK1 cells, a cell system established from tongue SCC, were examined for their expressions of PAR-2 andrelated molecules by immunofluorescence and RT-PCR to elucidate how hemophagacytotic signals affectoral SCC cell proliferation. Results: There was a definite co-localization between hemoglobin and PAR-2 inthe cytoplasm of SCC cells in cell proliferating zones, which were shown by Ki-67 immunohistochemistry,in tissue sections. When ZK-1 cells were stimulated by hemoglobin, those with hemophagocytosis
enhanced their PAR-2 expression at both protein and mRNA levels in dose-dependent manners. The PAR2 enhancement was also related with heme oxygenese-1 and keratin 17 expressions as well as fillopodia
formation, and eventually with cell proliferation. Conclusions: The results suggest that PAR-2, induced byhemoglobin endocytosis, plays an important role in cell proliferation of oral SCC.

38

38

1A-04

部分的に筋上皮細胞の増殖を認めた口蓋部腺様嚢胞癌の一例

A case of adenoid cystic carcinoma partially-observed growth of myoepithelial cells
中島 啓1，松坂 賢一1，村松 敬1，國分 克寿1，橋本 貞充2，井上 孝1
Kei Nakajima1, Kenichi Matsuzaka1, Takashi Muramatsu1, Katsutoshi Kokubun1,
Sadamitsu Hashimoto2 and Takashi Inoue1
1

東京歯科大学 臨床検査病理学講座
東京歯科大学 生物学研究室
1
Department of Clinical Pathophysiology, Tokyo Dental College
2
Department of Biology, Tokyo Dental College
2

今回我々は，口蓋部に生じた腺様嚢胞癌で，筋上皮細胞の増殖を部分的に認める症例を経験したので，報告する。
患者：69歳，男性。
主訴：口蓋部の無痛性腫瘤
現病歴：2000年より口蓋部の腫瘤を自覚するも放置していた。2010年11月に東京歯科大学千葉病院口腔外科を紹介受診した。
経過：造影CTおよびMRIの撮影にて唾液腺腫瘍が疑われ，2011年 4 月21日，全身麻酔科にて口蓋腫瘍切除術を施行し，プレートにて固定した。
病理学的所見：切除物は， 2 層性の腺管構造を伴う紡錘形の腫瘍細胞が増殖する深部および周囲に，被膜状の線維性結合組織を介して 2 層性の管状構造の増殖や篩状構造がみられた。特殊染色として，PASAlcian blue染色を行ったところ，篩状構造部にAlician blueに陽性の小嚢胞腔を認めた。免疫組織学的には，紡錘形の細胞が増殖する部はα-SMA，HHF-35およびp63に陽性の細胞が主体であり，腫瘍性筋上皮細胞の増殖像と考えられた。
以上の所見から，本症例は腺様嚢胞癌と考えたが，本症例の浅層部のような，胞巣を形成せずに筋上皮細胞が 2 層性の腺管構造を伴って充実性に増殖するものは腺様嚢胞癌の分類になく，この部分は腺様嚢胞癌と異なる腫瘍であることも考えられる。また，経過が10年と長いことを考慮すると，腫瘍性筋上皮細胞が優位な他の唾液腺腫瘍が存在し，発育中に深部から腺様嚢胞癌が発生したことや深部が悪性化した多形腺腫内癌腫の可能性も考えられる。今回は，過去の文献報告と合わせ本症例を提示する。
We report a case of adenoid cystic carcinoma with partially myoepithelial cells growth in the palate.
The patient was a 69-years-old man who complained painless swelling of palate. CT and MRI showedsalivary gland tumor-like lesion. The surgical resected specimen showed the cribriform pattern which
was positive for PAS-Alcian blue and diagnosis was adenoid cystic carcinoma. The superﬁcial part wasobserved the spindle-shaped myoepithelial cell which stained forα-SMA, HHF35 and p63. These staining
characteristics suggest superficial part is defferent from adenoid cystic carcinoma or cartinoma ex
pleomorphic adenoma.

3939

1A-05

症例検討Ⅰ

左舌口底部腫瘍の一例

A case of the tumor in the left inferolateral margin of the tongue
山根木 康嗣1，大山 秀樹1，和唐 雅博2，富永 和也2，国分 麻佑2,3，嘉藤 弘仁2,3，
益野 一哉2，西川 哲成2，田中 昭男2Koji Yamanegi1, Hideki Ohyama1, Masahiro Wato2, Kazuya Tominaga2,
Mayu Kokubu2,3, Hirohito Kato2,3, Kazuya Masuno2, Tetsunari Nishikawa2 andAkio Tanaka21

兵庫医科大学 病理学講座 機能病理部門
大阪歯科大学 口腔病理学講座
3
大阪歯科大学大学院 病理学専攻
1
Department of Pathology, Hyogo College of Medicine, Hyogo college of Medicine
2
Department of Oral Pathology, Osaka Dental University
3
Graduate Scool of Dentistry, Osaka Dental University2

症例：63歳，男性
臨床経過：平成21年３月左側舌扁平上皮癌（高分化型）に対して化学・放射線療法が施行され外来にてフォローアップ中であった。平成22年２月初旬より同側舌に腫瘤を認め急激に増大してきたため，当院歯科口腔外科を受診された。受診時舌口底部付近に，弾性軟で境界明瞭な，35mm×23mm大の隆起性病変が認められ，急激に増大する臨床経過および生検材料から悪性腫瘍が疑われ，腫瘍切除術が施行された。
摘出物所見：腫瘍は外方性増殖が著しく，太い径を持つポリープ状もしくはドーム状であった。割面は白色調，一部褐色調を呈していた。
組織学的所見：腫瘍表層は生検材料と同様に広範なﬁbrin析出を伴い，間質の著明な浮腫状変化および毛細血管増生，好中球を主体とする炎症細胞浸潤を認め，これらに混じって異型大型核を有する紡錘形細胞の増生も多数認められた。腫瘍中央部から深部にかけて，紡錘形細胞が密に増殖し，mitosisも比較的多く認められた。免疫組織化学染色では，紡錘形細胞はvimentinおよびα-SMAに強陽性を示し，AE1/AE3，
calponin，h-caldesmon，desmin，lysozyme，CD68，S-100は陰性であった。紡錘形細胞のKi-67陽性細胞の陽性率は10％程度であった。
検討事項：病理組織学的診断（良悪の鑑別）
The patient was a 63-year-old Japanese man who was treated with chemotherapy and radiation therapy
for squamous cell carcinoma of the left tongue in 2009. One year later, he complained of a rapidly
increasing mass without pain in the left inferolateral margin of the tongue. Histopathologicalexamination of the biopsy showed a predominant edematous change with some spindle-shaped cells
indicating atypia. The tumor excision with left radical neck dissection was performed. In addition,
immunohistochemical staining revealed that tumor cells were positive for vimentin and α-SMA, but not
for AE1/AE3.

4040

症例検討Ⅰ

1A-06

口唇部腫瘍

Soft tissue tumour of the lower lip
和田 裕子，清島 保，小林 家吉，藤原 弘明，坂井 英隆
Hiroko Wada, Tamotsu Kiyoshima, Ieyoshi Kobayashi, Hiroaki Fujiwara and
Hidetaka Sakai
九州大学大学院歯学研究院 口腔顎顔面病態学講座 口腔病理学研究分野
Laboratory of Oral Pathology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of
Dental Science, Kyushu University

69歳の女性。2006年に下唇左側の腫瘤を自覚し，症状がなかったため放置していたが，その後増大傾向を認めたため，2010年 3 月に九州大学病院顎口腔外科を受診した。腫瘤は，粘膜直下にあり，直径10mm程
度の類球形で，弾性硬・可動性を呈していた。粘膜表面には潰瘍等の所見はなかった。知覚異常は認められなかった。超音波検査で，腫瘤は不均一な高エコーを呈し，後方エコーの増強も見られた。MRIで，腫瘤は境界明瞭でT1・T2ともに高信号であった。摘出された腫瘤の割面は，黄白色・充実性の軟組織の中に一部骨様硬組織を認めた。配布標本は，下唇粘膜下の腫瘤の最大割面である。
A 69-year-old woman had a painless solitary mass of the left lower lip for 4 years. The patient had
neither trauma associated with the lesion nor medications for the lesion. She noticed an increase in thesize of the mass. So she was referred to the Department of Oral and Maxillofacial Surgery, Kyushu
University Hospital, for detailed examinations. The lesion showed a ﬁrm, non-ulcerated, and movablemass with 10 mm in size that is located in the submucosa of the left lower lip. No sensory or motor
paralysis was observed in the lower lip.

41

41

1A-07

症例検討Ⅰ

上顎腫瘍

Maxillary tumor
片瀬 直樹1，武部 祐一郎1，平田 泰久1，伊藤 聡1，玉村 亮1，真野 隆充2，
上山 吉哉2，長塚 仁1Naoki Katase1, Yuichiro Takebe1, Yasuhisa Hirata1, Satoshi Ito1, Ryo Tamamur1,
Takamitsu Mano2, Yoshiya Ueyama2 and Hitoshi Nagatsuka1
1

岡山大学大学院 医歯薬学総合研究科 口腔病理学分野
山口大学大学院 医学系研究科 歯科口腔外科学分野
1
Department of Oral pathology and Medicine, Graduate School of Medicine, Dentistry andPharmaceutical Sciences, Okayama University
2
Department of Oral and Maxillofacial Surgery, Yamaguchi University Graduate School of Medicine2【症例】70歳代，女性。
【臨床経過】左側上顎歯肉の違和感，出血を主訴として紹介により来院。初診時の口腔内所見では42×32mm大の潰瘍を伴う腫瘤形成が認められた。CTでは腫瘤は骨破壊を伴って左側上顎洞後壁，内側壁，硬口蓋に浸潤する像が観察され，PET-CTでは腫瘤部と左側顎下，上内深頸部リンパ節にFDG集積が認められた。上顎悪性腫瘍の臨床診断のもと，生検後に腫瘍切除術が施行された。
【摘出物所見】著明な骨破壊を伴って上顎骨から上顎洞に及ぶ腫瘤であり，腫瘤表層は潰瘍を形成していた。腫瘤の割面
は灰白色調であり，内部に壊死を伴っていた【組織学的所見】
腫瘍の表層には潰瘍形成を認め，深部に紡錘形の胞体と両端の丸い長楕円形の核を有する腫瘍細胞が束状構造をなして錯綜する像が認められた。腫瘍細胞は強い浸潤性を示し，既存の上顎骨を置換するように増殖しており，内部には壊死を伴って空洞状に脱落する部位が観察された。腫瘍細胞は異型には乏しい像であ り， 異 型 核 分 裂 像 は ほ と ん ど 認 め ら れ な か っ た。 免 疫 組 織 化 学 的 検 索 で は， 腫 瘍 細 胞 は 一 部 のCytokeratin, EMA, Vimentinに陽性を示し，S-100，αSMA，Desmin，Myosin，MyoD1，h-caldesmon，
CD34，CD99は陰性であった。Ki-67陽性率は10％程度であった。
【検討事項】病理組織学的診断
A72-years-old female patient referred to the hospital, complaining the bleeding from tumor mass at theleft upper gingiva. The lesion was 42 x 32 mm in size with ulcer. With the clinical diagnosis of malignant
tumor, surgical resection of the tumor was performed. Histologically, the tumor cells consisted fromspindle cells with round-edged nucleus. The tumor cells proliferate with bundle formation and exhibit
bone invasion. However, the tumor cells lack in cellular atypia. Immunohistochemistry revealed that thetumor cells were focally positive for EMA, Vimentin and some CK markers, but negative for S-100,
CD34, CD99 and myogenic markers.

4242

症例検討Ⅰ

1A-08

下顎腫瘍

Tumor of mandible山崎 学1，丸山 智2，程 珺1，藤田 一3,4，高木 律男3，林 孝文5，朔Manabu Yamazaki1, Satoshi Maruyama2, Jun Cheng1, Hajime Fujita3,4,
Ritsuo Takagi3, Takafumi Hayashi5 and Takashi Saku1,2

敬1,2

1

新潟大学大学院医歯学総合研究科 口腔病理学分野
新潟大学医歯学総合病院 歯科病理検査室3
新潟大学大学院医歯学総合研究科 顎顔面口腔外科学分野
4
新潟県厚生農業協同組合連合会けいなん総合病院 歯科口腔外科
5新潟大学大学院医歯学総合研究科 顎顔面放射線学分野
1
Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences
2
Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital
3
Division of Oral and Maxillofacial Surgery, Niigata University Graduate School of Medical and Dental
Sciences
4
Department of Oral Surgery, Keinan General Hospital
5
Division of Oral and Maxillofacial Radiology, Niigata University Graduate School of Medical and
Dental Sciences2

症例：31歳，女性。
臨床経過：初診の 1 か月前に家族性大腸腺腫症（FAP）および横行結腸癌に対して，本院外科にて大腸全摘術・回腸人工肛門造設術が施行され，FAP関連病変の精査目的に本院口腔外科を初診した。初診時，特記すべき自覚症状は見られなかったが，パノラマX線所見で，下顎右側第二大臼歯が水平位で完全埋伏し，同側第一〜第三大臼歯間に直径10mmの類円形の透過像が指摘された。CTで，同部には辺縁平滑，周囲に骨硬化像を伴う類球形，造影性を有する単房性病変が確認され，下顎腫瘍の臨床診断にて全身麻酔下で全摘生検が行われた。
摘出物所見：直径10mm大の球形腫瘤で，割面は淡褐色，充実嚢胞性であった。中心部で 2 分割して作製した切片を配布標本とした。
組織学的所見：粘膜下組織に存在する厚い線維性被膜に覆われた腫瘍組織で，混在する二つの異なった成分から構成されていた。主体をなす第一の成分は吻合状の索状胞巣を形成し，胞巣辺縁部には長楕円形核を有する高円柱状細胞が柵状に配列して，胞巣内部に紡錘形〜星状網様細胞が配置されていた。索状胞巣
間の間質は大部分で変性して間質嚢胞化していた。第二の成分は結節状の充実性胞巣からなり，第一の成分の胞巣間に点在して相互に連続していた。同部では，比較的に豊富な淡好酸性細胞質を有する多辺形細胞が渦巻き状に増殖するとともに，腺管様構造を形成し，その中心部にはPASおよびコンゴー赤陽性の好酸性硝子様物質を配していた。また，小石灰化物が散在していた。免疫組織化学的に，両成分ともに
keratin（K）19陽性を示し，第一の成分はK17強陽性・vimentin非陽性であるのに対し，第二の成分は
K17・vimentin一部陽性で，免疫組織化学的形質は異なっている。
検討事項：病理組織学的診断
A 31-year-old woman with familial adenomatous polyposis (FAP) was referred to our hospital for further
examinations. Radiologically, a well-demarcated round tumor, measuring 10 mm in diameter, was foundin her right molar region of the mandible. The resected tumor showed solid and cystic areas with tan
color surrounded by thick capsule. Hitopathologically, the tumor was composed of two different
components which were connected from each other: one was anastomosing nests consisted of columner
cells at the periphery and spindle/stellate cells in the center, and the other was solid nests with whirledcellular arrangement with gland-like structures and hyaline droplets.

43

43

特別講演
Special Lecture

45

第1日目

8月24日（水）特別講演「頭頚部骨軟部腫瘍および腫瘍類似病変の病理」
Ａ会場メインホール

11：00〜12：00

解剖症例の提示小田 義直

九州大学大学院 医学研究院
形態機能病理学【学歴】
昭和62年（1987）３月27日
平成元年（1989）４月１日
平成５年（1993）３月26日

九州大学医学部卒業
九州大学大学院医学系研究科外科系専攻入学
同上 修了

【学位】
平成５年（1993）３月26日

医学博士（九州大学医博甲978）【免許・資格等】
昭和62年（1987）５月25日
平成５年（1993）３月31日
平成10年（1998）２月28日
平成11年（1999）７月21日
平成14年（2002）12月27日

医師免許証（第307001号）
死体解剖資格認定（認定番号：6181）
日本整形外科学会認定医（認定番号：112779）
日本病理学会認定医（認定番号：2111）
日本臨床細胞学会細胞診指導医（認定番号：1960）【職歴】
昭和62年（1987）６月１日
平成５年（1993）10月１日
平成８年（1996）６月１日
平成８年（1996）10月１日
平成10年（1998）７月１日
平成11年（1999）４月１日
平成11年（1999）５月16日
平成20年（2008）３月１日
平成22年（2010）７月１日

佐賀県立病院好生館（研修医）（整形外科）
ドイツ連邦共和国 フンボルト財団奨学研究員
マグデブルグ大学病理学教室（Albert Roessner 教授）
九州厚生年金病院（整形外科医長）
九州大学医学部助手（整形外科学講座）
九州大学医学部助手（第二病理学講座）
九州大学大学院医学系研究科助手（第二病理学講座）
九州大学大学院医学系研究科講師（形態機能病理学）
九州大学大学院医学研究院准教授（形態機能病理学）
九州大学大学院医学研究院教授（形態機能病理学）
現在に至る【所属学会等】
日本病理学会
学術評議員，学術委員会委員，癌取り扱い規約委員会委員，
日本病理学会雑誌（Pathology International）常任刊行委員
日本整形外科学会，日本癌学会（評議員），日本臨床細胞学会，
International Academy of Pathology，International Skeletal Society【賞罰】
日本病理学会学術奨励賞（平成11年）
日本病理学会学術研究賞（平成13年）
International Academy of Pathology，Japan Division 病理診断学奨励賞（平成14年）
46

46

Special Lecture

頭頚部骨軟部腫瘍および腫瘍類似病変の病理
骨軟部腫瘍はその種類が極めて多く，経験豊富な診断病理医でもその確定診断にしばしば難渋する。本講演では頭頚部発生の比較的頻度の高い以下のような骨軟部腫瘍および腫瘍類似病変についてその臨床病理像を解説する。
骨腫瘍
顎骨発生の骨肉腫は他の大長管骨に発生するものと組織学的には大きな違いはないが，予後は良好である。頭頚部発生の他の悪性腫瘍の放射線照射後肉腫としては骨肉腫の頻度が高い。軟骨肉腫の中では特殊型である間葉性軟骨肉腫が上顎骨に好発する。顎骨の線維性骨異形成と骨形成線維腫は鑑別が問題となるが線維性骨異形成は特異的なGNAS1遺伝子の点突変異を有し鑑別に有用である。顎骨に発生する巨細胞修
復性肉芽腫と同じ組織像を呈する病変が他の顔面骨にも発生し，動脈瘤様骨嚢腫の充実部分と同じ組織であることより充実性動脈瘤様骨嚢腫とも呼ばれる。画像上骨破壊が顕著で，組織学的に類骨や骨形成が豊富 に 認 め ら れ る こ と も あ り， 骨 肉 腫 と 鑑 別 を 要 す る。 顎 関 節 に 発 生 す る 色 素 性 絨 毛 結 節 性 滑 膜 炎
pigmented villonodular synovitis（PVNS）の中には軟骨化生を伴うものがあり側頭骨原発の軟骨芽細胞腫との鑑別が必要となる。またこの軟骨化生を伴ったPVNSは臨床病理学的に腫瘤性CPPD結晶沈着症や滑膜性骨軟骨腫症との鑑別を要する。
軟部腫瘍
横紋筋肉腫は小児軟部肉腫の中で最も頻度の高いものであり，組織学的に胎児型，胞巣型，多形型に分けられ，他の小円形細胞肉腫との鑑別にはmyogeninの免疫染色が有用である。頭頚部は好発部のひとつであり，頭頚部発生例は予後不良であるとされている。胞巣型は胎児型に比較してやはり予後不良であり，治療法も異なるので両者を正しく鑑別して診断を行うことはその後の治療を行うためにも重要である。胞巣型には特異的なキメラ遺伝子であるPAX3あるいはPAX7-FKHRが検出される。軟部腫瘍の中で近年報告されている新たな疾患概念としては舌・口腔領域に発生する分化型脂肪肉腫と小児の舌に発生する胞巣状軟部肉腫が挙げられる。頭頚部に発生する脂肪肉腫の大部分は分化型脂肪肉腫であり，他の部位に発生するものに比較して予後は極めて良好である。小児の舌に発生する胞巣状軟部肉腫は組織学的に充実性発育パターンをとることが多く，小児の口腔領域に発生する先天性顆粒細胞腫と鑑別を要する。若年成人に発生する通常の胞巣状軟部肉腫に比較して予後良好である。1896年にKuttnerにより良性の腫瘍類似病変として提唱された慢性硬化性唾液腺炎は顎下腺に発生することが多く，現在ではIgG4関連硬化性疾患の一病変と考えられており膵や胆管病変を合併することもある。

47

47

ランチョンセミナーⅠ
Luncheon Seminar Ⅰ

49

第1日目

8月24日（水）ランチョンセミナーⅠ「シェーグレン症候群とその類似疾患の診断と治療」
B会場中ホール１

12：10〜13：00【学歴】
昭和51年３月 福岡県立筑紫丘高校卒業
昭和51年４月 九州大学歯学部入学
昭和57年３月 九州大学歯学部卒業
昭和57年４月 九州大学大学院博士課程歯学研究科歯学臨床系入学
昭和61年３月 九州大学大学院博士課程歯学研究科歯学臨床系満期退学
昭和61年12月 九州大学大学院博士課程歯学研究科歯学臨床系の歯学博士
号取得

中村 誠司

九州大学大学院歯学研究院
口腔顎顔面病態学講座
顎顔面腫瘍制御学分野【学位】
歯学博士（九州大学

第41号）

【資格】
歯科医師（昭和57年５月29日 歯科医籍登録第85461号）
日本口腔外科学会専門医（平成６年７月29日 第631号）
日本口腔外科学会指導医（平成10年10月１日 第545号）【経歴】
昭和61年４月 九州大学歯学部口腔外科学第二講座助手に就任
昭和61年８月 米国オクラホマ医学研究所免疫学部門に留学
昭和63年10月 米国バ−ジニア大学医学部内科学教室リウマチ学部門に留学
平成１年10月 九州大学歯学部口腔外科学第二講座助手に復職
平成６年６月 九州大学歯学部附属病院第２口腔外科講師に就任
平成16年12月 九州大学大学院歯学研究院口腔顎顔面病態学講座顎顔面腫
瘍制御学分野教授に就任（現在に至る）50

50

Luncheon SeminarⅠ

シェーグレン症候群とその類似疾患の診断と治療
Diagnosis and treatment for Sjögrenʼs syndrome
and the similar diseases
シェーグレン症候群（SS）は，ドライマウスを引き起こす代表的疾患として高く認識されている自己免
疫疾患であり，多くの歯科医師がその診断と治療に積極的に携わっている。しかしながら，ドライマウス
は様々な原因によって生じるためにその分類と診断は容易ではなく，特にSSの診断に際しては唾液腺の病
理組織学的検索が極めて重要である。今回のセミナーではシェーグレン症候群患者とその類似疾患の診断と治療の現状，さらには今後の課題や展望について述べるが，唾液腺の病理組織学的検索の意義を再認識する機会になれば幸いである。
ドライマウスの分類については様々な報告があるが，2008年に日本口腔粘膜学会が原因別の分類を示した（日口腔粘膜誌 14:86-88，2008）。この分類では，ドライマウスを１）唾液腺自体の機能障害によるもの，
２）神経性あるいは薬物性のもの，３）全身性疾患あるいは代謝性のものの３つに大別している。唾液腺自体の機能障害によるものとしては，SSが代表的なものであるが，放射線治療や加齢性変化による唾液腺障害も臨床的には重要である。神経性あるいは薬物性のものとしては，うつ病，ストレスなどの疾患や抗不安薬，抗うつ剤，降圧剤などの薬剤によるものが多い。全身性疾患あるいは代謝性のものとしては，脱水などによる全身的な水分欠乏，糖尿病，腎障害，貧血などの全身性疾患が主な原因であるが，口呼吸，過呼吸，開口，摂食嚥下障害などに伴う局所的な水分蒸発によるものも含まれる。ドライマウスを訴えて歯科を受診する患者の場合にはSS以外の原因が多く，SSは１〜２割程度に過ぎないとされている。治療に際しては原因を十分に考慮する必要があるため，原因を精査して的確に分類を行うことが求められる。このセミナーでは，1999年に改訂された本邦のSS診断基準を骨格としたドライマウスの診断の現状を解説する。また，SSの診断基準は国際的に統一されたものがなく，日本シェーグレン症候群学会では診断基準の再検討を進めているので，SSの診断基準に関する国際的動向についても解説する。
次に，Mikulicz病と血液幹細胞移植後に生じる慢性移植片対宿主病（GVHD）の２つの病態に焦点を当てたい。特に前者はIgG4関連疾患の一つとして注目されており，厚生労働省科学研究費補助金で２つの研究事業が進められ，IgG4関連疾患包括診断基準が作成されようとしている。両疾患ともに唾液腺の病理組織学的検索が極めて重要であるので，このセミナーではその動向を含めた最新情報を解説する。
最後に，これらの治療についても触れる予定である。SSにおけるドライマウス治療においては，唾液分
泌促進剤であるピロカルピン塩酸塩とセビメリン塩酸塩が極めて有効であり，これらの薬剤により治療効
果は大きく向上している。このセミナーでは，それらの効果を中心に，ドライマウスに対する治療の現状を解説する。また，ドライマウスによる口腔粘膜病変などの合併症に対しても積極的に治療が行われているので，ドライマウスの合併症の成因や治療法についても述べる。

51

51

ASOMP session

53

13:30-14:30

Keynote lecture

Histopathological characteristics of bisphosphonate-related osteomyelitis(osteonecrosis) of jaw
Chair: Takashi Takata

Hiroshima University

Akira Yamaguchi
Section of Oral Pathology, Graduate School of Medical and Dental Sciences,
Tokyo Medical and Dental University

CURRICULUM VITAE
Akira Yamaguchi
Professor, Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and
Dental University, Tokyo, Japan
Dr. Akira Yamaguchi received his D.D.S. from Tokyo Dental College in 1974 and Ph.D. degree from
Tokyo Medical and Dental University in 1980. He became an Assistant Professor of Department of Oral
Pathology, School of Dentistry, Showa University in 1980, and promoted as an Associate Professor in thesame Department in 1988. He was a visiting Assistant Professor in Washington University School of
Dentistry and St. Louis University School of Medicine (1985-1988). He was Chair and Professor of Oral
Pathology, Nagasaki University Dental School from 1998 to 2004. Dr. Yamaguchi was recruited back toTokyo Medical and Dental University as Chair and Professor of Oral Pathology in 2004. Dr. Yamaguchi
contributed the publication of about 150 scientific papers in SCI journals including American Journal of
Pathology, Journal of Cell Biology, Journal of Clinical Investigation, Nature Medicine, and Cell. His
current research interest is 1) molecular mechanism of bone formation and regeneration and 2) the
mechanism of bone destruction by oral cancer. Dr. Yamaguchi is currently serving on the Associate Editorsof Journal Bone and Mineral Metabolism and Japanese Dental Science Reviews, and on the Editorial
Boards of BONE, Oral Medicine and Pathology, Journal of Orthopaedic Science and Oral Science
International. Dr. Yamaguchi was a recipient of the Japanese Society for Bone and Mineral Research:
Academic Award (1993), the Japanese Society of Pathology: Pathology Research Award (1996), and theJapanese Pathology Award (2005).

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Keynote lecture

Histopathological characteristics of bisphosphonate-related
osteomyelitis (osteonecrosis) of jaw
Bisphosphonates (BPs) are potent inhibitors of osteoclastic bone resorption, and are widely used to prevent
excess bone resorption in osteoporosis, cancer bone metastases, and multiple myeloma. There have been
increasing reports showing that osteonecrosis of jaw infrequently occurred following the surgical treatments
such as tooth extraction in patients who have been treated with BPs, which is called bisphosphonate-related
osteonecrosis of the jaw (BRONJ).
There have been many reports on BRONJ, but the histopathological characteristics of BRONJ have notbeen well documented. We histopathologically investigated the characteristics of BRONJ in about 60 cases,
which were kindly provided by 22 dental facilities in Japan. Almost cases contained various amounts ofsequestrum (osteonecrosis) and many of these cases associated with bacterial growth. The vital bone tissues
surrounding the sequestrum showed a typical histology compatible with osteomyelitis. We compared thehistology of these areas to that of osteomyelitis patients who received no BP treatment. Basichistopathological findings were similar between these two groups except for osteoclast phenotype.
Osteoclasts in BP-treated cases showed larger size and increased number of nuclei compared to those in
non-BP-treated cases. BP-treated cases also often showed “floating osteoclast”, which are presumably nonfunctional osteoclasts detached from bone surface. These osteoclast phenotypes are compatible with thatobserved in bone biopsy specimens of alendronate-treated osteoporosis patients as reported by Weinstein, etal (N Engl J Med 2009).
Our histopathological investigation indicated that BRONJ is a kind of osteomyelitis of jaw associating withmodified osteoclast phenotype caused by BP action.

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14:30-15:30

Educational Symposium

Education of oral pathology in Asia, toward educational standardizationand mutual accreditation of oral pathologist in Asia
Chair: Sam-Pyo Hong
Hatsuhiko Maeda

Seoul National University
Aichigakuin University

14:30-14:35
Hatsuhiko Maeda
Introduction

Aichigakuin University

14:35-14:50
Tilakaratne WM
University of Peradeniya
Oral pathology in Asia; where are we?

14:50-15:05
Chun-Pin Chiang
National Taiwan University
Current status of education for the oral pathologist in Taiwan

15:05-15:20
Rosnah Zain
University of Malaya
Oral pathology specialty training in Asia – ensuring quality standards through strong partnerships

15:20-15:30
Panel discussion

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Educational Symposium

Introduction
Hatsuhiko Maeda
Department of Oral Pathology, School of Dentistry, Aichi-Gakuin University

CURRICULUM VITAE
Hatsuhiko Maeda
Professor, Department of Oral Pathology, School of Dentistry, Aichi-Gakuin University
Education:
1980 D.D.S., Aichi-Gakuin University, School of Dentistry
1984 Ph.D., Department of Pathology, School of Dentistry, Aichi-Gakuin University
Professional Training:1980 Passed the National Dental Board Examination
1980-1984 Graduate Student, Department of Pathology, School of Dentistry, Aichi-Gakuin University
1984-1987 Lecturer, Department of Pathology, School of Dentistry, Aichi-Gakuin University
1987 Assistant Professor, Department of Pathology, School of Dentistry, Aichi-Gakuin University
1989 Visiting researcher, The First Department of Pathology, School of Medicine, Nagoya City University.
1991-1992 Visiting researcher, Dept. of Oral Pathol. &Medicine, Faculty of Health Science, Copenhagen
University and University Hospital
1995 Associate Professor, Department of Pathology, School of Dentistry, Aichi-Gakuin University
2000 The examiner for Ph.D Defense, Dept. of Oral Pathology, Faculty of Dental Sciences, University of
Peradeniya, SRI LANKA.
2007-present Professor and Chair, Department of Oral Pathology, School of Dentistry, Aichi-Gakuin University
2009 Visiting Professor of Health Sciences University of Mongolia
2010 Honorary doctor of Maternal and Child Heath Research Center of Mongolia

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Educational Symposium

WM Tilakaratne
Department of Oral Pathology, Faculty of Dental Sciences, University of Peradeniya

CURRICULUM VITAE
WM Tilakaratne
Professor of Oral Pathology School of Medicine and Dentistry, Barts and the London Queen Mary
University of London, UK
Professor and Consultant in Oral Pathology, Head/ Division of Oral Pathology, Faculty of Dental Sciences,
University of Peradeniya, Sri Lanka
Email: wmtilak@pdn.ac.lk
TP: 94 8 387666, Fax: 94 8 388948
Professional Fellow to Queen Mary University of London
Councillor for Asia at the International Association of Oral Pathologists
Previous Appointments :* Professor of Oral Pathology, School of Medicine and Dentistry, Barts and the London Queen Mary
University of London, UK* Senior Lecturer (Clinical) in Oral Pathology, School of Medicine and Dentistry, Barts and the London
Queen Mary University of London, UK* Lecturer in Oral Pathology and Radiology, Guy's Hospital, London, UK, 1996-1999* Lecturer and in Oral Pathology, University of Birmingham, UK, 1999
* Visiting Professor to University of Niigata, Japan 2005
* Examiner for FDSRCS in the Royal College of Surgeons of England -1998* Proctor, University of Peradeniya, Sri Lanka 2007-2008* Warden, Senaka Bibile, University of Peradeniya 2001-2004
Qualifications: BDS (SL), MS (Col), PhD (JP), FDSRCS (Eng), FRCPath (UK)
University Education: University of Peradeniya, Sri Lanka

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Educational Symposium

Oral pathology in Asia; where are we?

Asia is a unique continent in the context of education compared to other parts of the world. The main
reason for the above scenario is the economic diversity that we experience in Asia. We have a mixture ofcountries ranging from a few most developed countries on earth to some of the poorest. There is asignificant gap in standards of education in different countries in Asia due to the direct relationship between
the level of education and economic status. It is well reflected in the specialty of Oral Pathology withregards to number of reporting Pathologists, standards of diagnostic Pathology, infrastructure facilities andtraining methodology. It is unfortunate that a few countries in Asia are without a single qualified Oral
Pathologist and all the diagnostic services are performed by medically qualified Pathologists. It has been
identified as a basic need to have at least a few Oral Pathologists to every country in a time that we discuss
about standardization and accreditation of Oral Pathology across Asian countries. Therefore, it is the needof the hour to plan and implement a training programme where trainees from those countries without Oral
Pathology services would benefit and start the specialty in their countries. That would be the stepping stone
to standardization of Oral Pathology services in Asia. In that respect International Association of Oral
Pathologists and Asian Society of Oral and maxillofacial Pathologists should start working together toachieve the said goal. Unless, this is done sooner rather than later, the specialty of Oral Pathology in Asia
may not achieve its targets.

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Educational Symposium

Chun-Pin Chiang
Graduate Institute of Oral Biology, Graduate Institute of Clinical Dentistry, School of
Dentistry, and National Taiwan University Hospital, National Taiwan University

CURRICULUM VITAE
Chun-Pin Chiang
Professor and Chairman, Department of Oral Pathology and Oral Diagnosis, School of Dentistry, National
Taiwan University, Professor and Director, Graduate Institute of Oral Biology, School of Dentistry,
National Taiwan University
Telephone: (02) 2312-3456 ext. 66855, FAX: (02) 2389-3853
E-Mail: cpchiang@ntu.edu.tw
Education:
National Taiwan University, Taipei, Taiwan, D.D.S., 1977, Dentistry
Harvard School of Dental Medicine, Boston, USA, D.M.Sc., 1989, Oral Pathology
Professional experience
Employment
2009-present Director, Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University
1999-present Professor, School of Dentistry, National Taiwan University, Taipei, Taiwan
1995-present Chairman, Department of Oral Pathology and Oral Diagnosis, National Taiwan University
Hospital, Taipei, Taiwan
1989-1999 Associate Professor, School of Dentistry, College of Medicine,National Taiwan University, Taipei, Taiwan
1982-present Attending Doctor, Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan
1982-1989 Lecturer, School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan
1985-1989 Research Fellow, Department of Oral Pathology, Harvard School of Dental Medicine, Boston, MA
1987-1989 Research Fellow, Department of Rheumatology and Immunology, Brigham and Women’s
Hospital, Boston, MA, USA
1986-1987 Research Fellow, Department of Dermatology, Brigham and Women’s Hospital, Boston, MA, USA
1977-1982 Teaching Assistant, School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan
1977-1982 Resident, Department of Dentistry, National Taiwan University Hospital
Academic position
2006-2009 President, Taiwan Academy of Oral Pathology, Taipei, Taiwan
2004-present Board member of Editorial Board of Journal of Oral Pathology and Medicine
2004-present Deputy Editor of Journal of Dental Sciences
2003-present Board member of Editorial Board of Journal of the Formosan Medical Association
2002-present Chairman, Taiwanese Board of Oral Pathology, The Executive Yuan, Taiwan. (Forcertification of oral pathology specialist)
1995-1997 President, The Academy of Oral Pathology, ROC, Taipei, Taiwan
1991-present Board Director, The Academy of Oral Pathology, ROC, Taipei, Taiwan
1989-1991 General Secretary, The Academy of Oral Pathology, ROC, Taipei, Taiwan
AwardsResearch Award, National Science Council, ROC (1982, 1983, 1993, 1995, 1998, 1999, 2000, 2002-2008)
Outstanding Teacher Award, National Taiwan University, Taipei, Taiwan (1995, 1999, 2001, 2003)
Fellow of the International College of Dentists, Taipei, Taiwan (since 1989)
Outstanding Medical Paper Award, Laser Medicine Society, ROC (1998)
Service Medal, The Executive Yuan, ROC (1992)
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Educational Symposium

Current status of education for the oral pathologist in Taiwan

The oral pathology training program in Taiwan is a 4-year program that includes 2-year training of general
dentistry, 1.75-year training of oral pathology, and 0.25-year training of general pathology. The 2-yeartraining of general dentistry includes a rotation in 9 dental divisions. The trainee has to complete theminimal requirements that are set by each division. During the 3-month training in general pathology, eachtrainee has to see the whole procedure of 2 autopsy cases and learn how to write the autopsy reports forthese 2 cases. In addition, he or she has to learn how to read the hematoxylin and eosin-stained andimmunostained histological tissue sections and write or sign out the biopsy reports of at least 500 cases.
During the 1.75-year training of oral pathology, each trainee has to examine and sign out at least of 300
oral and maxillofacial specimens. Furthermore, he or she has to attend the surgicopathological slide
conference once a week, the clinicopathological conference once a week, and oral and maxillofacial surgery
and oral pathology combined conference once a month. After finishing the 4-year oral pathology training
program, each trainee is qualified to take the oral pathology specialist examination provided by the Taiwan
Academy of Oral Pathology. This examination includes four writing tests for basic courses (oral histology
and oral pathology), clinical courses (oral diagnosis, oral medicine, and oral and maxillofacial radiology),
clinical slides (25-50 cases), and histopathological slides (15 cases). After passing these 4 tests, the examinee
has to pass the oral test to become a board-certified oral pathologist.

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Educational Symposium

Rosnah Binti Zain1 and Yeo Jin Fei2
1

University of Malaya and 2National University of Singapore

CURRICULUM VITAE
Rosnah Binti Zain F.A.Sc., BDSc (Qld), MS(Michigan), Fellow, AAOP(USA)
Dean and Professor, University of Malaya
Rosnah Zain received her Bachelor of Dental Science from the University of Queensland, Australia and did
her specialty training in Oral Pathology & Diagnosis at the University of Michigan, Ann Arbor. She has
been the Professor in Oral Pathology and Oral Medicine since year 2000 and currently is the Dean, Facultyof Dentistry as well as the Director, Oral Cancer Research and Coordinating Centre, Faculty of Dentistry,
University of Malaya. She has published widely with her main area of research being oral mucosal lesions
and oral cancer.
Among her major research endeavors is a collaborative research project with colleagues from Aichi Gakuin
University, Nagoya, Japan and the Oral Health Division, Ministry of Health Malaysia. This project is anationwide survey conducted in 1993/94 on the prevalence of oral mucosal lesions, which produced thefirst population-based prevalence data on oral cancer and precancer in the country. Arising from this, sheand her international colleagues developed a training module for oral cancer screening. Since 2002, she has
been actively conducting echo-training of trainers for the training of dental professionals for early detectionof oral cancer regionally.
Since 2003, she had initiated the Malaysian Oral Cancer Database and Tumour Bank System (a top-downgovernment funding), linking data and tissue providers, researchers of different disciplines. With such asystem, research on oral cancer in Malaysia shifted from individual/group research to the ‘team science’approach. This is a collaborative effort from different institutions namely University of Malaya, Universiti
Sains Malaysia, Cancer Research Initiatives Foundation (CARIF) and Ministry of Health Malaysia. As afollow-up to this, her effort was recognized by the University administration where a UM research centre
was officially recognized and supported by the University Management with the formation of the Oral
Cancer Research and Coordinating Centre at the University of Malaya (OCRCC-UM) in 2005, which she
is currently the Director.
Rosnah Zain is an ardent advocate of dental education of which she is very much involved as a lecturer.
During her years as an academician, she has dedicated herself towards teaching of dental students, which
includes leading the review of the undergraduate dental curriculum towards an integrated curriculum, andthe development of postgraduate curriculum in particular for Oral Pathology and Oral Medicine
benchmarking against many different international institutions.

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Educational Symposium

Oral pathology specialty training in Asia – ensuring quality standards
through strong partnerships
Currently in Asia, only a few countries conduct the training of Oral Maxillofacial Pathologists (OMFPs).
Curriculum for training has been individually developed by the respective training institutions with mostbenchmarking against international colleges in United Kingdom, USA and Australia/New Zealand. The
move towards training standardization would mean first to have a strong governing body which would
consists of special advisory committees for decisions on curriculum, training slots, teaching faculty,
examinations and assessments.
A society such as the Asian Society for Oral Maxillofacial Pathology (ASOMP) may function in a similar
fashion to the international colleges and a special advisory committee be set up consisting of experienced
OMFPs from Asian countries that has such training programmes. The key to success would require suchsaid society (i.e. ASOMP) to re-look at its functions and assesses the achievement of its objectives over thelast 4 years while willing to certain changes towards strengthening the society.
There may be a need to start and maintains a foundation to help in the training especially for countries
lacking in OMFPs. The base country for the training need to be selected and training may be as a joint
efforts (partnerships) on a modular basis with multiple training centres (with sufficient teaching materials)
in different countries. A concept of trainees’ rotation to different training centres and the roving teachingfaculties whereby, selected centres for the trainees will also have the assistance of selected teaching faculties
from other countries on a modular basis.
In the early stage, these suggestions would be more towards the training of OMFPs for countries in Asia
without OMFPs. The countries with existing training programmes shall continue for their own country’s
specialty requirements with efforts towards the use of similar curriculum. With time, there can be aconvergence of all the OMFPs training in Asia towards having an Asian Fellowship Examination asadditional Professional Qualifications to their respective academic qualifications.

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64

15:40-17:25

ASOMP Scientific Session

Frontier Research of Oral Pathology in Asia
Chair: Takashi Saku
Eun-Cheol Kim

Niigata University
Kyung Hee University

15:40-15:55
Kyoko Hida
Hokkaido University
A new insights into tumor endothelial cell

15:55-16:10
Kuo-Wei Chang
National Yang Ming University
MicroRNA alterations in oral carcinoma - a linkage to hypoxia regulation

Chair: Kazuo Komiyama
Yu ChenNihon University
Sichuan University

16:10-16:25
Yasusei Kudo
Hiroshima University
Identification of novel invasion related molecules in oral cancer

16:25-16:40
Seong-Doo Hong
Seoul National University
The role of Cripto-1 in the tumorigenesis and progression of oral squamous cell carcinoma

Chair: Akio Tanaka
Kuo-Wei Chang

Osaka Dental University
National Yang Ming University

16:40-16:55
Yu ChenSichuan University
Wnt-1/beta-catenin signaling and WIF-1 deficiency are important events in salivary gland adenoid cystic
carcinoma progression

16:55-17:10
Yuk-Kwan Chen
Kaohsiung Medical University
Study on different cryopreservations and hepatogenic differentiation of human dental pulp stem cells

17:10-17:25
Naozumi Ishimaru Tokushima University
Gender-based molecular pathogenesis of Sjögren’s syndrome

65

65

ASOMP Scientiﬁc session

Kyoko Hida1 and Masanobu Shindoh2
1

Dept. Vascular Biology, 2Oral Pathology and Biology, Hokkaido University Graduate
School of Dental Medicine

CURRICULUM VITAE
Kyoko Hida
Associate Professor, Dept. Vascular Biology, Hokkaido University Graduate School of Dental Medicine
Honors and awards:
Award of The 50th Japanese maxillofacial surgery meeting (2005.10.25)
The Japanese Society of Pathology: Pathology Research Award (2010.11.25)
Educational summary, Degrees, and Professional Experience:
Apr. 2009-Present: Associate Professor, Department of Oral Pathology and Biology, Division of Vascular
Biology, Hokkaido University Graduate School of Dental Medicine
Apr. 2007-Mar. 2009: Assistant Professor, Department of Oral Pathology and Biology,Division of Oral
Pathobiological Science, Hokkaido University Graduate School of Dental Medicine(Mentor: Prof. Masanobu Shindoh)
Apr. 2005-Mar.2007: Instructor, Department of Oral Pathology and Biology,Division Hokkaido University
Graduate School of Dental Medicine
July 2001-Mar. 2005: Post-doctoral fellow, Vascular Biology Program, Children’s Hospital, Harvard
Medical School (Mentor: Prof. Michael Klagsbrun)
Sep. 2000-Mar.2001: Clinical Fellow, Department of Oral Maxillofacial Suregery, Hokkaido University
Graduate School of Dental Medicine
Apr. 1998-Mar. 2000: Postdoctoral Fellow, Japan Society for the Promotion of Science
Mar. 1998: Ph.D.: Degree received (Mentor: Prof. Yasunori Totsuka)
Apr. 1992-Mar. 1995: Residency Training in Oral maxillofacial Surgery,Mar. 1992: D.D. S.: Degree received, Department of Dental Science , Hokkaido University Graduate
School of Dental Medicine, Japan

66

66

ASOMP Scientiﬁc session

A new insights into tumor endothelial cell

ABSTRACT
Tumor endothelial cells have been thought to be genetically normal. However tumor blood vessels havebeen shown to differ from their normal counterparts, for example, by changes in morphology. To develop
novel antiangiogenic therapies, understanding crosstalk between blood vessels and tumor microenvironmentis important.
We have reported that TECs are abnormal. TECs showed different gene profiles and angiogenic properties
than normal endothelial cells (NECs). In addition, TECs were cytogenetically abnormal (Cancer Res 2004,
Am J Pathol 2009) and resistant to paclitaxel or 5-FU. Furthermore, TEC showed stem cell characteristics,
consisting with a previous report (Dudley et al. Cancer Cell 2008). The multidrug resistance 1 (MDR1)mRNA which encodes p-glycoprotein (P-gp) was upregulated in TEC compared with NEC. Tumorconditioned medium (tumor CM) induced drug resistance via upreguration of MDR1 gene in NEC(HMVEC).
It was suggested that TEC abnormality might be caused by the factors in tumor microenvironment.

67

67

ASOMP Scientiﬁc session

Kuo-Wei Chang1,2, Meng-Miao Tsai1, Shu-Chun Lin1,2
1

School of Dentistry, National Yang-Ming University, Taipei, Taiwan, 2Department of
Stomatology, Veterans General Hospital

CURRICULUM VITAE
Kuo-Wei Chang
Professor, School of Dentistry, National Yang-Ming University, Taipei, Taiwan, Department of Stomatology,
Veterans General Hospital, Taipei, Taiwan
Education/Training
1977-1983 DDS, National Yang-Ming Medical College, Taiwan
1990-1994 PhD, Northwestern University, USA
1990-1993 Certificate (Oral Pathology), Northwestern University, USA
Positions and Honors.
2010-present: Editorial board, J Oral Pathol Med
2009-present: Editorial board, Oral Med & Pathol
2008-present: Research Fellow, Department of Stomatology, Taipei Veterans General Hospital
2007-2011: Outstanding Research Award, National Yang-Ming University
2006: Outstanding Teacher Award, National Yang-Ming University
2001-present: Professor, Department of Dentistry, National Yang-Ming University
2005-2006: President, Taiwan Academy of Oral Pathology
1999-2006: Head, Institute of Oral Biology, National Yang-Ming University
1998- present: Oral Pathologist, Taiwan Academy of Oral Pathology
1996-present: Member, American Association for Cancer Research
1995-2001: Associate Professor, Department of Dentistry, National Yang-Ming University
1992-present: Member, American Association for Oral Pathology
1990-1995: Resident, Department of Oral Pathology, Northwestern University Dental School
1985-1990: Resident, Department of Dentistry, Taipei Veterans General Hospital
1983-1985: Medical Officer, Army

68

68

ASOMP Scientiﬁc session

MicroRNA alterations in oral carcinoma - a linkage to hypoxia regulation

Abstract
Oral squamous cell carcinoma (OSCC) is a worldwide disease. MicroRNAs (miRNAs) are non-coding
RNAs that regulate biological and pathological processes by RNA interference. This study investigated thealterations of miRNA in OSCC. miR-31, miR-21 and miR-371 were found to be markedly up-regulated.
Exogenous miR-31 expression increased the oncogenic potentials of OSCC cells in normoxia culture, as
well as the growth of xenographic tumors. miR-31 blocker decreased the xenographic tumorigenesis of
OSCC cells. Factor Inhibiting HIF (FIH) inhibits the transcriptional activity of hypoxia inducible factor(HIF) in normoxia. miR-31 is predicted to target the 3’UTR of FIH. miR-31 expression decreased bothendogenous and exogenous FIH. Mutations within the predictive miR-31 target site in FIH 3’UTR
abrogated FIH repression driven by miR-31. Exogenous miR-31 expression increased HIF transactivation
activity and VEGF. FIH expression suppressed oncogenic phenotypes in normoxia and these can be
abrogated by functional mutations. The increase in miR-31 expression was related to decreased levels of
FIH in tumor tissues. This study concludes that miR-31 is contributive to OSCC development and its
oncogenic function links to HIF activation.

69

69

ASOMP Scientiﬁc session

Yasusei Kudo, Takashi Takata
Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical
Sciences, Hiroshima University

CURRICULUM VITAE
Yasusei Kudo
Assistant Professor, Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical
Sciences, Hiroshima University, Hiroshima, JAPAN.
Education
1996 DDS, Hiroshima University School of Dentistry
1999 PhD, Hiroshima University Graduate School of Dentistry
Positions and Employment
2003-present: Assistant Professor, Department of Oral Maxillofacial Pathobiology, Hiroshima University
Graduate School of Biomedical Sciences
2003: Research Associate, Department of Oral Maxillofacial Pathobiology, Hiroshima University Graduate
School of Biomedical Sciences
2001-2003: Research Assistant Scientist, Department of Pathology, New York University School of
Medicine [A fellow for IARC (International Agency for Research on Cancer) and a fellow forJapanese scholars & researchers to study abroad ]1999-2001: Research Associate, Department of Oral Pathology, Hiroshima University Faculty of Dentistry
Honors2008 Research Award of Japanese Society of Pathology
2007 Encouragement Reasearch Award of Japanese Society of Pathology
2005 Encouragement Award of Japanese Association of Oral Pathology
2000 IAOP (International Association of Oral Pathologists) prize
2000 Young Investigators Award of the Japanese Association for Oral Biology
1999 Encouragement Award of Hiroshima University, Faculty of Dentistry Alumni Assocaiation

70

70

ASOMP Scientiﬁc session

Identification of novel invasion-related molecules in oral cancer

Recent cumulative evidences show that microRNAs (miRNAs) play important roles in the invasion andmetastasis of various cancers. miRNA is consist of 21-24 nucleotides, bind to the 3’-UTR of specific target
mRNA and suppresses translation or induces degradation of the target mRNA. Among them, miR200
family is well examined and is involved in tumor progression via epithelial-mesenchymal transition (EMT).
In fact, miR200 family regulates E-cadherin transcriptional repressor, ZEB1 and ZEB2. We previously
established highly invasive clone (MSCC-Inv1) from parent OSCC cells (MSCC-1) by in vitro invasion
assay. Interestingly, highly invasive clone showed EMT feature such as loss of E-cadherin. By comparing thegene expression profiles of these cells, we previously could identify several invasion-related molecules suchas periostin, IFITM1 and Wnt-5b. Here we compared the gene expression profile of miRNAs between
MSCC-1 and MSCC-Inv1 by microarray. Interestingly, several miRNAs including miR-200 family were
downregulated in MSCC-Inv1 cells. We focused on some down-regulated miRNAs as a candidate ofinvasion related molecule in cancer. Now we are examining the detailed role of these miRNA in theinvasion of cancer cells. In this symposium, we will show our recent findings of invasion-related moleculesin oral cancer.

71

71ASOMP Scientiﬁc session

Seong-Doo Hong
Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul
National University

CURRICULUM VITAE
Seong-Doo Hong
Associate Professor, Department of Oral Pathology, School of Dentistry and Dental Research Institute,
Seoul National University, Korea
Educational BackgroundFeb. 1990. Seoul National University, Seoul, Korea (D.D.S.)
Feb. 1993. Seoul National University, Seoul, Korea (M.S.D.)
Feb. 1998. Seoul National University, Seoul, Korea (Ph.D.)
Training
Mar. 1990-Feb. 1991. Internship in Seoul National University HospitalMar. 1991-Feb. 1993. Resident course in Department of Oral Pathology, Seoul National University HospitalWork Experiences
2011-present Associate Dean of Student Affairs, School of Dentistry , Seoul National University
2010-present Associate professor at Department of Oral Pathology, School of Dentistry, Seoul National University
2003-2010 Assistant professor at Department of Oral Pathology, School of Dentistry, Seoul National University
2000-2002 Assistant professor at BK21 Human Life Sciences, Seoul National University
1998-2000 Clinical Fellow in Department of Oral Pathology, Seoul National University Hospital
1996-1998 Assistant, College of Dentistry, Kangnung National University
1993-1996 Served in Korean Army as Public Health Dentist (Chungju City Public Health Center)

72

72

ASOMP Scientiﬁc session

The role of Cripto-1 in the tumorigenesis and progression of oral
squamous cell carcinoma
Oral squamous cell carcinoma (OSCC), the most common malignancy of the oral cavity, remains a lethal
disease in over 50% of cases diagnosed annually, due mostly to late detection of this cancer in its advanced
stages despite the easy accessibility of the oral cavity for regular examinations. Cripto-1 is a member of theepidermal growth factor (EGF) - CFC protein family and is involved in the activation of several different
signaling pathways during embryonic development and cellular transformation. Although the Cripto-1
protein is overexpressed in several human cancers including breast, colon, cervix, gastric, and pancreaticcancer, no prior study has evaluated Cripto-1 expression in OSCC. Therefore, our aims in this study were
to examine Cripto-1 expression in clinical samples of OSCC patients using immunohistochemistry, toanalyze the correlation between Cripto-1 expression and clinicopathologic parameters, and to identify the
oncogenic roles of Cripto-1 in OSCC cell lines. Both epithelial dysplasia (73.3%) and OSCC (55.5%)
tissue samples showed significantly higher expression of Cripto-1 than normal mucosa (20%) (p =0.031).
In the OSCC samples, there was a significant correlation between Cripto-1 expression and the histologicaldifferentiation of OSCC (p= 0.015) and a high PCNA index (p= 0.011). The in vitro cell proliferation
assays demonstrated that recombinant human Cripto-1 (rhCripto-1) induced both SCC-4 and SCC-25
cells to proliferate as compared with control cells (p<0.05 and p<0.01, respectively). In in vitro migration
assays, treatment of SCC-4 and SCC-25 cells with rhCripto-1 protein induced a 2.4-fold and 1.7-foldincrease in cell migration, respectively (p=0.000 and p=0.008, respectively). Taken together, our datasuggest that Cripto-1 plays a role in the malignant transformation of the oral mucosa and is involved in thetumorigenesis and progression of OSCC by promoting the growth and migration of malignant cells.

73

73ASOMP Scientiﬁc session

Chen Y 1, Fang YR2, Wato M3, Tanaka A3
1

Department of Oral Pathology, West China College of Stomatology, Sichuan University,
China, Departments of 2Oriental Medicine and 3Oral Pathology, Osaka Dental University

CURRICULUM VITAE
Yu ChenProfessor, Department of Oral Pathology, West China College of Stomatology, Sichuan University, China
Education:
1987 DDS, West China Medical University, Chengdu, China
1999 Ph.D, Dept. Oral pathology, Tokyo Medical & Dental University, Tokyo, Japan
Academic and Social Activities
Professor on Oral Histology and Oral Pathology
Director, Dept. of International Services, West China College of Stomatology, Sichuan University, China
Vice Director, Department of Oral Basic Medicine, West China College of Stomatology, Sichuan
University, China
Chairman, Department of Oral Histopathology, West China College of Stomatology, Sichuan University,
China
Vice Director, Oral Pathology Committee, Chinese Stomatological Association
Editorial board member, Hua Xi Kou Qiang Yi Xue Za Zhi (chinese)
Editorial board member, Guo Ji Kou Qiang Yi Xue Za Zhi (chinese)

74

74

ASOMP Scientiﬁc session

Aberrant Wnt-1/beta-catenin signaling and WIF-1 deficiency areimportant events in salivary gland adenoid cystic carcinoma progression
Objective: In this study we investigated Wnt-1, beta-Catenin, E-cadherin and WIF-1 expressions in formalin
fixed paraffin embedding samples of salivary glands adenoid cystic carcinoma(SACC) and SACC cell lines.
We disclosed the potential relationship of Wnt-1/beta-catenin pathway, WIF-1 and SACC biologicalbehaviors.
Methods: Expressions of Wnt-1, beta-Catenin, E-cadherin and WIF-1 in human SACC cell lines, ACC-2,
ACC-M and T-ACC-M were detected by RT-PCR and western blot. T-ACC-M was collected by Transwellinvasion chambers coated with Matrigel and owned high metastasis ability. We also evaluated these factors
in SACC tissue microarray by immunohistochemistry. The data were analyzed using SPSS10.
Results: Wnt-1 overexpression was a frequent event in SACC and hints a close relationship between Wnt-1
and tumour cell which have a high invasion and metastasis activity. Beta-catenin stability in cytoplasm andtranslocation into cell nuclei activated canonical Wnt signaling pathway and implicated high invasion andpoor prognosis of SACC. WIF-1 deficiency or down-regulation indicated high metastasis and highrecurrence and poor prognosis of SACC. There was a strong correlation between Wnt-1/beta-cateninsignaling pathway activation and WIF-1 deficiency. E-cadherin expression was resembled beta-Catenin
pattern, which means the dysregulation of E-cadherin-beta-Catenin complex may result in loss ofintercellular adhesion, and possible consequently induce tumour cell invasion and tumour progression.
Conclusions: This study indicated that alterations of the correlative components in canonical Wnt pathway
might contribute to SACC invasion, metastasis and poor prognosis. Furthermore our findings reinforced
the therapeutic potential of inhibiting Wnt signaling pathway via such strategies as reversing WIF-1
inactivation.
Key Words: adenoid cystic carcinoma; Wnt-1; beta-catenin

75

75ASOMP Scientiﬁc session

Yuk-Kwan Chen1, Hsien-Cheng Huang1, Wing-Sang Chan2,
and Li-Min Lin1
1

Department of Oral Pathology, Faculty of Dentistry, College of Dental Medicine,
Kaohsiung Medical University, Kaohsiung, Taiwan; 2Yerkes National Primate ResearchCenter, Department of Human Genetics, Emory University School of Medicine

CURRICULUM VITAE
Yuk-Kwan Chen
Associate Professor, Department of Oral Pathology, Faculty of Dentistry, College of Dental Medicine,
Kaohsiung Medical University, Kaohsiung, Taiwan
Education
1987/09- Master, Graduate Institute of Dental Sciences,
1990/06 Kaohsiung Medical University, Kaohsiung, Taiwan
1989
Bachelor, School of Dentistry, Kaohsiung Medical University, Kaohsiung, Taiwan
Professional
2009/08-Present Associate Professor, School of Dentistry, College of Dental Medicine, Kaohsiung Medical University
2004/02-Present Head, Department of Oral Pathology, Division of Dentistry, Kaohsiung Medical University Hospital
1983/08-Present Visiting Staff, Department of Oral Pathology, Division of Dentistry, Kaohsiung Medical University Hospital
2003/02Assistant Professor
2009/07
School of Dentistry, College of Dental Medicine, Kaohsiung Medical University
AwardsBest Teacher Award of Kaohsiung Medical University, 2002
Best Teacher Award of Kaohsiung Medical University, 2008
Excellent Teacher Award of Kaohsiung Medical University, 2008
Best Research Award of Kaohsiung Medical University, 2008
Best Research Award of Kaohsiung Medical University, 2009
Best Teaching Material Award of Kaohsiung Medical University, 2009

76

76

ASOMP Scientiﬁc session

Study on different cryopreservations and hepatogenic differentiation ofhuman dental pulp stem cells
This study is firstly aimed to determine if human dental pulp stem cells (hDPSCs) can be derived from adiseased but vital tooth after cryopreservation of the intact teeth and the isolated dental pulp tissue
respectively. It is also intended to demonstrate that the hDPSCs derived from cryopreserved dental pulp
tissues are able to differentiate into hepatocyte-like cells.
Materials: Fifty tooth samples were divided into: Group A (n=20) - Freshly derived dental pulp tissues;Group B (n=20) - Liquid nitrogen (LN2) stored dental pulp tissues; Group C (n=10) - LN2 stored intact
teeth; and Group D - Hepatogenic differentiation (6 samples randomly selected each from Groups A & B).
Methods & Results: The male to female ratio of all the 50 tooth samples was 1:1.78 with an average age tobe 25.5 year-old ranging from 6 to 74 year-old. Groups A and B had a 100% successful rate on hDPSCs
isolation respectively whilst Group C had only a 20% successful rate. Groups A to C demonstrated selfrenewal properties and similar multipotent potential characteristics of adipogenic, chondrogenic, andosteogenic differentiation. There was no statistical significance on growth rate analyzed by MANOVA withthe whole model. Additionally, hDPSCs showed high expression for bone marrow mesenchymal stem cellmarkers (CD29, CD90 & CD105) and very low expression of specific hematopoietic cells markers (CD14,
CD34 & CD45). All the 12 isolated hDPSCs for Group D showed hepatogenic differentiation andmorphology changing from spindle into polygonal shape. The expression of differentiated hDPSCs for thehepatic metabolic function genes (αFP, Alb, CK-18, TO, G-6P) and liver-specific genes (C/EBPα,
HNF1 α and CYP1A1) were all positive for the differentiated hDPSCs. Glycogen storage in the
differentiated hDPSCs cells was also demonstrated. Positive immunofluorescence staining of low density
lipoprotein and albumin were observed commencing from the 14th day of differentiation medium
culturing. Urea concentration in the medium was noted from the 6th week.
Conclusion: The isolated hDPSCs can be stored in LN2 for future potential usage and their hepatogenic
differentiation properties would provide a potential source for autogenic transplantation.

77

77

ASOMP Scientiﬁc session

Naozumi Ishimaru
Department of Oral Molecular Pathology
Institute of Health Biosciences
The University of Tokushima Graduate School

CURRICULUM VITAE
Naozumi Ishimaru
Professor, Department of Oral Molecular Pathology, Institute of Health Biosciences, The University ofTokushima Graduate School
Biography
1994 D.D.S. Tokuhsima University School of Dentistry
1998 Ph.D. The University of Tokushima Graduate School
1999 Assistant Professor, Tokushima University Dental Hospital
2003 Associate Professor, Tokushima University School of Dentistry2003 Deputy Director of the Department of Pathology, Tokuhsima University Hospital
2011 Professor, Institute of Health Biosciences, The University of Tokushima Graduate School
Overseas Research Career
2003-2005 Research Associate, Department of Immunology, The Scripps Research Institute, USA
2009-2010 Visiting Professor, Garvan Institute of Medical Research, Australia

78

78

ASOMP Scientiﬁc session

Gender-based molecular pathogenesis of Sjögren’s syndrome

Sjögren’ syndrome (SS) is one of autoimmune diseases targeting lacrimal and salivary glands. Although SS is
known to develop in postmenopausal women, the mechanisms by which estrogen deficiency influencesautoimmunity remain unclear. It has been suggested that estrogenic action is responsible for the strong
female preponderance of autoimmune diseases including SS. Recently, we found that tissue-specific apoptosis
in the salivary and lacrimal glands spontaneously occurring in estrogen-deficient mice may contribute to thedevelopment of autoimmune exocrinopathy through one of cell cycle-related molecules, retinoblastomaassociated protein (RbAp) 48. We reported that transgenic (TG) expression of RbAp48 resulted in thedevelopment of autoimmune exocrinopathy resembling SS, in which salivary and lacrimal epithelial cells
produced IFN-γand IL-18. In addition, RbAp48-expressing epithelial cells together with IFN-γand IL-18
were observed in the salivary gland tissues of SS patients, but not controls. These results indicate a novel
immunocompetent role of epithelial cells, resulting in loss of local tolerance before developing gender-based
autoimmunity. Moreover, analyzing the expressions of these molecules may help diagnosing for SS or
establishing a better therapeutic strategy for autoimmunity.

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79

一般演題（口演）Ⅱ
Oral PresentationⅡ81

2A-01array-CGH法による口腔扁平上皮癌のゲノム異常の解析

Genomic proﬁle of oral squamous cell carcinoma by oligonucleotide-arraycomparative genomic hybridization
吉岡 俊一1,2，河野 憲司1Shunichi Yoshioka1,2 and Kenji Kawano1
1

大分大学医学部附属病院 歯科口腔外科
大分大学医学部 分子病理学教室
1
Department of Dentistry and Oral Maxillofacial Surgery, Oita University
2
Department of Molecular Pathology, Faculty of Medicine, Oita University
2【目 的】
口腔扁平上皮癌（OSCC）の頚部リンパ節転移は予後を規定する重要な因子である。今回我々は，OSCCの転移能獲得の鍵となる遺伝子の検出を目的として，本研究を行った。
【方 法】
大分大学医学部附属病院歯科口腔外科で治療を行ったOSCC25症例（頚部リンパ節転移例15例，非転移例10例）を対象とした。DNA抽出：原発巣，転移巣のホルマリン固定パラフィン包埋切片よりLaser Captured
Microdissection を用いて癌細胞を選択的に切り取り，ゲノムDNAを抽出した。Array-CGH：Agilent社
Whole Human Genome 4×44K Oligo Micro Array Kitを用い，同社のプロトコールに従ってゲノムコピー
数異常を検出した。
【結 果】
１）転移例の原発巣と転移巣の間でゲノムコピー数異常の頻度に有意差を認める領域は検出されなかった。
一方，各症例ごとの原発巣と転移巣の比較では異常プローブ数に有意差はなかったが，ゲノムプロファイ
ルを詳細にみると，原発巣と転移巣でそれぞれ異なる特異的なゲノム異常領域が検出された。２）転移例と非転移例の原発巣の比較では，非転移例の原発巣で1p，5q，9p，19p領域のゲノムコピー数の欠失が高頻度に検出された。３）非転移例の原発巣と転移例の転移巣の比較では，転移例の転移巣で7p，8q，17qのゲノムコピー数の増幅が高頻度に検出された。
【考 察】
転移巣と原発巣間の異常プローブ数に差がなかったことから，OSCCでは直線的なゲノム異常の付加で転移能を獲得するわけではないと考える。また，多くの転移例で原発巣と転移巣が異なるゲノム異常を持つことを見出だした。この結果から，原発巣と転移巣は異種性の細胞集団で構成されていることが示唆された。
Using array CGH, we analyzed the diﬀerence in genomic copy number aberration (CNA) in order toinvestigate lymph node metastasis-related genes in oral squamous cell carcinomas (OSCC). The
comparison among CNAs of each primary tumor with every metastatic ones revealed that the primaryand metastatic tumors from same patients showed the highest similarity but not completely same.
Moreover, no signiﬁcant diﬀerence in the CNAs between primary and metastatic tumors was found.
Taken together, our data suggest that the divergent clonal evolution rather than sequential acquisitionof CNAs is possibly involved in the process of lymph node metastasis.

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82

2A-02

The role of thrombospondin-1 (TSP1) in invasion of oral cancer
Samir Kumar Pal1,2, Kei Sakamoto1 and Akira Yamaguchi1,21Department of "Oral Pathology", Graduate School of Medical and Dental Science, Tokyo Medical and Dental
University
2
Global Center of Excellence (GCOE) program, "International Research Center for Molecular Science in Toothand Bone Diseases", Tokyo Medical and Dental University
Background: Thrombospondin-1 (TSP1) is a secretory glycoprotein that binds to many proteins andmediates diverse cellular functions. Its significance in oral carcinogenesis has been suggested, but is yet
poorly understood.
Materials and methods: Thirty formalin fixed, paraffin embedded specimens of surgically excised oral
squamous cell carcinoma (OSCC) were used for immunohistochemical analysis. Foe cells culture
experiments, we used human oral cancer cell lines (BHY, HSC3 and Ca9-22) and a mouse stromal cell line
(ST-2) was used to examine the proliferation, movement and invasion of cancer cells.
Results: In normal oral mucosa, TSP1 expression was observed preferentially in the capillary endothelial
cells. In OSCC, TSP1 expression became to be dominant at fibroblastic cells adjacent to cancer cells as wellas capillary endothelial cells, and TSP1 also accumulated in the extracellular matrix. Cell culture
experiments revealed that TSP1 induced no effects on cancer cell proliferation, but it promoted movementof both cancer cells and stromal cells. TSP1 also stimulated invasion of cancer cells.
Conclusion: TSP1 expressed in fibroblastic cells around cancer cells may play an important role in cell
movement and invasion of OSCC.

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83

2A-03The differential diagnosis and histopathogenesis of thyroglossal duct cyst:
a comparative immunohistochemical study
Henry Ademola Adeola1, Masayuki Tsuneki1, Manabu Yamazaki1, Satoshi Maruyama2,
Jun Cheng1 and Takashi Saku1,2
1

Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Graduate School of Medical
and Dental Sciences, Niigata University
2
Oral Pathology Section, Department of Surgical Pathology,, Niigata University Hospital
Background: Thyroglossal duct cyst (TDC) is believed to develop from vestigial elements of the thyroglossal
tract, though this pathogenetic concept is not always based on scientific evidence. It remains unknown
whether the cyst develops from ectopic thyroid gland follicles or from the thyroglossal duct itself. Our aim
was to compare immunohistochemical profiles between main and daughter cysts and associated thyroid
tissues of TDC and normal thyroid tissues for discussing its pathogenesis.
Materials and methods: Five surgical specimens of TDC and 4 autopsy specimens of normal thyroid gland
were selected. Formalin-fixed paraffin sections were used for immunohistochemistry for keratins 19 (K19),
7 (K7), and 13 (K13), p63 protein (P63), thyroglobulin, MUC-1, and Ki-67.
Results: Normal thyroid follicular epithelial cells were immunopositive for K7, MUC-1, and thyroglobulin.
Intrafollicular colloid was positive for MUC-1 and thyroglobulin. TDC Lining epithelia were classified into
four types: i) ciliated pseudostratified columnar, ii) two-cell-layered, iii) simple squamous, and iv) stratified
squamous. The whole layer of linings were positive for K7 and K19 but not for K13. P63 was positive inbasal cells of the cystic lining, while MUC-1 was localized in both basal and luminal cells. Thyroglobulin
was neither positive in the cystic lining nor in cystic contents. Ki-67-positive cells were occasionally found.
Discussion: This is the first immunohistochemical investigation on TDC. The differential expression
p r o f i l e s f o r t h e s e 7 m o l e c u l e s c o u l d s e r v e a s a n a i d f o r t h e d i a g n o s i s o f T D C . Fr o m t h eimmunohistochemical discrepancy between TDC epithelia and normal thyroid, TDC's thyroid follicularepithelial origin is unlikely.

84

84

Presentation

口腔病理基本画像アトラス

The Basic Oral Pathology Atlas
小宮山 一雄Kazuo Komiyama
日本臨床口腔病理学会教育委員会 口腔病理基本画像データベース作製小委員会
The Board of Education of the Japanese Society of Oral Pathologists
The database subcommittee of “The Basic Oral Pantology Atlas”

口腔は食物摂取，構音，呼吸に重要な役割を果たしており，この領域には奇形から感染症，炎症，腫瘍性病変まで様々な病変がみられます。口腔は表層を粘膜上皮に覆われていますが，その形態は部位により違いがみられ，口腔病変の発症と病態を特徴づけいます。また，歯とそれを植立する上下顎骨，唾液腺，舌などの臓器ではそれぞれの臓器に特有な病変がみられます。これら口腔領域に現れる病変を学習するうえで、参照できる基本病態の画像アトラスが必要であるとの考えから、日本臨床口腔病理学会教育委員会は
平成21年度にデータベース作製のため小委員会を組織し、全国の歯科医学教育施設の協力を得て病態画像を含む病理組織画像の収集を開始しました。このアトラスはWebを利用して，口腔病理学を学ぶ歯科大学
および歯学部学生，研修医，や衛生士学校の学生の皆さんに広く利用していただくことを目標としました。
また、掲載してある画像を用いて口腔病理組織所見を自主学習する為に重要所見を記載しております。さらに画像は口腔病理学の教材としても活用していただき，口腔領域の病変の理解を深めていただきたいと思います。アトラスは今秋の公開をを目指して作業中でありますが、その一部を会員各位にご覧いただきご意見等賜りたいと存じます。
口腔病理基本画像データベース作製委員会
日本大学歯学部
小宮山一雄
福岡歯科大学
谷口 邦久
日本大学松戸歯学部 久山 佳代
北海道医療大学（元）大内 知之
九州大学歯学部
清島保
福岡歯科大学大野純

大阪歯科大学田中 昭男
東京医科歯科大学 坂本啓

Oral cavity plays an important role in food intake, articulations, and respiratory infections. There isnumerous disease recognized in this area such as the malformation, infectious disease, various
odontogenic and non-odontogenic tumors, including cysts. Although oral mucosal surface is covered withthe epithelium, which forms diﬀerent appearance in each anatomical site, it is reﬂected into characterize
the onset of disease. In addition, upper and lower jaw and teeth, salivary glands and tongue develop
each tissue-speciﬁc disease. In order to study the oral lesions thatappear in these areas, the basic histopathology can see images ofAtlas. The Japanese Society of Oral Pathologists (JSOP) set up the
database subcommittee under the Board of Education at the 2009
annual meeting. The committee began collecting pathologicalimages of oral disease, including the clinical images with the help of
the Japanese Society of Oral Surgery and dental educational
institutions nationwide. Students, not only dental students but alsointern students, residents and hygienists, are able to learn oraldisease through “The Basic Oral Pathology Atlas” on the Web. We
have summarized the key points for self-study of histopathology
and clinical appearance with using posted images. We would like todeepen their understanding of lesions of the oral area with the Web
system. The Atlas is working toward the publication of this fall, andwe expect additional feedback from members of the JSOP.
Members of the database subcommittee
Kazuo Komiyama
Kunihisa Taniguchi
Kayo Kuyama
Tomoyuki Oouchi
Tamotsu Kiyoshima
Jun Ohno

Akio Tanaka
Kei Sakamoto

85

85

研修プログラム
Training Program

87

第2日目

8月25日（木）研修プログラム「口腔病理医の剖検」
Ａ会場メインホール

10：00〜12：00

解剖症例の提示【学歴】
2000年３月

福岡歯科大学歯学部卒業

４月
2005年３月

福岡歯科大学大学院 歯学研究科入学
同大学院 修了
学位取得，博士（歯学）2005年４月
2006年10月

福岡歯科大学専攻生（生体構造学講座病態構造学分野）
福岡歯科大学研究生へ種別変更（2010年3月まで）

【職歴】

江原 道子

朝日大学歯学部口腔病態
医療学講座口腔病理学分野
助教

2006年10月
2009年４月

福岡県済生会福岡総合病院 病理部
同院 病理診断科へ科名変更 医員

2011年４月

朝日大学歯学部口腔病態医療学講座口腔病理学分野【資格】
歯科医師免許医員
助教

2001年４月

死体解剖資格認定
2009年３月26日
口腔病理専門医認定 2010年７月28日
現在に至る

88

88

Training Program

An autopsy case of hemorrhagic shock by ruptured ofgastroesophageal varix
江原道子1，中島明彦2，青木良介2，永山元彦1，坂野美栄1，田沼順一1Michiko Ehara1, Akihiko Nakashima2, Ryosuke Aoki2, Motohiko Nagayama1, Yoshie Sakano1, Jun-ichi Tanuma11

朝日大学歯学部口腔病態医療学講座口腔病理学分野
済生会福岡総合病院病理診断科2
12

Department of Oral Pathology, Division of Oral Pathogenesis and Disease Control, Asahi University School of Dentistry

Division of Pathology, Saiseikai Fukuoka General Hospital【主病変】
1．食道・胃静脈瘤および破裂+出血【副病変】
1．アルコール性肝硬変 1560g
2．腹水 1500ml
3．脾腫 410g
4．急性尿細管壊死＋細動脈性腎硬化
5．肺のうっ血・水腫 445g / 565g
6．左胸水 50ml

190g / 200g

【臨床経過】
52才，男性。元来大酒家であり，アルコール性肝硬変を指摘されるも放置。死亡８日前の朝より３〜４回の吐血があり，14時の吐血の際，気が遠のく感じあり，救急車を要請し当院へ救急搬送された。緊急上部内視鏡検査を施行したところ，食道および胃に静脈瘤を認めた。EIS（endoscopic injection sclerotherapy）
は，T-Bil 6.0，Plt 8.0万，PT 51%であったため施行できず，EVL（endoscopic variceal ligation）を９カ所施行した。その後吐血なく経過していたが，死亡前日の19時頃より吐血を繰り返し，BP50台まで低下した。吐血量は推定2000ml，shock vitalの状態であったため，GIFは施行できなかった。また，T-Bil 5，PT
40%台であり，現在の肝機能からは出血および肝不全のriskが考えられ，治療の適応はないと判断，ご家族の同意のもと，DNARの方針となった。翌日の深夜，HR50~60台に低下を認め，その後 JCS 300，モニ
ター上，asystole，LR（−），心音・呼吸音（−）であり，死亡確認となった。
【入院時検査所見】
血液一般：RBC 262×104/μl, WBC 9.6×103/μl, Hb 8.9g/dl, Ht 27.2%, Plt 8.1104/μl
生化学：TP 7.1g/dl, Alb 3.0g/dl, AST 135IU/l, ALT 33IU/l, LDH 646IU/l, T-Bil 6.0mg/dl,
Na 135mEq/l, K 3.9mEq/l, Cl 94mEq/l, BUN 21.5mg/dl, Cr 1.5mg/dl, T-Cho 434mg/dl
免疫血清学：HBs-Ag/Ab, HCV-Ab いずれも陰性
尿検査：尿蛋白（1+），尿糖（−），潜血（2+）
【臨床の疑問点および検索希望事項】
・吐血の原因が，胃・食道静脈瘤破裂によるものかどうか
・肝硬変の程度【剖検時所見】胃および食道静脈瘤には３カ所のリングが残存していたものの，他の部位に関しては，既に外れていた。
明らかに破綻した静脈瘤は観察されなかったが，胃内に750mlの血性液状物がみられたことより，出血は持続していたと考えた。肝臓は肝細胞周囲性の線維化，脂肪沈着がみられ，全体に小葉を取り囲むように線維性結合織がみられた。全身諸臓器は貧血調であり，腎臓には出血性ショックに伴う尿細管の変性・壊死がみられた。
【死因】
胃食道静脈瘤からの出血による出血性ショックおよびそれに伴う多臓器不全【Major pathoanatomical diagnosis】
1．Ruptured gastroesophageal varix and hemorrhage【Minor pathoanatomical diagnosis】
1．Alcoholic liver cirrhosis
2．Ascites 1500ml
3．Splenomegaly 410g
4．Acute tubular necrosis and arteriolosclerotic nephrosclerosis 190g / 200g
5．Congestion and edema of the lung 445g / 565g
6．Pleural eﬀusion of the left 50ml89

89

Training Program

解剖症例の提示【学歴および職歴】
平成15年３月 九州大学歯学部卒業

平成15年４月
平成17年４月

九州大学病院 顎顔面口腔外科
九州大学歯学府大学院 入学

入局（研修医）平成21年３月
平成21年４月

九州大学医学部 病理病態学講座にて学位（歯学博士）取得
九州大学病院 病理部（医員）

平成22年８月

口腔病理専門医取得

鈴木 華子

九州大学大学院 医学研究院
病理病態学講座（九州大学病院 病理部 医員）

悪性リンパ腫の放射線治療後に発生した上顎洞骨肉腫の一剖検例
An autopsy case of osteosarcoma occurred in the maxillary sinus afterradiotherapy to malignant lymphoma

鈴木華子
Hanako Suzuki
九州大学大学院

医学研究院

病理病態学講座

Devision of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of
Medical Sciences, Kyushu University【症例】57歳女性。死亡７年前に左上顎洞のびまん性大細胞型悪性リンパ腫の診断のもと，放射線および化学療法が施行され腫瘍の消失を認めていた。同時期に甲状腺癌も指摘され，甲状腺全摘術を施行された。
死亡２年前，左上顎洞に骨破壊を伴う腫瘤を認め，骨肉腫と診断された。加療されるも腫瘍の増殖および肺転移を認め，徐々に全身状態が悪化し，死亡された。
【病理所見】左上顎洞を中心として，腫瘍の広範な浸潤は，左眼窩，左頬部から顎下部までの皮膚，左頬粘膜，両側上顎骨および鼻腔内におよんでおり，また後方への進展は判定が困難であった。組織学的には，腫瘍は紡錘形や多角形で，明瞭な核小体をもった細胞が腫瘍類骨形成をともなって充実胞巣状に増殖しており，骨肉腫の浸潤増殖の所見であり，壊死や出血も広範にみられた。検索範囲内に悪性リンパ腫の再発の所見は認められなかった。また，両肺に骨肉腫の多発転移巣を認めた。両肺とも軽度のうっ血水腫がみられ，好中球やマクロファージ主体の炎症細胞浸潤を局所に認め，気管支肺炎の像の所見を呈していた。
また，間質の浮腫および軽度の線維化，慢性炎症細胞浸潤がみられ，放射線性肺臓炎に矛盾しない所見であった。甲状腺は摘出後の状態であり，局所再発はみられなかったが，右頚部リンパ節，気管周囲リンパ節に転移がみられた。
【主病変】
多重がん
1．骨肉腫（左上顎洞原発，軟骨芽細胞型，化学療法後２年２ヶ月および炭素イオン線療法後２年の状態），
転移：両肺
2．悪性リンパ腫（左上顎洞原発，びまん性大細胞型，放射線化学療法後7年の状態），再発なし
3．甲状腺癌（乳頭癌，甲状腺全摘および左上内深頚リンパ節切除術術後7年およびヨード治療後３年の状態），浸潤転移：リンパ節（右頚部，気管周囲）9090

Training Program【副病変】
1．両肺放射線性肺臓炎
2．両肺気管支肺炎 うっ血水腫を伴う3．諸臓器うっ血：腎，副腎，脾
4．子宮平滑筋腫
5．副脾
6．動脈硬化（中等度：大動脈，総腸骨動脈
7．胆嚢摘出後16年の状態
8．虫垂摘出後38年の状態

軽度：冠状動脈）【死因】腫瘍死
【Major pathoanatomical diagnosis】
Multiple malignant tumors
1) Osteosarcoma (primary lesion: left maxillary sinus, chondroblastic type, 2 years and 2 month after
chemotherapy, 2 years after carbon-ion therapy), Bilateral lung metastasis
2) Malignant lymphoma (primary lesion: left maxillary sinus, Diﬀuse large B-cell lymphoma, 7 years after
chemo-radiation therapy), No recurrence3) Thyroid carcinoma (papillary carcinoma, 7 years after surgery: total thyroidectomy and left superior
internal jugular nodes dissection, 3 years after radioactive-iodin therapy), Lymph node metastasis (rightneck, paratracheal)【Minor pathoanatomical diagnosis】
1. Bilateral radiation pneumonitis
2. Bilateral bronchopneumonia, associated with edema and congestion
3. Organ congestion (kidney, adrenal gland, spleen)
4. Uterus leiomyoma
5. Accessory spleen
6. Arteriosclerosis (moderate: aorta, common iliac artery / mild: coronary artery)
7. 16 years after cholecystectomy
8. 38 years after appendicectomy【Cause of death】Tumor death【考察】死因は骨肉腫の局所進展および肺転移に加えて，放射線性肺臓炎および気管支肺炎による呼吸機能低下も関連したと考えられ，腫瘍死とした。放射線照射後肉腫の診断には１）放射線療法の既往があり，
２）その照射部位に一致し，３）照射から肉腫の発生まで５年以上の期間があり，４）組織学的に原発と異なった肉腫の診断がついたものとされている。本症例は放射線の照射から骨肉腫の発生までの期間が５年弱ではあるものの，それ以外は基準を満たしていた。

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解剖症例の提示【学歴】
平成11年３月 長崎大学 歯学部 歯学科 卒業
平成15年３月 東京医科歯科大学 大学院歯学研究科 口腔病理学専攻 修了（歯学博士）

石川 文隆

九州歯科大学 健康促進科学専攻
生命科学講座 口腔病態病理学分野
助教【職歴】
平成12年４月 東京都立広尾病院 検査科病理 非常勤研究員（平成13年３月まで）
平成13年４月 東京都立広尾病院 検査科病理 非常勤医員（現在に至る）
平成13年４月 東京都老人総合研究所 老年病のゲノム解析研究チーム
老年病・がんゲノム研究グループ 客員研究員（平成21年３月まで）
平成16年６月 東京女子医科大学 医学部 第二病理学講座 助教（平成21年３月まで）
平成16年６月 東京厚生年金病院 病理科 非常勤医員（平成19年６月まで）
平成18年４月 東京都老人医療センター 剖検病理科 非常勤医員（平成21年３月まで）
平成21年４月 九州歯科大学 健康促進科学専攻 生命科学講座
口腔病態病理学分野 助教（現在に至る）【資格】
口腔病理専門医（平成18年８月取得）
死体解剖資格（平成17年１月取得）

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臨床的に悪性リンパ腫の中枢神経浸潤再発が疑われたが，
剖検によりトキソプラズマ脳炎が明らかとなった１例

Toxoplasma encephalitis presenting clinically as a suspected relapse of malignant
lymphoma involving the central nervous system: an autopsy case石川文隆1，本田一穂2，松尾 拡1，小田秀明2
Ayataka Ishikawa1, Kazuho Honda2, Kou Matsuo1, Hideaki Oda2
1

九州歯科大学 健康促進科学専攻 生命科学講座 口腔病態病理学分野
東京女子医科大学 医学部 第二病理学講座
1
Division of Oral Pathology, Department of Biosciences, Science of Health Improvement, Kyushu Dental College
2
Department of Pathology, Tokyo Womenʼs Medical University, School of Medicine
2【症例】
66歳，男性。
【臨床経過】
2004年１月，血球貪食症候群にて発症した非ホジキンリンパ腫。CHOP，RICE療法にて軽快するも2006年
１月，中枢神経に再燃しauto-PBSCT施行。MTX-Ara-Cによる維持療法を施行していたが，2007年４月，
中枢神経病変再燃し，５月よりhigh dose MTX療法施行するも無効。呼吸，意識レベルが低下し，７月死亡された。
【臨床診断】
非ホジキンリンパ腫，中枢神経浸潤再発。
【臨床上の問題点および剖検精査希望事項】
High dose MTX療法後敗血症になり意識レベル低下。MRI検査では病変の増悪がみられたが，画像上認められた腫瘤状病変のみでは意識レベル低下の原因を説明しにくい。そのため，主病変以外に血管内悪性リンパ腫などの病変や虚血性変化の有無について精査希望であった。
【剖検肉眼所見】
脳（1580g）は肉眼的に軽度の浮腫がみられ脳溝はやや不明瞭。割面では左基底核から脳梁放線にかけて
6x3cm大，右基底核に3.5x2.6cm大の出血を伴う褐色病変を認めた。また，両側前頭葉，頭頂葉，側頭葉，
後頭葉の皮質表層部と皮質・白質境界部に3.2x1.5cm大までの出血を伴う褐色病変が多発。小脳皮質と歯状核には右に1 cm大まで，左に2cm大までの出血を伴う褐色病変が散在。
【病理組織学的所見】
１．大脳，小脳を中心に出血を伴う褐色病変には広範な壊死がみられ，出血とフィブリン析出，浮腫，多数のマクロファージ集簇，軽度〜中等度のリンパ球・形質細胞浸潤，軽度の好中球浸潤を伴っていた。
壊死巣周囲には軽度のグリオーシスがみられた。中脳，橋，延髄，頚髄には2mm大までの小壊死層が散在性にみられ，浮腫と軽度のリンパ球・形質細胞浸潤を伴っていた。これらの大脳，小脳，中脳，橋，延髄，頚髄の病変には多数のトキソプラズマ原虫が嚢胞形成性あるいは散在性にみられた。
２．剖検標本には明らかなリンパ腫細胞を認めなかった。
【免疫染色所見】
トキソプラズマ原虫は抗トキソプラズマ抗体に陽性。
【病理学的診断】１．トキソプラズマ脳炎（大脳，小脳主体で中脳，橋，延髄，頚髄に及ぶ）。
２．悪性リンパ腫，化学療法後【考察】
悪性リンパ腫の症例で臨床的にはMRI検査の結果から非ホジキンリンパ腫の中枢神経浸潤再発が疑われていたが，剖検により広範なトキソプラズマ脳炎が明らかとなった。このトキソプラズマ脳炎は化学療法に起因する免疫状態の低下により発症したと考えられる。標本上，トキソプラズマ原虫は大脳，小脳を主体
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として中脳，橋，延髄，頚髄に壊死巣を伴いながら広範に認められた。臨床的に考えられた悪性リンパ腫
細胞の浸潤は認められなかった。また，大量MTX療法が施行されているが散在性壊死性白質脳症の所見はみられなかった。大脳病変は局在性で層性皮質壊死はみられず敗血症性ショックによる影響も考えにくい。胸・腹部臓器の検索は許可されなかったが，トキソプラズマ脳炎が直接死因となった可能性が高いと考える。
【トキソプラズマ脳炎】
Toxoplasma gondii はネコを最終宿主とする原虫で，経口感染によって腸から侵入しほとんど増殖を止めた嚢子の状態で主に脳，リンパ節，筋肉に存在しているが多くは不顕性感染となる。しかし，AIDS，悪性腫瘍に対しての化学療法やステロイド療法の副作用などにより免疫不全状態となると再活性化されてト
キソプラズマ脳炎を生じる。組織学的には脳内に壊死性の炎症性病巣が散在し，病巣内には多数の虫体を含む嚢胞と実質内に撒布されたトキソプラズマ原虫がみられる。
本症例は東京女子医科大学病院血液内科の症例である。
Case:
We present the case of a 66-year-old male scheduled for autopsy. In January 2004, the patientdemonstrated symptoms of hemophagocytosis and was diagnosed with non-Hodgkinʼs lymphoma
following clinical examination. Temporary recovery ensued after chemotherapy with the CHOP and
RICE regimens. However, in January 2006, following symptoms which pointed towards a relapse
involving the central nervous system (CNS), auto-peripheral blood stem cell transfusion was performed.
Despite maintenance therapy with methotrexate (MTX) and cytarabine, the CNS lesion recurred in
April 2007; high-dose MTX therapy was administered from May 2007, but proved ineffective.
Subsequently, breathing and consciousness levels deteriorated and the patient died in July 2007.
Autopsy ﬁndings:
Macroscopically, slight edema was observed in the brain and the sulci were not clearly demarcated. In
the coronal section, a brown hemorrhagic lesion measuring 6 cm × 3 cm extended from the left basal
nuclei to the radiation of the corpus callosum and the right basal nuclei. Moreover, multiple identicallesions (2 cm) were seen involving the frontal, parietal, temporal, and occipital cerebral lobes, cerebellar
cortex, and dentate nucleus. Histologically, these lesions exhibited extensive necrosis with bleeding,ﬁbrin deposition, edema, multiple macrophage aggregations, mild‒moderate lymphoid inﬁltration, andmild neutrophilic inﬁltration. Mild gliosis was observed around the necrotic areas. In the midbrain,pons, medulla oblongata, and cervical spinal cord, small disseminated necrotic foci of up to 2 mm in size
were observed with edema and mild lymphoid inﬁltration. Extensive invasion by Toxoplasma gondii
was detected on the basis of cyst formation and dissemination of the lesions in the cerebrum,
cerebellum, midbrain, pons, medulla oblongata, and cervical spinal cord. However, lymphoma cells were
not observed in autopsy specimens. Immunohistochemically, anti-toxoplasma antibody positivity was
identiﬁed, which indicated Toxoplasma gondii infection.
Comments:
Following chemotherapy for malignant lymphoma, relapse involving the CNS was clinically suspectedfrom the results of MRI examination. Extensive encephalitis associated with toxoplasmosis was
confirmed at autopsy. This infection presumably occurred due to an immunocompromised status
following chemotherapy. The widespread presence of Toxoplasma gondii with extensive necrosis wasobserved in the cerebrum, cerebellum, midbrain, pons, medulla oblongata, and cervical spinal cord.
Invasion of malignant lymphoma cells, which was clinically suspected, was not observed on autopsy.
Moreover, although extensive MTX therapy was administered, disseminated necrotizing
leukoencephalopathy was not observed. The cerebral lesions were localized, and since laminar corticalnecrosis was not observed, it was difficult to envisage that septic shock was involved in thepathogenesis. Although examination of the chest and abdomen was not permitted at autopsy, on thebasis of histological ﬁndings, it was presumed that toxoplasma encephalitis was the main cause of death.

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総
【略歴】
昭和56年

出雲 俊之

埼玉県立がんセンター
病理診断科

96

96

括

岐阜歯科大学（現：朝日大学歯学部）卒業

昭和57年
昭和58〜61年

東京医科歯科大学大学院歯学研究科（口腔病理学）入学
東京都立駒込病院病理科研究員 兼務

昭和61年

癌研究会癌研究所病理部研究生 兼務
東京医科歯科大学大学院歯学研究科 修了

昭和61年〜
平成11〜15年

埼玉県立がんセンター研究所病理部 医員
東京大学医科学研究所病理研究部客員研究員〜現在

埼玉県立がんセンター病理診断科

副部長

兼務

Training Program

剖検症例のまとめ方
出雲俊之
Toshiyuki Izumo
埼玉県立がんセンター病理診断科

Department of Pathology, Saitama Cancer Center１．はじめに口腔病理専門医を目指す若手病理医および指導者に対して，剖検症例のまとめ方を理解してもらうのが，本研修プログラムの目的である。講演では実務的，具体的な解説をすることとして，ここでは長らく実施
委員，試験委員として口腔病理専門医試験に携わり，また，本年度承認された口腔病理専門医制度改定作業に加わった一人として，本制度について，また，口腔病理専門医に何が求められているのか，私見を述べておきたい。
口腔病理専門医制度は，制度設計上の観点から見ると整合性に問題のある制度で，これは我が国の医療が医師法と歯科医師法という二重構造で運用され，現実の社会システムに多くの矛盾が生じている一つの証左と考えられる。歯科医学教育では，コア・カリキュラムや教授要綱の内容が医学教育と大きく異なり，病気を抱えた人間を扱うという視点が希薄である。従って，口腔病理医は卒後研修において，教育内容の不備を個人的な努力で補うという大きな負荷を担うことになるが，さらに医療システムにおいて歯科が分離していることが，一般病理研修の大きな壁となっている。
本年度の制度改定は，専門医研修内容の明確化による研修システムの整備を図るものであるが，個々の教室に委ねていた口腔病理医の教育をopenなものにして，学会全体で担おうという意図もある。専門医同志の情報交換や生涯教育等も合わせて進めることにより，人事の流動化や学会の活性化が期待され，口腔病理学の質の向上に繋がるものと考える。
口腔病理専門医研修要綱細目には，「口腔病理専門医試験は，病理専門医試験と同一の全身病変と口腔病理専門医試験独自の口腔病変から構成され」，「口腔病変については専門性の高い内容を研修する必要がある」と記載されている。また，口腔病理専門医試験にⅢ型（剖検）問題が課されている意図については，
口腔病理専門医試験要綱に記載されているので，一度参照されたい。優れた口腔病理医とは，前提として優れた一般病理医であるという本質論から間違った制度ではないと考えるが，社会システムの矛盾解消は学会としての大きな課題である。恵まれない研修環境において切磋琢磨している後輩諸君には大変申し訳なく，本講演で少しでも勉強のお役に立てればと思う。また，たかだか100人ほどの専門医ギルド社会へ参加される諸氏を心から歓迎したい。
２．発表症例の総括
抄録のみ拝見した呈示３症例は，いずれもそのままⅢ型試験に使われることは無い比較的平易な剖検例である。そこで，これら各症例を素材として修正を加え，空想的Ⅲ型問題に作り変えてみることにした。
専門医試験では何が問われるのか，各臓器病理だけではなく統合的な病態理解が要求されていることなどを，具体的に理解して頂きたい。
３．剖検報告書のまとめ方
1）病理解剖の前提：医療行為のなされた遺体の解剖であり，検査結果に基づく臨床診断と治療に修飾された臨床経過がある。臨床診断の精度は85〜90％とされ，病理解剖による肉眼所見を加えれば，診断は95％以上絞られる。さらに組織所見によって，それらを確認，補足して最終的な病理解剖診断書となる。
2）暫定病理解剖（マクロ）診断書：臨床経過と肉眼所見に基づくマクロ診断書が重要。
（1）主要疾患による直接障害を考える
a）悪性腫瘍の場合 原発臓器，転移，組織型（WHO分類，規約），治療効果，副作用b）非腫瘍性疾患の場合 病理総論的病因分類，病変の拡がり，検査所見との相関，病変と副病変の鑑別，重要な所見から記載（2）臓器相関による間接的な障害を考える
主病変により障害された臓器の機能低下により他臓器にどの様な障害が及ぶか（3）主病変以外に死因がある場合
肺炎，心筋梗塞，出血，重症感染症，日和見感染，肺動脈血栓症etc.

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病理総論的病因分類，病変の拡がり，死因からの帰納的考察
3）望ましい病理解剖診断書（1）主病変と副病変が明確にわけられている（2）重要な所見から順序正しく診断が記載されている（3）死因が矛盾のないものになっている（4）臨床的問題点に対する病理学的に整合的な考察がなされている
4）病理学的考察：一般に，単一疾患のみに罹患していることはまれで，主病変，副病変，合併症，死因などを整理して考えなくてはならない。一連の臨床経過の中で病態・病状の変化を説明可能な場合もあるが，複雑な病態を考察しなければならない症例も少なくない。疾患の背景には，いわゆる生活
習慣病である高血圧，高脂血症，糖尿病，動脈硬化，肺気腫などが併存する頻度が高く，これらが関連する病態として，循環器（心血管，脳血管）疾患，腎疾患，感染症，呼吸器障害などが挙げられる。
各疾患について併存疾患，合併疾患，死因それぞれの病態生理と相互関連性について十分学習しておくことが重要。
5）フローチャート：複雑な臨床経過や病態を理解する上でフローチャート作成が有効。近年はそれ自体が設問として課される傾向。
４．Ⅲ型試験のポイント（傾向と対策）
1）既往問題の検討：
2011年 7/30施行
2010年 肺腺癌に由来するTrousseau症候群により多臓器梗塞･血栓症を来たした症例
2009年 糖尿病，動脈硬化症を背景に新旧の心筋梗塞発症例
2008年 薬剤性肝障害を基盤にサイトメガロウィルス腸炎合併症例
2007年 ステロイド治療がなされたSLE症例に多彩な感染症併発症例
2006年 全身性硬化症に伴う諸臓器病変に真菌感染，糖尿病性変化が加わった症例
2005年 糖尿病歴を有する患者における心筋梗塞症例
2004年 成人T細胞性白血病，肺癌，前立腺癌の同時性三重癌に日和見感染合併症例
2003年 肺腺癌，von Recklinghausen病，多発性GIST症例で多発性脳梗塞，気道閉塞等の多彩な副病変伴う症例
2002年 血球貪食症を併発した血管内悪性リンパ腫症例
2001年 日和見感染，薬剤性肝障害を伴う成人T細胞性白血病症例
2）設問形式：主病変＋副病変のまとめ，臨床病態の説明，フローチャート
3）時間配分：150分 マクロ診断（60）＋組織所見追加（60）＋診断書作成（30）4）採点：統一的採点基準 部分点加算or減点方式 最終調整の傾向
5）配点：答案100点＋面接点50点＝150点満点 90点（60％）合格が原則
6）面接の目的：病理専門医としてふさわしい人物像（1）論理性（知識，判断力，技能など）（2）対応能力（コミュニケーション能力，態度）についての適性を判定し不適格な人物を除外。
＊ 不適格な人物（dangerous pathologist）とは，病理の基本的な知識や診断能力に欠ける，判断力や集中力に欠ける，不注意な間違いが多い，臨床医や技師などとのコミュニケーションがとれない，他人の話を聞かず自己判断のみで物事を処理する，など病理専門医としての資質に欠ける人物をさす。
＜参考文献＞
1）日本病理学会口腔病理専門医制度規程，口腔病理専門医のための研修要綱，研修要綱細目，試験要綱，
研修手帳（基盤整備委員会案）
2）林 良夫 医療の中の口腔病理の位置づけ 病理と臨床27（臨時増刊号）:110-114,20093）黒田 誠 病理解剖学事始め 第15回日本口腔病理学会教育講演 2004
4）田村浩一 臨床研修必携 CPCレポート作成マニュアル 南江堂 2004
5）日本病理学会 新医師臨床研修制度におけるCPCレポート作成に関する資料一覧 2003

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ランチョンセミナーⅡ
Luncheon Seminar Ⅱ

99

第2日目

8月25日（木）ランチョンセミナーⅡ
B会場中ホール１

100

100

12：10〜13：00

症例検討Ⅱ
Case StudyⅡ103

2A-04

症例検討Ⅱ

耳下腺腫瘍の 1 例

A case of parotid gland tumor
浦野 誠，溝口 良順，黒田 誠
Makoto Urano, Yoshikazu Mizoguchi and Makoto Kuroda
藤田保健衛生大学医学部 病理診断科
Department of Diagnostic Pathology, Fujita Health University, School of Medicine

症例：89歳・男性
臨床経過：数年来の左耳下部腫脹あり，画像診断で耳下腺良性腫瘍として経過観察されていた。顔面神経麻痺なし。今回，増大傾向を認め穿刺吸引細胞診にて充実型腺様嚢胞癌が疑われ，耳下腺腫瘍摘出術が施行された。
摘出物所見：長径 2 cm大の灰白色調充実性腫瘍。
組織学的所見：被膜形成の不明瞭な充実性腫瘍で，周囲組織への浸潤増殖像がみられた。腫瘍の主体部分
では，小型核小体が出現した類円形〜多角形核と淡好酸性〜淡明な細胞質を有する比較的均一な腫瘍細胞が胞巣状および索状に増殖し，内部には大小不整な腺腔構造の介在をわずかに認めた。一部の腫瘍胞巣の最外層では核の柵状配列傾向がうかがわれ，真腔と偽腔からなる篩状構造部分や神経周囲腔浸潤像が観察された。また部分像として，腺腔構造とその周囲に淡明細胞が 2 相性をもって増殖する上皮筋上皮癌様の結節部分を認めた。非腺腔形成性腫瘍細胞には強拡大 1 視野中に 1 個程度の核分裂像がみられた。
検討事項：病理組織学的診断
A 89-year old male noticed a swelling for several years on his left parotid region. He had no facial nerve
paralysis. Adenoid cystic carcinoma was suspected on ﬁne needle aspiration cytology.
On the gross ﬁnding, well demarcated gray whitish tumor, 2cm in diameter was observed. Histologically,
the lesion mainly showed solid and trabecular pattern consisted of non-luminal clear cells which had
oval to polygonal shape nuclei and small nucleoli. A few glands intermingled with solid tumor nests. On
the periphery of the lesion, the tumor invaded surrounding tissue. A small focus of nodular epithelialmyoepithelial carcinoma-like lesion was seen.

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症例検討Ⅱ

2A-05

口蓋腫瘍の 1 例

A case of palatal tumor
松本 直行，迎 章太郎，尾曲 大輔，土屋 元美，津田 宏尚，浅野 正岳，
小宮山 一雄Naoyuki Matsumoto, Shotaro Mukae, Daisuke Oagari, Motomi Tsuchiya,
Hirotaka Tsuda, Masatake Asano and Kazuo Komiyama
日本大学歯学部 病理学教室
Department of Pathology, Nihon University School of Dentistry【症例】48歳，日本人男性。
【臨床経過】 2 年前から口蓋に無痛性の膨隆を自覚していたが，その他に症状は無く放置していた。腫脹
が持続するため近歯科医に紹介され，本学口腔外科を受診した。初診時，口蓋に約 5 × 5 mm大の，表面
滑沢，粘膜色，弾性軟の腫瘤を認めた。良性腫瘍の診断のもと，被覆粘膜を含めて腫瘍切除術が行われた。
【摘出物所見】10×15×15mm大の類球形腫瘤で，割面は淡黄色〜灰白色・充実性であった。
【組織学的所見】粘膜上皮の直下に，線維性被膜に覆われた腫瘍を認めた。腫瘍の大部分は充実性ないし腺管構造を呈し，腫瘍表層では乳頭状構造を示す上皮成分が錯角化を呈す重層扁平上皮に連続していた。
腺管構造は立方形ないし円柱形細胞が 2 層性に配列し，内部に好酸性物質が貯留していた。また，多角形
で豊富な細胞質を持つ上皮様細胞や小型の紡錘形細胞で構成される充実性構造を認め，膠原線維の硝子化を伴う間質を混じていた。一部の胞巣には扁平上皮化生を認めた。免疫組織化学的検索では，腺管構造の内面に位置する腫瘍細胞はcytokeratin 8，cytokeratin 18と，epithelial membrane antigenが陽性を示し，腺管構造の外側を構成する細胞と充実性構造をとる上皮様細胞や紡錘形細胞はS-100 protein，vimentinが陽性を示した。Alpha-smooth muscle actinは陰性を示す。少量のKi-67陽性細胞を散見した。
【検討事項】病理組織学的診断
The patient was 48-year-old Japanese male. He has had a palatal swelling for 2 years. In ﬁrst visit, 5×5mm, non-tender mass was noted on the palate. Histologically, the excised tumor was circumscribedwith ﬁbrous capsule and composed of papillary, ductual and solid epithelial structures. The papillary
structures are continued with covering epithelium. The inner cells of double-layered ductual structures
were positive for cytokeratin 8, cytokeratin 18 and epithelial membrane antigen. Outer cells and solid
areas were positive for S-100 protein and vimentin. Alpha-smooth muscle actin was negative for any
tumor cells. Few Ki-67 positive cells are dispersed.

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2A-06

症例検討Ⅱ

口蓋腫瘍

Palatal tumor
小川 郁子1，櫛谷 桂2，坂本 哲彦3，宮内 睦美4，井内 康輝2，高田 隆4
Ikuko Ogawa1, Kei Kushitani2, Tetsuhiko Sakamoto3, Mutsumi Miyauchi4,
Kouki Inai2 and Takashi Takata41

広島大学病院 口腔検査センター
広島大学大学院医歯薬学総合研究科 病理学研究室
3
マツダ病院 歯科口腔外科
4広島大学大学院医歯薬学総合研究科 口腔顎顔面病理病態学研究室
1Center of Oral Clinical Examination, Hiroshima University Hospital2
Department of Pathology, Graduate Shool of Biomedical Sciences, Hiroshima University
3
Oral and Maxillofacial Surgery, Matsuda Hospital
4
Department of Oral and Maxillofacial Pathobiology, Graduate Shool of Biomedical Sciences, Hiroshima
University2

症例：73歳，男性
臨床経過：初診約半年前より右側口蓋に腫瘤形成を指摘され，疼痛などの症状がないため放置していたが，精査加療を目的に来院した。初診時，右側軟口蓋に正常粘膜で覆われた約15mm大，弾性やや硬の腫瘤が認められた。周囲との癒着はなく，良性唾液腺腫瘍（多形腺腫の疑い）の臨床診断で切除された。
摘出物所見：腫瘍は，粘膜下に存在し，黄白色充実性で，周囲との境界は明瞭であった。腫瘍内には出血巣が散在していた。
組織学的所見：口蓋腺内に増殖する腫瘍が認められる。腫瘍と周囲組織との境界は，概して明瞭であるが，被膜を欠き，唾液腺内への浸潤像が観察される。腫瘍細胞は，好酸性胞体を有する多稜形〜短紡錘形で，シート状，梁状胞巣を形成して増殖し，細胞間に粘液様基質を伴う部分もある。また，胞巣内には小腺管が散見され，粘液細胞が腫瘍全体に渡って認められる。全体に細胞異型，分裂像ともに乏しく，Ki-67陽性
細胞率は 5 %以下である。腫瘍細胞の多くは，cytokeratinに加えてS-100タンパク, p63を発現し，GFAP,
α-SMA陽性を呈するものもある。
検討事項：病理組織学的診断（配布標本は，腫瘍の一部です。全体像は，バーチャルスライドでご覧下さい。）
A 73 year-old male had been pointed out a swelling in right side of the palate about half a year before.
Physical examination revealed a solid tumor, 15mm in diameter, covered by normal mucosa.
Histopathologically, the tumor is generally well-demarcated, but infiltrates into the salivary gland insome areas. The tumor consisted of solid or trabecular proliferation of polyhedral or short-spindle cellswith myxoid substances. Small lumina were sparsely present and mucous cells distributed throughout
the tumor. Nuclear atypia was absent and proliferative activity was low. The tumor cells expressed
cytokeratins, p63, S-100 protein, GFAP and α-SMA with various degrees.

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症例検討Ⅱ

2A-07

歯原性腫瘍の一例

A case of odontogenic tumor
永山 元彦，坂野 美栄，江原 道子，田沼 順一
Motohiko Nagayama, Yoshie Sakano, Michiko Ehara and Jun-ichi Tanuma
朝日大学歯学部 口腔病理学分野
Department of Oral Pathology, Asahi University School of Dentistry

症例：11歳, 女児
臨床経過：右側下顎犬歯の萌出不全を主訴に紹介来院した。エックス線画像にて右側犬歯の埋伏と周囲を一層のエックス線透過像で囲む不均一な不透過性病変を認め，一部は犬歯歯冠部を囲む透過像と接していた。歯牙腫の臨床診断下で，全身麻酔下にて病巣の摘出と犬歯部歯冠の開窓を行った。
摘出物所見：10mm× 5 mm大，白色の硬組織でこれを線維性の軟組織が包んでいた。
組織学的所見：脱灰後の病理組織標本では，エオジン好性で象牙細管を有する硬組織塊とヘマトキシリン
好性でエナメル小柱を示すエナメル質様硬組織塊が存在し，その間をヘマトキシリン好性の歯原性上皮細胞が細胞の疎密を示しながら占めていた。歯原性上皮細胞は立方状から紡錘形で濃い球形の核を有し，細胞間を網目状の結合を示しながら層状の角化を示す幻影細胞を認め，一部では高円柱状を示しながらエナ
メル質様硬組織に接していた。また明瞭な象牙細管を示さず細胞を封入したエオジン好性の異形骨様象牙質と思われる硬組織も認めた。
検討事項：病理組織学的診断
An 11-year-old girl was referred to our hospital for evaluation of a delay of right mandible canine tooth.
Radiographically, the lesion sized 10mm×5mm was located in the alveolus showing irregular radioopaque findings and connected to the impacted canine tooth through the radio-lucent material.
Histologically, the removal specimen revealed the mass growth showing columnar to cuboidal andreticular shaped odontogenic epithelium with keratinized ghost cells. Beneath these tumor cells,
immature enamel, dentin with dentinal tube and dysplastic dentin without dentinal tube were also seen.
Impacted canine tooth was surrounded with normal dental follicle connecting to the above lesion.

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公開シンポジウム
Public Symposium

109

第2日目

8月25日（木）公開シンポジウム「口腔がんに挑む細胞診−口腔病理医と開業歯科医の連携を目指して−」Ａ会場メインホール

14：30〜16：30

基調講演
【略歴】
1974年 東京歯科大学卒業
1974年 東京歯科大学病理学教室第二講座助手
1977年 イタリア政府奨学金留学生として留学
1979年 東京歯科大学病理学教室第二講座講師
1987年 慶應義塾大学中央臨床検査部病理助手
1994年 慶応義塾大学医学部専任講師
1998年 東京歯科大学市川総合病院臨床検査科助教授
2006年 同教授

田中 陽一

東京歯科大学市川総合病院
臨床検査科 教授

現在に至る

【資格】
歯科医師，歯学博士，死体解剖医（病理），日本病理学会認定口腔病理専門医，日本臨床細胞学会細胞診専門歯科医【略歴】
1989年３月
1989年４月
1990年８月
1990年９月
1991年４月
1996年６月
1999年９月
2002年４月

関根 浄治

島根大学医学部
歯科口腔外科学講座 教授

福岡歯科大学卒
福岡歯科大学大学院（口腔解剖学専攻）
同大学院中退長崎大学歯学部附属病院第二口腔外科研修医
長崎大学歯学部口腔外科学第二講座助手
長崎大学より歯学博士号授与（乙30号）
長崎大学歯学部附属病院第二口腔外科講師
長崎大学大学院講師 （医歯薬学総合研究科発生分化機能再建学講座・顎口腔機能再建学分野）
2005年７月 長崎大学医学部・歯学部附属病院経営企画部副部長
2006年９月−2007年５月 スウェーデンUmeå大学顎顔面口腔外科客員教授
2007年６月 島根大学医学部歯科口腔外科学講座教授
現在に至る【免許・資格など】
1989年６月 歯科医師免許（第108364号）
1998年10月 日本口腔外科学会専門医（第961号）
2000年12月 日本臨床細胞学会指導歯科医（第1769号）
2004年７月 臨床修練指導歯科医（第380号）
2004年10月 日本口腔外科学会指導医（第766号）
2008年12月 日本顎顔面インプラント学会指導医（第47号）
2009年９月 日本がん治療認定医機構 暫定教育医（第98109号）
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Public Symposium

オーガナイザー（座長）のことば
世界では, 毎年約30万人に口腔がんが発症し, その数は増加傾向にある。一方, わが国における口腔がんの死亡者数は, 年間約6,000人を突破した。このような状況下で, 口腔がんの治療法の進歩により, その5年生
存率は早期がんでは90%以上であるが, 進行がんでは50％程度にとどまっている。したがって, 口腔がんにおいても早期発見と早期治療が必要であることはいうまでもない。
Papanicolaouが細胞診を臨床医学に取り入れてから, すでに70年以上が過ぎようとしている。婦人科を中心に細胞診は臨床診断学の一部として確固たる地位を確立してきた。口腔細胞診の歴史について成書を紐解いてみると, 1949年にMedakらやMontogomery and von Haanによってなされた口腔悪性腫瘍細胞の報告に遡る。一方, 日本においても同時期に渡辺らによる口腔病変の剥離細胞診に関する報告がなされている。
口腔領域においては病変が可視的であること, 病理組織標本が容易に採取可能である等の理由から細胞診の価値がこれまで十分に理解されていなかった。しかし, 近年口腔細胞診断技術の進歩により, その有用性が見直され, かつ種々の口腔病変の細胞診断基準が確立されつつある。
われわれは, 口腔がんの早期発見を目指して, 細胞診を用いた検診システムを構築・運用してきた。本シ
ステムは, 開業歯科医院にて細胞診標本を採取して, 有資格者が診断するものである。通常, 集団検診におけるがんの発見率は0.09％程度とされているが, われわれのシステムでは１〜４%という頻度でがんの検出が可能である。
本シンポジウムは, 口腔がん検診に先駆的に携わっている口腔外科医, 口腔病理医, さらに本システムにより口腔がんを発見した開業歯科医らをシンポジストとしてお招きし, 開業歯科医院でおこなう口腔がん
検診（検査）の普及を目的に企画した。口腔がんの病態, 各施設における口腔がん検診システムの現況, さらに口腔細胞診専門医の育成についても併せ概説する。

参考文献
1．石橋浩晃, 関根浄治：大学病院とかかりつけ歯科医院との連携による細胞診を応用した口腔がん検診システム, the Quintessence, 30: 91-94, 2011
2．関根浄治：口腔がんの早期発見のための口腔病理医と口腔外科医の連携
外科YEAR BOOK

口腔外科医の立場から, 口腔口腔外科ハンドマニュアルʼ10, 35-40, 2010

3．田中陽一：口腔がんの早期発見のための口腔病理医と口腔外科医の連携

病理医の立場から, 口腔外科

YEAR BOOK 口腔外科ハンドマニュアルʼ11, 41-41, 2011
4．田中陽一：地域網羅的口腔がん早期発見システム（Oral Cancer Detection System Ichikawa Network:OCDSIN）構築のための戦略的研究，日本歯科医学会誌, 29: 32-36, 2010
5．久山佳代, 松本 敬, 山本浩嗣：口腔領域の細胞診, Medical Technology, 38: 1017-1023, 2010
6．田中陽一: 口腔粘膜疾患における細胞診について, 日本歯科評論増刊, 33-38, 2007
7．関根浄治: 細胞診の口腔外科臨床への応用 −口腔外科医の立場から−, 日本口腔腫瘍学会誌, 19: 190-194,
2007
8．久山佳代, 山本浩嗣：細胞診による口腔癌検診, 日本口腔腫瘍学会誌, 19: 201-205, 2007
9．石橋浩晃, 河野真太郎, 窪田泰孝, 他: 頭頸部病変の病理診断における針生検の有用性, 日本口腔腫瘍学会
誌, 19: 206-210, 2007

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111

Public Symposium

口腔病変の臨床像，開業歯科医向け病変発見方法，
鑑別，細胞診による検診システム提示
【略歴】
1989年

石橋 浩晃

島根大学医学部
歯科口腔外科学講座 准教授

九州大学歯学部卒業

1993年
同

九州大学大学院歯学研究科単位取得退学
九州歯科大学口腔外科学第二講座助手

1995年
同

歯学博士（九州大学）
九州大学歯学部附属病院第二口腔外科医員

1997年
1998年

九州大学医学部病理学教室第一講座助手
九州大学歯学部口腔外科学第二講座助手

2000年

九州大学大学院歯学研究院口腔顎顔面病態学講座
口腔顎顔面外科学助手（助教）

2007年
2009年

島根大学医学部歯科口腔外科学講座講師
同 准教授
ドイツ・フライブルク大学口腔顎顔面外科客員教授
現在に至る【専門医等】
日本口腔外科学会 指導医・専門医
日本病理学会 口腔病理専門医
日本顎顔面インプラント学会

指導医

臨床医の立場から多彩な口腔病変を的確に診断し科学的な治療を行うには，臨床的な基盤だけではなく病理学的な理論武装が重要である。歯科医師あるいは口腔外科医として口腔病変を病理学的にも理解できれば，診断の確定だけではなく，病変の発生機序，病態の形成，さらに治療法の選択や予測される治療効果について，豊富な情報を組織切片から収集できる。しかし，電子化が進んだ現代の診療体系では，歯科医師や口腔外科医と病理医の連携が電子カルテによる限られた情報の共有だけに制限され，正確な診断や効果的な治療法の選択について最も重要な病理と臨床の連携が困難となっている。
演者は口腔外科学会会員の中で唯一，日本病理学会が認定する「口腔病理専門医」の資格を有しており，病理医と口腔外科指導医としての双方の立場から，病理と臨床の密接な情報の共有・交換が，良質な医療の提供に極めて重要であることを痛感している。そこで，歯科医師，口腔外科医，病理医にとって重要な口腔病変の所見について，臨床所見と病理所見（組織診・細胞診）の関連を供覧しながら，臨床医が病理医に望むこと，逆に病理医が臨床医に望むことについて解説する。
さらに，我々が島根県を中心に展開している口腔がん検診や，歯科医院と連携する口腔がん検査（CytoPhoto-Medicine）における細胞診の有効性について解説する。

112

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Public Symposium

臨床像に対応する病理像と細胞像，細胞診をもちいた口腔がん検診の実際【経歴】
1990年３月
2001年４月

日本大学松戸歯学部卒業
日本大学松戸歯学部口腔病理学講座

講師
現在に至る

【資格】
口腔病理専門医
細胞診専門歯科医

久山 佳代

口腔衛生認定医日本大学松戸歯学部
口腔病理学講座 講師

口腔癌検診（従来型検診）の現状報告
日本の口腔癌の死亡率は，平成21年度厚生統計要覧によると微増を続けており，他の先進諸国と比較してその検診システムの構築が大きく遅れている。開業歯科医は，１口腔単位を診療対象とするため口腔癌を発見する機会が最も多い。そこで日本大学松戸歯学部口腔病理学講座は，開業歯科医が患者への教育を含めて口腔癌検診の主役となるべくシステム構築し，その手法として口腔擦過細胞診を用い，細胞検査士と口腔病理医（細胞診専門歯科医）は標本と開業歯科医との橋がけの役割を担っている。今回のシンポジ
ウムでは２種類の口腔癌検診システムについて紹介し，それぞれの実績について報告する。具体的には，
柏歯科医師会主催で柏市口腔衛生大会の一事業として開始した柏市口腔癌検診（平成５年〜，19年間継続，総検診者数約5,050人，癌発見率0.09%）と，玉川歯科医師会主催の玉川口腔癌検診（平成14年〜，10年間継続，総検診者数約900人，癌発見率1.03%）のそれぞれの検診方式を紹介し，利点欠点や受診者の特徴などを分析し，報告する。さらに口腔癌検診システムにおける開業歯科医の役割および歯学部口腔病理学講座とのつながりについて詳細に解説する。

113

113

Public Symposium

細胞診専門医の現状【略歴】
1999年３月

長崎大学歯学部歯学科 卒業

1999年４月

大分医科大学（現在大分大学医学部）
歯科口腔外科医員（研修医）

2004年６月
2004年７月

大分大学医学部大学院博士過程 卒業
大分大学医学部歯科口腔外科医員

2006年４月
2008年４月

大分大学医学部附属病院検査部（病理部）医員
大分大学医学部診断病理学講座助教
現在に至る

矢田 直美

大分大学医学部
診断病理学講座 助教【資格】
口腔病理専門医，細胞診歯科専門医

細胞診の利点と欠点と細胞診専門医の現状
細胞診は組織診に比べ，情報量が少なく診断が困難であるという印象が強く，病理専門医であっても，細胞診への関心が少ない人も多い。しかし，患者さんにとっては，生検よりも採取が容易であり，侵襲も少なく，反復検査も容易である。細胞診は情報量が少なくても，細胞の発する情報が組織診の細胞よりも多く，場合によっては生検組織診よりも診断により近くなることがある。形態学的に診断していく上で，必要なツールのひとつと考える。
とくに, 口腔領域の扁平上皮細胞の細胞診の診断は非常に難しく，その理由として，子宮頸部や肺の扁平上皮癌と異なり，表層分化型の扁平上皮癌があり，子宮頸部などの診断基準をそのまま当てはめることができないことが挙げられる。
現在, 21名の細胞診歯科専門医を中心に, 口腔細胞診ワーキンググループを発足し，口腔細胞診の診断基
準確立を目指している。口腔細胞診の診断基準を標準化し広めていくには，口腔細胞診の専門医の育成が必須である。
今回は細胞診の利点と欠点，細胞診の診断方法，細胞診専門医の現状と併せて細胞診歯科専門医の必要性と今後口腔がん検診での活用時に細胞診をもちいる場合の注意点について述べたいと思う。

114

114

Public Symposium

実際に口腔がん検診システムでがんを見つけた歯科医師会からのコメント【略歴】
1990年４月

髙倉 克博

市川市歯科医師会
学術担当理事，たかくら歯科院長

東京歯科大学入学

1996年３月
1996年４月

東京歯科大学卒業
東京歯科大学オーラルメディシン講座

入局

1997年４月
2000年３月

東京歯科大学オーラルメディシン講座
東京歯科大学オーラルメディシン講座

病院助手
退局

2000年４月
2003年４月

医療法人社団セイコー会
東京歯科大学歯学研究科

2007年２月
2007年３月

たかくら歯科 開設
東京歯科大学歯学研究科博士課程修了

2011年４月

市川市歯科医師会学術担当理事

勤務
入学
歯学博士号取得
現在に至る

口腔がん検診と口腔がん早期発見システムの両立−千葉県市川市での現状−
市川市では1998年より口腔がん集団検診を年１回，約200名の受診希望者を対象に行っている。集団検診は市川市歯科医師会が主催し，東京歯科大学市川総合病院歯科・口腔外科（オーラルメディシン・口腔外科学講座）および同大学同学口腔がんセンター医局員が検診を担当している（がん発見率0.23%）。
2007年市川市歯科医師会は，同大市川総合病院臨床検査科病理とオーラルメディシン・口腔外科学講座，
口腔がんセンターと共にOCDSIN（Oral Cancer Detecting System ICHIKAWA Network）を立ち上げた。
これは「日常の歯科診療時に口腔粘膜へ眼を向け，口腔がんをより早期に発見する」ことを目的とし，月
１回，年10回の講義，実技，症例検討を行い，認定証を発行している（現在104名）。近年は近隣区郡市からも参加者が増加している（2.22％）。
2009年度より市川市では委託事業として個別口腔がん検診が始まった。この検診はOCDSIN認定医を市
川市指定医とし，通年指定歯科医院にて視診，触診を中心とした診察と細胞診を行う。異常の場合は速やかに専門病院へ紹介し精密検査を行っている（0.07％）。
以上のように，市川歯科医師会は集団検診と個別検診の２通りの方法を軸に活動しているが，その基盤にはOCDSINという開業医と口腔病理医，口腔外科医の連携を基盤としたシステムがある。今回はこの３つの活動の意義を報告したい。

115

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一般演題（示説）
Poster Presentation

117

P-01

Immunohistochemical localization of Notch signaling molecules inameloblastomas
Katsutoshi Kubo1, Keisuke Nakano2,3, Hatsuhiko Maeda1, Mitsuhiro Takayama1, Masato Jinno1,
Waka Yoshida1, Hiromasa Hasegawa2,3 and Toshiyuki Kawakami2
1

Department of Oral Pathology, School of Dentistry, Aichi Gakuin University
Hard Tissue Pathology Unit, Matsumoto Dental University Graduate School of Oral Medicine
3
Department of Oral Pathology, Matsumoto Dental University School of Dentistry2

Background: We examined Notch signaling molecules in large cases of solid/multicystic ameloblastoma.
Materials and methods: A total of 40 cases of typical solid/multicystic ameloblastoma were selected. We
examined on the distribution of transcription factors of Notch1 and Jagged1 by immunohistochemical(IHC) techniques. The number of positive cells was totaled, and the ratio of the number of positive cells to
the total of the object cells of the strong enlarged image by a light microscope was assumed to be the CSindex. Results: Histopathologically, the peripheral layered cells of these cell nests were columnar or
cuboidal, hyperchromatic, and lined up in a palisade fashion. The peripheral layered cells resembled internal
dental epithelium or preameloblasts. The central cells were loosely arranged, showing stellate reticulum.
Furthermore, the central cells sometimes showed squamous metaplasia. Through IHC, we described using
the following criteria. 1) Peripheral cuboidal cells of nests: Notch-positive products were detected in thecytoplasms of the cells in frequently. In the same cells, Jagged-positive cells were occasionally positive, butless so than Notch-positive cells. 2) Peripheral columnar cells of nests: Notch-positive cells were observed in
the cytoplasm of most columnar cells, but Jagged was frequently detected in the cells. 3) Central reticular
cells of nests: The central reticular cells showed frequently positive to both of Notch and Jagged. 4) Central
squamous cells of nests: Both Notch- and Jagged-positive cells were frequently detected in the squamous
cells. Conclusion: The results showed the Notch and related factors are closely related to cytologicaldifferentiation in ameloblastomas.

118

118

P-02

Immunohistochemical observation of Notch signaling in a case of
calcifying cystic odontogenic tumor
Toshiyuki Kawakami1, Chong Huat Siar2, Keisuke Nakano1, Mihoko Tomida3,
Hidetsugu Tsujigiwa4 and Hitoshi Nagatsuka4
1

Hard Tissue Pathology Unit, Matsumoto Dental University Graduate School of Oral Medicine
Department of Oral Pathology, Oral Medicine & Periodontology, Faculty of Dentistry, University of Malaya
3
Department of Oral Physiology, Matsumoto Dental University School of Dentistry4
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry & Pharmaceutical
Sciences, Okayama University
2

Purpose: Calcifying cystic odontogenic tumor (CCOT) is characterized by odontogenic epithelial islands
having ghost cells and calcified foci within the neoplastic epithelial cell nests and sometimes in theectomesenchymal and/or stromal tissues. Furthermore, neoplasm dysplastic dentin may be observed. We
examined Notch and Jagged and their genes in a CCOT. Materials and Methods: A CCOT was theexamined specimen, and an ameloblastic fibroma (AF) and odontogenic myxoma (OM) served as control
specimens. The materials were examined by IHC and ISH techniques for Notch and Jagged. Results:
Regarding Notch and Jagged, IHC staining showed positive both of the epithelial components andectomesenchymal components. In the dentinoid area, the Notch- and Jagged-positive products were
present in the cytoplasms of just adjacent cells of the dentinoid tissues and/or the embedded cells. In ISH,
the mRNA of the Notch and Jagged were in the cytoplasms of both the epithelial and mesenchymal cells.
In the dentinoid formation area, the Jagged gene signals were observed in the cytoplasms of the IHCpostitive cells. Regarding AF, IHC examination showed Notch positive products existed in bothmesenchymal cells and epithelial nest cells. Jagged peptide was observed in the same cells. In ISH, they weredetected as the mRNAs of both of Notch and Jagged. OM was no epithelial islands. In IHC and ISH, noNotch related positive products were observed all over the specimens. Conclusion: The results showed thatthese Notch and related factors are closely related to cytological differentiation in neoplastic cells especiallyin relation between epithelial-mesenchymal interactions.

119

119

P-03

Differential expression of Notch receptors and their ligands in calcifying
epithelial odontogenic tumors
Chong Huat Siar1, Kee Seng Chuah1, Keisuke Nakano2, Rosario Santod Rivera3,
Hidetsugu Tsujigiwa4, Hitoshi Nagatsuka4, Kok Han Ng5 and Toshiyuki Kawakami2
1

Department of Oral Pathology, Oral Medicine & Periodontology, Faculty of Dentistry, University of Malaya
Hard Tissue Pathology Unit, Matsumoto Dental University Graduate School of Oral Medicine
3
Gleneagles Intan Medical Centre, Malaysia
4
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry & Pharmaceutical
Sciences, Okayama University
5
Formerly Unit of Stomatology, Cancer Research Centre, Institute for Medical Research2

Purpose: Dysregulation of Notch has been implicated in the tumorigenesis of some odontogenic neoplasms
but its role in the calcifying epithelial odontogenic tumor (CEOT) remains unclarified. The aim here was toinvestigate Notch expression in CEOT and to speculate on its significance. Materials and methods:
Receptors Notch1-4 and their ligands ( Jagged1, Jagged2 and Delta1) were examined
immunohistochemically in six CEOT cases. Expression levels were quantified according to the percentage
of positive tumor cells, amyloid-like proteins and calcifications: (-), negative staining; (+), mild and focal
positivity <25%; (++), moderate positivity in significant areas 25-50%; (+++), strong positivity inpredominant areas >50%. Results: CEOT epithelium demonstrated variable expression levels for Notch1, 3,
4, Jagged1 and Delta1 suggesting upregulation of these molecules at sites of tumor differentiation.
Distribution patterns were distinct with some overlap. Their localizations were largely membranous and/or
cytoplasmic. Notch2 and Jagged2 were absent. Amyloid-like materials strongly expressed Jagged1 but
variably Notch1, 3 and Delta1 implicating that these signaling proteins maybe competitive substrates with
CEOT amyloid-like proteins for proteolysis. Notch2, 4 and Jagged2 were absent. Mineralized substances
including Liesegang rings were negative for Notch receptors and ligands suggesting that calcification process
is associated with downregulation of these molecules. Stromal endothelium and fibroblasts were stained
variably positive. Conclusion: The current data suggest that Notch receptors and their ligands may playdiffering roles in the acquisition of cell fates in CEOT. Notch. Notch accumulations within amyloid-likeprotein suggest impaired proteolysis.

120

120

P-04

Co-expression of BMP-2 and -7 in the epithelium of calcifying epithelial
odontogenic tumor with selective BMP-7 expression in amyloid materials
Hidetsugu Tsujigiwa1, Chong Huat Siar2, Keisuke Nakano3, Phuu Pwint Han4,
Mihoko Tomida5 , Hitoshi Nagatsuka1, Kok Han Ng6 and Toshiyuki Kawakami3
1

Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical
Sciences, Okayama University
2
Department of Oral Pathology, Oral Medicine & Periodontology, Faculty of Dentistry, University of Malaya
3
Hard Tissue Pathology Unit, Matsumoto Dental University Graduate School of Oral Medicine
4
School of Dentistry, University of Southern California
5
Department of Oral Physiology, Matsumoto Dental University School of Dentistry6
Formerly Unit of Stomatology, Cancer Research Centre, Institute for Medical Research
Purpose: The calcifying epithelial odontogenic tumor (CEOT) has a distinguishing feature of presence of
extracellular eosinophilic amyloid material. We examined the BMP expression in this neoplasms by IHC.
Materials and methods: The test sample consisted of six CEOT cases. Examination was carried out by
histopathology with HE and Congo red, by IHC for BMP-2 and -7. BMP distribution pattern and levelsof staining intensity in all six CEOT cases were evaluated. Results: Histological examination revealed
interspersed extracellularly among these epithelial sheets are amyloid-like substances occurring as
eosinophilic amorphous globules or as diffuse stromal deposits. These amyloid globules were Congo-red
positive and gave an apple-green birefringence under polarized light. Scattered foci of basophilic acellular
calcified materials, some exhibiting concentric laminations (Leisegang rings) were present. BMP-2 protein
distribution was detected in all six CEOT cases. Positive staining was observed heterogeneously in the
sheets, strands and islands of polyhedral epithelial cells. Expression levels ranged from mildly focal tomoderately strong and extensive. Amyloid-like protein products were consistently negative for BMP-2.
Calcified materials and Liesegang rings were non-reactive for BMP-2. Regarding BMP-7, all six CEOT
cases demonstrated overexpression in both the tumoral epithelium as well as the amyloid protein globules.
Protein localization was membranous and/or cytoplasmic. In the stromal endothelium and fibroblasts,
BMP-7 was weak to barely detectable. Conclusion: The results suggests that these protein molecules most
likely participate in the process of cellular proliferation and differentiation in this neoplasm. The strong
BMP-7 expression in CEOT-associated amyloid-like substances is a novel finding.

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P-05

Ameloblastic carcinoma of the maxilla.
Anuudari Erkhembaatar1,2, Katsutoshi Kubo1,3, Yoshihiko Sugita1,3, Emiko Sato1, Waka Yoshida1,
Mitsuhiro Takayama1, Masato Jinno1, Yuma Honda1 and Hatsuhiko Maeda1,3
1

Department of Oral Pathology, Graduate School of Dentistry, Aichi Gakuin University
Maternal And Child Health Research Center
3
Aichi Gakuin University Dental Hospital2

Ameloblastic carcinoma (AC) is a rare lesion of odontogenic origin. It is defined as a malignant epithelial
odontogenic tumor that histologically has retained the features of ameloblastic differentiation and also
exhibits cytologic features of malignancy.
A 45 year-old woman presented at Aichi Gakuin University Dental Hospital, complaining of a persistentswelling in her upper right jaw for approximately 1 month. Histopathological findings included basal cells
that were columnar, hyperchromatic, and arranged in a palisaded fashion. In some areas, however,peripheral palisading and polarization were not always evident. Classic stellate reticulum-like areas were
almost completely absent, or were present in only small amounts. In the central part of islands, squamous
metaplasia were observed. In some areas, the epithelial component exhibited a cytologic malignancy
characterized by an increased nucleus-to-cytoplasm ratio and nuclear pleomorphism. In addition, perineuralinvasion was clearly visible. The immunohistochemical profile of the present case was positive for CK5, 14,
18, 19, Ki67, PCNA, P-63, P-53, vimentin, syndecan-1, calretinin, EMA, GFAP and CB1, but negative
for CK13, αSMA, podoplanin and HPV. These features were consistent with a diagnosis of ameloblastic
carcinoma.

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P-06

Ameloblastoma, - a case report and treatment conditions in Laos.
Souksavanh Vongsa1, Daovone Thepsouvanh2, Bounthome Samountry3, Phounsiri Vorrasak4,
Sengphouvanh Ngonephady4, Aloungnadeth Sitthiphanh4, Naoyuki Matsumoto5 andKazuo Komiyama5
1

Department of Oral Surgery, Faculty of Dentistry, University of Health Sciences, Lao P.D.R
Cancer Center of Mittaphap Hospital
3
Faculty of Basic Sciences, University of Health Sciences
4
Faculty of Dentistry, University of Health Sciences
5
Department of Pathology, Nihon University School of Dentistry
2

There are three major hospitals in Vientiane, Laos. Generally, the Mahosot Hospital focuses on tumor ofthe digestive system, the Setthathilath Hospital focuses on tumor of the breast and uterus. The Mittaphap
Hospital focuses on the cases of Oro-facial tumors. All of them are cooperating each other about the patientcare. In 2008, Minister of Ministry of Health developed the Lao National Cancer Center at Mittaphap
hospital. The Head & Neck Surgery division collected 237 cases of Oro-facial tumors from 2004-2010,
including 36 cases (15.18%) of Ameloblastoma, 16 females and 20 males with an age range of 11-60 years,
with a mean age at presentation of 31(±3.8) years, the patients received following treatment; Tumor
Enucleation, Resection interrup-trice or Hemi-mandibuloectomy.
Case report;
A 20-years-old male visited to the local doctor with complain of mandible swelling in right angle of thechin. The patient was referred to the Head & Neck Surgery Division of Mittaphap Hospital for further
examination. The patient did not complain of pain. On the X-ray examination, a cyst-like radiolucent
lesion was recognized in the right mandible. The marked root absorption was identified on the 31-33 and41-48. The patient received a hemimandibularectomy. The patient revealed good prognosis with nosymptoms.
Conclusion:
Most patients with Ameloblastoma admitted to the hospital in the advanced stage of disease. They werereceived hemimandibularectomy, and then they have lost a chewing function after the surgery. Thus, it isimportant that patients receive a diagnosis and treatment in early stage of ameloblastoma.

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P-07

角化嚢胞性歯原性腫瘍に対する臨床病理学的研究

Clinicopathological study in keratocystic odontogenic tumors
堀井 活子，大西 祐一，中嶋 正博，覚道 健治
Katsuko Horii，Ohnishi Yuichi，Nakajima Masahiro．Kakudo Kenji
大阪歯科大学 口腔外科学第二講座
Second Department of oral and maxillofacial Surgery, Osaka Dental University

歯原性の発育性嚢胞であった歯原性角化嚢胞（以下OKCとする）は他の歯原性嚢胞に比べて上皮細胞の増殖活性が高くその発育は浸潤性で再発も多いことより，2005年に改訂された歯原性腫瘍WHO組織分類では角化嚢胞性歯原性腫瘍（以下KCOTとする）という名称で歯原性腫瘍として取り扱われるようになった。
しかし裏装上皮が錯角化重層扁平上皮であってもその程度が軽度なもので埋伏歯を含まないものは原始性
嚢胞，埋伏歯を含むものは含歯性嚢胞と歯原性嚢胞に分類されている。また上皮が正角化を示すものは正角化性歯原性嚢胞（以下OOC）と分類されているが正角化と錯角化が混在するものに関しては分類がなされていない。このように歯原性上皮性嚢胞のうち，KCOTとの診断基準があいまいなままのものがある。
今回過去15年に大阪歯科大学付属病院口腔外科第 2 科で摘出術を受け病理組織学的にKCOTと確認された174例を対象とし臨床病理学的検討を行った。さらに診断基準があいまいとなっているKCOTと鑑別診断の必要な病変について問題点を抽出し臨床病理組織学的に検討を行ったので報告する。
臨床診断で術前にKCOTと診断されたものは半数に満たなかった（47％）。これらは生検ではKCOTの診断がなされなかった例（16％）を含め，歯原性嚢胞（原始性嚢胞，含歯性嚢胞，歯根嚢胞など）の臨床診断
で摘出術を行っていた。また44％が生検を行わず摘出生検を行っておりこれらの正診率は45％であった。
KCOTの再発の原因として娘嚢胞の存在，上皮島の存在，上皮の性状（剥離性）等があげられているが今回の再発例では明らかな共通点が認められなかった。再発例のうち娘嚢胞，上皮島を有するものは44％，剥離性上皮を有するもの20％であった。また初診時と再発時の上皮の形態，性状が異なるものが40％あった。さらに再発例の20％に錯角化と正角化が混在していたことより正角化と錯角化が混在する嚢胞性疾患
はKCOTに分類することが妥当と考えられた。
In the 2005 WHO classiﬁcation, odontogenic keratocyst (OKC) was categorized as a benign odontogenic
tumor under the name of keratocystic odontogenic tumor (KCOT).
Parakeratosis of the lining epithelium KCOT, the orthokeratosis were classified as orthokeratinizedodontogenic cyst (OOC) .
However,there is no statement concerning combination, in this classiﬁcation.
In this retrospective study, we examined 174 KCOTs treated at the Osaka Dental University Hospitalfrom 1995 to 2009.In particular, we examined what has become ambiguous with respect to diagnostic
criteria. Those with combinated lining epithelinm was considered reasonable to classify the KCOT.

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P-08

MNU誘発ラット臼歯部Malassez上皮遺残の動向

Fate of epithelial cell rests of Malassez on MNU-induced rat molar regions
木村 彩子，義澤 克彦，三城 弥範，上原 範久，圦 貴司，螺良 愛郎
Ayako Kimura, Yoshizawa Katsuhiko, Miki Hisanori, Uehara Norihisa,
Yuri Takashi and Tsubura Airo
関西医科大学 病理学第二講座
Department of Pathology 2, Kansai Medical University［目的］Malassez上皮遺残は加齢に伴って減少するが歯根膜内に生涯存在し，歯根膜の恒常性維持，エナ
メル芽細胞への分化誘導，神経終末誘導を担い，健常では休止状態にあるが，炎症刺激で活性化すると嚢胞の裏装上皮となり，歯原性腫瘍の発生にも関与するが，その詳細は明らかではない。化学発癌物質であるN-methyl-N-nitrosourea（MNU）をラット腹腔内に単回投与し，Malassez上皮遺残の動向を観察検討した。
［方法］ 4 週齢雌Lewisラットに50mg/kg MNUを腹腔内に単回投与し，12，18，30週齢で屠殺，上下顎を採取，10%中性ホルマリン固定，10%EDTA脱灰後パラフィン包埋し，4μm毎に薄切，H-E染色および歯周組織内の上皮巣を観察，免疫組織学的染色を行った。なおMNU未処置のものを対照群とした。
［結果と考察］対照群と比較してMNU投与群の臼歯部歯周組織には，大型のMalassez上皮遺残からなる細胞巣が有意に多く認められた。経時的に増大傾向にあり，30週齢では腫瘍化を認めた。本Malassez上皮遺残について免疫組織学的染色結果をもとに文献的考察を加えて報告する。
Epithelial cell rests of Malassez becomes the epithelial lining of an odontogenic cyst due to the active
inflammation, and it later forms the odontogenic tumor. However, the detailed mechanisms are
unknown. Female Lewis rats were treated i.p. with 50mg/kg N-methyl-N-nitrosourea (MNU) at 4 weeks
of age. At the age of 12, 18 and 30weeks, rats were sacriﬁced to sample maxilla and mandible areas with
H&E staining. The MNU-treated group showed greater number of epithelial cells in each nest comparedwith the controls. We report histological result of the epithelial cell nests and bibliographic consideration.

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P-09

4NQO誘発ラット舌癌モデルを用いた前癌病変の病理組織学的検索

Histopathological analysis of the precancerous lesion using 4NQO-induced rat
tongue carcinogenesis experimental model.
親里 嘉貴，平野 真人，嶋 香織，仙波 伊知郎
Yoshitaka Oyazato, Masato Hirano, Kaori Shima and Ichiro Semba
鹿児島大学医歯学総合研究科 口腔病理解析学分野
Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Kagoshima University

目的：口腔粘膜前癌病変の実験モデル確立のため，4-nitroquinoline-1-oxide（4NQO）誘発Rat舌癌モデルを用いて舌粘膜に扁平上皮癌及び前癌病変を作製し，病理組織学的検索を行った。
方法：4NQO舌癌好発系統Rat（Dark-agouti，雄性 6 週令33匹）に10mg/lの4NQOを連続経口投与し，投与後 2 週から12週まで隔週で舌粘膜肉眼所見と組織所見とを対比した。また，投与 2 週から 4 週に肉眼的に認められた炎症性変化と腫瘍性病変を鑑別するため，一部は 6 週から12週の4NQO投与完了後，更に 4
週ないし 6 週間通常飼育し，炎症性変化の回復を図った。屠殺60分前にBrdU（50mg/kg）を腹腔内投与し，舌粘膜の病理組織学的検索とGST-p，各種サイトケラチンの発現，BrdUによる細胞増殖活性を免疫組織学
化的に検索した。解剖時に採取した舌粘膜及びパラフィン標本から病変部のDNAとRNAを抽出した。
結果：4NQO投与 2 週で肉眼的に舌前方部粘膜に炎症性変化と考えられる水疱やびらんが認められた。投与 5 週には炎症性変化は肉眼的に消失し，同時に舌前方から中央部に乳頭消失や白斑形成，角化亢進が組
織学的に認められた。さらに，投与 6 週には腫瘍性変化と考えられる白斑や隆起性病変が認められ，組織学的に乳頭や上皮脚形態の変化，角化亢進，基底細胞や有棘細胞の細胞異型が種々の程度に認められた。
投与 2 週から微小なGST-p陽性病巣が出現し，投与 4 週以降はその発生頻度や大きさが増加し，投与 8 週
ではGST-p陽性の初期浸潤癌が認められた。投与12週では舌隆起部から舌後方部にかけて初期浸潤癌が高頻度に発生していた。
考察：経時的な舌粘膜の肉眼観察と組織検索により，4NQO投与で誘発される前癌病変の形態特徴と進行を明らかにでき，field発癌や前癌病変のモデルとして有用であると考えられた。また，4NQO投与 6 週完了後，更に 6 週間通常飼育した個体にも初期浸潤癌が認められ，投与 6 週までに見られた粘膜病変は前癌病変と考えられた。今後，これらの前癌病変について遺伝子変化の解析を行う予定である。
To establish an experimental model of oral carcinogenesis, we made cancerous and precancerous lesions
in tongue mucosa with 4-nitroquinoline-1-oxide (4NQO)-induced rat tongue carcinogenesis experimental
model. 4NQO susceptible Dark-agouti rats given 10 ppm 4NQO containing were sacriﬁced every week
to evaluate histological and immunohistochemical examinations. At the sixth week after dose, neoplastic
white patches and protruded lesions were observed, and at the eighth week early invasive cancer wasobserved in the posterior tongue mucosa. The 4NQO-induced carcinogenesis model was useful for
analyses of ﬁeld cancerization and precancerous lesion.

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P-10

Cytokeratin expression in oral epithelial hyperplasia
Takanaga Ochiai and Hiromasa Hasegawa
Department of Oral Pathology, Matsumoto Dental University
Cytokeratin (CK) analyzes are useful for diagnosing oral borderline malignancies such as CK13, CK17 andCK19. Therefore, we evaluated CK distribution in epithelial hyperplasia. We performed immunohistochemical
examination of epithelial hyperplasia arising in mucous cysts. In the controls, CK13 was expressed inparabasal to superficial layers, and CK19 localized in basal layers, while CK17 was not present. In theepithelial hyperplasia, CK13 and CK19 were not shown, although CK17 was localized in parabasal tosuperficial layers. Ki-67 was irregularly distributed in basal and parabasal cells. Abnormal CK13, CK17 andCK19 expression signify not only borderline malignancy but also epithelial hyperplasia.

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P-11

Laser light-mediated topical photodynamic therapy for oral precancers
Hung-pin Lin1,3, Hsin-ming Chen1,2,3, Yi-ping Wang1,3 and Chun-pin Chiang1,2,3
1

Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University
Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University
3
National Taiwan University Hospital, National Taiwan University
2

Background: Oral leukoplakia (OL), oral erythroleukoplakia (OEL), and oral verrucous hyperplasia (OVH)
are three common oral precancerous lesions. One of the best oral cancer prevention strategies is to eliminate
oral cancers at their precancerous stage to stop their further malignant transformation.
Methods: In this study, a topical 5-aminolevulinic acid-mediated photodynamic therapy (topical ALAPDT) with the 635-nm laser light was used to treat 40 OVH, 40 OEL and 40 OL lesions once a week andanother 40 OL lesions twice a week.
Results: We found that all the 40 OVH lesions exhibited complete response (CR) after an average of 3.6
PDT treatments. Of the 40 OEL lesions, 38 showed CR after an average of 3.4 PDT treatments and 2
showed partial response (PR). The 40 OL lesions treated once a week demonstrated CR in 7, PR in 20 andno response in 13. Furthermore, the 40 OL lesions treated twice a week showed CR in 17 and PR in 23.
Chi-square test showed that the twice-a-week treatment modality is better than the once-a-week treatment
modality for OL lesions. In general, better PDT outcomes were significantly associated with OVH, OEL
and OL lesions with the smaller size, pink to red color, epithelial dysplasia, or thinner surface keratin layer.
Conclusion: The laser light-mediated topical ALA-PDT is very effective for treatment of OVH and OEL
lesions. Therefore, topical ALA-PDT using either the laser or light emitting diode (LED) light may serve as
the first-line treatment of choice for OVH and OEL lesions.

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P-12

口腔癌におけるTrk familyの役割
A role of Trk family in oral cancer

笹平 智則1,2，上田 順宏2，栗原 都1,2，山本 一彦2，桐田 忠昭2，國安 弘基1
Tomonori Sasahira1,2, Nobuhiro Ueda2, Miyako Kurihara1,2, Kazuhiko Yamamoto2,
Tadaaki Kirita2 and Hiroki Kuniyasu1
1

奈良県立医科大学 分子病理学講座
奈良県立医科大学 口腔外科学講座
1
Deapartment of Molecular Pathology, Nara Medical University
2
Department of Oral and Maxillofacial Surgery
2

Tropomyosin receptor kinase (Trk) familyは神経系の発生，分化，維持に関与する。Trk familyにはTrkA，TrkB，ならびにTrkCが存在し，それぞれニューロトロフィンであるNGF，BDNF，NT3の高親和性受容体である。がんにおいては一般的にTrk familyはoncogeneとして作用すると言われているがneuroblastoma等においてはTrkAおよびTrkC発現症例は予後良好であるなど，がんにおけるTrk familyの役割は非常に複雑で詳細な機能についてはいまだに明らかにされていない点が多い。今回，われわれは口腔扁平上皮癌の臨床検体ならびにin vitroにおいてTrk familyの発現と役割，機能を検討した。その結果，１）進行症例，リンパ節転移症例ほどTrkCが高発現していた。２）TrkBないしTrkC陽性症例は有意に予後不良であった。３）TrkBおよびTrkCは口腔扁平上皮癌の血管新生，リンパ管新生を促進することが明らかとなり，特にTrkCはVEGF familyシグナルを介さずに直接的に血管新生，リンパ管新生を誘導する可能性が示唆された。４）RUNX3がTrk familyの発現を負に制御することを見出した。５）Trk family
はリガンドと相互作用することで口腔扁平上皮癌の増殖，浸潤，アポトーシス抵抗性の獲得に関与している可能性が示唆された。がんで新生された血管やリンパ管は腫瘍の進展に密接に関与する一方で，形態異常をきたすことで脈管としての機能を果たしておらず，腫瘍局所への抗癌薬の到達を困難にしていると考えられている。近年，irregularになった血管・リンパ管を正常化することで，容易に癌細胞に抗癌薬を到達させようとする『vascular normalization』という概念が提唱されている。Trk familyは口腔癌におけるvascular normalization therapyの標的と成り得る可能性も大いに期待される。
Member of the tropomyosin receptor kinase (Trk) contains TrkA, TrkB, and TrkC and activation ofTrks is observed in many tumors. We examined the role of Trk family in oral squamous cell carcinoma(OSCC). TrkB or TrkC expression were significantly related with microvessel density (MVD),
lymphovessel density (LVD), and poor prognosis. A strongly relationship was found between expression
levels of TrkB and VEGF-A, VEGF-C, or VEGF-D, however, no significantly association was foundbetween expression of TrkC and VEGF family. These results suggested that Trks might be a usefultherapeutic target of OSCC.

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P-13

口腔がんに対する抗シスプラチン耐性遺伝子検索の新たな方法
New methods to identify resistant genes for chemotherapy.

北村 哲也1，松田 彩1，樋田 京子2，東野 史裕1，進藤 正信1
Tetsuya Kitamura1, Aya Matsuda1, Kyoko Hida2, Fumihiro Higashino1 andMasanobu Shindoh1
1

北海道大学大学院歯学研究科 口腔病理病態学教室
北海道大学大学院歯学研究科 血管生物学教室
1
Department of Oral Pathology & Biology, Hokkaido University Graduate School of Dental Medicine
2
Department of Vascular Biology, Hokkaido University Graduate School of Dental Medicine
2

口腔がんにおいてシスプラチンは広く用いられている抗癌剤の一つである。しかしその奏効率は十分とはいえず，また奏効するかどうかの予測も現状では困難である。今日まで抗癌剤耐性マーカーに関する研究は広く行われており，特にマイクロアレイに網羅的検索が可能となってからは多くの抗癌剤耐性遺伝子が同定された。しかし実際の腫瘍において，これらの抗癌剤耐性遺伝子の発現と，実際の薬剤抵抗性の関連性は期待したほど高くないことが報告され，問題となっている。現在では口腔がんでは根治性の観点から外科的切除が第一選択となるが，それによる機能的，審美的障害は大きく非観血的処置の確立が求められていることから抗癌剤耐性マーカー同定の意義は大きいと考えられる。
抗癌剤耐性遺伝子は大きく 2 つに分けられる。ひとつは，耐性細胞において本質的に発現が高い遺伝子群，
もうひとつは抗癌剤の暴露によって発現が上昇する遺伝子群である。これまでの抗癌剤耐性遺伝子の研究は，まず耐性細胞を樹立し親株との比較することで進められてきた。しかし，この方法では抗癌剤の暴露による遺伝子群が多く検索されてしまう。抗癌剤耐性マーカーとして用いることができるのは前者の耐性遺伝子であるため，先の問題が生じると考えられた。
そこで今回我々は本質的に発現が高い遺伝子群のみを検索する方法を考案し，いくつかの耐性遺伝子を同定した。口腔癌培養細胞株HSC-3細胞を限界希釈し，十数種類のサブクローンを得た。このうち 4 つのサ
ブクローン株についてDNAマイクロアレイを施行した。次にそれら細胞株をシスプラチン（CDDP）で処理し，CDDPに対する耐性の程度について検索した。耐性の度合いと，遺伝子発現が正の相関をを示す遺伝子，つまり耐性が強いほど多く発現している遺伝子群を抽出し耐性遺伝子の候補とした。この中でosteopontinは強制発現させるとCDDPに対する抵抗性を示し，siRNA導入により感受性が亢進した。現在，この他の遺伝子についても解析を進めている。
Anti-cancer drug resistance genes are divided into the intrinsic resistance gene that highly express inresistant cell properly, and the acquired resistance gene that is induced by anti-cancer drug exposure.
The resistant cell lines have advanced most of the researches identifying anti-cancer drug resistantgene; however, candidate genes from the methods contain many acquired resistance gene.
Therefore we established the new method to extract only intrinsic resistance gene, and osteopontin
was identiﬁed as the intrinsic resistant gene. The reduction of sensitivity for cisplatin was observed inosteopontin tranfected cells, and knock down of osteopontin induced the sensitivity for cisplatin.

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P-14

Investigation into Notch-1 expression and its role in oral squamous cell
carcinoma.
Ryoji Yoshida1,2, Kennta Kawahara1, Yoshihiro Nakagawa1, Masashi Nagata1, Takuya Tanaka1,
Hideki Nakayama1, Masanori Shinohara1 and Tkaaki Ito2
1

Department of Pathology and Experimental Medicine/Oral and Maxillofacial Surgery, Graduate School of Life
Sciences, Kumamoto University
2
Department of Pathology and Experimental Medicine,, Graduate School of Life Sciences, Kumamoto University
Introduction: Involvement of Notch signaling in several malignant tumors is well known, but its role inoral squamous cell carcinoma (OSCC) remains poorly characterized. The purpose of this study was toinvestigate the role of Notch signaling in the development and progression of OSCC.
Materials and Methods: Immunohistochemical analysis for Notch-1, Jagged1 (Jag1, one of the important
ligands for Notch-1 receptor) and Laminin5γ2 chain (L5γ2, a marker of invasiveness) was performed onformalin-fixed, paraffin-embedded oral tissues, which included various pathological tissues. An OSCC cellline, SAS, harboring high Notch-1 expression was used for examining the Notch-1 dependent proliferation
activity and invasiveness in vitro.
Results: The rate of Notch-1, Jag1 and L5 γ 2 positive specimens tended to increase in relation toprogression of the mucosal neoplasm. A statistically significant (p < 0.001) strong correlation (r = 0.738)
was observed between Immunostaining scores of Notch-1and that of L5γ2. In OSCC specimens, Notch-1
positive cells mainly distributed at the invasive front of tumor and co-localized with L5γ2. in vitro studies,
growth activity was significantly suppressed under the Notch-1 knocked down or γ-secretase inhibitor
treated conditions. In additions, the invasiveness of SAS was activated by TNF-α and that was inhibitedby γ-secretase inhibitor. Moreover, these TNF-α dependent activation of cell invasiveness was notobserved in the Notch-1 knocked down condition.
Conclusions: Our results suggested that Notch-1 probably play an important role in development andprogression of OSCC. Furthermore, Notch-1 may contribute to invasion activity in cancer cells via
TNF-αdependent manner.

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P-15

MUC1 expression in squamous cell carcinoma of the tongue
Yoshinori Jinbu1, Hiroto Itoh1, Norito Miyagi1, Mikio Kusama1 and Keiichi Tsukinoki2
1

Department of Dentistry, Oral and Maxillofacial Surgery, Jichi Medical University
Departmennt of Diagnostic Science,Division of Pathology,Kanagawa Dental College

2

Mucins are high-molecular-weight glycoproteins with oligosaccharides attached to serine or threonine
residues of the mucin core protein backbone by o-glycosidic linkages. In the recent reports, MUC1 mucin
is associated with invasive growth of the tumors and poor outcome of the patients.
We performed immunohistochemical staining of MUC1 and analyzed the relation with theclinicopathologic characteristics in human tongue cancers.
Oral biopsy speciments of 30 cases of tongue cancer diagnosed and treated at Jichi Medical University
Hospital were used. Clinical information for the subjects was reviewed and statistical analysis was performed
using the chi-square test.
The overall MUC1 positivity was 60%. The percentage of MUC1-positive specimens in the T3+T4 group(86%) was higher than that in the T1+T2 group (52%). The percentage of MUC1-positive specimens in
the N+ group (67%) was slightly higher than that in the No group (58%). A higher percentage of MUC1
expression was shown in the advanced mode of invasion (4C) group (71%) compared with that of themode of invasion (2+3) group (56%). The percentage of MUC1-positive specimens in the postoperative
neck lymph node metastasis group (75%) was higher than that in the no metastasis group (54%). However,statistical significance was not found.
MUC1 was preferentially expressed in advanced and metastatic squamous cell carcinoma of the tongue andappears to be one of predictive marker for lymph node metastasis.

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P-16

CXCR-4 overexpression increases the cell proliferation and invasion via
MAPK/ERK signaling in oral cancer cells.
Ji soo Hong, Kyoung ok Hong, Yoo jin Lee, Jae il Lee, Sam pyo Hong and Seong doo Hong
Department of Oral Pathology, School of Dentistry, Seoul National University
Chemokines are small molecules that regulate leukocyte trafficking and homing. Their receptors are seventransmembrane, G-coupled proteins. Recent data suggest that the interactions between chemokines andtheir receptors are also critical components in the regulation of tumor progression and metastasis in breast
cancer and other tumors. However, there are few reports about the role of chemokine receptors in oral
cancer behavior. In this study, we induced CXCR-4 overexpression in oral cancer cells, and examined theeffect of CXCR-4 in tumourigenesis. CXCR-4 overexpression induced morphological change to spindle
shape and increased cell proliferation in oral cancer cells. Also, in vivo study, CXCR-4 overexpression inoral cancer cells increase tumor size. In addition, CXCR-4 overexpression increased migration and invasionin vitro study. The effects of CXCR4 overexpression were correlated with SDF-1 mediated activation ofdownstream signaling via p-ERK1/2. Together, these results demonstrate that enhanced CXCR4 signaling
is via increased MAPK signaling. These findings suggest that CXCR-4 could be a useful molecular target for
the treatment of oral cancer and mitogen-activated protein kinase/ERK signal transduction pathway may
be involved in SDF-1α mediated proliferation and migration of oral cancer cells.

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P-17

Intraductal papilloma with peri-luminal extension of the minor salivary
gland: a new disease entity by clinicopathological analysis of 82 cases
Jun Cheng1,2,3, Wu Lanyan2, Maruyama Satoshi3, Yamazaki Manabu1 and Saku Takashi1,31Division of Oral Pathology Department of Tissue Regeneration and Reconstruction, Graduate School of Medical
and Dental Sciences, Niigata University
2
Department of Oral Pathology, West China College of Stomatology, Sichuan University
3
Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital
Background: Intraductal papilloma (IDP) has been considered to be a rare salivary gland tumor
characterized by its papillary growth within a unicystic ductal space. However, it is rare to encounter such atypical histology when IDP arises in minor salivary gland within the oral cavity. To prove our hypothesisthat IDP does not limit its growth to the luminal space only but involve the outside of the primary ductwall and that “extra-luminal IDP” involving the peri-luminal space is often misdiagnosed as pleomorphic
adenoma (PA), we examined our archives of intraoral PA cases retrospectively.
Materials and methods: Reviewing oral pleomorphic adenoma cases filed at Niigata University and Sichuan
University in the last thirty-year period, we found 82 typical cases of extra-luminal IDP. They were
examined for common clinicopathological characteristics as IDP. In addition, immunohistochemical
profiles for the constituent tumor cells were investigated.
Results: Histopathologically, IDP had dilated cystic spaces, which were basically lined by two-cell layered
duct epithelium-like cells, in the periphery of the tumor but had no complete intraluminal growth. There
was definite papillary proliferation of two-cell layered cells with hyaline stroma containing blood vessels.
The luminal cells were immunohistochemically keratins 7/19 positive, while basal cells were positive forvimentin, calponin, and occasionally S-100 protein.
Discussion: The present result indicates that the extra-luminal IDP is not so rare but accounts for about
10% of PA, which may be nearly the same as the frequency of myoepithelioma. There was no apparent
difference in prognoses between IDP and PA.

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P-18

miR-146a expression is associated with the oncogenicity of oral carcinoma
Shu-chun Lin1,2, Pei-shi Hung1, Shou-yen Kao1,2 and Chung-ji Liu1,3
1

Institute of Oral Biology, National Yang-Ming University
Department of Stomatology, Taipei Veterans General Hospital3
Department of Oral and Maxillofacial Surgery, Taipei MacKay Memorial Hospital2

MicroRNAs are short, non-coding RNAs that regulate gene expression and crucial for tumorigenesis. Oralsquamous cell carcinoma (OSCC) is a prevalent malignancy worldwide. miR-146a has been reported toregulate Toll-like receptor and cytokine signaling. Up-regulation of miR-146 was identified in OSCC
tissues. However, it roles in carcinogenesis appear controversial as it was shown suppressive to breast, colonand gastric carcinomas. The present study investigated the pathogenic implications of miR-146a in oral
carcinogenesis. Microdissected OSCC exhibited higher levels of miR-146a expression than matchedadjacent matched mucosal cells. The plasma miR-146a level in patients was significantly higher than control
subjects, and it decreased drastically after tumor resection. Infection of a lentivirus carrying pre-miR-146asequence increased the miR-146a expression. The activity of ectopic miR-146a was demonstrated by areporter assay, the down-regulation of both IRAK1 and TRAF6, and the decreased NF-κB activities.
Exogenous miR-146a expression significantly increased the in vitro oncogenic phenotypes, and the
xenografic growth and metastasis of OSCC cells. Administration of miR-146a antagonist also significantly
inhibited the growth of xenographic OSCC tumors. Interestingly, knockdown of both IRAK1 and TRAF6
drastically increased the oncogenic phenotypes and tumorigenesis of OSCC cells. Evidences from this study
substantiate that miR-146a expression might be contributive to oral carcinogenesis by targeting IRAK1 andTRAF6.

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P-19

Nuclear Survivin expression is well correlated with tumor progression ofhead and neck cancer
Intan suraiya Merican Aljunid merican1, Yasusei Kudo1, Guangying Qi1, Ikuko Ogawa2 andTakashi Takata1
1

Department of Oral & Maxillofacial Pathobiology, Graduate School of Biomedical Sciences, Hiroshima University
Center of Oral Clinical Examination,, Hiroshima University Hospital2

Survivin is a member of the inhibitors of apoptosis (IAP) family. Besides its role as IAP, Survivin recently
appears to function as a subunit of the chromosomal passenger complex (CPC) for regulating cell division
with other CPC proteins including Aurora-B and INCENP. Nuclear Survivin is suspected to control cell
division, whereas cytoplasmic Survivin is considered cytoprotective. Here we examined cytoplasmic andnuclear Survivin expression and its functional correlation with Aurora-B in head and neck squamous cell
carcinoma (HNSCC). In HNSCC, high expression of nuclear and cytoplasmic Survivin was well correlatedwith malignant behaviors. Nuclear Survivin expression was significantly correlated with Ki-67 and
Aurora-B expression. Notably, HNSCC cases with nuclear Survivin and Aurora-B expression exhibited
marked malignant behaviors. Interestingly, Aurora-B expression was decreased by Survivin knockdown, andSurvivin expression was decreased by Aurora-B knockdown. Moreover, accumulation of Survivin or
Aurora-B protein was induced by proteasome inhibitor treatment in siRNA treated cells, suggesting thatinteraction between Survivin and Aurora-B may regulate their protein stability. Importantly, both Survivin
and Aurora-B knockdown inhibited cell growth and tumorsphere formation. Overall suggest that nuclear
Survivin may be involved in tumor progression, and that Survivin can be useful diagnostic markers andtherapeutic targets of HNSCC.

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P-20

Proteomic profile of VX2 induced rabbit OSCC (early- and late- stage)- preliminary report
Li-min Lin1 and Yan-hsiung Wang2
1

Departments of Oral Pathology, School of Dentistry, Kaohsiung Medical University
School of Dentistry, Kaohsiung Medical University

2

Oral squamous cell carcinoma (OSCC) is the most common malignant form of oral cancer. It seems notmany reliable and predictable serum biomarkers can be found in the literature. The purpose of study is try
to use a proteomic analysis in VX2 induced rabbit OSCC in order to observe the difference between earlyand late stage of tumors, ultimately to identify novel-invasive serum biomarkers of OSCC.
Ten adult white New Zealand male rabbits, each normal and experimental rabbit were anesthetized
intramuscularly by ketamine. Venous blood were drawn from each rabbit. All serum samples were separated
from whole blood by centrifugation at 800 g for 10 minutes and aliquoted for storage at -80°C.
Before 2D gel electrophoresis analysis, the sera were treated with Affi-Gel Blue Gel to remove albumin. The
sera were separated using 18 cm, pH 3-10 IPG strips for the first dimension and 10% sodium dodecyl
sulfate-polyacrylamide gel electrophoresis for second dimension. Protein spots were visualized by silver
staining and identified by liquid chromatography/ tandem mass spectrometry.
Nineteen protein-spots of sera samples show significantly changed during the development of VX2-induced
rabbit submandibular carcinomas. Transthyretin, paraoxonase 1, paraoxonase 1B, alpha-2-glycoprotein 1
and alpha 1B-glycoprotein-like, were identified by mass spectrometry. Among them, transthyretin andparaoxonase 1 was strongly decreased after tumor inoculation.
The application of proteomic technologies in VX2-induced rabbit submandibular carcinomas animal model
would be helpful to evaluate reliable cancer-associated biomarkers. The relationship between thesebiomarkers and OSCC development remains to be further tested in cancer patients.

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P-21

舌の上皮性異形成，上皮内癌と扁平上皮癌におけるcytokeratin，
p53についての免疫組織学的検討

Immunohistochemical study of cytokeratin-13, -17 and p53 in epithelial dysplasia
and carcinoma of the tongue
岡田 康男，森出 美智子，柬理 賴亮，大窪 泰弘，長谷川 仁
Yasuo Okada, Michiko Moride, Yoriaki Kanri, Yasuhiro Ohkubo andHitoshi Hasegawa
日本歯科大学新潟生命歯学部 病理学講座
Department of Pathology, School of Life Dentistry at Niigata, The Nippon Dental University

臨床診断名としての白板症の多くは，病理組織学的には，上皮性異形成を伴わない角化亢進と上皮性異形成を伴う角化亢進であるが，上皮内癌や浸潤癌の状態をみる場合もある。近年，口腔前癌病変や扁平上皮癌に対するサイトケラチンやKi-67の免疫組織化学染色についての報告がなされているが，複数の免疫組織
化学染色の組み合わせについての報告は少ない。そこで，舌に発現した上皮性異形成を伴わない角化亢進，上皮性異形成を伴う角化亢進，上皮内癌および扁平上皮癌のそれぞれ10例ずつ計40例についてCK13，
CK17およびp53の免疫組織化学染色を行い発現の違いについて比較検討した。その結果，CK13は上皮性異形成を伴わない角化亢進では，10例全例が陽性，上皮性異形成を伴う角化亢進，上皮内癌および扁平上皮癌では全例が陰性であった。CK17は上皮性異形成を伴わない角化亢進では10例中 9 例が陰性，上皮性異形成を伴う角化亢進，上皮内癌と扁平上皮癌では10例全例が陽性だった。p53は上皮性異形成を伴わない角化亢進では10例中 2 例のみが基底層細胞の一部に陽性を呈した。上皮性異形成を伴う角化亢進と扁平上皮癌では10例中 9 例が陽性を呈し，陽性率は高かったが，一方で，上皮内癌は10例中 5 例でのみ陽性だった。
サイトケラチンの染色性の違いは，Ohkuraら（Oral Oncol 41: 607-613）の遺伝子的解析に一致し重要な所見であるが，腫瘍そのものを指し示すものではないため，いわゆるoblique lineを認識する上で有用と考えられた。p53の染色結果は，中等度や高度上皮性異形成のp53の発現率が上皮内癌や高分化型扁平上皮癌より高いという報告（Maoら）や実験的研究報告（Okazakiら）に一致ないし類似しており，上皮内癌においてはp53陽性率が高くないことを十分考慮する必要があると考えられた。本研究の一部は，J Hard
Tissue Biology 19: 123-130, 2010において報告した。
It is known that several percent of leukoplakia that develop in the oral mucosa become cancerous.
Leukoplakia is a clinical diagnostic term, and histopathologically most cases show hyperkeratosis withepithelial dysplasia or hyperkeratosis without epithelial dysplasia. On the other hand, difficulties inhistopathological diagnosis of severe epithelial dysplasia and carcinoma in situ are often encountered. In
the present study, with the objective to achieve a higher precision in histopathological diagnosis, we
conducted and compared the immunohistochemical stainings of CK13, CK17 and p53 in 10 cases each of
hyperkeratosis without epithelial dysplasia, hyperkeratosis with epithelial dysplasia, carcinoma in situ ,and SCC in the tongue. The following results were obtained. CK13 was positive in all 10 cases ofhyperkeratosis without epithelial dysplasia, and negative in all cases of hyperkeratosis with epithelial
dysplasia，carcinoma in situ , and SCC. CK17 was negative in 9 of 10 cases of hyperkeratosis without
epithelial dysplasia, and was positive in all 10 cases of hyperkeratosis with epithelial dysplasia, carcinoma

in situ , and SCC. For p53, positive reaction was observed in some cells of the basal cell layer in 2 of 10
cases of hyperkeratosis without epithelial dysplasia, while high positive rates were found in
hyperkeratosis with epithelial dysplasia (9 of 10 cases) and SCC (9 of 10 cases). On the other hand, only 5of 10 cases of carcinoma in situ were positive for p53.

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P-22

Roles of N-cadherin in head and neck squamous cell carcinoma
Phuong thao Thi Nguyen1, Yasusei Kudo1, Ikuko Ogawa2 and Takashi Takata1
1

Department of Oral & Maxillofacial Pathobiology, Graduate School of Biomedical Sciences, Hiroshima University
Center of Oral Clinical Examination, Hiroshima University Hospital2

The loss of E-cadherin and the gain of N-cadherin expression are known as the “cadherin switching”.
Cadherin switching is a major hallmark of epithelial-mesenchymal transition (EMT). EMT is a crucial
process in cancer progression providing cancer cells with the ability to escape from the primary focus, toinvade stromal tissues and to migrate to distant regions. We found that high expression of N-cadherin wasobserved in 52 of 80 head and neck squamous cell carcinoma (HNSCC) cases and was significantly
correlated with malignant behaviors. Cadherin switching was observed in 30 of 80 HNSCC cases and waswell correlated with histological differentiation, pattern of invasion and lymph node metastasis. Moreover,N-cadherin expression was observed in 7 of 16 HNSCC cell lines, and cadherin switching was observed in
2 of 4 HNSCC cells with EMT features.
To know the utility of N-cadherin as a therapeutic target for HNSCC, I treated N-cadherin antibody in
HNSCC cells with EMT features (HOC313 cells). We found that N-cadherin antibody suppressed theproliferation and the invasion of HOC313 cells. N-cadherin antibody treated HOC313 cells showedmorphologic changes from a spindle shape to a cobblestone-like shape. We also found the reduced
expression of Snail1, vitronectin and MMPs including MMP3, MMP7, MMP9, MMP10, MM12 and
MMP13 in HOC313 cells with N-cadherin antibody treatment.
In conclusion, we suggest that i) N-cadherin may play an important role in malignant behaviors of
HNSCC, and ii) blocking function of N-cadherin can be a therapeutic target for HNSCC.

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P-23

Comparison of expression profiles of MMP2 and MMP9 in primary andmetastatic OSCCs in relation to CD68 positive macrophage distribution.
Daisuke Omagari, Shotaro Mukae, Naoyuki Matsumoto, Masatake Asano andKazuo Komiyama
Department of Pathology, Nihon University School of Dentisry
Objective: Oral squamous cell carninoma (OSCC) has highest incidence among malignant tumor of headand neck. Matrix metaloproteinases (MMPs) and tumor associated macrophages (TAMs) play importantroles in the tumor metastasis. In this study, we attempted to compare the intensities of MMP2 and MMP9
between primary and metastatic lesions in relation to the distribution of TAMs.
Materials and Methods: Total of 29 OSCC cases were examined. The subjects contained 13 cases of lingual,14 cases of gingival, and 2 cases of buccal OSCCs.
Formalin fixed, paraffin-embedded sections were stained with anti-MMP2, MMP9 and CD68 antibodies
as primary antibodies, followed by HRP-conjugated IgG Ab.
Result: Both MMP2 and MMP9 tend to be expressed stronger in metastatic lesion than primary lesion. In
MMP2, most of primary lesion showed negative or weak staining, but metastatic lesion showed higher
staining intensity.
While, MMP9 was detected positive staining in the primary lesion, and showed much stronger positive
staining in the metastatic lesion.
Next, we compared the MMPs staining intensity of metastatic lesion between the gingival and lingual
cancer. MMP2 staining intensities were stronger in gingival cancer than lingual cancer, however MMP9
expression showed no difference.
In interestingly, the number of TAMs showed much higher in the primary lesion than that of the metastatic
lesion.
Conclusion: These results indicated that MMPs staining intensities and the number of TAMs in the lesion
were in negative correlations. Moreover, MMP2 might play relevant roles for the metastasis of the gingival
cancer.

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P-24

口腔前癌病変および口腔癌におけるpodoplanin発現の意義

Signiﬁcance of podoplanin expression in oral precancerous and cancerous lesions
井上 ハルミ1，宮崎 裕司2，菊池 建太郎2，井出 文雄2，草間 薫2
Harumi Inoue1, Yuji Miyazaki2, Kentaro Kikuchi2, Fumio Ide2 andKaoru Kusama2
1

明海大学大学院歯学研究科 形態系 病態形態研究群（口腔病理学）
明海大学歯学部 病態診断治療学講座 病理学分野
1
Research Group in Oral Pathology, Meikai University Graduate School of Dentistry2
Meikai University School of Dentistry, Division of Pathology, Department of Diagnostic & Therapeutic
Sciences2

Human podoplanin is a type-1 transmembrane sialomucin-like glycoprotein consisting of 162 amino acids.
The protein was originally detected in puromycin-induced nephrosis on the surface of rat podocytes asa 38-kDa mucoprotein and is now utilized as a specific marker for recognizing lymphatic vessels.
Recent studies have shown that podoplanin is expressed in not only normal tissues but also abnormal
tissues with dysplalstic changes, or in various malignant neoplasms. It has been implicated that
podoplanin can be involved in tumor cell invasion and metastasis. However, the role of the protein in
physiological and pathological conditions has been retained unclear. In this study immunohistochemical
and molecular biological analyses were performed to examine the importance of podoplanin expressionin oral precancerous and cancerous lesions.
One hundred and three samples of epithelial precancerous lesions were classiﬁed according to the gradeof epithelial dysplasia by HE staining and analyzed by immunohistochemical examination using the
primary antibody against human podoplanin (D2-40). Fruthermore, 69 samples of oral squamous cell
carcinomas (OSCCs) were divided into 2 groups; with PN+ and PN-, and in each group the samples wereclassiﬁed according to the degree of diﬀerentiation and then analyzed by immunohistochemical methods.
In addition, Ca9-22, HSC-2, -3 and -4 cells were incubated with growth factors and then subjected to realtime RT-PCR and western blotting assay to examine the effects of each factor on the podoplanin
expression.
Podoplanin expression correlates with severity both of the epithelial dysplasia and the diﬀerentiation ofcarcinoma.
Human podoplanin is a type-1 transmembrane sialomucin-like glycoprotein consisting of 162 amino acids.
It has been implicated that podoplanin can be involved in tumor cell invasion and metastasis. In thisstudy immunohistochemical and molecular biological analyses were performed to examine theimportance of podoplanin expression in oral precancerous and cancerous lesions. In OSCCs, most of thecases showed the positivity for podoplanin and the poorer differentiated OSCCs were, the stronger
reactions for podoplanin were found.

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P-25

ピルビン酸キナーゼ・アイソザイムの口腔扁平上皮癌における発現
Expression of pyruvate kinase isozymes in oral squamous cell carcinoma

栗原 都1,2，笹平 智則1，山本 一彦2，桐田 忠昭2，國安 弘基1
Miyako Kurihara1,2, Tomonori Sasahira1, Kazuhiko Yamamoto2, Tadaaki Kirita2
and Hiroki Kuniyasu1
1

奈良県立医科大学 分子病理学講座
奈良県立医科大学 口腔外科学講座
1
Department of Molecular Pathology, Nara Medical University
2
Oral and maxillofacial surgery, Nara Medical University2

がんが正常細胞とは異なり嫌気性解糖によりエネルギー産生を行うという特徴は，Warburg効果として知られている。
ピルビン酸キナーゼ（PK）は，嫌気性解糖を行うEmbden-Meyerhof経路の最終反応であるホスホエノー
ルピルビン酸からADPへのリン酸基転移を行うが，この反応の生成物であるピルビン酸は好気性解糖を行うクエン酸回路に供給される。PKにはPKM1とPKM2というアイソザイムが存在し，前者は生後PKのほとんどを占めるのに対し，後者は胎生期及び腫瘍に特異的に発現している。今回，われわれは，口腔扁平上皮癌（OSCC，17例），dysplasia/leukoplakia（DPLP， 8 例）
，炎症性疾患（ID， 8 例）に対して，免疫染
色によりPKM1，PKM2の発現と，発現比を検討した。OSCCでは全例でPKM2の強発現とPKM1発現低下が見られたが，DPLPでは，PKM2発現亢進・PKM1発現低下とも中等度で，両者の間でPKM2/PLM1発現比に有意差が認められた（P=0.0043）。一方，IDでは，PKM2発現亢進・PKM1発現低下とも軽度であった。
以上より，PKM1・PKM2の発現は口腔扁平上皮癌の新たな診断のマーカーとなる可能性が示唆された。
Unlike normal cells, which metabolize glucose by oxidative phosphorylation, tumor cells preferentiallymetabolize glucose by anaerobic glycolysis. The metabolic shift is partly achieved by a switch in the
splice isoforms of the pyruvate kinase. Although normal cells express the pyruvate kinase M1 isoform(PKM1) , tumor cells express the M2 isoform(PKM2). We prompted to verify the PKM1-PKM2 switchingas a marker of malignancy.
We examined the expression of PKM1 and PKM2 and the ratio of PKM2/PKM1 by IHC in OSCC,
dysplasia/leukoplakia(DPLP) and inﬂammation tissue (ID). The ratio of PKM1/PKM2 may be useful forthe distinguishing OSCC from benign lesions.

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P-26

Relationship between the expressions of PD-L1 and tumor-infiltrating
lymphocytes in oral squamous cell carcinoma
Young-ah Cho, Hye-jung Yoon, Jae-il Lee, Sam-pyo Hong and Seong-doo Hong
Department of Oral Pathology, School of Dentistry, Seoul National University
Objectives: Tumor-infiltrating lymphocytes (TILs) are considered to represent immune reactions of the hostto a malignant tumor. Tumor cells defend against the actions of TILs by expressing molecules that hinder
host immunity, such as programmed death receptor ligand-1 (PD-L1). In the present study, we investigatedthe densities of CD4+/CD8+TILs and PD-L1 expression of tumor cells in oral squamous cell carcinoma(OSCC).
Methods: Forty-five cases of OSCC were selected. We evaluated PD-L1 expression and the infiltration
degree of each lymphocyte by immunohistochemical examination. TILs were separately assessed in tumor
cell nests and in the stroma near the invasive front of the tumor. These data were analyzed in connection
with clinicopathological factors.
Results: Peritumoral CD8+ TILs were observed in every patient with OSCC, and their densities werecorrelated with lymph node metastasis (P<.001), tumor size (P=.003), and clinical stage (P<.001). PD-L1
expression on OSCC cells was observed in 39 cases and was associated with the density of intratumoral
CD8+TILs (P=.047). PD-L1 expression of tumors <4cm in size was correlated with the histological gradeof the tumor (P=.022). Patient survival and immunohistochemical results were not associated.
Conclusion: Some clinical parameters such as the size of tumor, lymph node metastasis and tumor stage,
were significantly associated with the densities of peritumoral TILs. PD-L1-positive tumor cells were foundin most OSCC patients, and which were associated with the densities of intratumoral TILs. The
development of a strategy to block the interactions of PD-L1 with TIL would be a useful tool for inhibiting
tumor growth.

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P-27

Ni2+ ion inhibited the secretion of IL-8 by oral squamous cell carcinoma
cells (OSCCs).
Shigeki Endo1, Daisuke Omagari2, Yasuhiro Okazaki2, Hirotaka Tsuda2, Masatake Asano2 andKazuo Komiyama2
1

Department of Partial Denture Prosthodontics, Nihon University School of Dentistry
Department of Pathology, Nihon University School of Dentistry2

Objective: OSCCs express TLR4 and respond to LPS by producing proinflammatory cytokines. Recently,
nickel (Ni2+) ion was shown to interact with TLR4 and induce the inflammatory reactions. In the present
study, we attempted to examine the effect of Ni2+ ion on the IL-8 secretion by OSCCs.
Materials and methods: Three different OSCCs, HSC2, HSC3 and Ca9-22, were used. The cells were
cultured with or without various concentrations of Ni2+ ion for indicated length of times. The culture
supernatants were harvested and IL-8 concentrations were measured by ELISA. Contribution of TLR4 to
Ni2+ ion-mediated IL-8 secretion was examined by anti-TLR4 antibody pre-incubation. Luciferase assay
was performed with pNF-kappaB-Luc plasmid, which contains 6 NF-kappaB-binding sites.
Results: All three OSCCs secrete IL-8 spontaneously. The most active production was observed in HSC3
cells. Secretion of IL-8 was partially inhibited by NF-kappaB specific inhibitors indicating that spontaneous
IL-8 production was attributed to aberrant NF-kappaB activity. The effect of Ni2+ ion was examined.
Surprisingly, Ni2+ ion inhibited the secretion of IL-8 in a dose- and time-dependent fashion. Pre-incubationof HSC3 cells with anti-TLR4 specific antibody recovered the secretion of IL-8. The effect of Ni2+ ion on
the activity of NF-kappaB was further examined by luciferase assay. Ni2+ ion reduced NF-kappaB activity
after 1 h of stimulation. All these results indicated that Ni2+ ion has an inhibitory effect on the secretion of
IL-8 by OSCCs.
Conclusions: Ni2+ ion inhibited spontaneous IL-8 secretion of OSCCs by inhibiting the activity of NFkappaB through TLR4.

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転移能の異なる腫瘍由来の血管内皮細胞の特性解析
大賀 則孝1，石川 修平1，樋田 泰浩2，秋山 広輔1，間石 奈湖1，川本 泰輔1，近藤 美弥子1，進藤 正信3，樋田 京子1
Noritaka Ohga1, Shuhei Ishikawa1, Yasuhiro Hida2, Kosuke Akiyama1,
Kazuko Kitayama1, Miyako Kondou1, Nako Maishi1, Taisuke Kawamoto1,
Takahiro Ohsawa1, Kazuyuki Yamamoto1, Masanobu Shindoh3, Kyoko Hida1
1

北海道大学歯学研究科 血管生物学教室
北海道大学医学研究科 腫瘍外科学教室
3
北海道大学歯学研究科 口腔病理病態学教室
1
Dept. Vascular Biology, Hokkaido Univ.Grad.Sch.Dent.Med2
Dept. Surg.Oncol., Hokkaido Univ.Grad.Sch.Med
3
Dept. Oral Pathol.biol., Hokkaido Univ.Grad.Sch.Dent.Med
2

腫瘍の増殖と転移において腫瘍血管が重要な役割を担っていることから，血管新生阻害療法に関する研究が盛んに行われている。われわれはこれまで腫瘍血管内皮を分離・培養し，それらが正常血管内皮と比べて，特異遺伝子の発現を亢進していることや（Cancer Res 2006），growth factorや特定の薬剤に対する感受性が，異なることなどを報告してきた（Cancer Res 2005, Cancer sci 2009，Int J Cancer 2011）。さらに腫瘍血管内皮細胞には，aneuploidyが認められ，それらが染色体不安定性をもつことが示唆された（Cancer Re 2004, Am J Pathol 2009）。腫瘍血管の異常性が徐々に解明されつつあるが，異なる腫瘍血管
内皮間での生物学的性質の違いについては未だ不明である。今回，転移能の異なる腫瘍から分離・培養された腫瘍血管内皮細胞の生物学的な特性の違いを比較・検討した。
今回，低転移性と高転移性のヒト腫瘍細胞株をヌードマウスに皮下移植し，腫瘍血管内皮細胞を分離・培養した。低転移性腫瘍由来血管内皮に比べ，高転移性腫瘍由来血管内皮は，増殖能及び遊走能が高く，
VEGF-Aに対する感受性が高かった。さらに，高転移性腫瘍由来血管内皮は，VEGFR-2，VEGF-A, HIF-1αなどの血管新生関連遺伝子や薬剤耐性遺伝子MDRの発現が亢進し，Paclitaxelに対する薬剤抵抗性を示した。また，高転移性腫瘍由血管内皮は幹細胞マーカーであるSca-1の発現が高く，stem cell spheroid
assayにおいてsphereを形成し，幹細胞性が高いことが示唆された。
転移能の異なる腫瘍では，腫瘍間質を構成する血管内皮の性質にも違いあることが示され，血管新生阻害療法を行う際には，その腫瘍血管内皮の特性を考慮する必要性が示唆された。
Comparative characterization of tumor endothelial cells isolated from highly and low metastatic tumors
It has been an important concept of tumor angiogenesis that tumor endothelial cells (TECs) are
genetically normal and homogenous.
However, we have reported that the TECs are diﬀerent from normal endothelial cells (NECs). Whether
there were differences in tumor endothelial cells derived from many type of tumors remains to beunclear. In this study, to investigate this question, we isolated two types of murine TECs from humantumor xenografts; highly metastatic melanoma (HMM) and low metastatic melanoma (LMM) in nude
mice and investigated whether there were phenotypic and genetic diﬀerences between these TECs.

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粘表皮癌におけるPTHrPの発現

Expression of PTHrP in mucoepidermoid carcinoma
長峯 杏介1,2，北村 哲也1，松田 彩1，樋田 京子3，東野 史裕1，戸塚
進藤 正信1
Kyosuke Nagamine1,2, Tetsuya Kitamura1, Aya Matsuda1, Kyoko Hida3,
Fumihiro Higashino1, Yasunori Totsuka2 and Masanobu Shindoh1

靖則2，

1

北海道大学大学院歯学研究科 口腔病理病態学教室
北海道大学大学院歯学研究科 口腔顎顔面外科学
3
北海道大学大学院歯学研究科 血管生物学
1
Department of Oral Pathology & Biology, Hokkaido University Graduate School of Dental Medicine
2
Department of Oral and Maxillofacial Surgery, Hokkaido University Graduate School of Dental Medicine
3
Department of Vascular Biology, Hokkaido University Graduate School of Dental Medicine2

粘表皮癌は唾液腺悪性腫瘍の中で最も多く，良性腫瘍に近いものから転移や再発をきたし予後が不良なものまで様々な生物学的性状の違いがある。副甲状腺ホルモン関連タンパク（PTHrP）は肺癌や大腸癌，前立腺癌の骨転移に伴う高カルシウム血症を引き起こす主要な因子として発見され，副甲状腺ホルモン（PTH）と同様に骨芽細胞に作用しRANKLの発現を亢進することで破骨細胞を誘導し骨吸収を促進することが知られている。我々は，これまでに，口腔がんとPTHrPの発現による悪性形質について検索し，口腔がん細胞株ではPTHrPが高発現していること，PTHrPをノックダウンすることでがん細胞の増殖抑制や浸潤活性が低下することを見出した。今回，北海道大学病院歯科診療センターで粘表皮癌と診断され治療を行った21症例を対象にPTHrPの発現を検索し，臨床病理学的パラメーターとの比較検討を行った。21例
中，転移と再発を７例でみとめた。PTHrPの発現は21例中17例に認められたが，PTHrPは中間細胞や扁平上皮様腫瘍細胞で発現する傾向が高く，PTHrPを発現する中間細胞が多い腫瘍ではリンパ節転移や再発の危険性が増すことを示された。このような所見は，PTHrPの発現が粘表皮癌の予後予測因子の一つになる可能性を示唆するものであった。
PTHrP is known to induce bone resorption by activating RANKL as well as PTH. We have reported
that PTHrP is expressed in oral squamous cell carcinoma cell lines, and PTHrP expression is correlatedwith malignant phenotype of oral cancer cells. Immunohistochemical detection of PTHrP was performed
in 21 cases of mucoepidermoid carcinoma in head and neck region. PTHrP was highly detectable inintermediate cells and it may concern lymph node metastasis or recurrence of tumor.

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免疫三重染色を用いた唾液腺腫瘍への応用

Application of salivary gland tumors using triple-immunostaining method
和唐 雅博，嘉藤 弘仁，国分 麻佑，益野 一哉，富永 和也，西川
田中 昭男
Masahiro Wato, Hirohito Katou, Mayu Kokubu, Kazuya Masuno,
Kazuya Tominaga, Tatsunari Nishikawa and Akio Tanaka

哲成，

大阪歯科大学 口腔病理学講座
Department of Oral Pathology, Osaka Dental University【目的】唾液腺腫瘍の組織型の各特徴を明らかにするためにDAB, PermaBlue，PermaGreenおよびPermanent Redの各種発色剤を用いた免疫三重染色法にて検討した。
【材料と方法】多形腺腫，Warthin腫
瘍，腺様嚢胞癌および粘表皮癌のホルマリン固定パラフィン切片を用い，腫瘍性筋上皮細胞と導管上皮細胞を検出する最適な抗体と発色剤の組み合わせを検討した。まずp63を反応させ，ついで 4 種類の発色剤のいずれかと反応させた。ついでcytokeratin 8（CK8）と反応後，いずれかの発色剤と反応させ，最後にα-Smooth muscle actin（α-SMA）と反応後，いずれかの発色剤と反応させた。
【結果】ｐ63は，腫瘍性筋上皮細胞や導管の基底細胞の核，α-SMAは腫瘍性筋上皮細胞の細胞質，CK8は導管上皮の細胞質にそれぞれ陽性であった。免疫三重染色における発色剤の組み合わせは，ｐ63をDABで発色させ，CK8および
α-SMA は，PermaBlueもしくはPermanent Redのいずれかの組み合わせが，良好なコントラストを呈した。しかし，PermaGreenは，他の発色剤との組み合わせで良好なコントラストを得られなかった。【まとめ】免疫三重染色は適当な発色剤と抗体を組み合わせれば，唾液腺腫瘍における多彩な組織型の特徴を把握するのに有用である。
We examined the histological pattern of salivary gland tumors using triple-immunostaining method.
Formalin-fixed, paraffin-embedded sections of pleomorphic adenoma, Warthin tumor, adenoid cystic
carcinoma and mucoepidermoid carcinoma were stained by the triple-immunostaining method using
DAB, PermaBlue，PermaGreen and Permanent Red as chromogens. DAB，PermaBlue and Permanent
Red of chromogens make high contrast to observe. The triple-immunostaining was a useful tool to
examine the histological pattern of salivary gland tumors.

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High-grade transformation in adenoid cystic carcinomaの 3 例の組
織学的検討
High-grade transformation in adenoid cystic carcinoma: report of three caseswith histological study.
佐藤 由紀子Yukiko Sato
がん研究会がん研究所 病理部
Japanese Foundation for Cancer Research, The Cancer Institute, Division of Pathology

Adenoid cystic carcinoma（AdCC）は大唾液腺，小唾液腺のいずれにも発生する， 2 番目に多い悪性唾液
腺腫瘍である。AdCCに生じるHigh-grade transformation（HGT）は近年認識された現象である。我々は耳下腺と口蓋にHGTを生じたAdCCの 3 例を経験したので報告する。患者の年齢は31-74歳で平均57歳，いずれも男性だった。組織学的に腫瘍はhigh-grade成分が主体を占め，通常型のAdCC成分の量は症例ごとに異なった。 1 ，3 例目は典型的な像をとり，それぞれの成分の間には移行像がみられた。 2 例目では特に通常型の成分が少なく診断に苦渋した。免疫組織化学染色にてhigh-grade成分は通常型の部に比べp53の強陽性像が確認された。HGTは確立されつつある概念であるが，いまだ十分認知されているとはいえないと考え報告した。
Adenoid cystic carcinoma (AdCC) is the second common malignant tumor involving both the major andminor salivary glands. High-grade transformation (HGT) in AdCC is a recently recognized entity. We
report three cases of AdCC with HGT arising in the parotid glands and hard palate. The patients' ages
(3 male) ranged from 31 to 74 years (median, 57 y). The tumor was composed predominantly of highgrade component with various amount of conventional AdCC. Immunohistochemical study of the highgrade component as compared to conventional AdCC showed greater over-expression of p53.

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頬粘膜部小唾液腺と耳下腺にみられた異時性多形腺腫由来癌

A case of metachronous carcinoma ex pleomorphic adenoma arising from thebuccal minor salivary gland and the contralateral parotid gland
藤田 修一1，佐野 和生2，池田 通1
Shuichi Fujita1, Kazuo Sano2 and Tohru Ikeda1
1

長崎大学大学院医歯薬学総合研究科 医療科学専攻生命医科学講座 口腔病理学分野
福井大学医学部 感覚運動医学講座 歯科口腔外科学領域
1
Department of Oral Pathology and Bone Metabolism, Unit of Basic Medical Sciences, Course of
Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences
2
Division of Dentistry and Oral Surgery, Department of Sensory and Locomotor Medicine, Faculty of
Medical Sciences, University of Fukui
2多発性唾液腺腫瘍としてWarthin腫瘍が両側耳下腺に発生することがあることがよく知られているが，悪性腫瘍では稀である。我々は，異時性に頬粘膜部小唾液腺と対側耳下腺に発生した多形腺腫由来癌を経験したので報告する。症例は71歳の女性。1997年，右頬粘膜の緩徐に増大する無痛性の腫脹を主訴に，長崎大学歯学部附属病院口腔外科を受診した。CTでは右下顎枝前方から側頭窩に至る腫瘤がみられ，上顎洞の狭窄も認められた。生検では充実性または管状構造をなす腫瘍が粘液様または硝子様基質を伴って増殖し，線維性被膜もみられた。多形腺腫の病理診断後，摘出された。手術材料では組織学的に，濃染する核を有した異型細胞からなる充実性または梁状の組織が，良性の多形腺腫から移行して増殖していた。悪性領域では，細胞質の明るい淡明細胞も含まれており，被膜外の脂肪組織に浸潤していた。免疫組織化学的にcytokeratin AE1/AE3, S-100, α-SMA, p63, calponinなどに陽性で，悪性領域については腺管構造がきわめて少なく，筋上皮癌とみなされ，頬粘膜部小唾液腺の多形腺腫由来癌と診断した。2001年，CTで左耳下腺に腫瘤が確認された。徐々に増大したため，2003年に長崎大学病院耳鼻咽喉科にて摘出された。病変は組織学的・免疫組織化学的に，周辺部に主に筋上皮癌の領域があり，被膜外の耳下腺リンパ節への直接浸潤もみられた。癌腫部分は内部の壊死組織に移行し，硝子様基質を伴う異型性の乏しい二層性腺管構造も含まれていた。後者は多形腺腫とみなされ，病理組織学的に耳下腺の多形腺腫由来癌と診断された。頬粘膜部腫瘍とは異なり，癌腫部分に淡明細胞は含まれていなかった。さらに，2006年左耳下腺に再発と思われる病変が認められ，腫瘍摘出術及び左側頸部郭清術が行われた。組織学的には良性領域はみられず，淡明細胞を伴わない筋上皮癌が主体で，角化傾向を持つ扁平上皮癌への移行もみられた。再発性多形腺腫由来癌と診断されたが，リンパ節には転移は認められなかった。
We report a case of rare metachronous carcinoma ex pleomorphic adenoma (Ca-ex-PA). In 1997, a
71-year-old woman was referred to Nagasaki University Hospital because of a painless swelling of theright buccal mucosa. Biopsy indicated PA, but the removed tumor included PA as well as myoepithelial
carcinoma. In 2003, a slowly growing mass of the left parotid gland was detected. The lesion wascomposed of myoepithelial carcinoma. Histopathological diagnosis of Ca-ex-PA was made because PA
was intermingled. Recurrent tumor in the parotid gland was found in 2006, and histologically determined
as recurrent Ca-ex-PA including myoepithelial carcinoma and squamous cell carcinoma.

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唾液腺の粘表皮癌：特異な 3 例の提示

Mucepidermoid carcinoma of the salivary glands: three unusual examples.
原田 博史
Hiroshi Harada
市立堺病院 病理・研究科
Department of Pathology and Research, Sakai Municipal Hospital

粘表皮癌は唾液腺に発生する悪性腫瘍の中で最も頻度が高く，組織学的なバリエーションも極めて豊富である。今回は演者へのコンサルト症例から 3 例を選んで供覧する。 1 例目は77歳女性の口蓋に発生した脱分化型粘表皮癌であり，組織学的には奇怪な大型核を有する腺癌NOSの成分を主体とし，豊富な粘液を有する印環細胞様細胞とともにclear cell成分からなる粘表皮癌成分が混在していた。 2 例目は44歳女性の耳下腺に発生し，肉腫様変化を伴った高悪性症例で，comedo壊死を伴う充実性胞巣と細胞成分に富む間質領域からなり，両者の境界はしばしば不明瞭であった。いずれの領域にもrhabdoid cellが少数散見された。
3 例目は79歳男性の顎下腺に発生し，比較的角化傾向の明瞭な扁平上皮と少数の粘液細胞からなり，間質にはtumor-associated lymphoid proliferationとともに特徴的な硬化像と夥しい好酸球浸潤がみられることから，組織学的には甲状腺に稀にみられるsclerosing mucoepidermoid carcinoma with eosinophiliaと同等のものとみなされた。当日はさらに詳細な組織像を示し，討議を仰ぐ。
Mucoepidermoid carcinoma is the most common malignant tumor of the salivary glands and has a wide
histomorphologic spectrum. Three examples were selected from presenterʼs own consultation ﬁles. The
first case was dedifferentiated mucoepidermoid carcinoma mainly consisted of bizarre pleomorphic
round cells with clear cell foci scatteringly intermingled. The second was a high-grade tumor withsarcomatoid foci, which presented solid nests with comedo-necrosis and cellular “stroma” including
rhabdoid cells. The last was a tumor histologically consistent with sclerosing mucoepidermoid carcinoma
with eosinophilia rarely found in the thyroid gland. The detail of each case would be described anddiagnostic problems discussed.

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下顎骨浸潤を示す舌下腺に生じた粘表皮癌の１例

Mucoepidermoid carcinoma of the sublingual gland with mandibular invasion: acase report靍岡 祥子1，石川 文隆2，原田 博史3，山本 哲彰1，清宮 弘康1，宮本 郁也1，
山下 善弘1，松尾 拡2，高橋 哲1
Shoko Tsuruoka1, Ayataka Ishikawa2, Hiroshi Harada3, Noriaki Yamamoto1,
Hiroyasu Kiyomiya1, Ikuya Miyamoto1, Yoshihiro Yamashita1, Kou Matsuo2 andTetsu Takahashi11

九州歯科大学生体機能科学専攻 口腔顎顔面外科学講座 形態機能再建学分野
九州歯科大学健康促進科学専攻 生命科学講座 口腔病態病理学分野
3
市立堺病院 病理・研究科
1
Division of Oral and Maxillofacial Reconstructive Surgery, Department of Oral and Maxillofacial
Surgery, Kyushu Dental College
2
Division of Oral Pathology, Department of Biosciences, Science of Health Improvement, Kyushu
Dental College
3
Department of Pathology, Sakai Municipal Hospital
2

緒言：粘表皮癌は大唾液腺では耳下腺に好発するが，舌下腺に生じることはまれである。今回，われわれは舌下腺に生じ下顎骨髄質への浸潤を伴う粘表皮癌を経験したので報告する。
症例：48歳，女性。半年前より口底部の違和感を認めていたが放置していた。 1 ヶ月前より口底部の腫脹と疼痛を自覚したため近歯科医院を受診したところ当科を紹介され受診した。初診時，左側口底部に周囲に硬結を伴う20x15mm大の腫瘤を認めた。CTとMRIにて左側舌下腺を中心に30x20x20mm大の腫瘤を認め，隣接する舌側皮質骨は消失し海綿骨への浸潤が疑われた。また，PET-CTにてSUV max 7.75の集積を認めた。口底部悪性腫瘍（T4N0M0）の診断下に口底腫瘍切除術，下顎骨区域切除術，両側肩甲舌骨筋上頸部郭清術，肩甲骨弁再建術が施行された。切除標本では，舌下腺から口底部，舌側歯肉にかけて腫瘍がみられ，下顎骨髄質への圧迫型浸潤を認めた。組織学的には，軽度〜中等度の細胞異型を示す扁平上皮様細胞の胞巣状，細索状の浸潤増殖がみられ，一部の腫瘍胞巣辺縁部には柵状配列を認めた。また，少数の腺管構造がみられ，Alcian blue-PAS染色では，少数の粘液細胞を認めた。免疫染色では，多数の腫瘍細胞がp63陽性であったが，α-SMA，S-100は陰性だった。以上の所見から粘表皮癌と診断した。また，頸部リンパ節転移はみられなかった。現在，術後 5 ヶ月であるが再発は認めず，経過良好である。
Mucoepidermoid carcinoma (MEC) of the sublingual glands is a rare entity. We report the case of a48-year-old woman with MEC of the left sublingual gland, accompanied by invasion into the mandible.
Histopathological examination of the resected specimens revealed nests of squamous epithelial cells with
peripheral palisading that had proliferated in a solid cord pattern. In addition, mucin staining revealed a
few ductal structures and mucous cells. Most tumor cells demonstrated p63 positivity on
immunohistochemical examination; however, the samples were negative for myoepithelial markers. A
good response to treatment was observed in the ﬁve-month postoperative follow-up period.

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Endoglin expression in oral hemangioma - A comparative study withexpression of endothelial markers and angiogenic factors Motomi Tsuchiya1, Matsumoto Naoyuki1, Vongosa Souksavanh2, Omagari Daisuke1,
Asano Masatake1 and Komiyama Kazuo1
1

Department of Pathology, Nihon University School of Dentistry
Faculty of Dentistry, University of Health Sciences

2

Both of capillary and cavernous hemangioma is relatively common benign oral tumor conditions.
However, the precise etiology of hemangioma remains unclarified. We examined the characteristics of
capillary and cavernous hemangioma with endoglin expression. It is a component of TGF-β receptor,
which is synthesized in activated endothelial cells (ECs). We also examined for the proliferation activity andangiogenic factors.
Immunohistochmistry was performed for 32 capillary hemangiomas, 33 cavernous hemangiomas, and 5
non-pathological oral mucosa with using following antibodies; CD34, endoglin, von Willebrand factor(vWF), podoplanin, alpha-SMA, VEGF, COX-2 and Ki-67. The results assessed by the staining grade
system and Ki-67 labeling index (LI).
All of capillary hemangiomas showed the endoglin in high expressions, whereas low in the cavernous
hemangioma. An intense expression of CD34 found in non-pathological conditions, while low expression
in the cavernous hemangioma. Ki-67 LI revealed higher in capillary hemangioma than that of cavernous
hemangioma.
These results suggest the ECs of capillary hemangioma show more proliferative nature, which are
regulated by VEGF. Whereas, the ECs of cavernous hemangioma have weak proliferative activity. One
possible explanation for the etiology of cavernous hemangioma is not angiogenesis but the dilation of bloodvessels because the vessel is lining discretely with alpha-SMA positive cells. Moreover, the biological profilesof both ECs in capillary and cavernous hemangiomas are obviously different.

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舌縁部に発生した平滑筋腫の一例

A case of leiomyoma arising in the lingual edge
平井 千浦子，竹内 真衣，神澤 真紀，山崎 隆，川上 史，原 重雄，
伊藤 智雄
Chihoko Hirai, Mai Takeuchi, Maki Kanzawa, Takashi Yamasaki,
Fumi Kawakami, Shigeo Hara and Tomoo Ito
神戸大学大学院医学研究科医科学専攻 病理学講座 病理診断学分野
Department of Diagnostic Pathology, Kobe University Graduate School of medicine【症例】25歳女性。平成19年 9 月頃より，右舌縁部に腫瘤を自覚し，精査を指示されるも圧痛，接触痛等ないため放置していた。平成22年11月頃より増大傾向を認め，当院歯科口腔外科受診。静脈内鎮静法併用
局所麻酔下に周囲筋組織の一部を含めて切除術を施行した。腫瘤は被膜に覆われ，ほぼ核摘術となった。
腫瘤と連絡する神経は明らかではなかった。
【病理所見】切除された腫瘤は18×15×7mm，表層は滑沢で白色調の半球状腫瘤であり，弾性に富む。割面では境界明瞭な白色充実性腫瘤を認めた。組織学的には異型性の乏しい紡錘状細胞が疎らに配列し，myxoidな基質の増生を伴う。免疫染色ではα-SMA，desminが陽性，S100，EMAが陰性を示すことより平滑筋腫と診断された。
【考察】平滑筋腫は平滑筋由来の良性腫瘍であり，40代ではもっとも出現率が高い。平滑筋腫は子宮筋層，消化管，皮膚に好発するが，顎口腔領域においては構成筋に平滑筋は含まれておらず，発生することはまれとされている。今回，我々は舌縁部に発生した平滑筋腫を経験したため，文献的考察を加えて報告する。
Leiomyoma is the benign neoplasm derived from smooth muscle tissue and usually affects uterus,
gastrointestinal tracts and skin, whereas oral leiomyoma is unusual entity with less than 150 reported
cases among the English literature. In addition to the histological study, the diagnosis of leiomyoma
requires immunohistochemical examination to show smooth muscle diﬀerentiation. We describe a rarecase of leiomyoma arising in the lingual edge of 25-year-old female. The tumor was encapsulated massmeasuring 18x15x7mm and consisted of bland-looking spindle cells with myxoid stroma. In
immunohistochemical study, tumor cells were positive for α-SMA and desmin, conﬁrming the diagnosisof leiomyoma.

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下口唇にみられたmyxoid tumorの一例
A case of myxoid tumor of the lower lip

杉田 好彦1,2，久保 勝俊1,2，佐藤 恵美子1,2，吉田 和加1,2，水野 進3，
前田 早苗3，加藤 俊男4，前田 初彦1,2
Yoshihiko Sugita1,2, Kubo Katsutoshi1,2, Emiko Sato1,2, Waka Yoshida1,2,
Susumu Mizuno3, Sanae Maeda3, Toshio Kato4 and Hatsuhiko Maeda1,2
1

愛知学院大学歯学部 口腔病理学講座
愛知学院大学 未来口腔医療センター
3
大雄会総合病院 歯科口腔外科
4
大雄会総合病院 臨床病理科1
Department of Oral Pathology, School of Dentistry, Aichi Gakuin University
2
Center for Future Oral Medical Research, Aichi Gakuin University
3
Department of Oral and Maxillofacial Surgery, Daiyukai General Hospital
4
Department of Clinical Pathology, Daiyukai General Hospital2

症例：68歳
臨床経過：女性

2011年 2 月中旬ごろ，下顎左側下口唇の腫瘤を自覚し，近在歯科医院を受診。
下口唇腫瘍疑いにて大雄会病院歯科口腔外科を紹介された。初診時，口唇軟部腫瘤は幅17mm，造影CTか
らは腫瘍または膿瘍が疑われた。下唇腫瘍疑いのもと， 3 月24日に腫瘍摘出術が施行された。
既往歴：骨粗鬆症，37年ほど前に卵巣嚢腫切除，2009年12月ごろ下顎左側第二大臼歯抜去後に下唇麻痺の既往あり。
摘出物所見：摘出物は10mm×12mmで薄い線維性の被膜を有し，割面は黄白色の粘液腫状であった。
組織学的所見：全周性にほぼ横紋筋に囲まれた境界明瞭な結節性病変で，粘液腫様基質を背景に異型のみられない紡錐形，多角形あるいは星状の細胞が微細な血管の形成を伴いながら分葉状に増殖し，束状，錯綜配列する部位もみられた。腫瘍の辺縁部では脂肪細胞も認められた。病変周囲には薄い線維性被膜がみられたが，一部では被膜が不明瞭な部位も認められた。免疫染色では，S-100, Vimentin, CD34陽性，
pankeratin, CD68, Desmin, NSE, α-SMA陰性であった。
検討事項：病理組織学的診断
A 68-year-old female patient had noticed swelling at the lower lip. Clinical examination showed a softmass located in the lower lip, measuring 10mm×12mm. The lesion was well demarcated, tender topalpation, and covered by normal tissue. The clinical diagnosis of a tumor, the mass was surgicallyremoved. Histologically, the lesion showed it to be composed of spindle and stellate cells in a
myxomatous substance. Some area of the lesion at the periphery was composed of some adipocytes.
Tumor cells were positively stained for S-100 protein, vimentin, and CD34, and negatively for pankeratin,
CD68, desmin, NSE and α-SMA.

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Carcinoma cuniculatum の免疫組織化学的研究

Immunohistochemical study of carcinoma cuniculatum-subtype of oral squamouscell carcinoma
孫 燕1，久山 佳代1，Burkhard Arne2，山本 浩嗣1
Yan Sun1, Kayo Kuyama1, Arne Burkhard2 and Hirotsugu Yamamoto1
1

日本大学松戸歯学部 口腔病理講座
Nihon University Graduate School of Dentistry at Matsudo, Department of Oral Pathology
2
Pathologie-Praxis Reutlingen
1

Purpose: Carcinoma cuniculatum (CC) is a distinct variant of oral squamous cell carcinoma characterizedwith keratin filled crypts and cuniculatum architecture which are unique and different from othersubtypes. The immunohistochemical analysis of CC was rare. Methods: The present series included 15
patients. The immunohistochemical study of Ki-67, p53, p63, and cytokeratins were performed. Results:
CC was low expressed in p53 and Ki-67. High expression of p63 in the basal and suprabasal cells
consisted with unique architecture of CC. CC was high positive in CK10 while low expressed or negative
in CK13 and CK17. Conclusion: CC is a well-diﬀerentiated variant.

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舌のlarge cell neuroendocrine carcinomaの１例

A case of large cell neuroendocrine carcinoma of the tongue
河合 繁夫1，逢坂 竜太2,3，内田 育宏2
Shigeo Kawai1, Ryuta Osaka2,3 and Ikuhiro Uchida21

国立国際医療研究センター病院 中央検査部 臨床病理室
がん・感染症センター 都立駒込病院 歯科口腔外科
3
東京歯科大学 口腔外科学講座
1
Pathology Division of Clinical Laboratory, National Center for Global Health and Medicine
2
Department of Dentistry and Oral Surgery, Tokyo Metropolitan Cancer and Infectious diseases
Center Komagome Hospital3
Department of Oral and Maxillofacial Surgery, Tokyo Dental College
2【緒言】Neuroendocrine carcinoma（NEC）はさまざまな臓器に発生しうる稀な癌腫で，なかでもlarge
cell neuroendocrine carcinoma（LCNEC）は比較的稀な亜型である。今回我々は極めて稀な舌のLCNECの１例を経験したので報告する。
【症例】60歳代 男性。【現病歴】 2 年前から左舌部に潰瘍を自覚したが放置。潰瘍と疼痛が増悪し，都立駒込病院歯科口腔外科を受診した。
【口腔内所見】左舌縁部に 8 × 4 cm大の潰瘍・壊死を伴う腫瘤性病変を認めた。
【画像所見】CTにて左舌に80×33mm大の淡く造影される不整な腫瘤を認め，両側顎下部に最大13mm大の腫大リンパ節が散見された。肺を含めて他臓器に異常所見は認められなかった。
【処置】生検にて低分化扁平上皮癌が疑われ，5-FU+CDDPによる術前化学療法を１クール施行後，舌全摘・左全頸部郭
清・右上頸部郭清，副咽頭腔郭清・遊離腹直筋皮弁再建術を施行した。
【病理所見】好酸性の細胞質を有する多角形から紡錘形の異型細胞が，不整な充実性胞巣あるいは索状構造を示して増殖・浸潤していた。
腫瘍細胞は粗糙なクロマチンと明瞭な核小体を有していた。胞巣辺縁では腫瘍細胞はしばしば柵状配列を示し，索状増殖部分ではリボン状を呈していた。またときにロゼット様構造も認められた。核分裂像が多く見られ（約30ヶ/10HPF），著明な凝固壊死を伴っていた。角化や細胞間橋あるいは腺腔形成や粘液産生は認められなかった。腫瘍は所々で粘膜被覆扁平上皮と連続していたが，扁平上皮癌の成分は確認できな
か っ た。 免 疫 組 織 化 学 的 に， 腫 瘍 細 胞 は A E 1 / A E 2（+），3 4 β E 1 2（−），c h r o m o g r a i n A（+），
snaptophysin（+）を示した。CK20では核周囲のドット状の陽性像は認められなかった。リンパ節に転移は認められなかった。改めて生検材料を見直したところ，形態学的にも免疫組織化学的にも手術材料とほぼ同様の所見であった。以上の所見から舌原発のLCNECと診断した。
Neuroendocrine carcinoma (NEC) is a rare neoplasm that may occur in various organs. Large cell
neuroendocrine carcinoma (LCNEC) is a subtype of NEC. In oral cavity, LCNEC is extremely rare. We
report a case of LCNEC of the tongue. A man of 60's admitted to our hospital with the tumor of the
tongue. The patient underwent surgical resection after neoadjuvant chemotherapy. Histologicalexamination revealed the tumor was composed of atypical cells forming nests and cords with necrosis,
rosette formation, and peripheral palisading pattern. Immunohistochemically, tumor cells were positive
for AE1/AE3, chromograninA and synaptophysin. The tumor was diagnosed as LCNEC.

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パノラマX線写真で唾石様の像を示した広範な骨化を伴う毛母腫の１例
Pilomatricoma with extensive ossiﬁcation mimicking a salivary stone in a
panoramic photograph: a case report

清宮 弘康1，山本 哲彰1，石川 文隆2，靍岡 祥子1，宮本 郁也1，山下 善弘1，
松尾 拡2，高橋 哲1
Hiroyasu Kiyomiya1, Noriaki Yamamoto1, Ayataka Ishikawa2, Shoko Tsuruoka1,
Ikuya Miyamoto1, Yoshihiro Yamashita1, Kou Matsuo2 and Tetsu Takahashi11

九州歯科大学生体機能科学専攻 口腔顎顔面外科学講座 形態機能再建学分野
九州歯科大学健康促進科学専攻 生命科学講座 口腔病態病理学分野
1
Division of Oral and Maxillofacial Reconstructive Surgery, Department of Oral and Maxillofacial
Surgery, Kyushu Dental College
2
Division of Oral Pathology, Department of Biosciences, Science of Health Improvement, Kyushu
Dental College
2

緒言：毛母腫は若年者の顔面，頭部に好発する毛母，毛幹への分化を示す良性腫瘍で，組織学的には陰影細胞と好塩基細胞から構成されるが，陳旧化すると陰影細胞の割合が増加し，石灰化，骨化がみられる。
今回，われわれはパノラマX線写真で唾石様の像を示した広範な二次性骨化を伴う毛母腫を経験したので報告する。
症例：56歳，女性。幼少時より右側頬部の腫瘤を自覚するも明らかな増大傾向を認めなかったため放置していた。近歯科医院にて歯科治療時にパノラマX線写真を撮影したところ，右側下顎枝下縁部に不透過像を認め唾石が疑われたため当院を紹介受診した。初診時，口腔内に唾石を確認できなかったが，右側下顎枝下縁部皮下に腫瘤を触知し同部の皮膚に色素沈着を認めた。CTでは同部皮下に境界明瞭な不透過像を認めた。頬部良性腫瘍疑いにて局所麻酔鎮静下に腫瘍摘出術が施行された。腫瘍は6x6mm大，乳白色，骨様硬で周囲組織との癒着を示さず容易に摘出できた。脱灰後に標本を作製したところ，腫瘍は海綿骨様小片
で骨梁を形成する骨組織に連続して陰影細胞と少数の好塩基細胞が認められ，陰影細胞周囲には異物型多核巨細胞が散見された。骨梁間には通常の海綿骨と同様の線維脂肪髄がみられた。以上の所見から陳旧化
し広範な二次性骨化を伴う毛母腫と診断した。現在，術後 1 ヶ月であるが再発は認めず経過は良好である。
Although calcification is common in pilomatricoma, it is rare that all tumors show ossification. We
report a case of pilomatricoma with extensive ossification in a 56-year-old woman. The tumor wasobserved in the subcutaneous part of her right cheek with skin pigmentation. In a panoramic
photograph, the tumor appeared similar to a salivary stone. Histopathologically, the excised specimen
showed that the tumor consisted of cancellous bone with ﬁbro-fatty bone marrow. Some tumor cells,such as shadow cells with a few basaloid cells, were observed over the underlying trabecular bone. The
one-month post-operative follow-up showed good response to treatment.

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Mast cell and myofibroblast in denture-related fibrous hyperplasia
Misa Kiuchi1, Yasuhiro Okazaki2, Naoyuki Matsumoto2 and Kazuo Komiyama2
1

Department of Partial Denture Prosthodontics, Nihon University School of Dentistry
Department of pathology, Nihon University School of Dentistry2

Denture-related fibrous hyperplasia (DRFH, so-called denture fibroma) is a non-tumor condition, is often
found in the denture edge. This lesion is relatively common disorder in varied size, the lesion composed offibrous tissue over growth. However, precise mechanism of the exforic lesion development is poorly
understood. Recent contemporary finding showed that the presence of mast cells and myofibroblasts areprobably contributes to wound healing and organ fibrosis. We have examined the presence of two types ofmast cells (MT and MT/C) and myofibroblasts in the denture-related fibrous hyperplasia to investigate itsrole in progression of the lesion.
The serial sections from surgically excised 33 cases of DRFH were stained immunohistochemically fortryptase and chymase to determine subpopulation density and distributions. In addition, alpha smoothmuscle action is also stained to identify the myofibroblast differentiation.
The samples revealed that the female-mail ratio was 5:3, and the age distribution at age 58 to 82 years, theaverage was 69.7. A 68% of patients wear the full denture. The lesion size varied from 5mm to 85cm indiameter.
The lesion split into two parts such as granular layer and fibrotic layer, the presence of both MT and MT/
C were clearly higher in the granular layers. Moreover, clearly high numbers of MT presented than MT/C.
Myofibroblast defferntiation was identified 40% of the lesion, where located close to granular layers.
The results suggest that mast cells subpopulations may contribute to DRFH development. The
differentiation of myofibroblast was recognized DRFH, indicates remodeling of extracellular matrix.

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抗リウマチ薬MTXに関連した上顎歯肉潰瘍の 1 例

A case of maxillary gingival ulcer in relation to the Antirheumatic drug (MTX)柬理 頼亮，大窪 泰弘，岡田 康男
Yoriaki Kanri, Yasuhiro Ookubo and Yasuo Okada
日本歯科大学新潟生命歯学部 病理学講座
Department of Pathology, School of Life Dentistry at Niigata, The Nippon Dental University

慢性関節リウマチ（RA）の薬物療法においてmethotrexate（MTX）は第一選択薬として用いられている。
MTXは元々抗癌剤で，顎口腔領域では骨肉腫などに使用されているが，骨髄抑制，肝障害，間質性肺炎の副作用がある。今回，リウマトレックスカプセル 内服中に歯肉潰瘍を認めた 1 例を経験したので報告する。患者80歳，男性。主訴：さし歯が取れたことを理由に来院。その際 7 口蓋側歯肉に異常はみられなかった。既往歴：RAのためリウマトレックスカプセルを，また腎疾患に対してプレドニゾロンを内服中。原
病歴： 6 7 口蓋部歯肉に発赤が出現，含嗽剤を処方するも改善せず，潰瘍が出現した。 3 日後には潰瘍の範
囲拡大がみられ，薬剤性潰瘍や悪性腫瘍が疑われ，生検が施行された。病理組織学的に潰瘍部や周囲の上皮が残存する部位の粘膜固有層にリンパ球や形質細胞，好酸球の浸潤している中に大型リンパ球様細胞が散見されるが，DLBCLは否定的でMTX内服中止後に潰瘍が改善したため，以上より，MTXによる骨髄抑制の前駆症状としての歯肉潰瘍と考えた。
免疫染色結果CD3ε:（−）, CD20:（+）, CD79:（+）, Bcl-2:（+）, CD45RO:（+）, CD56:（+）, Ki-67:（+）（40%/20倍， 1 視野当たり）, CD68:（+）
Although methotrexate (MTX) is used in several medical specialties including dermatology,
rheumatology, and oncology, drug-induced mucocutaneous ulcerations rarely are reported. We present
oral event related to dose methotrexate in RA patient. A case is 80-year-old male with RA who take
MTX and prednisolone. He revealed ulcer of the left maxillary gingiva. Histopathlogically, erosions andulcerations on his disappearanced oral epithelium area and lymphocyte, plasma cell and eosinocyte
become highly inﬁltrate in subepithelial area. In this case, we speculated that ulceration of oral mucosa
may began with prodromal symptoms of bone-marrow suppression . MTX therapy induces impairments
in oral mucosa.

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成人女性に生じた口腔原発非流行地型 Burkkittʼs lymphoma の１例
A case of primary oral sporadic-Burkkitt's lymphoma in an adult female

菊池 建太郎1，井上 ハルミ1，宮崎 裕司1，井出 文雄1，坂下 英明2，草間 薫1
Kentaro Kikuchi1, Harumi Inoue1, Yuji Miyazaki1, Fumio Ide1, Hideaki Sakashita2
and Kaoru Kusama1
1

明海大学歯学部 病態診断治療学講座 病理学分野
明海大学歯学部 病態診断治療学講座 第二口腔外科学分野
1
Division of Pathology, Department of Diagnostic & Therapeutic Sciences, Meikai University School of
Dentistry2
Division of Second Oral and Maxillofacial Surgery, Department of Diagnostic & Therapeutic Sciences,
Meikai University School of Dentistry2

Burkkittʼs lymphoma（BL）は節外性を主体とする高悪性度リンパ腫であり，アフリカやニューギニアにみられる流行地型（endemic BL），欧米やわが国でみられる非流行地型（sporadic BL），さらにHIVもしくは移植後にみられる免疫不全関連型（immunodeﬁciency-associated BL）の 3 型がある。Sporadic BLは悪性リンパ腫全体の 1 − 2 %程度で，その多くが小児に発症するが，成人発症例は希であり，かつ口腔領域に生じた報告はほとんど認められない。
今回，我々は61歳日本人女性の口腔に生じたBLの１例を経験したので報告する。
【症例】61歳，女性。
【主訴】左側下口唇と下顎臼歯部の知覚鈍麻および鈍痛。
【現病歴】本年 1 月，左側
下口唇の知覚鈍麻と下顎臼歯部の鈍痛を自覚し近歯科医院を受診。精査目的に当大学病院口腔外科を紹介により受診。
【現症】初診時，口腔内・外およびオルソパントモグラムに異常所見は認めず，感染症を疑い抗生剤投与を行った。数週間後，左側耳前部皮下および口腔内頬粘膜下に急速な腫脹・増大が認められ，開口障害を呈した。【画像所見】CTで左側咬筋・内側翼突筋部に比較的境界明瞭な筋と同程度のdensityを示す病変が認められた。【臨床診断】悪性リンパ腫の疑い。生検が施行された。【病理組織学的所見】筋線
維束間にびまん性融合状で密に破壊性浸潤を示す異型リンパ球が認められ，starry sky appearanceを伴っていた。
【免疫組織学的所見】異型リンパ球は，CD20, CD79a, CD10およびKi-67（ほぼ100%）陽性。TdT,
bcl-2, CyclinD1, CD3, CD5, CD30およびEBV-LMP-1陰性。【病理組織診断】malignant lymphoma, mostcompatible with Burkitt's lymphoma.
【経過】某医科大学血液内科に転院。R-hyper CVAD/R-HD MTX AraC交替療法で加療を開始し，現在，腫瘍は著明に縮小している。
【遺伝子検査】c-myc転座95％陽性。
We report a case of sporadic-Burkkittʼs lymphoma of the oral cavity in a 61-year-old Japanese female.
She was aware of paresthesia and dull pain in the lower lip and mandibular posterior tooth. Rapid
swelling of left face with trismus was noted. CT showed a mass lesion in masseter and medial pterygoid
muscle area. Histopathologically, tumor cells were medium-sized lymphoid cells and showed a diﬀuse
monotonous pattern with “starry sky” appearance. Immunohistochemically, the tumor cells were positive
for CD20, CD79a, CD10, and Ki67 (nearly 100%). In genetic test, c-MYC translocation was positive (95%).

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Areca nut extract reduces the phagocytic function of human peripheral
blood mononuclear cells
Lien-yu Chang1,2,3, Tzu-husan Yu1,2, Yi-chun Lin1,2, Shan-ling Hung1,2,3 and Yu-lin Lai1,21Institute of Oral Biology, Dental Department, School of Dentistry, National Yang-Ming University
Department of Stomatology, Taipei Veterans General Hospital3
Department of Teaching and Research, Department of Dentistry, Taipei City Hospital2

Areca chewing, a popular oral habit in Taiwan and some Asia countries, is highly associated with several
oral diseases. Inflammation is known to modulate and enhance the progression of diseases. Extract of arecanut (ANE) enhances the production of inflammatory mediators by immune cells, but reduces the activationof T cells. The study was to determine the possible effects of ANE on the phagocytic activity of humanimmune cells, peripheral blood mononuclear cells (PBMC). Flow cytometry and confocal laser scanningmicroscopy were the methods used in this research. The results revealed that the uptake of both opsonized(C-Beads) and non-opsonized (Beads) fluorescent microspheres by PBMC, especially the mononcytes gate,
was dose-dependently reduced in the cell group with 24-h ANE treatment, but not for that with 4-h ANEtreatment. The levels of internalized fluorescent microspheres in monocytes decreased significantly when 20
ug/ml of ANE was used. Furthermore, the inhibitory effects of ANE on the phagocytic function of PBMC
could be reversed by PI3K inhibitor (LY294002) and GSK-3 inhibitor X, but not by the antioxidant DPI.
Taken together, ANE impaired the phagocytic function of human PBMC might be via the signaling
pathways such as PI3K and GSK, but not via the generation of reactive oxygen species. Alterations in the
defensive properties of PBMC by ANE might promote colonization of microorganisms and reduce
phagocytic clearance during inflammation, and this could result in oral infection and prolonged
inflammation.

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Expression of hBD-2 and infiltration of T lymphocytes in chronic
hyperplastic candidiasis
So-young Choi, Dae-woong Yoon, Young-ah Cho, Hye-jung Yoon, Seong-doo Hong, Jae-il Lee
and Sam-pyo Hong
Department of Oral Pathology, School of Dentistry, Seoul National University
Objectives: Chronic hyperplastic candidiasis (CHC) is characterized by epithelial hyperplasia of the oral
mucosa associated with candidal hyphae. The immune status of host is one of the factors that induce
clinically evident candidal infection. Host defense mechanisms include inflammatory cells, epithelial
barrier, and antimicrobial peptides such as human beta-defensin-2 (hBD-2). In the present study, weinvestigated the densities of CD4+/CD8+ T lymphocytes and hBD-2 expression of epithelial cells in CHC.
Methods: Immunohistochemical staining was performed on 10 cases of CHC using CD4, CD8 and hBD2. Ten specimens of chronic mucositis were selected for comparison, and went through the same
examination.
Results: hBD-2 was expressed in the stratum granulosum and stratum spinosum of 7 CHC patients, while
the epithelium of chronic mucositis did not demonstrate the hBD-2 expression except for one case. Also,hBD-2 expression was stronger when the hyphae invaded the upper stratum spinosum (P=.019). BothCHC and chronic mucositis showed the infiltration of CD4+ and CD8+ T lymphocytes. There was nodifference in the densities of lymphocytes recruited under the epithelium between the two conditions.
However, the densities of intraepithelial CD8+ T lymphocytes were lower in the patients expressing hBD-2(P=.018), suggesting that the ability of CD8+ T cells to enter the epithelium and target the pathogenic
hyphae was decreased in CHC.
Conclusion: Increased hBD-2 expression was significantly associated with the candidal infection, while notpromoting the cell-mediated immune reaction in CHC.

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miR-214はアデノウイルスの増殖に抑制的にはたらく

miR-214 acts as a repressor of adenovirus proliferation by inactivating E1A.
松田 彩1，北村 哲也1，樋田 京子2，東野 史裕1，進藤 正信1
Aya Matsuda1, Tetsuya Kitamura1, Kyoko Hida2, Fumihiro Higashino1 andMasanobu Shindoh1
1

北海道大学大学院歯学研究科 口腔病理病態学教室
北海道大学大学院歯学研究科 血管生物学教室
1
Department of Oral Pathology & Biology, Hokkaido University Graduate School of Dental Medicine
2
Department of Vascular Biology, Hokkaido University Graduate School of Dental Medicine
2

アデノウイルスはヒト細胞に感染し，急性気道疾患や流行性角結膜炎などを起こすが，この際，アデノウ
イルス初期転写遺伝子E1Aが最も早期に発現し，E1Aは他の初期遺伝子の発現を誘導し，ウイルスの感染・複製に最も重要な役割を演じていることが知られている。miRNAはノンコーディングRNAの一種で，哺乳動物のゲノムには1000種類程のmiRNAがコードされていることや，哺乳動物の遺伝子の少なくとも30%はmiRNAの発現により制御されていることが推定されている。標的遺伝子の一部領域と相補的配列をもつmiRNAが標的mRNAの分解や翻訳抑制に働くことが示され，発がん等に関与することが知られている。しかし，ウイルスの細胞感染とmiRNAについての検索はほとんどなされていない。今回，ヒトアデノウイルスの増殖効率におよぼすmiRNAの役割について検索を行った。
ヒトアデノウイルス 5 型（hAd5)）をHeLa細胞とSaos-2細胞に感染させたところ，Saos-2でのhAd5増殖効率は有意に低かったが，ウイルスレセプターCARの発現はHeLaとSaos-2で有意な差はみられなかった。この際，hAd5E1A mRNAの発現に有意な差はみられなかったが，E1AタンパクはSaos-2で有意に発現低下がみられた。in silico検索でhAd5 E1Aを標的とする可能性があるmiRNAを数種類同定し，その中のmiR214の発現はSaos-2で有意に高いことが示された。E1AmRNA 3ʼUTRを組み込んだルシフェラーゼレポー
タープラスミドの転写効率は，Saos-2で有意に抑制された。さらに，miR-214をHeLaに強制発現しアデノウイルスを感染させると，E1Aタンパクは有意に発現が低下した。
以上の結果は，miR-214がアデノウイルスの感染に抑制的に働き，miR-214をもつ細胞のアデノウイルス感
染に対する防御機構の一端を担っていることを示唆するものであった。
Adenovirus early-transcribed gene E1A plays the most important role in virus infection and duplication.
We have identiﬁed miR-214 that might assume hAd5 E1A by in silico experiment. hAd5 was introduced
in HeLa and Saos-2 cells, and adenovirus productivity was lower in Saos-2 cells although the CAR, an
adenovirus receptor, was expressed in both cells. miR-214 was highly expressed in Saos-2, andexpression of luciferase reporter gene fused with E1A 3ʼ UTR was decreased in Saos-2. These results
indicate that cellular miR-214 is capable of inhibiting adenovirus replication by degrading E1A mRNA.

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Adenovirus E4orf6/7 activates ASPP1 that induces apoptosis
Mohammad Towfik Alam1,2, Shigeru Yamano2, Tetsuya Kitamura1, Aya Matsuda1,
Fumihiro Higashino1, Motoyasu Nakamura2 and Masanobu Shindoh1
1

Department of Oral Pathology and Biology, Graduate School of Dental Medicine, Hokkaido University
Department of Oral Radiology, Graduate School of Dental Medicine, Hokkaido University

2

E4orf6/7 is one of the early gene products of human adenovirus. E4orf6/7 is known to form a stablecomplex with E2F transcription factor to transactivate both viral and cellular genes. It is suggested that thisfunction is partly responsible for the induction of p53-dependent apoptosis. However, none of the target
gene for E4orf6/7 to induce apoptosis has been identified to date.
ASPP1, apoptosis-stimulating protein of p53, is one of the ASPP family recently identified to induce
apoptosis in p53-dependent manner. Promoter analysis revealed that E2F binding sites exist in ASPP1
promoter region, and E2F was shown to increase ASPP1 expression.
We investigated the effects of adenovirus E4orf6/7 on E2F and ASPP1 mediated cellular apoptosis. Wildtype E4orf6/7 transfection into 293T cells induced PARP cleavage. When the wild-type or C-terminus
conserved E4orf6/7 expression plasmids were transfected, increased expression of ASPP1, and its nuclear
localization were observed. However, little upregulation and nuclear localization of ASPP1 were seen in
C-terminus deleted E4orf6/7 mutant transfectants. Our results suggested the significance of E4orf6/7 in
ASPP1 mediated apoptosis.

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Immunohistochemical expression of HSP27 in the mouse periodontal
tissues due to orthodontic mechanical stress
Rina Muraoka1,2, Keisuke Nakano1,3 and Toshiyuki Kawakami1,3
1

Hard Tissue Pathology Unit, Matsumoto Dental University Graduate School of Oral Medicine
Department of Orthodontics, Matsumoto Dental University School of Dentistry3
Hard Tissue Pathology Unit, Matsumoto Dental University Institute for Oral Science2

Purpose: Immunohistochemical (IHC) expression of HSP27 and p-HSP27 were simultaneously examined
after subjecting the periodontal tissues to mechanical stress by orthodontic movement. Materials andmethod: The Waldo method of inducing mechanical stress-load in mouse periodontal tissues was followed.
The maxillary molar with the periodontal tissues were removed were examined by IHC. Results: In the 10
minutes group, HSP expression localized in the PDL fibroblasts in the tension side was slightly stronger
compared to the control group. In the 20 minutes group, cytoplasmic IHC expression of HSP27 on the
PDL fibroblasts seen in the tension and pressure sides was stronger than the 10 minutes group. In the 3hours group, the PDL fibroblasts and cementoblasts in the tension side strongly expressed HSP27. At thispoint, p-HSP27 expression showed no difference in strength. In the 9 hours group, HSP27 was strongly
expressed in the cytoplasm of PDL fibroblasts and cementoblasts as well as in osteoblasts. In this period,
p-HSP27 started to become strong in the “pressure” side. In the 24 hours group, HSP27 was strongly
expressed in the “tension” side by the entire PDL fibroblasts and cementoblasts as well as by osteoblasts.
Conclusion: The study suggests that HSP27 has been closely involved in the repair of tissue to maintainhomeostasis of the periodontal tissues. Also, the data adds to the existing trend in role of Msx2 and Runx2
in the activation of osteoblasts during bone formation suggesting the role of HSP27 as a molecularchaperone during orthodontic treatment induced by mechanical stress.

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Promoting effect of mechanical stress to transplanted bone marrowderived cell migration into periodontal tissues
Mihoko Tomida1, Hidetsugu Tsujigiwa2, Keisuke Nakano3, Rina Muraoka3,4, Hitoshi Nagatsuka2
and Toshiyuki Kawakami3
1

Department of Oral Physiology, Matsumoto Dental University School of Dentistry
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry & Pharmaceutical
Sciences, Okayama University
3
Hard Tissue Pathology Unit, Matsumoto Dental University Graduate School of Oral Medicine
4
Department of Orthodontics, Matsumoto Dental University School of Dentistry2

Background: Bone marrow-derived cells have abilities of cell migration and differentiation into teeth andrelated tissues/organs, especially into periodontal ligament fibroblast cells. We examined the effect oforthodontic mechanical stress to the transplanted bone marrow-derived cell migration into periodontal
tissues. Materials and methods: Bone marrow-derived cells from green fluorescence protein (GFP)
transgenic mice were transplanted into C57BL/6 immunocompromised recipient mice, which had
undergone 10Gy of lethal whole-body irradiation. After successful transplantation, the mice received
orthodontic mechanical stress using the Waldo method in 5 weeks. After that, the regional tissues were
immunohistochemically analyzed using a Dako Envision+Kit-K4006 (Dako, Glostrup, Denmark) and a
primary anti-GFP-polyclonal rabbit antibody (#598; 1/500; MBL, Nagoya, Japan). Results: The
immunohistochemistry revealed that GFP-positive cells were detected in the periodontal tissues, both in theexperimental and control specimens. In the experimental group, there were numerous GFP-positive cells
appearing in the experimental periodontal tissues which received intermittent stimulation of orthodontic
mechanical stress, but there were few GFP-positive cells in the control specimens. Thus, these data indicatedthat orthodontic mechanical stress acts as a possible promoting factor of transplanted bone marrow-derived
cell migration into periodontal tissues, and of differentiation to fibroblasts and capillary endothelial cells.
Although the clinical implications of adult bone-marrow cell plasticity are still unclear, focusing on themechanisms in which cell ascertains fate in human is likely to benefit the areas of cell therapy andregenerative medicine. Conclusion: This phenomenon suggests that the possibility of short-term
orthodontic treatment with of transplantation of bone marrow cells.

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Strawberry gingivitis as the first presenting sign of Wegener's
granulomatosis: Report of a case
Keisuke Nakano1,7, Chong Huat Siar2, Kian Boon Yeo3, Hitoshi Nagatsuka4,
Hidetsugu Tsujigiwa5 , Kok Han Ng6 and Toshiyuki Kawakami7
1

Department of Oral Pathology, Matsumoto Dental University School of Dentistry
Department of Oral Pathology, Oral Medicine & Periodontology, Faculty of Dentistry, University of Malaya
3
Gleneagles Intan Medical Centre
4
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry & Pharmaceutical
Sciences, Okayama University
5
Department of Oral Physiology, Matsumoto Dental University School of Dentistry6
Formerly Unit of Stomatology, Cancer Research Centre, Institute for Medical Research
7
Hard Tissue Pathology Unit, Matsumoto Dental University Graduate School of Oral Medicine
2

Case report: A 50 year-old male was referred to the Oral Medicine Clinic, University of Malaya for
management of unusual gingival lesions. Accordingly, the patient first attended the Primary Dental Care
Unit here for a routine dental check-up. During the course of intraoral examination, large lobulated
purplish-red swellings were found affecting the labial gingival mucosa extending from the distal of the rightmaxillary first premolar to the distal of the left maxillary central incisor. Histopathology: Histopathology
showed covering parakeratinized stratified squamous epithelium with an irregular lobular surface andexhibiting pseudoepitheliomatous hyperplasia. In the underlying connective tissues, a granulomatous
inflammatory response was observed. A diffuse mixed inflammatory cell infiltrate comprising mostly
neutrophils which formed subepithelial abscesses and smaller numbers of eosinophils, plasma cells andlymphocytes was present. Scattered multinucleated giant cells, some resembling Langhans-type giant cellswith horse-shoe arrangement of their nuclei, were occasionally seen. However necrotizing vasculitis was notevident. Special stains were negative for fungi and mycobacterial bacilli. Based on the findings, a diagnosis
of Wegener's granulomatosis was made. Management: The patient was referred to the Medical Department
for a systemic work-out. Investigations yielded normal indices for haemoglobin, complete blood count,erythrocyte sedimentation rate and urine analysis. Chest X-rays were also normal. ANCA test was notavailable. A decision was taken to treat the patient with prednisolone 60 mg daily and cyclophosphamide
100mg daily. At one and three weeks post-treatment, a dental evaluation showed that the gingival swellings
had completely resolved. Subsequent reviews were uneventful.

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Notch signaling proteins in primary and recurrent chondrosarcoma of thejaw: A case report
Kok Han Ng1, Chong Huat Siar2, Lwin Oo Aung3, Keisuke Nakano4, Hidetsugu Tsujigiwa5 ,Hitoshi Bagatsuka5 and Toshiyuki Kawakami4
1

Formerly Unit of Stomatology, Cancer Research Centre, Institute for Medical Research
Department of Oral Pathology, Oral Medicine & Periodontology, Faculty of Dentistry, University of Malaya
3
Department of Oral & Maxillofacial Surgery, Faculty of Dentistry, University of Malaya
4
Hard Tissue Pathology Unit, Matsumoto Dental University Graduate School of Oral Medicine
5
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry & Pharmaceutical
Sciences, Okayama University
2

Background: Aberrant Notch activity has been implicated in numerous human diseases including cancers;
however its role in chondrogenic tumors has not been clarified. Materials and methods: Tissue samples
from a case of primary chondrosarcoma of the maxilla and its recurrent tumor were examined
immunohistochemically for Notch1-4 and their ligands (Jagged1, Jagged2 and Delta1) expression.
Immunoreactions were performed using the Dako Envision Kit. Results: Both primary and recurrent
tumors were histopathologically diagnosed as conventional hyaline chondrosarcoma (WHO Grade I).
Hypercellular tumor areas strongly expressed Notch3 and Jagged1 in spindle and pleomorphic cells
suggesting up-regulation of these protein molecules at sites of tumor proliferation. Expression patterns weredistinct with some overlap. Differentiated malignant and atypical chondrocytes demonstrated variable
expression levels of Jagged1, and weak to absent staining for Notch1, 4 and Delta1. Protein
immunolocalization was largely membranous and cytoplasmic, sometimes outlining the lacunae ofmalignant chondrocytes. Hyaline cartilage demonstrated a diffuse or granular precipitation of Jagged1
suggesting presence of soluble Jagged1 activity at sites of abnormal chondrogenesis. No immunoreactivity
for the other Notch members was observed. Calcified cartilage was consistently Notch-negative indicating
down-regulation of Notch with cartilage maturation. Stromal components namely endothelial cells andfibroblasts variably expressed Notch1, 3 and Jagged1 but were mildly or non-reactive for the othermembers. Conclusion: The results indicate that Notch signaling pathway may participate in cellulardifferentiation and proliferation in chondrosarcoma. Findings implicate Notch3 and Jagged1 as key
molecules that influence the differentiation and maturation of cells of chondrogenic lineage.

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Low level laser therapy at acupuncture points in temporomandibular joint
disorderYu-feng Huang1,2, Chuan-hang Yu1,2, Yu-hsien Lee2 and Jung-chih Lin3
1

College of Oral Medicine, Chung Shan Medical University
Oral Medicine Center, Chung Shan Medical University Hospital3
Department of Integrated Chinese and Western Medicine, Chung Shan Medical University Hospital2

Introduction: Low level laser therapy (LLLT) has been used to treat temporomandibular joint disorder(TMD) for years. In this study, we reported the clinical outcomes of 6 patients with TMD treated with
LLLT at acupuncture points.
Materials & Methods: Six (6) TMD patients were treated with diode K-Laser (wavelength 800 nm) at 4
acupuncture points once a week. The selected acupuncture points were ipsilateral points at ST6 (Jiache),ST7 (Xiaguan), one ashi point, and a contralateral point at LI4 (Hegu). The treatment outcome was
evaluated with a visual analog scale (VAS) at each appointment.
Results: All 6 patients exhibited free of pain after an average of 4 (rage 2-7) visits. In addition, VAS
evaluation showed an average of 38% (range 9-67%) pain reduction after each LLLT treatment. There is norecurrence of pain of the 6 patients after a follow up period of 2-4 months.
Conclusion: LLLT at acupuncture points is an effective alternative treatment for TMD.

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口腔扁平上皮癌を対象とした新規細胞診用ブラシキットの開発にむけて
A comparative study of seven devices used for oral squamous cell sampling

伊川 裕明1，山科 光正1，片倉 朗1,2，山根 源之1,2，田中 陽一3
Hiroaki Ikawa1, Mitsumasa Yamashina1, Akira Katakura1,2, Ganyuki Yamane1,2
and Yoichi Tanaka31

東京歯科大学 オーラルメディシン・口腔外科学講座
東京歯科大学 口腔がんセンター
3
東京歯科大学市川総合病院 臨床検査科病理1
Department of Oral Medicine, Oral and Maxillofacial Surgery, Tokyo Dental College
2
Oral Cancer Center, Tokyo Dental College
3
Clinical Laboratory, Division of Surgical Pathology, Ichikawa General Hospital, Tokyo Dental College
2【目的】近年，口腔癌の早期発見において歯科診療所での細胞診の有用性が報告されはじめている。一方，口腔での細胞診においては，婦人科領域と比較して細胞数が少ない点が問題としてある。一般歯科診療所
での細胞診の普及のためには，このような問題を手技および器具の面から解決する必要がある。本研究の目的は，細胞採取用のブラシを新たに開発し，画一的に細胞の採取が可能となる細胞採取ブラシが開発されることにより，任意の歯科医師が細胞診を行っても診断に十分な細胞採取を可能とすることである。
【方法】模擬患者の口腔内各部位より細胞を採取し，採取された細胞数をカウントする。
口腔内細胞採取部位は口蓋，上顎歯肉，頬粘膜，下顎歯肉，舌，口底前方部の 6 カ所よりそれぞれ細胞採取を行った。使用するブラシは以下の通りとする。
1 . Cytobrush Plus GT, CooperSurgical, INC
2 . EndoCervex-Brush, 原田産業株式会社
3 . 歯間ブラシ，各サイズ ライオン株式会社
4 . 細胞診用ブラシ（仮） 当講座教授片倉朗およびライオン株式会社協同開発中【結果】口腔内各部位で採取される細胞数は，サイトブラシプラスおよび細胞診用ブラシが他のブラシと比較し多く細胞採取が可能であった。両ブラシ共に柄の形態が直線的であり，細胞を採取する際にブラシの回転を容易に行う事が出来る。さらにブラシ部分の針金は口腔内各箇所の解剖学的形態に合わせる事が可能となっている。また，ブラシ部分の毛束が密に設計されており，上記の点から多くの細胞を採取する事が可能であったと考察される。一方で口蓋や上顎歯肉のような凹状の部位から採取された細胞数は多部位と比較して少ない。細胞採取は口腔粘膜性状にも異なるが，口腔癌では表層細胞のみの採取では診断の感度が上がらず，いかにより深層の細胞を採取するかが今後の課題として望まれる。
It has been recently reported that oral brush cytologic examination in private dental clinics is quite
eﬀective to detect oral early cancers. There are many brushes available for the examination which we
can select on the market and under development, but it has not been reported which brush is the mostuseful to gather enough amount of cells for the examination. A purpose of this study is to propose abrush which any dentist can easily collect enough amounts of cells for diagnosis, in order to spread theexamination in our country.

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市川市口腔がん早期発見システムの現状

The current state of the Oral Cancer Detecting system ICHIKAWA Network(OCDSIN)
佐藤 一道1，山科 光正2，野口 沙希2，外木 守雄2，片倉 朗1,2，高倉 克博3，
石井 広志3，長谷川 勝3，山根 源之2，田中 陽一4
Kazumichi Sato1, Mitsumasa Yamashina2, Sunaki Noguchi2, Morio Tonogi2,
Akira Katakura1,2, Katsuhiro Takakura3, Hiroshi Ishii3, Masaru Hasegawa3,
Gen-yuki Yamane2 and Yoichi Tanaka41

東京歯科大学 口腔がんセンター
東京歯科大学 オーラルメディシン・口腔外科学講座
3㈳市川市歯科医師会
4東京歯科大学市川総合病院 臨床検査科病理1
Oral Cancer Center, Tokyo Dental College, Tokyo Dental College
2
Department of Oral Medicine, Oral and Maxillofacial surgery, Tokyo Dental College
3
Ichikawa Dental Association
4
Division of Surgical Pathology, Clinical Laboratory, Ichikawa General Hospital, Tokyo Dental College
2

直視直達が可能な口腔は他臓器と比較し，悪性病変の早期発見が可能な領域である。我々は2007年より開業歯科医院の日常診療において，口腔内を診察し，口腔がんを早期に発見するという目的の，口腔がん早期発見システム（以下OCDSIN）を開始し2008年の本会で報告した。OCDSINでは液状細胞診を利用したが，今回，検出された口腔がん症例を再検討し，システムに関する評価を行なったので報告する。【症例１】73歳，男性，舌扁平上皮癌（T2N0M0）。義歯調整希望で近歯科医院を受診。右舌縁に腫瘤を認め，細胞診を施行（Class V）。その後 2 次医療機関へ紹介となる。【症例２】80歳，女性，舌扁平上皮癌（T3N0M0）。
２年前より左側舌縁腫瘤を自覚。接触痛が強くなり，近歯科医院を受診。同院にて細胞診施行（Class II）。
症状改善なく 2 次医療機関へ紹介となる。
【症例３】94歳，女性，舌扁平上皮癌（T4aN2cM0）。下顎義歯
不適合を主訴に近歯科医院を受診。右舌縁に易出血性，膨隆性の潰瘍を認め細胞診施行（Class II）。潰瘍に変化なく， 2 次医療機関へ紹介となる。【症例４】81歳，女性頬粘膜扁平上皮癌（T2N0M0）。左側頬部
誤咬を主訴に近歯科医院を受診。義歯調整および軟膏塗布を行うも改善認めず細胞診施行（Class V）し，
2 次医療機関へ紹介となる。【症例 5 】68歳，男性，舌扁平上皮癌（T1N0M0）。近歯科医院にて左側舌側縁の白色病変の細胞診施行（Class II）。症状緩解なく 2 次医療機関へ紹介となる。今回の症例はすべて65歳以上であるように，高齢者の口腔がん患者が今後，開業歯科医院を訪れる機会は増えると考える。高齢者においても，治療の肉体的・精神的な負担軽減に，早期発見・治療が重要である。このため開業歯科医
院での口腔がんのスクリーニングは意義がある。本システムでは，明らかな悪性病変はすみやかに 2 次医療機関へ紹介し，何らかの病態に対して，液状細胞診を利用した。細胞診の結果の取り扱いの重要性を再認識するとともに，システムに関わる歯科医師の研修事業はさらに重要な課題であった。
The oral cavity is amenable to both direct visualization and direct palpation by clinicians. Therefore,
malignant tumors in the oral cavity can be detected earlier than other organʼs tumors. We have started
an oral cancer detecting system in routine practice in a private dental clinic since 2007, which wereported at annual meeting of JSOP in 2008. And liquid based cytology is used in this system. In thisstudy we investigated the cases of oral cancer had been detected using the liquid based cytology, andevaluated this system.

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擦過細胞診による白板症経過観察の有効性−Proliferative Verruccous
Leukoplakiaの一例
Usefulness of Oral Exfoliative Cytology as a Follow-up Examination for
Leukoplakia

西久保 周一1，山科 光正1，田中 陽一2，佐藤 一道3，山根 源之1，外木 守雄1，
片倉 朗1,3
Shuichi Nishikubo1, Mitsumasa Yamashina1, Yoichi Tanaka2, Kazumichi Sato3,
Gen-yuki Yamane1, Morio Tonogi1 and Akira Katakura1,3
1

東京歯科大学 オーラルメディシン・口腔外科学講座
東京歯科大学市川総合病院 検査科病理3
東京歯科大学口腔がんセンター
1
Department of Oral Medicine, Oral and Maxillofacial Surgery, Tokyo Dental College
2
Division of Surgical Pathology Clinical Laboratory, Ichikawa General Hospital , Tokyo Dental College
3
Oral Cancer Center, Tokyo Dental College
2【緒言】当院では，非侵襲的な検査の一つとして擦過細胞診を前癌病変のフォローにルーチンに行っている。細胞診は，経時的，連続的に行うことで，診断補助材料としてその有効性が増すことが知られている。
今回，Proliferative Verruccous Leukoplakiaの一例についてその概要を細胞診の結果と併せて報告する。
【患者】初診時，71歳，男性【主訴】義歯の破折【現病歴】初診時，義歯の破折により義歯修理を主訴に来院された。その際に右側舌縁部に白色病変を認め，細胞診（ClassⅡ）施行。その後来院途絶えたが， 4年が経過し，右側舌縁部に違和感を自覚し，再来院となった。境界明瞭，無痛性表面滑択，無痛性の白色病変を認めた。 4 年前と比較し，白色病変の拡大を認めた。細胞診（ClassⅠ）施行し，臨床所見より白板症と診断し，手術計画するも，徐脈頻脈症候群を発症し，ペースメーカー挿入のため，手術延期となった。
その後 2 年が経過し，右側舌縁部の違和感の増悪を主訴に再来院となった。【手術前所見】右側舌縁部に境界明瞭，表面粗造で不染帯を伴う白色病変を認めた。細胞診では，核形不正，核クロマチン濃縮等の異型角化扁平上皮細胞の小集塊を認め，ClassⅣとし，扁平上皮癌が疑われた。
【処置および経過】全身麻酔
下に腫瘍切除術を施行した。手術断端は陰性で，術後の経過は問題なく，再発も認めていない。
【病理組
織学的所見】腫瘍は，Hyperkeratosis の目立つ乳頭状発育を認め，rete ridgeは肥厚し，Verruccous様の形態が目立っていた。異型は軽度で明らかな浸潤像は認めず，確定診断は，Proliferative Verruccous
Leukoplakiaとした。
Development of medical science makes it possible to cure many diseases, but problems which we cannot
solve remain in super aging societies. It is difficult to deal with aged patients suffering from serious
underlying diseases. Such diseases occasionally prevent the patients from undergoing appropriate
medical procedures, especially operations. We report a case that we had to postpone an operation for
Proliferative Verruccous Leukoplakia because of patientʼs atrial ﬁbrillation and bradycardia-tachycardia
syndrome, from the point of view of cytopathology and histopathology.

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口腔擦過細胞診による診断が有効であった早期癌の２例

Oral exfoliative cytology is useful in diagnosing early cancer; report of two cases
吉田 佳史1，山科 光正1，佐藤 一道2，外木 守雄1，片倉 朗1,2，山根 源之1,2，
田中 陽一3
Yoshifumi Yoshida1, Mitsumasa Yamashina1, Kazumichi Sato2, Morio Tonogi1,
Akira Katakura1,2, Gen-yuki Yamane1,2 and Yoichi Tanaka31

東京歯科大学 オーラルメディシン・口腔外科学講座
東京歯科大学 口腔がんセンター
3
東京歯科大学市川総合病院 臨床検査科病理1
Department of Oral Medicine, Oral and Maxillofacial surgery, Tokyo Dental College
2
Oral Cancer Center, Tokyo Dental College
3
Division of Clinical Laboratory, Ichikawa General Hospital, Tokyo Dental College2

侵襲の少ない口腔擦過細胞診は扁平上皮癌に対する有用な診断手段と考える。今回，初診時の肉眼所見では悪性病変の診断が困難であったが，擦過細胞診でclassⅤと診断され，その後の切除検体にて扁平上皮癌の診断に至った 2 例を経験したので報告する。
【症例 1 】55歳，男性。舌扁平上皮癌（T1N0M0）。2011年 1 月に舌の違和感を主訴に当院を受診された。
初診時の所見で右側舌縁部に10mm大の軽度のびらんを認めた。
【症例 2 】57歳，女性。舌扁平上皮癌（T1N0M0）。2011年 2 月に舌下部の精査目的に当院を受診された。初診時の所見で右側舌下部に18×10mm大のびらんを認め，現病歴から常用薬の停滞による化学的損傷が疑われた。症例１， 2 ともに初診時の肉眼所見では悪性病変の診断は困難であったが，初診時に施行した細胞診所見では，いずれも表層型，深層型細胞に核種大やクロマチンの濃染性といった細胞異型を認め，Papanicolaou分類のclassⅤと診断した。その後，切除生検を施行し，病理組織診断は高分化型扁平上皮癌であった。また，患者の希望もあり，術後補助療法は行わず経過観察を行っているが再発，転移所見は認めていない。
今回の 2 症例は切除後の組織標本より，病変のごく一部に限局した浸潤像を認めた。いずれも初診時において肉眼的には不明瞭で判断のつきにくい症例であった。このような初期癌では，低侵襲かつ広範囲から細胞を採取することができる，ブラシを用いた液状細胞診が有効であったと考えられた。
Oral exfoliative cytology, has been recognized as a useful and less-invasive examination in diagnosing
squamous cell carcinoma.
We present two cases of carcinoma that Oral exfoliative cytology was effective in detecting earlycancer. Both cases had only slight erosion and appeared nonmalignant clinically when ﬁrst diagnosed.
We diagnosed them as ClassⅤ, Papanicolaou classiﬁcation. Because their superﬁcial and parabasal cells
had atypical findings, such as nucleo enlargement and deeply-stained chromatins. Finally, they werediagnosed as well-diﬀerentiated squamous cell carcinoma by excisional biopsy.

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Histone deacetylases (HDACs) inhibitor, Trichostatin A, induces G2/M
phase arrest and apoptosis in oral squamous carcinoma YD-10B cells
Sang-Gun Ahn and Jung-Hoon Yoon
Department of Pathology, School of Dentistry, Chosun University
Histone acetylation is one of the key chromatin modifications that control gene transcription during
development and tumorigenesis. Recently, it was reported that histone deacetylase inhibitor, Trichostatin A(TSA), is a well-known antitumor agent that induces tumor growth arrest and apoptosis. However, themolecular mechanisms of their effects are not clear. The purpose of this study was to investigate the effectsof TSA on human oral squamous carcinoma cells and its underlying mechanisms. MTT assay showed that
TSA inhibited cell proliferation in YD-10B cells. TSA arrested effectively cell cycle progression at G2/M
phase through up-regulation of p21waf expression, down-regulation of Cyclin B1 as well as inhibitory
dephophorylation of Cdc2. In addition, mitochondrial membrane destruction was induced by TSA
treatment for 48h. TSA also induced cytochrome c release and proteolytic activation of caspase 3 andcaspase 7 in YD-10B cells. Taken together, these observations suggest the potential value of TSA in oral
cancer YD-10B cells.
This study was supported by a grant of the NRF funded by the MEST (No.R13-2008-010-00000-0).

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Inhibition of autophagy enhances apicidin-induced apoptosis in humanoral squamous carcinoma cells
Jung-Hoon Yoon, Sang-Gun Ahn
Department of Pathology, School of Dentistry, Chosun University
Objectives: Apicidin acts as a potent histone deacetylases (HDAC) inhibitor and the precise mechanism for
its anti-tumor activity in human oral squamous cell carcinoma (OSCC) cells has not been examined. The
aim of this study was to evaluate the anti-tumor efficacy of apicidin through apoptosis and autophagy in
OSCC cells.
Materials and Methods: Cells were treated with apicidin and cell death was quantified. Cell cycle andapoptosis were measured using flow cytometry assay, immunoblot. Autophagy was characterized by theincrease of LC3B-II and the formation of acidic vesicular organelles (AVOs).
Result: Apicidin significantly inhibited the proliferation of OSCC cells in a dose-dependent manner.
Apicidin markedly up-regulated p21WAF1 led to G2/M phase arrest. Apicidin significantly increased thenumber of apoptotic cells compared to untreated control. Apicidin induced not only apoptosis but also
autophagy in OSCC cells. Apicidin dramatically increased the levels of LC3 type II expression, ATG5
protein expression and the accumulation of AVOs. Inhibition of autophagy enhanced apicidin-mediatedcytotoxicity through an increase in apoptotsis.
Conclusion: These results suggest that apicidin exerts anti-tumor effects by inducing apoptosis andautophagy and provide novel evidence of apicidin-induced autophagy and autophagy inhibition enhances
apicidin-mediated apoptosis in OSCC cells. This study was supported by a grant of the NRF funded by the
MEST (No.R13-2008-010-00000-0).

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In vitro and in vivo photodynamic therapy using pheophorbide A induces
apoptosis in mouse oral cancer AT-84 cells
Jung-Hoon Yoon, Sang-Gun Ahn
Department of Pathology, School of Dentistry, Chosun University
This study was examined the therapeutic effect of photodynamic therapy using the photosensitizer
Pheophorbide a (Pa-PDT) in mouse oral squamouse cell carcinoma AT-84 cells. Pa-PDT treatment
significantly induced cell growth inhibition and the intracellular ROS generation, which is critical for cell
death induced by PDT. Cell cycle analysis showed the increased sub-G1 proportion of cells in Pa-PDT
treated cells. Induction of apoptotic cell death was confirmed by DAPI staining and the reduction of
mitochondrial membrane potential (∆Ψ (m)). The changes in apoptosis-related molecules were next
examined using Western blot after Pa-PDT treatment. The release of cytochrom C and the cleavage ofcaspse-3, PAPR were exhibited, whereas Bcl-2 protein level was decreased. To determine the therapeutic
effect of Pa-PDT in vivo, mouse oral squamous cell carcinoma animal model was established. Treatment ofmice with Pa-PDT significantly inhibited tumor growth. Immunohistochemistry and TUNEL assay
showed decreased PCNA expression and increased apoptotic cells compared to vehicle-treated controls. Ourfindings suggested the therapeutic potential of Pa-PDT in the oral squmouse cell carcinoma both in vitro
and in vivo. This study was supported by a grant of the NRF funded by the MEST (No.R13-2008-01000000-0).

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P-60

Effect of Dentin Sialoprotein on Proliferation, Migration and
Differentiation in Human Dental Pulp Cells
Eun-Cheol Kim
Department of Maxillofacial Tissue Regeneration, School of Dentistry and Institute of Oral Biology, Kyung Hee University
Background and Objectives: Dentin sialophosphoprotein (DSPP) is an extracellular matrix, typicallydentin-and bone-specific gene, which plays an important role in dentin mineralization and toothdevelopment. DSPP is cleaved into dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). In
developing dentin, DSP is expressed in odontoblasts and in preameloblasts. However, little is known about
the direct role of DSP in human dental pulp cells (HDPCs). This study was conducted to investigate theeffects of DSP on proliferation, migration and odontoblastic differentiation in the HDPCs.
Methods: Cell proliferation and migration were determined by MTT assay and chemotaxis cell migration
assay, respectively. Differentiation were measured by alkaline phosphatase (ALP) activity, calcified nodule
formation by alizarin red staining, and odontoblastic/osteoblastic marker mRNA expression by reverse
transcription polymerase chain reaction (RT-PCR). MAPK, AKT, NF-κB, smad 1/5/8 and beta-catenin
expression evaluated by western blotting.
Result: Cell proliferation and migration were increased in dose- and time dependent manner in HDPCs.
ALP activity, the mineralization and mRNA expression for odontoblastic/osteoblastic markers wereenhanced by DSP in HDPCs. DSP showed degradation and phosphorylation of IκB-α, activation of p65
in dose dependent manner stimulated phosphorylation of Akt, ERK, p38, JNK with a maximal response
within 10 min in HDPCs. DSP induced IκB-α phosphorylation, subsequent degradation of IκB-α,
and nuclear translocation of NF-κB p65 subunit. Also, phosphorylation of Smad1/5/8 and active β-Catenin protein levels were up-modulated by DSP treatment
Conclusion: Our studies demonstrated that DSP-induced growth promotion, migration and odontoblastic
differentiation of HDPCS are mediated by p38, ERK, JNK MAPK, Akt, NF-κB and β-Catenin signaling
pathways. Thus, DSP can be crucial in the repair and regeneration of human dental pulp.
ACKNOWLEDGEMENTS: This study was supported by a grant from the Korea Healthcare technology
R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea. (A084458)”

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The Role of SIRT1 on Angiogenic and Odontogenic Potential in Human
Dental Pulp Cells
Jong-Jin Kim1, Eun-Cheol Kim2
1

Department of Animal Biotechnology, College of Animal Biosciences & Technology, Konkuk Unversity
Department of Maxillofacial Tissue Regeneration, School of Dentistry and Institute of Oral Biology, Kyung Hee University

2

Background and Objectives: Sirt1, a NAD+-dependent histone deacetylase, controls critical functions ofmammalian cell physiology including differentiation in skeletal muscle cells and and adipocytes. However,
the role of Sirt1 in human dental pulp cells (HDPCs) is unknown at present. Therefore, the aim of thisstudy was to evaluate expression of Sirt1 and its effect on the odontoblastic and vascular differentiation in
HDPCs.
Materials and Methods: Odontoblastic and angiogenic differentiation ability was evaulated by Alizarin Red
S stain, reverse transcription polymerase chain reaction (RT-PCR).
Results: Treatment with resvaratrol, a SIRT1 activator, increased odontoblastic genes such as alkaline
phosphatase (ALP), osteopontin (OPN), dentin matrix protein (DMP-1), and dentin sialophosprotein(DSPP) as well as gene expression of agngiogenic markers such as vascular endothelial growth factor(VEGF), endothelial cell adhesion molecules (VE-Cadherin, peCAM), and basic fibroblast growth factor(FGF-2), and enhanced calcification of the extracellular matrix in a time and dose dependent manner in
HDPCs. In contrast, downregulation of SIRT1 expression by SIRT1 inhibitor, and SIRT1 siRNA which
inhibit odontoblastic differentiation and mRNA expression for angiogenic marker. Furthermore, adnovirusmediated overexpression of SIRT1 induced odontoblastic and vascular differentiation markers.
Conclusions: These results imply that SIRT1 may have a pivotal role in odontogenesis and angiogenesis of
HDPCs. Furthermore, this study suggests that either the administration of SIRT1 donors or themodulation of the endogenous production of SIRT1 may be therapeutic benefit in the pulp regeneration
and revascularization.
Key Words; SIRT-1; Differentiation; Human Dental Pulp Cells
ACKNOWLEDGEMENTS: This study was supported by a grant from the Korea Healthcare technology
R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea. (A084458)”

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下唇に発生した腺房細胞癌の一例

A case of acinic cell carcinoma arising in the lower lip
橋本 和彦1，村松 敬1，國分 克寿1，村上 聡1，松坂 賢一1，高野 正行2，
井上 孝1
Hashimoto Kazuhiko1, Muramatsu Takashi1, Kokubun Katsutoshi1,
Murakami Satoshi1, Matsuzaka Kenichi1, Takano Masayuki2, and Inoue Takashi11

東京歯科大学臨床検査病理学講座
東京歯科大学口腔健康臨床科学講座口腔外科学分野
1
Department of Clinical Pathophysiology, Tokyo Dental College
2
Department of Clinical Oral Health Science
2【目的】腺房細胞癌は漿液性腺房細胞へ分化した腫瘍細胞が充実性に増殖することを特徴とするが，多彩な細胞型・組織型を示すこともある。今回，われわれは下唇に発生し乳頭嚢胞型を示した，比較的稀な腺
房細胞癌の一例を経験したので報告する。
【症例】患者；62歳，女性。現病歴；平成21年，右側下唇部に
指頭大の腫瘤を自覚したため近医歯科を受診し，経過観察を続けていたが，平成22年12月に腫瘤が急に増大してきたことから，平成23年１月，本学水道橋病院口腔外科を受診となった。初診時口腔内所見；右側下唇部に20×12mm大，暗紫色，弾性硬の腫瘤を認めた。経過；平成23年１月，穿刺吸引細胞診を施行したところ，腫瘍細胞等は認められなかった（class I）。その後，20×25mmと腫瘤の増大を認めたことから，
局所麻酔下にて腫瘍切除術を施行した。病理組織学的所見；好酸性の内溶液を含んだ嚢胞構造がみられ，嚢胞を裏装する菲薄な扁平上皮の一部が，嚢胞腔内に向かって乳頭状に増殖する部が観察された。腫瘍細胞は細い結合組織を伴って分枝状に増殖しており，hobnail appearanceや細胞内小空胞もみられた。免疫組織化学染色においてamylase，lactoferrin弱陽性，keratin，CEA陽性，組織化学染色ではmucicarmin陰性であり，最終的に介在部導管型細胞からなる乳頭嚢胞型腺房細胞癌と診断した。
【考察】腺房細胞癌は約80％が耳下腺に好発し，小唾液腺での発生は約17％といわれている。特に，小唾液腺では口蓋部や頬粘膜部における報告例が多くみられるが，下唇に発生した報告例は本邦において過去25年間で２例のみであった。また，本症例の細胞型は介在部導管型細胞，組織型は乳頭嚢胞型であったが，介在部導管型細胞の発生頻度は全症例の1/3，乳頭嚢胞型の発生頻度は充実型，小嚢胞型に次ぐといわれている。今回，比較的稀と考えられる腺房細胞癌の一例を，文献的考察を加えて報告する。
We present a case of acinic cell carcinoma with papillary-cystic pattern arising in the lower lip of a62-years-old female. Histopathologically, tumor had numerous, variably sized cystic structures, whichgrew papillary toward the cystic lumen with single-layered lining epithelium. Immunohistochemically,
the tumor cells were positive for S-100 protein, keratin, and a few tumor cells were positive for amylase,and lactoferrin. Histochemically, a few tumor cells were positive for PAS but were negative for
mucicarmine. Therefore, this case was diagnosed as acinic cell carcinoma with papillary-cystic pattern.

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Efficacy of fine needle biopsy in the diagnosis of oral and maxillofaciallesions
Yoshihiko Kaneda1, Hiroaki Ishibashi1, 2, Yoshiki Nariai2, Yoko Toshihiro2, Kyotaro Nogami2,
Kazuyuki Kawamura2, Sayoko Oka2, Aya Yoshino2, Katsumi Hideshima2, Joji Sekine1, 2
1Division of Oral Medicine, Department of Oral and Maxillofacial Surgery, Shimane University Hospital
Department of Oral and Maxillofacial Surgery,Shimane University Faculty of Medicine

2This study was planned to reveal the efficacy of histopathological examination using fine needle biopsy(FNB) with the new Monopty biopsy instrument (MBI; Bard Urologic Division; Covington, GA) andFINCORE (Dr.JAPAN Co., Ltd., Tokyo, Japan) in the diagnosis of oral and maxillofacial lesions. We
applied FNB to 8 lesions using MBI and FINCORE in oral and maxillofacial lesions including lymph
nodes, salivary glands, facial skin, and other oral tissue. The tissue samples were processed for routine
paraffin embedded specimens, high-quality histopathological specimens were obtained with MBI andFINCORE without using any special technique.
The histopathological aspect by FNB was compared with the final diagnosis from the surgically resected
tissue. The target lesions were accurately biopsied by FNB in all cases, and the accuracy rate of FNB
diagnosis was 87.5%.
No complication such as abnormal hemorrhage or nerve damage was seen in all cases. This techniquewould be a safe, effective means of obtaining adequate tissue for histopathological examination of oral andmaxillofacial lesions.

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Effect of surgical instruments on cytological features
Katsumi Hideshima1, Satoko Yamazaki1, Taisuke Higashi1, Yoshiki Nariai1, Takaya Yamada2,
Miki Tongu2, Chie Yanai3, Hiroaki Ishibashi1, Joji Sekine1
1

Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine
Department of Experimental Animals Center for Integrated Research in Science, Shimane University
3
Oral and Maxillofacial Surgery, Nippon Dental University Hospital2

In the oral cancer surgery, composite resection is indicated. Enough surgical margin is needed to achieve
the complete resection. We maxillofacial surgeons are always worrying over how to examine that thesurface of surgical margin is cancer free or not. Histopathological examination using frozen-section during
surgery is the most common technique to examine the surgical margin. However, it is nothing but
checking a part of the lesion.
Then we have applied cytological examination using ultrafast Papanicolaou staining. In this technique, as
surgical margin is stamped on the slides, overall surface would be able to be examined. However, as
cytological features were degenerated by heating using electric scalpel, accurate cytological evaluation was
difficult in some cases. This study was then planned to reveal the effect of surgical instruments oncytological feature.
Five-week-old, 20 - 25 g, male C3H/HeNCrj mice (n = 6) were used. NR-S1 mouse squamous cell
carcinoma was transplanted to the middle of the toungue. Tumors that grew to about 7 x 7 mm in size by
about 10 days after transplantation were resected by conventional surgical scalpel (No. 11), electric scalpel
and Harmonic ScalpelTM . Resected surface was stamped on the slides and stained by routine
Papanicolaou and Giemsa. Following the preparation of cytological sample, tissues were processed forparaffin embedded sections.
Thermal degenerative changes were seen especially in the nuclei of tumor cells resected by electric scalpel.
Morphological changes were not so specific in the specimens by Harmonic ScalpelTM. Detailed cytologicalaspect is discussed comparing with histological findings.

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Our cytological approach to oral lesions
Katsumi Hideshima1, Takashi Koike1, Megu Kikuchi1, Masaaki Watanabe1, Mayumi Ueno1, 2,
Masayoshi Egawa1, 2, Takayuki Kato1, Yoshiki Nariai1, Hiroaki Ishibashi1, 2, Joji Sekine1, 2
1

Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine
Division of Oral Medicine, Department of Oral and Maxillofacial Surgery, Shimane University Hospital2

In the field of oral and maxillofacial surgery, various lesions are manifested including tumor, cyst andinflammation. As most of the oral lesions are visible, biopsy is easily applied. Regarding the history of oral
cytology, first case of oral malignancy was reported in 1950’s. Detailed diagnostic standard has not been
established. In our hospital, cytology is widely applied for screening of oral lesions.
This study presents our cytological approach to oral lesions. A total number of 754 cytological samples(male: 324, female 430, mean age 64.6-yr-old) were examined from June 2007 to March 2011. Samples
were taken from tongue (237 cases), buccal mucosa (138 cases), maxillary gingival (129 cases), mandibular
gingival (113 cases), palate (33 cases), lower lips (22 cases), oral floor (16 cases), and upper lips (8 cases),others (58 cases). Papanicolaou classification was Class Ⅰ (51 cases), Class Ⅱ (311 cases), Class Ⅱ or Ⅲ (57cases), Class Ⅲ (98 cases), Class Ⅲ or Ⅳ (12 cases), Class Ⅳ (17 cases), and Class Ⅴ (21cases).
Biopsy was done in 13 of 57 Class II to III cases, 18 of 98 Class III cases and 10 of 10 Class III to IV cases.
Histopathologically, malignancy was detected in 15.4 % in Class II to III cases, 77.8 % in Class II cases,
and 100 % in Class III or IV cases with the diagnosis of squamous cell carcinoma, verrucous carcinoma,
carcinoma in situ. In this presentation, detailed cytopahological findings are discussed.

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Feasibility of cytological examination of oral and maxillofacial lesions
Mayumi Ueno1, 2, Hiroaki Ishibashi1, 2, Kentaro Ouchi2, Tomoko Ichiyama2, Koichiro Ohira2,
Masaaki Karino2, Fumihiko Kimura2, Masatoshi Hattori2, Katsumi Hideshima2, Joji Sekine1, 2
1Division of Oral Medicine, Department of Oral and Maxillofacial Surgery, Shimane University Hospital
Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine

2

Cytological examination of oral and maxillofacial lesions is minimum invasive and feasible method forbenign and malignant lesions, and plays an important role for the making the clinical diagnosis in manycases. In our department, the number of the cases examined by cytology has been increased steadily inevery year. And we depend throughly on the cytological examination for the making the clinical diagnosis
and follow up study of benign and malignant cases.
For making the correct diagnosis of cytological examination, an accurate knowledges for histopathologicalfeatures of the lesions are important for the cytologist and pathologist. In the present study, we show the
relationship between the histopathological, cytological and clinical features in the precancerous lesions,precancerous conditions and malignant lesions. In addition, clinical findings for oral and maxillofaciallesions are also important for the cytological diagnosis.
Thus, we also present and discuss the point aimed at early detection for oral and maxillofacial region for thecytologist and pathologist with special attention to the abnormality of color and shape as compared withnormal region in the oral cavity.

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Oral cancer detection by mass screening using smear cytology in Shimane
prefecture
Masaaki Watanabe1, Hiroaki Ishibashi1, 2, Masayoshi Egawa2, Takayuki Kato1, Hiroto Tatsumi1,
Kasumi Tatsumi1, Aya Yoshino1, Koji Tsunematsu1, Katsumi Hideshima1, Joji Sekine1, 2
1

Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine
Division of Oral Medicine, Department of Oral and Maxillofacial Surgery, Shimane University Hospital2

We have established oral cancer detecting system using smear cytology in collaboration with generalpractitioners and Shimane University Hospital. From December 2008 to February 2011, we haveexamined 151 cytological specimens, and 5 cases of squamous cell carcinoma were detected
histopathologically. Incidence of oral cancer detected in our system was 3.3 percent, suggesting thefeasibility of individual screening in oral cancer detection.
However, mass screening is also important for cancer detection, as reported in the other field ofmalignancies. This time, we had examined about 1,000 people to detect oral cancer following regular
general and dental checkup in Iinan-cho, Shimane Prefecture from May to July, 2011.
Following the dental checkup by one dental surgeon, accredited maxillofacial surgeons examined extraoral
conditions including cervical lymph nodes and oral cavity bimanually. Cytology was applied to the ulcerlike or swelled lesions with the color of red, white and black while the subjects were seated in the chair
under ideal light. Cytological samples taken by cotton swab from tongue, gingival, oral floor, buccal
mucosa, palate and other soft tissue in the oral cavity, which were sent to our laboratory and diagnosed
following Papanicolaou Classification by specialists in our department. Before and after the screening,questionnaire regarding oral symptom and general knowledge of oral cancer was done to all examinees.
As of 20 June, 510 subjects were examined, and 71 cytological samples were taken. Though no cancer was
detected, 16 cases of epithelial dysplasia were pointed out. This paper describes the detailed data at the endof this mass screening scheduled to be completed at the end of this July.

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