第 104 回日本病理学会総会コンパニオンミーティング 1

日本婦人科病理学会

平成 27 年 4 月 30 日

名古屋国際会議場 B 会場 18:40～20:10

卵巣非上皮性腫瘍

診断困難例における実際的アプローチ
オーガナイザー

福永真治（東京慈恵会医科大学附属第三病院 病院病理部）
座⾧

九島巳樹（昭和大学江東豊洲病院 臨床病理診断科）
松本俊治（順天堂大学附属練馬病院 病理診断科）

CM-1-1

福永真治（東京慈恵会医科大学附属第三病院 病院病理部）

CM-1-2

名方保夫（大阪愛仁会千舟病院 臨床検査科）

CM-1-3

山田隆司（大阪医科大学 病理学教室）

Clinical history
A 66-year-old, gravida 2, para 2, Japanese female
presented with low abdominal discomfort andabnormal vaginal bleeding. Imaging analyses
indicated a pelvic mass probably arising from leftovary.
The general laboratory examinations revealed nosignificant abnormalities.
Under a clinical diagnosis of ovarian sarcoma,bilateral salpingo-oophorectomy and simple
abdominal hysterectomy.
She had postoperative chemotherapy. The patient
was well with disease at 16 months after surgery.

Case 1
A 66-year old female
with ovarian tumor
Masaharu Fukunaga

Dept. Pathology, Jikei University Daisan Hospital,Tokyo, Japan.
I have no conflicts of interests.

Specimen for intraoperative consultation
The predominat components show spindle cell or pleomorphic sarcomatous features.

Sarcomatous components with marked cellular atypia and pleomorphism.

12x10x7.5cm

Alpha-SMA

The cut surface was a fleshy and yellowish-white and solid tumor
with scattered cysts containing greenish liquid and focal calcification (asterisks).

desminSpindle and pleomorphic cells are positive for alpha-smooth muscle actin (left)
but negative for desmin (right).

1

Immunohistochemistryof the high grade spindle tumor
component
Vimentin (+)
Alpha-SMA (+)
HHF35 (+)
CD117 (+)
Wide keratin (+)
Desmin (-)
CD34 (-)
S100 (-)
CAM5.2 (-)
Thyroglobulin (-)

Benign-looking thyroid componet with focal calcification and ossification.

Immunohistochemistry
Thyroid follicles

Thyroglobulin• Thyroglobulin (+)• EMA (+)• CMA5.2 (+)• Wide keratin (+)• TTF-1 (+)• Alpha-SMA (-)• Vimentin (-)• HHF35 (-)

TTF-1

Follicles and spindle cells are positive for thyroglobulin (left) and TTF-1(right).

2

Spindle cells adjacentthyroid tissue• Thyroglobulin (+)• EMA (+)• CAM5.2 (+)• Wide keratin (+)• TTF-1(+)• Alpha-SMA (+)• Vimentin (+)• HHF35(+)

Microscopic features

Pathologic diagnosis• Predominant element
High grade spindle cell sarcomatous component
without specific differentiation• Minor component
Benign looking thyroid tissue with reactive
ossification and calcification
Mildly or moderately atypical spindle cellproliferation adjacent thyroid follicles.
They were positive for thyroglobulin and TTF-1.
・ No other teratomatous elements were observed• Malignant struma ovariiwith a predominant componetof anaplastic carcinoma

Discussion 1

Prognosis of malignant struma ovarii

Rates of death of disease in 105 malignant struma ovarii• Macroscopically, the presence of green tobrown color of cyst contents or lining is a clue
to the correct diagnosis of struma ovarii.
• In this case the sarcomatous element could
be interpreted as dedifferentiation.
• Any type of thyroid cancer can arise instruma ovarii. Papillary carcinoma is mostcommon.

Histological type

Death of disease

Papillary carcinoma (53cases)

7%

Typical follicular carcinoma (31cases)

Highly differentiated follicular carcinoma of ovarian origin(HDFCO) (18cases)
Undifferentiated (anaplastic) carcinoma (3case)

Risk factors

Low riskTumor size < 2cmDiscussion 2100%

High risk

Tumor size≧ 2cm• The presence of
extraovarian extension.
•High grade histology:
anaplastic carcinomaConclusion• There were three cases of malignant struma
ovarii with focal anaplastic carcinomatous
elements in papillary carcinoma.
• Tumors diagnosed as malignant struma ovarii on
histologic grounds are rarely clinically malignant
and do not require radical treatment.
• The lack of correlation between morphology andoutcome in proliferative and histologicallymalignant struma ovarii is striking, making thebehavior of these tumors particularlyunpredictable.

14%

0%

• This type of malignant struma ovarii may leaddiagnostic problems, and sampling anddifferential diagnosis among sarcomatous
ovarian tumors are important for making thediagnosis.

3Case 2
A 34-year old female with ovarian andomentum tumors

omentum• Peritoneal carcinoma with dissemination wasclinically suspected.
• Metastatic lesions in lung, liver, spleen and bone
(TH12) were suspected.
• Serous levels of CA１２５ were elevated (148U/ml,normal＜35U/ml).
• Salpingooophorectomy and partial omentectomy
was performed.
• Discussion points : Pathologic diagnosis

Right ovary

Right ovary

4

Left ovary

AE1/AE3

Factor- 8

CD31

5Vimentin

D2-40

Immunostains

Left ovary• Vimentin, CD31:(++)• D2-40, p53: (+)• AE1/AE3, CD34, factor 8: 一部（+）• Calretinin, CEA, S100, CK7, CAM5.2, C-kit, SMA,desmin, HMB45, Melan A:（-）

左卵巣Omentum

大網大網

6

Diagnosis

Epithelioid angiosarcoma• Epithelioid angiosarcoma
metastasis to bilateral ovaries.
Primary: Omentum, most likely• Epithelioid, trabecular, tubular or alveolar
arrangements of atypical cells• Extensive necrosis and hemorrhage• Positive for endothelial markers• Epithelial markers are positive in one third ofpatents• Metastasis to lung, liver, bone, lymph nodes• Poor prognosis. One half of patients die of
disease in one year.

Differential diagnosis• Metastatic adenocarcinoma• High grade serous carcinoma• Malignant mesothelioma• PEComaCase 3: A 37-year-old female
with a right ovarian tumor

The patient presented with lower abdominal
pain. Physical examination, CT and MRI
indicated a right ovarian tumor. Abdominal
hysterectomy, bilateral salpingo-oophorectomy,
omentectomy and pelvic lymph node dissection
were performed. Serum calcium levels werewithin normal range. She died of the spreaddisease 4 months after surgery.

7

8

CAM5.2

Immunohistochemical study• CAM5.2 (+) （follicular areas)• CK7(+) (follicular areas)• EMA(+) (follicular areas)• LCA (-)• Inhibin-alpha(-)• Calretinin (-)• CD99(-)• Chromogranin A (-)• Synaptophysin (-)• Inhibin-alpha (-)• INI 1(-)
EMADiagnosis

Small cell carcinoma of the ovary,hypercalcemic type
With extraovarian involvement:
omentum, subserosa of the uterus.
She died of the spread disease 4 months
after the surgery.

Omentum involvement

9Summary of small cell carcinoma of theovary, hypercalcemic type

Differential diagnosis of small cell carcinoma
of ovary, hypercalcemic type• Young adults (mean age, 24 years)• About 60% of the tumors are accompanied withhypercalcemia. It may be related to PTHrp in tumorcells.
• About 50% of the tumors have spread beyond theovary at the time of laparatomy• Diffuse sheet-like, follicle-like, cord-like arrangementsof small closely packed epithelial cells.
• EMA, WT-1, calretinin positivity, inhibin and INI 1
negativity• Differential diagnoses are wide.
• Poor prognosis: Most pts with high stage tumor havedied of disease, usually within 2 years.
• Uncertain histogenesis.

• Granulosa cell tumor, adult and juvenile types• Small cell (neuroendocrine) carcinoma,pulmonary type
• Dysgerminoma• Secondary involvement ; malignant lymphoma,malignant melanoma, intraabdominal
desmoplastic small cell tumor• Primary or secondary primitive neuroectodermal
tumor (PNET)

Thank you very muchfor your attention.

10

第104回日本病理学会総会コンパニオンミーティング １
日本婦人科病理学会

千船 病理学会（名古屋）

卵巣非上皮性腫瘍
診断困難例における実際的アプローチ
CM－１－２
社会医療法人 愛仁会 千船病院 病理診断科
名方 保夫
2015.4.30.

卵巣転移性悪性黒色腫
Metastatic malignant
melanoma of the ovary.
原発巣 皮膚
Primary site; Skin.

① 卵巣転移性悪性黒色腫 （原発巣 皮膚）② 卵巣未熟奇形腫 （未熟成分の解釈、診断）

症例；４０歳代後半、女性
１、左腋窩リンパ節腫大 →→外科
左側胸皮膚に4X5cm大の黒色病変（生下時から）
２、骨盤腔から右腎門レベルにまで達する20cm程度の巨大腫瘤 →→婦人科
３、前頭葉正中底部に転移巣 PET‐CT1112S100p

HMB45

MelanA13HMB45

S100p

MelanAVimentin

14卵巣転移性悪性黒色腫の報告
１）Remadi S et al:Ovarian metastatic melanoma. A diagnostic pitfall
in histopathologic examination. Arch Anat Cytol Pathol 1997, 45:43‐46.
２）Oliver R et al:Ovarian malignant melanoma:unusual presentationof a solitary metastasis. Gynecol Oncol 2005, 99:412‐414.
３）Sbitti Y et al:Diagnostic challenge for ovarian malignant melanoma
in premenopausal women: primary or metastatic?.
World J Surg Oncol 2011, 9;65.
４）Berisavac M et al:Metastatic malignant ovarian melanoma—a casereport. Vojnosanit Pregl 2013, 70:229‐232.

卵巣悪性黒色腫の集計報告
Gupta D et al.:Malignant melanoma involveing the ovary:a clinicopathologic andimmunohistochemical study of 23 cases.
Am J Surg Pathol 2004, 28:771‐780.

The architectual pattern
nodular 8, diffuse 6, nodular and diffuse 5, nested 3,
lentiginous arising in a teratoma 1. (*)(*)one was the patient with arising within a teratoma.
The tumor cell type
epithelioid 19, spindled 2, mixed epithelioid and spindled 1,small cell 1.
In 8 cases,
initial diagnosis included
sex cord stromal tumor.
grem cell tumor.
sarcoma.
undifferentiated carcinoma.

Ovarian malignant melanoma(MM)Primary or metastatic , is an extremely rare tumor.
The patiens’ age; 14‐53 age(mean 35.7 yaers)
A previous history of MM=14 patients.
interval between the primary MM and ovarian metastasis
15‐228 months(mean 77.7 months)
Unilateral in 19 and bilateral in 4 cases.
The tumor size;4.5‐23 cm(mean 10cm)
a case;Primary MM=cystic teratoma 0.2mm in thickness.
Grossly pignanted in 8 cases(35%)

卵巣原発悪性黒色腫の報告１）Mccluggage WG et al:Primary malignant melanoma of the ovary:a report of 9 definite or probable cases with emphasis on theirmorphologic diversity and mimicry of other primary andsecondary ovarian neoplasms. Int J Gynecol Pathol 2006, 25:
321-329.

MM involving the ovary is a rare disease.
Predominantly seen in women of reproductive age.
Poor prognosis.
Nodular or diffuse pattern an epithelioid cell type.
→mistaken for germ cell and sex cord stromal tumors.

→ all the primary tumors likely are of teratomatous origin.
２）Hyun HS and Mun ST:Primary malignant melanoma arising in a
cystic teratoma. Obstet Gynecol Sci 2013, 56:201-204.
３）Lee J et al:Primary malignant melanoma of the ovary arising ina cystic teratoma;case report and review of the literature.
Dermatol Online J 2014, 20:15

奇形腫 Teratoma
1. 2胚葉性あるいは３胚葉性奇形腫 Biphasic or triphasic
teratomaa, 未熟奇形腫 Immature teratomab, 成熟奇形腫 Mature teratoma
1) 充実性 Solid2) 嚢胞性 Cystic {皮様嚢腫 Dermoid cyst}3) 胎児型 Fetiform {こびと型 Homunculus}

卵巣未熟奇型腫（Immature teratoma of the ovary)
未熟成分の解釈、診断

卵巣腫瘍取扱い規約 第2版 ２００９．

Germ cell tumours
Dysgerminoma
Yolk sac tumour
Embryonal carcinoma
Non-gestational choriocarcinoma
Mature teratoma
Mature cystic teratoma = dermoid cyst
Mature solid teratoma
Immature teratoma
Grade 1
Grade 2
Grade 3Glomatosis peritonei
Mixed germ cell tumor

未熟奇形腫のgrade 分類 その１
第1度 Grade 1
未熟な成分がわずかに認められる。核分裂像は乏しい。
第２度 Grade 2
未熟な成分が中等度に認められる。核分裂像を散見する。
第3度 Grade 3
未熟な成分が広範囲に存在する。核分裂像が目立つ
神経膠播種（腹膜神経膠腫症） ＝ 第0度 Grade 0
卵巣腫瘍取扱い規約 第1版 1990

WHO組織分類 第4版 ２０１４．

未熟奇形腫のgrade分類 その２
Grade 0:すべての成分が成熟した組織よりなる
Grade 1：未熟組織が少量みられ、成熟組織と混在する。核分裂像は少ない。未熟な神経上皮成分は、標本あたり低倍率（対物 X4)で１視野を超えない。
Grade 2:未熟な成分が中等量みられ、核分裂がかなりみられる。
未熟な神経上皮成分は、標本あたり低倍率（対物 X4)で3視野を超えない。
Grade 3:未熟組織と未熟神経上皮が広範囲に存在する。未熟な神経上皮成分は、標本あたり低倍率(対物 X4)で4視野あるいはそれ以上存在する。
稀に神経上皮成分よりも細胞成分に富む未熟な間葉成分が主体を占める例もあり、その場合は神経上皮以外の未熟成分の割合で異型度判定される。

未熟奇形腫のgrade分類 その３
Grade 1; Tumours with rare foci of immature neuroepithelialtissue that occupy <1 low power field(40X) in anyslide(low-grade).
Grade 2; Tumours with similar elements, occupying 1-3 lowpower fields(40X) in any slide (high-grade).
Grade 3; Tumours with large amount of immatureneuroepithelial tissue occupying >3 low powerfields(40X) in any slide (high-grade).
WHO組織分類 ２０１４

卵巣腫瘍取扱い規約 第２版 200916

MIB117

AE1/AE318

Diffrential diagnosis.
1, Mature solid teratomas with minimal immaturity.
→Such tumors are not classified as immature teratomas.
2, Thurlbeck and Scully showed that immature cartilage anddeveloping cortex were not sufficient because these element
were present after fetal life.
3, Carcinosarcoma contain a mixture of primitive-appearing
tissues, but these do not organize into coordinated tissue
units with recognaizable embryonal or fetal structures.

Assessments of grade were based on the overall extent of immatureneuroepithelium. In retrospect, the slection of neuroepithelium as the barometer of malignancy was due to fact that
this tissue was the most recognizable and increased reproducibly
In the grading system.
→tumor grading systems used in the past have been tailoredto estimate the amount of immature tissue in the teratoma.

Differential diagnosis
4, In mixed germ cell tumors, exclusion of other elements isimportant, as they may contribute to recurrences, paticularlyin the pediatric age group.
Heifetz et al. observerd that central pathology review ofimmature pediatric teratomas uncovered subtle patterns suchas hepatoid and lung or intestinal-like glandular differentiation
in yolk sac tumors. Exclusion of these subtle components ofmixed germ cell tumor was impotant from a prognostic
perspective.

19Glial implant(gliomatosis peritinei)の報告
１）Wu PS and Lai CR:Ovarian immature teratoma with gliomatosis
pertoneal and pleural glial implant;A case report. Int J Surg Pathol
2015, in press
2)Gheorghisan-Galateanu A et al. :Immature ovarian teratoma withunusual gliomatosis. J Ovarian Res 2013, 6;283)Calder CJ et al:Immature ovarian teratoma with mature peritoneal
metastatic deposite showing glial, epirhelial, and endometrioid
differentiation; a case report and review of the literature. Int Jgynecol Pathol 1994 13;279-282.
4)Bassier R et al:Nodular and tumorlike gliomatosis peritonei withendometriosis caused by a mature ovarian teratoma. Pathol ResPract 1982 175:392-403.

GFAP20第 104回日本病理学会 コンパニオンミーティング
2015年 4月30日

症 例 １
患 者：36歳・女性
主 訴：腹部腫瘤の精査
妊娠歴：3回経妊、3回経産
現病歴：3ヶ月前に帰省分娩で第3子を自然経腟分娩した。以前から卵巣腫瘍を指摘されていたため、MRI検査を行ったところ胚細胞性腫瘍の疑いがあったた
め紹介受診となる。血中腫瘍マーカーはCEA: 0.9ng/ml, CA19-9: 6.6 U/ml, SCC: 0.8 ng/ml, CA125:15.6 U/ml, AFP: 4.2 ng/ml, HCG-β: <0.1 ng/mlと正常値であったが、悪性も否定できず分娩8ヶ月後に摘出手術となった。

卵巣非上皮性腫瘍－診断困難例における実際的アプローチ＜性索間質性腫瘍＞

大阪医科大学 病理学教室

山田隆司

MRI
術中所見

画像診断： germ cell tumor(鑑別診断： malignant lymphoma, fibrothecoma, GIST)

15-03159

15-0315921

15-003159-3 x1

15-003159-3 x020

15-003159-3 x100

15-003159-3 x400

病理診断

鑑別診断
Fibroma
Adult granulosa cell tumor
 Sclerosing stromal tumor
 Steroid cell tumor
 Smooth muscle neoplasm

Rt-ovarian tumor(ｆibrothecoma)

22

症 例 2

診断のポイント
Rt-ovarian tumor (ｆibrothecoma) 臨床情報10年前から指摘され、3回の妊娠出産を経ても大きさは変わっていない。腫瘍は右卵巣の正常部分を有しながら発育していた。


患 者：75歳・女性
主 訴：不正性器出血
妊娠歴：5回経妊、3回経産既往歴：23歳：虫垂切除、63歳：狭心症、 74歳：胆石で胆嚢摘出
現病歴：約8年前から少量の不正性器出血がみられていたため当院受診したところ、細胞診・組織診の結果からatypical endometrial hyperplasiaの診断となり、悪性も否定できないことから腹式単純子宮全摘出＋両側付属器摘出手術となった。術前の血中腫
瘍マーカー・ホルモン値は測定されていなかった。

肉眼所見 割面の色・性状・硬さ
術式の変更
腹腔鏡下手術（摘出範囲）
追加治療の必要性

MRI

血液所見（術翌日）
CEA:
CA19-9:SCC:
CA125:

1.4
23.3
2.1
33.1

ng/ml,U/ml,ng/ml,
U/ml,

LH:
FSH:E2:

34.3↓
27.1↓
30.6↑

mIU/mlmIU/mlpg/ml

画像診断：
LEGH-like
Adenomyosis
Leiomyoma(susp)

13-08835

13-088352313-08835-30

13-08835x1

13-08835-30

13-08835-30

x020

x100

免疫染色
陽性
α-inhibin, vimentin, αSMA
陰性
AE1/AE3, desmin

13-08835-30
x400

24

13-08835-19

13-08835-19 x1x020

病理診断

鑑別診断
Endometrioid adenocarcinoma
with sex cord-like differentiation
 Carcinoid tumor
 Fibroma/thecoma/fibrothecoma Sex cord-stromal tumor withannular tubules Endometrial stromal sarcoma

Lt-ovarian tumor(adult granulosa cell tumor)
Endometrial hyperplasia, complex,
Adenomyosis症 例 3診断のポイント


患 者：44歳・女性
主 訴：腹部腫瘤感覚
妊娠歴：0回経妊、0回経産
既往歴：26歳：虫垂切除
現病歴：約4年前から不妊治療中であったが、腹部腫瘤感があり、前医受診したところ画像で8cm大の多胞性腫瘍がみられたため、当院紹介受診となった。画像所見・血液所見から悪性が強く疑われたため、開腹手術が施行された。

高齢者の女性ホルモンの影響
子宮頸部：頸管腺の発達・扁平上皮の肥厚
細胞診で表層系の細胞出現
子宮内膜：肥厚

女性ホルモン産生部位（腫瘍）女性ホルモンの補充（療法）

画像所見の確認（放射線科医）

25

MRI

血液所見（術前）
CEA:
CA19-9:SCC:
CA125:

15.0↑ ng/ml
1696.0↑ U/ml
0.9 ng/ml
303.4↑ U/ml

LH:
FSH:
E2:
TS:

17.5↓ mIU/ml
16.4↓ mIU/ml
167.4↑ pg/ml
1.11↑ pg/ml (0.11-0.47)

画像診断：
malignant ovarian tumor

13-00970

13-00970

13-00970

13-00970-17x1

26

13-00970-17x020

13-00970-17x100

免疫染色
陽性
EMA, vimentin, AE1AE3, CK7,PgR, ER
陰性
CEA, CK20, AFP, CD30,
α-inhibin

13-00970-17
x400

病理診断

鑑別診断


Sertoli-Leydig cell tumor
Adult granulosa cell tumor
 Metastatic adenocarcinoma (colon,breast, uterus)
 High-grade serous carcinoma
 Female adnexal tumor of probable
Wolffian origin
 Carcinoid tumor, insular or trabecular

Lt-ovarian tumor
endometrioid adenocarcinoma

27

症 例 4診断のポイント


患 者：67歳・女性
主 訴：腹部膨満感
妊娠歴：0回経妊、0回経産
既往歴：36歳：C型肝炎、42歳：子宮内膜症、67歳：痛風・高血圧
現病歴：腹部膨満感があり、近医受診したところCT検査で、腹部腫瘤と両側水腎症がみられたため、当院に紹介受診となった。水腎症については両側尿管にステント挿入で腎機能が改善されたことと腫瘍が悪性の可能性が考えられたことから開腹手術となった。

女性ホルモンの高値
 男性ホルモンの軽度高値
免疫染色
α-inhibinが陰性
上皮系マーカーが陽性

MRI

血液所見（術前）
CEA:
CA19-9:SCC:
CA125:8.8<0.62.5↑
28.7

LH:
FSH:
E2:
TS:

7.5
mIU/ml0.2
mIU/ml163.6↑ pg/ml
5.63↑ pg/ml (0.11-0.47)

画像診断：
Malignant tumor(endometrioid
carcinoma fromadenofibroma)

ng/ml
U/ml
ng/ml
U/ml

鑑別診断：
Malignant Brenner
否定的Fibrothecoma
Granulosa cell tumor

13-10206

13-1020628

13-10206

13-10206-38

13-10206-38

13-10206-38

x020

x100x1

免疫染色陽性
α-inhibin
陰性
EMA, CEA, vimentin, AE1AE3,CK7, CK20, AFP, CD30, ER, PgR

13-10206-38x400

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病理診断
Rt-ovarian tumor
Sertoli-Leydig cell tumor ofintermediate differentiation

13-10206-11
x1

Endometriosis
Endometrial polyp

診断のポイント

鑑別診断

男性ホルモン産生腫瘍
女性ホルモンも産生
 臨床症状
男性化徴候
 術中迅速診断では要注意
術式が決定される（良性～悪性）

Sertoli cell tumor Adult granulosa cell tumor
 Endometrioid adenocarcinoma
 Serous borderline tumor

ホルモン産生卵巣腫瘍

まとめ
臨床情報は重要（可能な限り得る）
 症状
 血液検査 画像所見 手術所見 腫瘍の所見（割面・内容液の性状）
Tanaka YO,et al. Radiographics 2004; 24 Suppl 1:S147-166.

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