oral CIS catalog
histopathological variations

2005-2007 effort report
working committee on new histopathological criteria
for borderline malignancies of oral mucosa JSOP

Oral Carcinoma in-Situ(JSOP) Catalog
histopathological variations

A 2005-2007 Effort Report ofThe Working Committee on New Histopathological
Criteria for Borderline Malignancies of the Oral Mucosa
The Japanese Society for Oral Pathology

Oral Carcinoma in-Situ (JSOP) Catalog
histopathological variations

A 2005-2007 Effort Report of the Working Committee on
New Histopathological Criteria for Borderline Malignanciesof the Oral Mucosa, the Japanese Society for Oral Pathology

Supported by a Grant-in-Aid for Scientific Research (C) fromthe Japan Society for the Promotion of Science (18639016)
March 22, 2007
91 pages
Sunashobo Publishing, Co. Ltd., Tokyo, Japan

Contents
Preface …………………………………….……..
Acknowledgement……………………………..…
Definition..............……………………………..…
CIS (JSOP), differentiated type…………………..
CIS (JSOP), basaloid type………………………..
Normal reference……………………………..…..

12
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1Preface
This product is the result of a recent two-year effort of the Working
Committee for New Histopathological Criteria for Borderline
Malignancy of Oral Mucosa (WCHC), which was first organized in May,
2004 under The Japanese Society for Oral Pathology (JSOP), and wasre-organized in January, 2006.
The primary committee proposed “Guidelines for Histopathological
Diagnosis of Borderline Malignancies of the Oral Mucosa” in 2005
mainly focusing on the categorization of borderline malignancies. After
this preliminary proposal, the committee received many valuablecomments from the JSOP members as well as from oral pathologists andgeneral pathologists around the world. Incorporating the criticism, theWCHC members came to realize that it would take more time tocomplete a categorization standardization which could be commonlyaccepted. Thus, our actual goal for the next-step activity was scaled
down and involved consolidation of at least the concept of carcinoma insitu (CIS), because it was considered of primary importance todiscriminate CIS from epithelial dysplasias and/or from microinvasive
carcinomas.
To this end, the WCHC committee collected cases which had been
diagnosed as CIS in the individual hospitals where the committee
members work. HE-stained sections from more than 160 collected cases
were circulated among the twenty-five committee members for theirdiagnoses. Their diagnoses were totaled, and cases which werediagnosed as CIS by more than 70% of the members were selected for
objectives to be discussed in the following meetings, which were to takeplace ten times at Nihon University and Nippon Dental University,
Tokyo. Finally, 39 cases were adopted as variations of CIS. They wereroughly classified into two categories mainly based on the extent of theirdifferentiation: differentiated type and basaloid type.
In this monograph named “catalog,” our intent is to show histologicalvariations of CIS rather typical to that of the oral mucosa. Thesevariations may be wider in range than what CIS had been expected, forinstance, than the WHO criteria in the last three editions up to the 2005
version. What we would like to emphasize is that it is different from thecervix uteri or esophagus; oral CIS (JSOP) has a definite tendency
towards keratinization or oral CIS is well-differentiated.

2

Now in 2007, when we are able to introduce many of the scientificdevices into our routine diagnostic services, the use of only HEhistology does not seem sufficient for the final diagnosis of oral CIS.
The committee members have discussed the usefulness of
immunohistochemistry or the other tools in CIS diagnosis. A small
number of examples of immunohistochemistry for Ki-67 andcytokeratins, which were considered to be valuable for the diagnoses,
were thus included in this catalog.
It is our hope that these histological variations of oral CIS documented
in this catalog would be of some help for routine diagnostic activities oforal and general pathologists. We would appreciate it very much if
critical comments were provided by the readers for the improvement of
the criteria for borderline malignancies of the oral mucosa wereprovided by the readers.

Takashi Saku, Chairperson
The Working Committee for New Histopathological Criteria for
Borderline Malignancies of the Oral Mucosa, The Japanese Society for
Oral Pathology

Acknowledgement
This project was supported by a Grant-in-Aid for Scientific Research (C)(18639016) from the Japan Society for the Promotion of Science, 2006.
The committee members thank their colleague oral surgeons for providing
us with clinical information of the patients, including pictures. They arealso grateful to their colleagues in their individual laboratories for theirtechnical assistances and continuous support in various ways.

3Definition

4Carcinoma in-situ (JSOP)
Carcinoma in-situ (specially designated as CIS (JSOP)) is asquamous cell carcinoma which has not yet invaded into thesubepithelial layer of the oral mucosa. There are several
variations in its histology, in addition to those mentioned in
the definition in the WHO classification. Its most commonand distinct histological variations are recognized asdifferentiated and basaloid types. There are transitionalvariations between the two types. It is characterized by thepresence of front formation against surrounding normal
epithelia and dense lymphocytic infiltrations in thesubepithelial layer. Immunohistochemistry for Ki-67 andkeratin species is helpful to recognize the extension areas of
CIS (JSOP).

上皮内癌（日本口腔病理学会）
口腔粘膜の未だ上皮層下へ浸潤していない段階の扁平上皮癌。病理組織学的にはWHO分類で定義された病変以外のバリエーションがある。主たる組織型としてつぎのとおり分化型と基底細胞型の二型が区別されるが、両者の移行型も存在する。隣接上皮との界面形成がみられることや上皮層直下のリンパ球浸潤をともなうことが多い。診断の補助手段として、Ki-67やケラチン分子種の免疫組織化学が有用である。本疾患概念を上皮内癌（日本口腔病理学会）CISで、WHO分類ほかのCIS概念と区別している。

(JSOP)とよん5

Differentiated typeCIS with a definite tendency towards keratinization andorganized squamous cell stratification in which basal,prickle, and keratinized layers are distinguishable.
Variations in the thickness of the epithelial layer, shapes ofrete processes, modes and levels of keratinization, andstructural and cellular atypia can be observed.
重層扁平上皮としての層分化（基底層、棘細胞層、角化層が区別できる）があり、とくに角化傾向の明らかなタイプ。上皮層の厚さ、釘脚の形状、角化の様式と程度、構造異型および細胞異型の程度には種々のバリエーションがある。

Basaloid typeCIS with a monotonous proliferation of basal cell-like(basaloid) cells, which have relatively narrow cytoplasm,
enlarged nuclei without distinct nucleoli, and increased N/Cratios, within the entire epithelial layer. It is alsocharacterized by drop-shaped rete ridges, loss of basal cellalignment, and spindle cell shapes, while minimal
keratinization tendencies are recognized in the surface. It
has atrophic variants.
主として基底細胞様細胞（比較的乏しい細胞質と腫大した濃染核、高N/C比、核小体は不明瞭）の増殖からなるタイプ。滴状釘脚が特徴的で、基底層の柵状配列の不明瞭化、紡錘形細胞化、ある程度の角化傾向もともなうなどのバリエーションがある。釘脚が小型化する萎縮型もある。

7CIS (JSOP)differentiated type8

Case 1iodine

28 M, tongue

9

10

Case 2

cytokeratin 13

Ki-67

50 M, tongue

11

12

Case 346 F, tongue

13

14

Case 4

94 F, tongue

15

16

Case 573 M, gingiva

17

18

Case 667 F, tongue

19

20

Case 760 M, tongue

21

22

Case 868 F, buccal mucosa

23

cytokeratin 13

Ki-67

24

Case 962 F, tongue

25

26

Case 1071 M, tongue

27

28

Case 1164 M, buccal mucosa

29

30

Case 1268 M, gingiva

31

32

Case 1346 M, tongue

33cytokeratin 13

Ki-67

34

Case 14 83 M, buccal mucosa

cytokeratin 13

Ki-67

35

36

Case 1570 F, tongue-oral floor

37

38

Case 16

76 F, buccal mucosa

39

40

Case 1745 F, tongue

41

42

Case 18

cytokeratin 13

Ki-67

71 M, tongue

43

44

Case 19

Ki-67

67 F, tongue

45

46

Case 20

61 F, tongue-oral floor

47

49

CIS (JSOP)basaloid type

50

Case 2155 M, oral floor

51

cytokeratin 13

Ki-67

52

Case 22

cytokeratin 13

Ki-67

68 M, buccal mucosa

53

54

Case 23cytokeratin 13Ki-67

65 M, oral floor

55

56

Case 24

74 M, gingiva-buccal mucosa

57

58

Case 25

32 F, tongue

59

60

Case 26 88 F, palate

61

62

Case 27

61 M, palate

63

64

Case 28

68 F, tongue

65

cytokeratin 13Ki-67

66

Case 29

65 M, tongue-gingiva

67

68

Case 30

68 F, buccal mucosa

69

70

Case 3185 F, tongue-oral floor

71

72

Case 32

Ki-67

46 F, tongue

73

74

Case 33

43 M, tongue

75

76

Case 34

30 F, tongue

77

78

Case 35

32 F, tongue

79

80Case 36

65 F, tongue

81

82

Case 37

56 M, tongue

83

84

Case 38

iodine74 F, tongue

85

86

Case 39

53 F, oral floor

87

Ki-67

89

Normalreference

90

Normalcytokeratin 13

Ki-67

43 M, oral floor

91

Normalcytokeratin 13

Ki-67

55 M, tongue