1	Endometrial carcinoma: histological typing Dr. G. Jacomen AZ St Maarten Duffel
2	Prevalence of endometrial Ca Flanders 1997-1999: 670 new cases/year 5,3 % of all malignancies in women third after breast (34%) and colorectum (13%) Increase !! 2000-2001: 761 new cases/year
3	WHO-classification of EM-Ca Endometrioid adenoCa Special types: Villoglandular Secretory Ciliated cell With squamous differentiation Mucinous Ca Serous Ca Clear cell Ca Mixed cell adenoCa Squamous cell Ca Transitional cell Ca Small cell Ca Undifferentiated Ca Others
4	Endometrioid Carcinoma NOS Glands resembling those of normal endometrium in proliferative phase Max 10% zones with squamous, serous, clear cell, mucinous differentiation If >10% : mixed type
5	Endometrioid Ca, NOS
6	Endometrioid Ca: grading Mostly based on architectural grade Nuclei only important if grade 3
7	Architectural grade Depends on the extent of solid zones in comparion to the glands Do not consider squamous zones !!
8	Architectural grade Grade1: Max 5 % solid Grade 2: 6-50 % solid Grade 3: > 50 % solid
9	Cytological grade Nuclei grade 1: oval slightly enlarged fine dispersed chromatin Nuclei grade 3: strongly pleomorphic strongly enlarged unregular coarse chromatin prominent eosinophilic nucleoli
10	Cytological grade Nuclei grade 2: between 1 and 3 Number of mitosis not important
11	Determination of grade Architectural grade primordial Cytologic grade 3 augments architecturale grade 1 or 2 by 1 If really discordant: think of Serous Ca Clear cell Ca
12	Examples Arch 1 + Cyt 1 or 2 è Grade 1 Arch 1 + Cyto 3 è Grade 2 Arch 2 + Cyt 1 or 2 è Grade 2 Arch 2 + Cyt 3 è Grade 3
13	Grade can be very heterogenic 1 tumour with zones grade 1 and zones grade 3
14	Grading Heterogeneity in grade very often Reason for discordance between curettage and hysterectomy Grade 1 remains grade 1 in 45%
15	Grade 1 + undifferentiated Ca Silva: Association of low-grade endometrioid Ca of the uterus and ovary with undifferentiated Ca: a new type of dedifferentiated Ca? I J Gynecol Pathol (2006) 25: 52-58 Indicates aggressive behavior In asynchronous cases: can explain absence of second primary
16	Endometrioid Ca: variants Villoglandular Ca Secretory Ca Ciliated cell Ca Endometrioid Ca with squamous differentiaton
17	Villoglandular Ca Numerous villous fronds, long and slender Delicate fibrovascular core Columnar cells , polarity maintained Nuclei: usual grade 1 or 2
18	Villoglandular Ca
19	Villoglandular Ca
20	Villoglandular Ca
21	Villoglandular Ca: DD Villoglandular Ca: long papillae slender papillae fibrovascular connective tissue little atypia regular luminal border cohesive cells Serous Ca: short papillae broad papillae fibrous connective tissue severe atypia irregular luminal border: micropapillae dyscohesive cells
22	Villoglandular Ca
23	Serous Ca: typical presentation
24	USC: cave slender papillae
25	Villoglandular USC
26	CAVE !!!!! Micropapillary variant of endometrioid Ca Short papillae, not complex Bland cytology Cells not dyscohesive Not an official WHO-variant Prognosis worse than endometrioid NOS
27	Micropapillary endometrioid Ca
28	Endometrioid Ca: micropapillary
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31	Secretory Ca resembling early secretory endometrium vacuoles in cytoplasm of most cells sub- or supranuclear nuclei usual grade 1 without stratification
32	Secretory Ca
33	Secretory Ca
34	Secretory Ca: DD Secretory Ca glandular endometrioid NOS cells columnar nuclei eccentric grade 1 Clear Cell Ca often solid serous Ca cells round, polygonal nuclei central severe atypia frequent hobnail
35	Secretory Ca vs Clear cell Ca
36	Ciliated cell Ca Almost always grade 1 often cribriform pattern prominent eosinophil cytoplasm Cilia (not always) - cuticula Nuclear membrane irregular Coarse chromatin Prominent nucleoli
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38	Ciliated cell carcinoma
39	Ciliated cell Ca Associated with endometrioid Ca NOS, or mucinous Ca Cilated cells must predominate
40	Endometrioid Ca with squamous differentiaton = adenosquamous Ca + adenoacanthoma is squamous component malignant ? difficult to assess no clinical significance
41	Endometrioid Ca with squamous differentiaton 10% of the tumour has to be squamous Sometimes only intraluminal Glandular component predominates
42	Squamous differentiation: intraluminal
43	Squamous differentiation: surface
44	Endometrioid Ca with squamous differentiaton: grading Prognosis does not depend on assessment of malignancy of squamous zones Architectural grade of glandular component Identify squamous zones and IGNORE them while grading
45	Endometrioid Ca with squamous differentiation: grading
46	Endometrioid Ca with squamous differentiaton Solid zones of undifferentiated cells: regard as glandular unless: Intercellular bridges Large cells with eosinophilic cytoplasm and clear cellboundaries
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48	Endometrioid Ca with squamous differentiaton: DD Atypical hyperplasia with metaplasia/EIN Granuloma High-grade non-squamous component !!! Primary Cx: Signet cells: rather in Cx
49	Endometrioid Ca with squamous diff: metastasis Remains glandular and squamous 20% only glandular component 8% only squamous component
50	Endometrioid Ca with squamous differentiation and keratingranulomas If keratin without viable tumourcells: ignore while staging Consider only as tumour if also viable tumourcells are present !!!
51	Keratingranuloma
52	Keratingranuloma
53	Glassy cell carcinoma Very rare in Em: no official variant More frequent in cervix Considered to be an undifferentiated adenosquamous Ca Very aggressive
54	Glassy cell Carcinoma Polygonal cells in solid sheets “glassy” cytoplasm Fibrous stroma Abundant inflammatory cells In Cx: eosinophils !!
55	WHO-classification of EM-Ca Endometrioid adenoCa Mucinous Ca Serous Ca Clear cell Ca Undifferentiated Ca Mixed cell adenoCa Squamous cell Ca Transitional cell Ca Small cell Ca Others
56	Mucinous carcinoma Rare in pure form Looks like mucinous Ca of endocx 50 % of cells : PAS+ mucin in cytoplasm diastasis resistent
57	Mucinous carcinoma (villo)glandular pattern uniform columnar cells HE: granular, not clear ! dilated glands with mucin and leukocytes
58	Mucinous Ca
59	Mucinous Ca
60	Mucinous Ca
61	Mucinous carcinoma: nuclei Few mitoses mild to moderate atypia minimal stratification
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64	Grading mucinous carcinoma No rules !!! By convention : rules of endometrioid Most are grade 1
65	Mucinous Ca: DD Other types Em Ca MGH Cx Mucinous Ca Cx
66	Mucinous Ca: DD with other types of Em-Ca serous Ca, clear cell Ca: PAS: not diastasis resistent morphology: clear or eosinophil, not granular cells more polygonal, hobnail atypia secretory Ca clear cytoplasm
67	Mucinous Ca: DD
68	Mucinous Ca: DD with benign MGH microglandular hyperplasia cx: age less atypia, less complex mitoses: up to 3/1O HPF in MGH subnuclear vacuoles only in MGH subcolumnar squamous metaplasia: MGH Vim - in MGH, + in 90% of MGC
69	Microglandular Ca Variant of mucinous Ca
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71	DD Em - endocervical ? Site Age HE IHC
72	HE in DD Em-Endocx Foam cells Squamous component Mucinous component Endometrioid
73	Foam cells Not only in carcinoma If in carcinoma: rather Em than Ecx
74	Squamous component Benign squamous component: EM Extensive squamous component: EM Luminal squamous component: EM
75	Mucinous component Endocx: more atypia hyperchromatic nuclei more mitoses and apoptosis coarse chromatine Look for associated CIN or EGD
76	Endometrioid features Endometrioid Ca of endocx is NOT recognised by most authors Considered to be “Mucinous Ca with little or no mucin” Endometrioid features do NOT help
77	Em Ca vs Ecx Ca: IHC McCluggage: A panel of immunohistochemical stains, including CEA, Vim and ER, aids in the distinction between primary endometrial and endocervical adenoCa Int J Gynecol Pathol 2002; 21: 11-15 Kamoi: Immunohistochemical staining in the distinction between primary endometrial and endocervical adenoCa: another viewpoint Int J Gynecol Pathol 2002; 21: 217-223
78	DD Em/Cx: IHC Primary Em ER + Vim + CEA - P16 - Primary endocx ER - Vim - CEA + P16 +
79	Endometrial Ca: Receptor +
80	Vimentin Dabbs: Intermediate filaments in endometrial and endocervical carcinomas. The diagnostic utility of vimentin patterns. Am J Surg Path 1986; 10: 568-576 Endometrial Ca +, Ecx - Not completely specific
81	CEA Cohen: Endocervical and endometrial adenocarcinoma: an immunoperoxidase and histochemical study. Am J Surg Pathol 1982; 6:151-157 Often present in Ecx Ca, not in Em Ca Not completely specific
82	DD Em - Ecx: p16 Mc Cluggage: p16 may assist in distinction between endometrial and endocx adenoca I J Gynecol Pathol 2003, 22: 231-235 Ecx: 22/23 diffusely + Em: most are + but focal (sometimes 100 % +)
83	Type I endometrial Ca Endometrioid Ca Villoglandular Secretory Ciliated cell With squamous differentiation Mucinous Ca