1	Benign mimics of endometrial carcinoma Dr. G. Jacomen AZ St Maarten Duffel
2	Benign vs malignant 1. Epithelial cytoplasmic change 2. Hyperplasia with atypia vs EIN 3. Diagnosis of grade 1 carcinoma 4. EIC 5. Endometrial polyps
3	Epithelial cytoplasmic change Syn = metaplasia Common in hyperplasia DD : atypia ECC by themselves have no neoplastic potential
4	Types of cytoplasmic change Squamous Ciliated cell Eosinophilic Mucinous Secretory: Clear cell Hobnail cell
5	Squamous differentiation Sign of estrogenic stimulation Often in hyperplasia Can be found in all grades of carcinoma
6	Squamous differentiation: histology Often nonkeratinizing Keratinizing: more often in carcinoma Morules Solid nests of uniform eosinophilic cells Indistinct cell borders Often intraluminal Central necrosis can occur
7	Squamous differentiation: cytology Bland cytology Nuclei: uniform, round to oval centrally placed Rare mitosis Small nucleoli Cytoplasm: dense eosinophilic
8	Morulae
9	Morulae
10	Morulae ¹ squamous !!! Morulae are often CK - S100 + Probably neurogenic differentiation Makishi: Morules and morule-like features associated with carcinomas in various organs: report with immunohistochemical and molecular studies JCP 59 (2006): 95-100
11	Morulae
12	Ciliated cell change Syn = tubal metaplasia Ciliated cells can normally occur along surface epithelium Glands lined by ciliated cells are not normal !
13	Ciliated cell change: significance Sign of unexposed estrogens Can occur in hyperplasia
14	Ciliated cells: histology Small groups between nonciliated cells Cytoplasm: pale to eosinophilic Luminal border: Cilia Cuticle of dense cytoplasm
15	Ciliated cells: cytology Nuclei: mildly stratified round to oval slightly enlarged even chromatin distribution Small nucleoli No mitosis
16	Ciliated cell change
17	Ciliated cell change
18	Ciliated cells: DD Nuclear features of enlargement and more rounded appearance è DD atypical hyperplasia
19	Eosinophilic cell change Can be variant of : Ciliated cells Squamous cells Oncocytes Eosinophilic syncytial change
20	Eosinophilic cell change Can occur in Atypical hyperplasia Low-grade adenoCa Important not to overlook a (pre)malignant process
21	Eosinophilic cell change
22	Eosinophilic cell change
23	Eosinophilic syncytial cell change
24	Mucinous change: histology Abundant mucinous cytoplasm Resembles normal endocervix Often small papillary projections
25	Mucinous change: cytology Columnar cells Basal nuclei, small and uniform Abundant pale supranuclear cytoplasm Rarely goblet cells: “intestinal metaplasia”
26	Mucinous cell change
27	Mucinous change: importance Most often in association with carcinoma or atypical hyperplasia Careful examination of the rest of the endometrium is necessary
28	Secretory cell change Exclude progestin-related effects If excluded: very rare Usually focal: limited to scattered glands
29	Secretory cell change: cytology Clear cytoplasm: glycogen Resembles secretory or gestational endometrium Hobnail cells can occur Resembles Arrias-Stella
30	Secretory cell change In endometrium with estrogenic effects: hyperplasia to carcinoma
31	Secretory cell change Diffuse secretory change in hyperplasia: “ secretory hyperplasia “ In pre- or perimenopausal women with hyperplasia and sporadic ovulation or treatment with progestins
32	Secretory cell change
33	Secretory cell change
34	Epithelial cytoplasmic change: DD with atypia Atypia Nuclei enlarged Nuclei rounded Vesicular chromatin Irregular nuclear membrane Nuclei stratified ECC Relative bland features
35	EIN or atypical hyperplasia? EIN ¹ EIC !!!!! Clonal proliferation of mutated cells PTEN suppressor gen deficient
36	EIN: diagnostic criteria Area of glands greater than stroma VPS < 50 % Morphometry In this focus: abnormal cytology Size > 1 mm IHC: PTEN -
37	Hyperplasia: WHO classification Simple hyperplasia without atypia Complex hyperplasia without atypia Simple hyperplasia with atypia Complex hyperplasia with atypia
38	Simple or complex ? Complex = adenomatous Degree of glandular crowding and structural complexity Often coexistence No clinical importance
39	Atypical or not ? Specific nuclear features Nuclei round and enlarged, not oval Loss of polarity, stratification Vesicular coarse chromatine Prominent nucleoli
40	EIN or atypical hyperplasia ? Still debate !!! Future will tell EIN offers pathogenetic model, PTEN and morphometry not always available Use of WHO (atypical hyperplasia) is standard, reproducible, well known by pathologists and clinicians
41	Criteria for the diagnosis of grade1 carcinoma = criteria for identification of stromal invasion 3 features, 1 is sufficient
42	Criteria for stromal invasion Confluent glandular pattern Desmoplastic reaction of stroma Extensive papillary pattern
43	Confluent glandular pattern Individual glands merge No intervening stroma Cribriform pattern
44	Confluent glandular pattern
45	Confluent glandular pattern
46	Desmoplastic reaction Stromal cells that are more spindle-shaped Nuclei elongated Eosinophilic appearance
47	Desmoplastic stroma
48	Desmoplastic stroma: DD Dense stroma in polyps Stromal alteration due to marked inflammation Stroma of lower uterine segment Stroma of atypical polypoid adenomyoma
49	Fibrous stroma in polyp
50	Extensive papillary pattern Feature of villoglandular carcinoma Stroma is not desmoplastic
51	Villoglandular Ca
52	Identification of stromal invasion Features should be quantitatively significant At least half of a low-power field (x4) = 2 mm Don’t use this too rigid !!
53	Endometrial intraepithelial carcinoma Precursor of type 2 carcinoma Do NOT confuse with EIN (precursor of type 1)
54	EIC severe atypical cells on surface and in glands hobnailcells p53 diffuse and intense + (not always)
55
56	EIC: cytology
57	EIC: importance Can be disseminated even in absence of invasive carcinoma Mimics metastatic serous carcinoma of ovary
58	EIC: DD Arias-Stella Reactive hobnailcells due to polyp, post biopsy, … Metaplasia
59	EIC or not? Hobnailcells Less cohesion Atypia Age: 29 Rest:
60	Arias-Stella
61	EIC or not? Large cells Atrophic endometrium Little atypia Post-curetting
62	EIC or not ? Large cells Eosinophilic cytoplasm No nuclear enlargment No atypia Metaplasia
63	Endometrial polyps: diagnosis Large tissue fragments Surface epithelium on 3 sides Dense stroma, sometimes fibrous Thick-walled vessels
64	Polyp Large fragment Surface epithelium on 3 sides Irregular and dilated glands Fibrous stroma
65	Polyp Large fragment Irregular glands Thick walled vessels Fibrous stroma
66	Thick walled vessels
67	Endometrial polyps: glands Glands more irregular, tortuous and dilated than normal glands Glands appearing “out-of phase” Distinct fragments with different appearance than other fragments
68	Polypous and non-polypous fragments Distinct appearance Glands irregular, tortuous Epithelium out of phase
69	Polyp with non-polypous endometrium
70	Endometrial polyps: helpful feature Normal glands have their axes perpendicular to the surface In polyps: glands loose their orientation Long axis parallel to surface Kim: A diagnostically useful histopathologic feature of endometrial polyp Am J Surg Pathol (2004) 28: 1057-1062
71	Endometrial polyp: axis of gland
72	Endometrial polyps: patterns Proliferative/hyperplastic Atrophic Functional Mixed endometrial-endocervical Adenomyomatous Atypical polypoid adenomyoma
73	Proliferative/hyperplastic polyp Irregular proliferating glands Pseudostratification nuclei Mitosis Looks like disordered proliferation or hyperplasia without atypia Identifying noninvolved endometrium !!
74	Endometrial polyp: hyperplastic type
75	Atrophic polyp Atrophic glands Low columnar epithelium Often dilated and cystic glands Dense fibrous stroma
76	Endometrial polyp: atrophic type
77	Functional polyp Difficult to diagnose Haphazard distribution of glands Loss of orientation
78	Endometrial polyp: functional type
79	Mixed endometrial/endocervical pattern Originiate in LUS or upper endocx Both endometrial and endocervical-type epithelium Fibrous stroma (like LUS)