FNAC of epithelial borderline and in situ lesions of the breast. FNAC of microcalcifications

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1 FNAC of epithelial borderline and in situ lesions of the breast FNAC of microcalcifications 1 Torill Sauer, Department Torill Sauer, Department of Pathology, of Akershus University Hospital University Hospital

2 Lesions included Ductal carcinoma in situ (DCIS) High grade Non-high grade Atypical ductal hyperplasia (ADH) Columnar cell lesions (CLL), including flat atypia Lobular neoplasi Atypical lobular hyperplasia (ALH) Lobular carcinoma in situ (classical) Pleomorphic lobular carcinoma in situ 2

3 Breast lesions associated with radiological microcalcifications Atrophy, inflammatory lesions Benign non-tumour conditions Adenosis UDH (usual ductal hyperplasia) Benign tumours papilloma fibroadenoma adenomyoepithelioma Borderline proliferative lesions (= columnar cell lesions) PLCIS Ductal carcinoma in situ Invasive lesions 3

4 Ductal carcinoma in situ (WHO definition) A neoplastic proliferation of epithelial cells confined to the mammary ductal-lobular system A subtle to marked cytological atypia An inherent but not necessarily obligate tendency for progression to invasive breast cancer 4

5 (Histologic) growth pattern subtypes of DCIS Solid Cribriform Micropapillary Papillary Comedo Non-comedo Apocrine Signet ring type Clear cell type Flat/ clinging All subtypes are reflected in the cytological specimens 5

6 (Histological) grading of DCIS Depends primarily on the nuclear atypia Low nuclear grade Small monomorphic cells (growing in arcades, micropapillae, cribriform or solid patterns) Intermediate grade Cells with mild to moderate variability in shape, size, chromatin pattern and variably prominent nucleoli Comedo type necrosis may be present High nuclear grade Highly atypical cells 6

7 Grading of DCIS Sauer T, Lømo J, Garred Ø, Næss O. Cytologic features of ductal carcinoma in situ in fine-needle aspiration of the breast mirror the histopathologic growth pattern heterogeneity and grading. Cancer Cytopathol 2005;105:21-7. (modified Van Nuy) Cytological grading of DCIS high grade DCIS G3 (irrespective of growth pattern as well as comedo type necrosis or not): > 2 x RBC non-high grade DCIS: < 2 x RBC comedo type necrosis seen: G2 Concordance with histology 95 % 7 Torill Sauer, Department Torill Sauer, of Pathology, Department Akershus of Pathology, University Akershus Hospitak University Hospital

8 In a setting of mammographic microcalcifications WITHOUT a tumour the following features are characteristic of high grade DCIS: 8

9 Threedimensional solid or cribriform aggregates 9

10 Nuclei > 2 x RBC 10

11 Comedo type necrosis 11

12 Microcalcifications 12

13 Ocassionally papillary or micropapillary 13

14 Variable number of single cell component Note also the microcalcifications! 14

15 Dissociation in single cells is (still) a criterion of malignancy, But it is NOT a feature of invasiveness 15

16 Diagnostic considerations high nuclear grade DCIS Some cases of IDC grade 3 may present cytologically with necrosis and microcalcifications on FNAC, but the radiology will be that of a tumour A few DCIS may be tumour-forming (-8 % with radiological mass or assymetry) Palpable tumours with cytologic characteristics like DCIS are invasive in 97 % of the cases Microinvasion will not be sampled Invasive lesions not recognised radiologically will not have been sampled and about 20 % of radiological DCIS will have an invasive component in the surgical specimen Single cells are not a feature of invasion 16

17 DCIS varia In a setting of microcalcifications without tumour a diagnosis of high grade DCIS may be given The question is not «invasive OR in situ», but «is there an invasive component in addition to the DCIS?» The larger the extent of high grade DCIS, the larger the risk of an additional invasive component In a setting of radiological tumor, approx 97 % of the lesions are invasive (with or without an in situ component) 17

18 non-high grade DCIS In a setting of microcalcifications without tumor, the following is characteristic of a none-high grade DCIS (low and intermediate grades) 18

19 Very large three-dimensional aggregates;solid, cribriform and often more cohesive than high grade lesions 19

20 Cell monotony 20

21 Micropapillary groups 21

22 True papillary structures 22

23 Monolayer (two-dimensional) sheets +micropapillary 23

24 Variable number of single cells 24

25 Microcalcifications 25

26 Occasional comedo type necrosis 26

27 Low to moderate/intermediate nuclear atypia 27

28 Diagnostic pitfalls and considerations in low- and intermediate-grade DCIS The cytological criteria overlap with epithelial hyperplasia with and without atypia (ADH, columnar cell lesions) A diagnosis suggestive of non-high grade DCIS should ONLY result in a diagnostic biopsy for confirmation, never mastectomy or ALND Some of the lesions might appear deceivingly monotonous, in contrast to some benign, hyperplastic lesions with a polymorphous cell pattern Numerous single cells are not indicative of an invasive lesion Myoepithelial cell nuclei on the epithelial groups are no «proof» of a benign lesion. Pure subtypes as to growth pattern is virtually non-exisent 28

29 Diagnostic categories low grade DCIS Equivocal C3-C4 proliferative with low grade atypia suspicious for low grade DCIS/ADH 29

30 Columnar cell lesions (WHO) CCC and CCL are lesions of the terminal-duct lobular unit (TDLU) enlarged, variably diated acini lined by columnar epithelial cells Flat epithelial atypia is a neoplastic alteration of the TDLU replacement of the native epithelial cells by one to several layers of a single epithelial cell type showing low-grade (monomorphic) cytological atypia Radiologically seen as grouped microcalcifications 30

31 Cytological features of the columnar cell lesions have not been published in the cytological literature, but. 31

32 Monolayer sheets, microcalcifications and debris 32

33 Crowded palisading strips 33

34 Complex sheet/aggregate 34

35 Secretoric debris/mucous material, macrophages, microcalcifications 35

36 CLL diagnostics and pitfalls/caveats The full spectrum of cytologic features is not known The entity of CLL harbor a continous spectrum of architectural and cellular/nuclear changes from «benign» to «flat atypia» Myoepithelial cells/nuclei are often absent None or low grade nuclear atypia Is a risk lesion for simultaneous ILC TUB LCIS/ALH Low grade DCIS/ADH Risk of over- and underdiagnosis Reporting category: proliferative, with or without atypia, and with a reccommendation of biopsy 36

37 Example CLL 65 yrs Group of microcalcifications 1 cm US-guided FNAC 37

38 38

39 TUB CLL 39

40 Lobular neoplasia lobular carcinoma in situ several variants of lobular carcinoma in situ (LCIS) have been recognized classical type pleomorphic LCIS (PLCIS) LCIS with Comedo Necrosis carcinoma in situ with mixed ductal and lobular features clear cell variant signet ring cell variant 40

41 Pleomorphic lobular carcinoma in situ (PLCIS) Sneige N et al. Mod Pathol 2002 Cells appear dyshesive More pleomorphism than in classical LCIS Usually abundant cytoplasm Cytoplasm may appear eosinophilic or granular (apocrine appearance) Comedo type necrosis and microcalifications common 41

42 PLCIS radiologically they appear as suspicious microcalcifications (almost always present) can be difficult to differentiate from ductal carcinoma in situ (on histology) The dyshesive appearance of the cells is helpful in making this diagnosis, lack of E-cadherin 42

43 Immunophenotype of PLCIS ER/PgR positive E-cadherin negative may show HER2 protein overexpression/gene amplification (particularly if associated with invasive carcinoma) may show p53 positivity moderate to high Ki67 labeling index 43

44 Cytologic features of PLCIS Solid three-dimensional aggregates Dyscohesive with loosely cohesive cells and often abundant single cells Variable, but often abundant cytoplasm; often granular and eosinophilic Distinct cellular pleomorphism with variable cellular size and shape Often plasmacytoid Cytoplasmic vacuoles more common in PLCIS than in DCIS Distinct nuclear pleomorphism with nuclear size up in the range of high grade DCIS (> 2x RBC) Comedo type necrosis and microcalcification AS IN DCIS 44

45 Cell dissociation and pleomorphism 45

46 Comedo necrosis and microcalcifications 46

47 Microcalcification 47

48 Solid, threedimensional aggregates and myoepithelial cells 48

49 Cytoplasmic vacuoles and amount of cytoplasm 49

50 PAP and ThinPrep morphology 50

51 Which means: Nuclear features, amount and appearance of cytoplasm, dissociation and pleomorphism are not distinguishable from high nuclear grade DCIS No cytomorphological feature(s) that definitely separates PLCIS and high grade DCIS 51

52 If you consider PLCIS: E-cadherin ICC 52

53 Diagnostic considerations PLCIS Obviously malignant cells Radiological microcalcification without tumour, suspicious of high grade DCIS Total overlap with cytological criteria of high grade DCIS Perhaps more plasmacytoid in appearance and with more cytoplasm than most DCIS Cytoplasmic vacuoles more common than in DCIS Nuclear size > 2 x RBC, but usually not very much larger Previously diagnosed as DCIS in histology and cytology As of today: no difference in treatment 53

54 End of session! 54

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