Cytology of papillary lesions of the breast

Transcription

1 Cytology of papillary lesions of the breast Are you ready?

2 Papillary lesions include Intraductal papilloma Intraductal papilloma Intraductal papilloma with atypical ductal hyperplasia Intraductal papilloma with ductal carcinoma in situ Intraductal papilloma with lobular neoplasia (florid) papillomatosis of the nipple Intraductal/intracystic papillary carcinoma Encapsulated papillary carcinoma solid papillary carcinoma Invasive papillary carcinoma Invasive micropapillary carcinoma

3 Epidemiology and clinical features of intraductal papillomas Approx 5 % of benign breast lesions Most of them located centrally Mean age 48 yrs, but commonly also presents in the 6 th and 7 th decades Central papillomas may present with unilateral bloody or serous-bloody nipple discharge Less common presentation as palpable mass Mx circumscribed (retroareolar) benign appearing mass, a solitary (retroareolar) dilated duct and rarely microcalcifications US well defined smooth-walled cystic nodule with solid components Peripheral lesions often clinically occult, but may also cause nipple discharge and evt a mass as a result of a small cluster of papillomas Peripheral lesions tend to be mx occult, but may present as microcalcifications Size from a few mm up to > 5 cm

4 Cytological findings in plain intraductal papillomas Variable cellularity with a basic benign pattern The epithelial cells are often seen as small groups Complex, folded three dimensional epitehlial aggregates Stromal fragments

5 monolayer small groups benign nuclei macrophages

6 Large monolayer complex folded sheets

7 In PAP Monolayer Myoepithelial benign nuclei

8 Cohesive papillary clusters

9 (Micro-)papillary clusters, bipolar cells

10 Papillary stromal fragments

11 Apocrine cells A small amount of debris and macrophages

12 Can we make a definite/confident diagnosis of benign intraductal/intracystic papilloma? The Accuracy of the Triple Test in the Diagnosis of Papillary Lesions of the Breast. Papeix G.a Zardawi I.M.b Douglas C.D.d Clark D.A.d Braye S.G.c. Acta Cytologica 2012;56:41 46 (DOI: / ) Background and Objective: The literature on fine-needle aspiration (FNA) cytology for papillary lesions presents a very mixed picture. Many authors advocate mandatory excision of these lesions. This recommendation is largely based on the atypical nature of the FNA report. The aim of this work is to see if breast papillomas can be treated conservatively. Study Design: We report a retrospective study of outcomes for patients with a provisional diagnosis of a papillary breast lesion based on assessment by palpation (no clinically suspicious features), sonography (benign or probably benign according to the Breast Imaging Reporting and Data System BI- RADS ), and FNA (benign cytological category with a papillary architecture) findings from one integrated breast service. Results: Thirty-six cases were identified over a period of 6 years. Thirty-four of the patients had surgical excision. All of the 34 surgical cases were confirmed to be benign in nature on histopathology (intraduct papilloma). The remaining 2 cases were stable on follow-up. Conclusion: We believe that a policy of mandatory excision of papillary lesions of the breast is unnecessarily cautious.

13 Cytological findings in cellular papillary lesions Marked epithelial proliferation Hyperplasia with and without atypia A mixed cell population, both benign and irregular/atypical Threedimensional aggregates that may resemble ADH/low grade DCIS solid cribriform Papillary fragments and fibrovascular stalks

14 Cellular papillary lesion Moderate to distinct cellular/nuclear pleomorphism but with a fine chromatin pattern Nucleoli may be distinct Usually the epithelial fragments are rather cohesive but a population of single cells is not uncommon

15 Cytological immunophenotype benign papillary tumours benign intraductal/intracystic papilloma, including cellular due to adenosis, UDH etc p63 positive cells in papillary fronds HMW cytokeratins (5/6 and 14) positive in myoepithelial cells and in UDH ER/PgR patchy positive Intraductal/intracystic papilloma with ADH/DCIS In the benign cell population as above In aggregates of ADH/DCIS p63 and HMW cytokeratin are negative ER/PgR uniform positive

16 Reporting strategy cellular papillary lesion C2-C3-C4 In text: cellular papillary lesion with/without atypia; favor. cellular papillary lesion with low grade atypia/population of low grade atypical cells; uncertain benign or low grade malignant Recommendation: histological confirmation/local excision

17 Florid papillomatosis of the nipple (subareolar papillomatosis) A benign epithelial proliferation localized within and around the collecting ducts of the nipple < 1 % of breast specimens Age range yrs with a mean of 43 yrs About 2/3 present with nipple discharge About 1/3 present with nipple erosion or a nodule Clinical impression might mimic Paget s disease of the nipple

18 Cytologic findings in subareolar papillomatosis Moderate or high cellularity with a basic benign pattern Adenosquamous nests may be apparent Small amount of debris, inflammatory cells and siderophages may be found

19 Aggregates and smaller groups, background debris

20 Basically cohesive, irregular aggregates

21 Irregular shapes

22 Micropapillary, macrophages, naked nuclei

23 Uniform nuclei with finely distributed chromatin and small nucleoli

24 Little anisonucleosis, occasional hyperchromatic nuclei possible

25 (Occasional) dispersed epithelial cells

26 Apocrine cells may be present

27 Intraductal/intracystic papillary carcinoma (in situ) Non-invasive Clear or blood stained nipple discharge More peripheral lesion may present as a mass Mx microcalcifications Ducts or TDLU with slender, branching fibrovascular stalks covered by a single cell population of neoplastic cells Micropapillary, cribriform and solid growth patterns also Neoplastic, columnar cells in one or several layers Cells deceptively bland; low grade atypia ER/PgR positive; HER2 negative

28 Cytological findings 1 Cystic Micropapillary groups True papillary fragments with a fibrovascular core Denuded fibrovascular core

29 Cytological findings 2 Monotonous tumour cell population, usually with a very discrete nuclear/cellular atypia Variable single cell population

30 Intracystic papillary carcinoma in situ grade 3

31 Encapsulated papillary carcinoma A variant of papillary carcinoma characterized by fine fibrovascular cores covered by neoplastic cells of low or intermediate grade and surrounded by a fibrous capsule In the majority of cases there are no myoepithelial cell layer within the papillae or at the periphery of the lesion Circumscribed round mass With or without nipple discharge frank invasive part is usually IDC ER/PgR positive; HER2 negative

32 Cytological findings Few macrophages Abundant cell material Single cell population Fibrovascular cores

33 Monolayer sheets

34 Siderophages, irregular groups

35 Discrete nuclear/cellular atypia

36 Solid papillary carcinoma Closely apposed expansile nodules Delicate fibrovascular cores within the nodules Frequent neuroendocrine differentiation Conventional invasive growth may be present, often having mucinous or neuroendocrine features < 1 % of breast carcinomas (???) Occurs usually in menopausal women, mean in the seventh decade Bloody discharge in % Mx abnormality, may be palpable Size from few mm to several cm ER/PgR positive; HER2 negative

37 Cytological findings Few if any macrophages Abundant cellularity Often columnar Intracytoplasmic vacuoles are not rare neuroendocrine differentiation common

38 (pseudo)-papillary arrangement of cells

39 Low grade nuclear/cell atypia

40 Often extensive dissociation in single cells In this case also neurendocrine differentiation

41 Cytological features of papillary carcinomas (cystic in situ, encapsulated and solid) May be cystic on aspiration Cell material is usually abundant Epithelial cells are monotonous and appear monoclonal Anisonucleosis, hyperchromasia, coarse chromatin and prominent nucleoli are uncommon Benign bipolar cells are absent from the background and myoepithelial cells are not seen within the groups Large papillary cell clusters forming arborising arrays bearing overlapping, palisaded cells on a fibrovascular core may be present (as in papilloma) Cells may be dispersed and the fibrovascular cores denuded Cells are often distinctly columnar in appearance Evaluation of invasive component not possible Usually G1, but occasionally G2 or G3 Microcalcifications are common findings

42 Reporting categories papillary carcinomas C3-C4 In text Cell material consistent with/ suspicious of papillary carcinoma; cannot evaluate invasiveness

43 Invasive papillary carcinoma (WHO definition) Predominantly papillary morphology (> 90 %) in the invasive component No specific known clinical characteristics Rare No specific epidemiological data available Main differential diagnosis is a papillary carcinoma metastatic from another organ site, particularly ovary and lung

44 Diagnostic considerations cellular (benign) papillary lesions vs papillary carcinoma (1) Cellular papillary lesion Heterogeneous ( polyclonal ) cell population Basic benign pattern, but may have a population of cells showing low grade nuclear atypia/anisonucleosis Straight or curved tubular structures representing adenosis in papilloma Mostly cohesive, but with single cells Papillary carcinoma Monomorphous ( monoclonal ) cell population More discohesive, often extensive

45 Diagnostic considerations cellular (benign) papillary lesions vs papillary carcinoma (2) Threedimensional cells aggregates representing/resembling low grade DCIS, solid and/or cribriform can be found in both lesions Papillary and micropapillary groups in both lesions Fibrovascular stalks in both lesions Debris and macrophages in both lesions A distinct population of cells epithelial groups with positivity for p63 and HMW cytokeratins speak in favor of a benign lesion Uniform and distinct positivity for ER/PgR speak in favor of a papillary carcinoma

46 Invasive micropapillary carcinoma Composed of small, hollow and morula-like clusters of cancer cells and surrounded by clear stromal places Usually a reversed polarity, a in side out growth pattern whereby the apical pole of the cells faces the stroma and not the luminal surface % of invasive breast cancers Up to 7.4 % may show invasive breast cancers may have partial micropapillary growth pattern Mean age as IDC Usually present as a palpable mass 75 % are grade 2 and 3 ER/PgR positive; HER-2 +/- (Luminal A/Luminal B)

47 You will see a number of papillary lesions in the workshop