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1 Enterprise Interest None

2 B3 lesions of the breast What are they at surgery? Case 4 Edi Brogi MD PhD Attending Pathologist - Director of Breast Pathology Memorial Sloan Kettering Cancer Center New York City NY 29 th European Congress of Pathology September 3rd, 2017

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4 Case 4 Clinical History 37 yo Female Imaging showed a 1.8 x 1.6 x 1.0 cm complex solid and cystic mass with increased vascularity in the solid component CBX diagnosis at an outside hospital: Atypical papilloma Excision case sent in consultation I requested to review the CBX

5 Case 4 CBX

6 Case 4 CBX

7 Case 4 - CBX

8 Case 4 Original CBX Diagnosis: Atypical papilloma

9 Case 4: Excision 1.3 x 1.2 x 1.0 cm irregular piece of tissue; entirely submitted

10 Case 4 - Solid and papillary neoplasm

11 hyalinized fibrovascular cores palisading

12 Solid proliferation of monotonous cells

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14 Small tubules and glands

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16 Case 4: Immunohistochemistry Antigen Result p63 Positive CK5/6 p40 CK5/6 Smooth muscle myosin CD10 Estrogen Receptor Progesterone Receptor Chromogranin Positive Positive Negative Negative Negative (<1%) Negative Negative P63

17 Differential Diagnosis Breast Solid and papillary carcinoma Mass-forming Invasive Lobular Carcinoma with solid growth / mass-forming LCIS mimicking a papillary carcinoma Invasive triple negative carcinoma? Papillary transitional cell carcinoma

18 DDX: Solid and papillary carcinoma Synaptophysin Estrogen Receptor(+++) Chromogranin(+/-) and/or synaptophysin(+/-) P63(-) and CK5/6(-)

19 DDX ER(+++) P63(-) and CK5/6(-)

20 LCIS with solid pattern normal duct ER(+++) P63(-) and CK5/6(-)

21 DDX very rare Mooney EE and Tavassoli FA Mod Pathol 1999:12:

22 DDX very rare Mooney EE and Tavassoli FA Mod Pathol 1999:12: No evidence of recurrent or metastatic disease was found in the four patients for whom follow-up was available; the length of follow-up ranged from 18 months to 11 years.

23 DDX very rare Mooney EE and Tavassoli FA Mod Pathol 1999:12: No evidence of recurrent or metastatic disease was found in the four patients for whom follow-up was available; the length of follow-up ranged from 18 months to 11 years. The transitional-like variant seems to behave in a fashion similar to that of other types of papillary carcinoma of the breast. Distinction of this malignant lesion from various benign lesions that occur in the same region is mandatory.

24 Differential Diagnosis Breast Solid and papillary carcinoma Mass-forming solid LCIS mimicking a papillary carcinoma Skin Nodular hidradenoma (aka eccrine acrospiroma) Invasive Triple negative carcinoma Invasive carcinoma with urothelial differentiation

25 Nodular hidradenoma (acrospiroma) Benign skin adnexal neoplasm eccrine or apocrine Sporadic, men=women, usually in adults Scalp, trunk, proximal extremities, hands, feet, eyelids Nodular (solid and cystic) mass in the dermis papillary (hidradenoma papilliferum) Cellular composition: Clear / pale cells containing glycogen (clear cell hidradenoma) Squamoid cells, central nucleus and eosinophilic cytoplasm Mucinous cells (uncommon) Cuboidal or columnar cells (lining tubules) Stroma often hyalinized Malignant transformation uncommon Complete excision is curative

26 Case 4 Dx: Nodular hidradenoma (acrospiroma) Benign skin adnexal tumor Initially misdiagnosed as atypical papilloma of the breast

27 Misdiagnosed as: Sclerosing papilloma (CBX) Carcinoma with urothelial differentiation (Excision) Breast Journal 2015: 21(6): eccrine acrospiroma CNB: one case misdiagnosed as sclerosing papilloma Mooney EE and Tavassoli FA Mod Pathol 1999:12:

28 Case #4 DX: Nodular hidradenoma Take Home Message Not all tumors involving the breast are mammary tumors If morphology and/or immunoprofile do not fit any specific breast lesion consider: Neoplasms of the skin adnexa Extra-mammary malignancy

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31 Management of Papillary Lesions Diagnosed at Rad-Path Concordant CNB Papilloma??? Atypical papilloma EXCISION Papillary DCIS EXCISION Papillary Carcinoma EXCISION

32 Factors that affect the rate of upgrade at EXC of papilloma w/o atypia Type and size of the imaging target mass lesion Ca 2+ MRI mass- or non-mass-like enhancement Needle gauge (14G) or vacuumassisted biopsy Fragmented vs non-fragmented cores Fragmentation more common for larger and more complex lesions The epithelium may be more difficult to evaluate in a fragmented specimen Complete removal by CNB Small papillomas and/ or vacuum assisted CNB

33 Upgrade rates to carcinoma or atypia in F/U EXC author year # # carcinoma at EXC total invasive DCIS atypia predictors of upgrade recommend Mercado (6%) 0 2 (5%) 8 (22%) none EXC Bernik (9%) NS NS 13 (28%) none EXC Lu (6%) 0 4 (6%) 8 (12%) none EXC Fu (6%) 0 12 (5.9%) 41 (20%) none EXC Tseng (29%) 2 (8%) 6 (25%) 0 none EXC Rizzo (9%) 2 (0.9%) 19 (8.1%) 42 (17.9%) none EXC Foley (14.3%) 7 (3.7%) 20 (10.6%) 21 (11%) older age EXC Glenn (4.7%) NS NS 25 (17%) none EXC Ahmadiyeh (3%) 0 1 (3%) NS none No EXC Li (2%) 1 (0.3%) 5 (1.3%) 1 P-LCIS (0.3%) 48 (13%) calcifications* No EXC (except*) Swapp none No EXC Hong (6%) 5 (2%) 9 (4%) NS age >54 y; size >1 cm No EXC Kim (2.6%) 2 (0.8%) 4(1.8%) 8 (5.6%) none No EXC Nakhlis (6.6%) 1 (2.2%) 2 (4.4%) NS palpable mass No EXC Pareja (2.3%) 2 (1.1%) 2 (1.1%) 39 (22.8%) TOTAL /2011 (7%) 22/ 1818 (1.2%) 86/1818 (4.7%) 1 PLCIS 253/ 1703 (15%) synchronous carcinoma No EXC

34 At present, no size cutoff for the DX of papilloma

35 Morphologic mimics of (micro)papilloma at CNB myoepithelial hyperplasia papillary usual ductal hyperplasia

36 (Micro)papilloma completely excised at rad-path concordant CNB No EXCISION

37 CNB Dx of papillary lesion w/o atypia Guidelines for management of high risk lesions American Society of Breast Surgeons The decision to excise a papillary lesion without atypia needs to be individualized based on risk, including such criteria as size; symptomatology, including palpability and presence of nipple discharge; and breast cancer risk factors. Those not excised should be followed closely with imaging. Palpability alone is not an absolute indication for excision. Papillary lesions Excision OR clinical and imaging F/U - Excise palpable lesions and those with atypia - Incidental, benign papillary lesions can be followed

38 Patient Management following CNB Dx of papilloma without No excision required Rad-path concordant findings No clinical symptoms Routine radiologic F/U planned (micro)papilloma completely removed by CNB Excision Recommended Rad-path discordant findings Patient is symptomatic (nipple discharge/ palpable mass) Patient undergoing surgery for synchronous breast cancer