BSD 2015 Case 19. Female 21. Nodule on forehead. The best diagnosis is:

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1 BSD 2015 Case 19 Female 21. Nodule on forehead. The best diagnosis is: A. mixed tumour of skin B. porocarcinoma C. nodular hidradenoma D. metastatic adenocarcinoma

2 BSD 2015 Case 19 Female 21 Nodule on forehead

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5 BSD 2015 Case 19 Female 21. Nodule on forehead. The best diagnosis is: A. mixed tumour of skin (chondroid syringoma) B. porocarcinoma C. nodular hidradenoma D. metastatic adenocarcinoma

6 BSD 2015 Case 19 mixed tumour of skin (chondroid syringoma) Clinical features: Male, middle age commonest Slow growing nodule Dermis and/or fat Head and neck mainly, can be trunk or extremities

7 BSD 2015 Case 19 mixed tumour of skin (chondroid syringoma) Histological features: Apocrine > eccrine Mulilobulated Well circumscribed Variable nests, cords, glandular structures, cystic spaces Can show clear cell change or mucinous metaplasia like hidradenomas Also mixed sebaceous or follicular differentiation in some Metaplastic fat, chondroid material, bone in some

8 BSD 2015 Case 19 mixed tumour of skin (chondroid syringoma) Histological features: No nuclear pleomorphism, necrosis or increased mitotic index Myoepithelial cells present May be plasmacytoid (similar to hidradenoma) Inner cell layer AE1/AE3, CEA, EMA, GCDFP-15 pos Outer layer S100 pos, SMA may be pos

9 BSD 2015 Case 19 mixed tumour of skin (chondroid syringoma) PLAG1 rearrangement as in salivary gland pleomorphic adenoma Distinct from skin/soft tissue myoepithelioma Jo VY, Fletcher CD Head Neck Pathol Mar;9(1):32-8. Epub 2015 Mar 25. Myoepithelial neoplasms of soft tissue: an updated review of the clinicopathologic, immunophenotypic, and genetic features.

10 BSD 2015 Case 19 mixed tumour of skin differential diagnosis: porocarcinoma porocarcinoma strands of tumour raining down

11 BSD 2015 Case 19 mixed tumour of skin differential diagnosis: porocarcinoma porocarcinoma malignant duct lumen porocarcinoma normal pre-existing sweat duct

12 porocarcinoma CEA highlights malignant duct porocarcinoma DPAS highlights malignant duct cuticle surrounding central mucin globule

13 BSD 2015 Case 19 mixed tumour of skin differential diagnosis: nodular hidradenoma

14 BSD 2015 Case 19 mixed tumour of skin differential diagnosis: nodular hidradenoma

15 BSD 2015 Case 19 mixed tumour of skin differential diagnosis: metastatic adenocarcinoma

16 Cytokeratin 15, podoplanin and p63 positive in most primary skin adnexal neoplasms and negative in metastatic adenocarcinoma Cytokeratin 15 Expressed in sebaceous glands, outer root sheath of the hair follicle including bulge area, adult epidermis most specific for primary skin adnexal carcinomas (98%) P63 member of p53 gene family transcription factor for maintaining epithelial stem cell proliferation normal expression basal and lower part of epidermis, peripheral cells of eccrine ducts, apocrine glands, basal cells of sebaceous glands % of adnexal neoplasms, 14% of metastatic adenocarcinomas most sensitive of these markers Podoplanin : strongly positive in normal basal cells of sebaceous glands basal layer of outer root sheath of hair follicles including the bulge area basal layer of epidermis stains 0-4% of metastatic adenocarcinomas only 86% of primary skin neoplasms (but 65% only focally positive) Malignant stained more than benign 40% basal cell carcinomas positive for podoplanin Positivity for all 3 makers very good evidence for primary skin adnexal carcinoma

17 Cytokeratin 15, podoplanin and p63 positive in most primary skin adnexal neoplasms and negative in metastatic adenocarcinoma Plaza JA, Ortega PF, Stockman DL, Suster S. Value of p63 and podoplanin (D2-40) immunoreactivity in the distinction between primary cutaneous tumors and adenocarcinomas metastatic to the skin: a clinicopathologic and immunohistochemical study of 79 cases. J Cutan Pathol Apr;37(4): Liang H, Wu H, Giorgadze TA, Sariya D, Bellucci KS, Veerappan R, Liegl B, Acs G, Elenitsas R, Shukla S, Youngberg GA, Coogan PS, Pasha T, Zhang PJ, Xu X. Podoplanin is a highly sensitive and specific marker to distinguish primary skin adnexal carcinomas from adenocarcinomas metastatic to skin. Am J Surg Pathol Feb;31(2): Mahalingam M, Nguyen LP, Richards JE, Muzikansky A, Hoang MP. The diagnostic utility of immunohistochemistry in distinguishing primary skin adnexal carcinomas from metastatic adenocarcinoma to skin: an immunohistochemical reappraisal using cytokeratin 15, nestin, p63, D2-40, and calretinin. Mod Pathol May;23(5):713-9.

18 P63 expression: normal skin D2-40 (podoplanin) normal skin may also show staining of base of epidermis (not seen here)

19 P63 normal skin P63 mixed tumour

20 D2-40 (podoplanin) normal skin D2-40 (podoplanin) mixed tumour D2-40 (podoplanin) sebaceoma

21 Metastatic colorectal adenocarcinoma P63 negative CK7 negative (stains adnexal structures) D2-40 (podoplanin) negative

22 Metastatic colorectal adenocarcinoma P63 negative D2-40 (podoplanin) negative CK20 positive

23 Mixed tumour: Cytokeratin 7 Mixed tumour: Cytokeratin 20

24 Malignant Mixed tumour: Infiltrative growth pattern cytological atypia necrosis increased mitotic activity BSD 2015 Case 19 Female 21. Nodule on forehead. The best diagnosis is: mixed tumour of skin porocarcinoma nodular hidradenoma metastatic adenocarcinoma

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