Case 12 Female 71. Longstanding nodule from shoulder recently enlarging. Clinically sebaceous cyst

Case 12 Female 71. Longstanding nodule from shoulder recently enlarging. Clinically sebaceous cyst

Case 12 Malignant areas with marked atypia

Case 12: Malignant (spiradenocarcinoma), poorly differenated, arising in a benign spiradenoma – a relavely rare occurence

Spiradenocarcinoma:

spiradenocarcinoma either 1) well differenated and low grade resembling spiradenoma and retain lobularity, but no lymphocytes or two cell paern, or 2) Poorly differenated with no obvious spiradenomatous differenaon & rely on benign counterpart for diagnosis (as in this case) & Shows typical features of a malignant neoplasm:

spiradenoma • infiltrave border • lacks organised structure of spiradenoma • Lacks clearly demarcated two cell populaon of spiradnoma

Case 12: Malignant spiradenoma (spiradenocarcinoma), poorly differenated, arising in a benign spiradenoma – a relavely rare occurence

spiradenocarcinoma • typical features of a malignant neoplasm:

• Larger cells , overlapping nuclei.

• Increased mitoc acvity and cellular pleomorphism.

spiradenoma • Necrosis may occur (but can get degnerave change in spiradenoma mimicking necrosis)

• Oen long history, elderly, at any site

Spiradenoma Spiradenocarcinoma

Case 12: Malignant spiradenoma (spiradenocarcinoma), poorly differenated, arising in a benign spiradenoma – a relavely rare occurence

•72 paents in metaanlysis •35 paents with no distant metastasis, local resecon resulted in100% disease-free survival. •12 had lymph node metastases but no distant metastases • Of 7 paents with lymph node but no distant metastasis treated with surgical resecon and lymph node dissecon, 6 paents remained disease-free at final follow-up evaluaon

•24 cases with confirmed distant metastac disease •median survival 16 mpnths • paent survival did not significantly differ between local resecon and surgery with adjuvant chemoradiotherapy

CONCLUSIONS: An aggressive surgical approach is supported in the absence of metastasis. When lymph nodes are not clinically involved, sennel node may have a role followed by lymph node dissecon in paents with a posive node.

Andreoli MT, Itani KM. Malignant eccrine spiradenoma: a meta-analysis of reported cases. Am J Surg. 2011 May;201(5):695-9

Spiradenoma (eccrine spiradenoma)

• Well circumscribed dermal or somemes dermal and subcutaneous nodule

• may have mulple lobules and therefore may be incompletely excised. • If excised completely do not recur

Spiradenoma (eccrine spiradenoma)

Intermingled dual cell populaon of epithelial cells (corresdpond to ductal and myoepithelial cells)

• Striking “peppering” with lymphocytes.

• Rounded larger lobules lack “jigsaw puzzle” paern of but have eosinophilic PAS posive basement membrane material around lobules

• Ducts seen in most cases

• Generally lack mitoc acvity or cellular pleomorphism.

Spiradenoma (eccrine spiradenoma)

• Oen very vascular with haemorrhage

• Oedema in “lymphnagiomatous” variant (as in areas of this case)

• Tumours showing a combinaon of spiradenomatous and cylindromatous features are common (spiradenocylindroma or cylindrospiradenoma).

• Usually solitary , oen blue, 3mm -50mm dermal nodule, especiially head and neck • Mulple lesions on the face and scalp in the inherited autosomal dominant Brooke- Spielger syndrome (with cutaneous , , spiradenocylindromas and ) and a germline mutaon in the CLYD gene.

Spiradenoma (eccrine spiradenoma) differenal diagnosis

• Very characterisc morphology so few close mimics

• Cylindroma

• Other benign adnexal neoplasms

• Malignant spiradnoma: (NB can see pseudoinvasion inside a benign spiradenoma - pictured - but not beyond the lesion unless traumased)

Spiradenoma (eccrine spiradenoma) resemblance to eccrine sweat ducts

Case 12: Malignant spiradenoma (spiradenocarcinoma)

differenal diagnosis primary or secondary adenoid cysc carcinoma

Case 12: Malignant spiradenoma differenal diagnosis: porocarcinoma

Ulcerated porocarcinoma – strands of tumour “raining down” porocarcinoma – maligant duct lumen

porocarcinoma – normal pre-exisng sweat duct porocarcinoma – DPAS highlights malignant duct cucle surrounding central mucin globule

porocarcinoma – CEA highlights malignant duct Case 12: Malignant spiradenoma differenal diagnosis: Metastasis – oen central necrosis, immunohistochemical proflie

Cytokeran 15, podoplanin (D2-40) and p63 posive in most primary skin adnexal neoplasms and negave in metastac adenocarcinoma

• Plaza JA, Ortega PF, Stockman DL, Suster S. Value of p63 and podoplanin (D2-40) immunoreacvity in the disncon between primary cutaneous tumors and adenocarcinomas metastac to the skin: a clinicopathologic and immunohistochemical study of 79 cases. J Cutan Pathol. 2010 Apr;37(4): 403-10. • 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 sensive and specific marker to disnguish primary skin adnexal carcinomas from adenocarcinomas metastac to skin. Am J Surg Pathol. 2007 Feb;31(2):304-10. • Mahalingam M, Nguyen LP, Richards JE, Muzikansky A, Hoang MP. The diagnosc ulity of immunohistochemistry in disnguishing primary skin adnexal carcinomas from metastac adenocarcinoma to skin: an immunohistochemical reappraisal using cytokeran 15, nesn, p63, D2-40, and calrenin. Mod Pathol. 2010 May;23(5):713-9. Cytokeran 15, podoplanin and p63 posive in most primary skin adnexal neoplasms and negave in metastac adenocarcinoma

Cytokeran 15 Expressed in sebaceous glands, outer root sheath of the follicle including bulge area, adult epidermis most specific for primary skin adnexal carcinomas (98%)

P63 member of p53 gene family transcripon factor for maintaining epithelial stem cell proliferaon normal expression basal and lower part of epidermis, peripheral cells of eccrine ducts, apocrine glands, basal cells of sebaceous glands 91-100% of adnexal neoplasms, 14% of metastac adenocarcinomas most sesn

Podoplanin : strongly posive 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 metastac adenocarcinomas only 86% of primary skin neoplasms (but 65% only focally posive) Malignant stained more than benign 40% basal cell carcinomas posive for podoplanin

Posivity for all 3 makers very good evidence for primary skin adnexal carcinoma P63 expression: D2-40 (podoplanin) normal skin normal skin may also show staining of base of epidermis (not seen here) Metastac colorectal adenocarcinoma P63 negave

CK7 negave D2-40 (podoplanin) negave (stains adnexal structures) Mixed tumour (chondroid ) Cytokeran 7 Cytokeran 20 P63 normal skin P63 mixed tumour D2-40 (podoplanin) D2-40 (podoplanin) mixed normal skin tumour

D2-40 (podoplanin) sebaceoma