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 spiradenoma (spiradenocarcinoma), poorly differenDated, arising in a benign spiradenoma – a relavely rare occurence Spiradenocarcinoma: spiradenocarcinoma either 1) well differenDated and low grade resembling spiradenoma and retain lobularity, but no lymphocytes or two cell paern, or 2) Poorly differenDated with no obvious spiradenomatous differenDaon & 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 differenDated, arising in a benign spiradenoma – a relavely rare occurence spiradenocarcinoma • typical features of a malignant neoplasm: • Larger cells , overlapping nuclei. • Increased mitoDc acDvity and cellular pleomorphism. spiradenoma • Necrosis may occur (but can get degnerave change in spiradenoma mimicking necrosis) • OOen long history, elderly, at any site Spiradenoma Spiradenocarcinoma Case 12: Malignant spiradenoma (spiradenocarcinoma), poorly differenDated, arising in a benign spiradenoma – a relavely rare occurence •72 paents in metaanlysis •35 paents with no distant metastasis, local resecDon 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 resecDon and lymph node dissecDon, 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 resecDon and surgery with adjuvant chemoradiotherapy CONCLUSIONS: An aggressive surgical approach is supported in the absence of metastasis. When lymph nodes are not clinically involved, senDnel node may have a role followed by lymph node dissecDon in paents with a posiDve 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 someDmes dermal and subcutaneous nodule • may have mulDple 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 cylindroma but have eosinophilic PAS posiDve basement membrane material around lobules • Ducts seen in most cases • Generally lack mitoDc acDvity or cellular pleomorphism. Spiradenoma (eccrine spiradenoma) • OOen 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 , oOen blue, 3mm -50mm dermal nodule, especiially head and neck • MulDple lesions on the face and scalp in the inherited autosomal dominant Brooke- Spielger syndrome (with cutaneous cylindromas, spiradenomas, spiradenocylindromas and trichoepitheliomas) and a germline mutaon in the CLYD gene. Spiradenoma (eccrine spiradenoma) differenDal diagnosis • Very characterisDc 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) differenDal diagnosis primary or secondary adenoid cysDc carcinoma Case 12: Malignant spiradenoma differenDal diagnosis: porocarcinoma Ulcerated porocarcinoma – strands of tumour “raining down” porocarcinoma – maligant duct lumen porocarcinoma – normal pre-exisDng sweat duct porocarcinoma – DPAS highlights malignant duct cuDcle surrounding central mucin globule porocarcinoma – CEA highlights malignant duct Case 12: Malignant spiradenoma differenDal diagnosis: Metastasis – oOen central necrosis, immunohistochemical proflie Cytokeran 15, podoplanin (D2-40) and p63 posiDve 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) immunoreacDvity in the disDncDon 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 sensiDve and specific marker to disDnguish 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 diagnosDc uDlity of immunohistochemistry in disDnguishing primary skin adnexal carcinomas from metastac adenocarcinoma to skin: an immunohistochemical reappraisal using cytokera6n 15, nesDn, p63, D2-40, and calreDnin. Mod Pathol. 2010 May;23(5):713-9. Cytokeran 15, podoplanin and p63 posiDve in most primary skin adnexal neoplasms and negave in metastac adenocarcinoma Cytokeran 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 transcripDon 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 posiDve 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 posiDve) Malignant stained more than benign 40% basal cell carcinomas posiDve for podoplanin PosiDvity 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 syringoma) Cytokeran 7 Cytokeran 20 P63 normal skin P63 mixed tumour D2-40 (podoplanin) D2-40 (podoplanin) mixed normal skin tumour D2-40 (podoplanin) sebaceoma .