Sebaceous neoplasms occur sporadically or in the setting of Muir-Torre syndrome. The data regarding the correlation of pathologic features and DNA mismatch repair (MMR) staining pattern in sebaceous tumors of the skin are very scanty and based on relatively small series of patients. The goal of this study was to correlate MMR staining pattern with selected morphological features in a series of 145 sebaceous neoplasms (sebaceous adenoma, sebaceoma, and extraocular sebaceous carcinoma) from 136 patients. Cystic change, intratumoral mucin deposits, squamous metaplasia in the absence of keratoacanthoma-like changes, ulceration, intratumoral and peritumoral lymphocytes (in cases without epidermal ulceration), and intertumoral heterogeneity proved to be significantly associated with MMR deficiency. Identification of any of these changes, alone or in combination, should prompt further investigation of the patient to exclude Muir-Torre Syndrome. Our study also confirms the previously published observation that the diagnosis and tumor location are significantly associated with MMR deficiency.

Bioptical Laboratory Pilsen Czech Republic; and

Department of Dermatology University Hospital Zurich Switzerland

Department of Pathology Clinical Research and Practical Center for Specialized Oncological Care Saint Petersburg Russia

Department of Pathology Medical Faculty Saint Petersburg State University Saint Petersburg Russia

Department of Pathology Saint Petersburg Medico Social Institute Saint Petersburg Russia

Sikl's Department of Pathology Medical Faculty in Pilsen Charles University Prague Pilsen Czech Republic

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Rutten A, Burgdorf W, Hugel H, et al. Cystic sebaceous tumors as marker lesions for the Muir-Torre syndrome: a histopathologic and molecular genetic study. Am J Dermatopathol. 1999;21:405–413.

Schwartz RA, Torre DP. The Muir-Torre syndrome: a 25-year retrospect. J Am Acad Dermatol. 1995;33:90–104.

Orta L, Klimstra DS, Qin J, et al. Towards identification of hereditary DNA mismatch repair deficiency: sebaceous neoplasm warrants routine immunohistochemical screening regardless of patient's age or other clinical characteristics. Am J Surg Pathol. 2009;33:934–944.

Burgdorf WH, Pitha J, Fahmy A. Muir-Torre syndrome. Histologic spectrum of sebaceous proliferations. Am J Dermatopathol. 1986;8:202–208.

Fahmy A, Burgdorf WH, Schosser RH, et al. Muir-Torre syndrome: report of a case and reevaluation of the dermatopathologic features. Cancer. 1982;49:1898–1903.

Kazakov DV, Michal M, Kacerovska D, et al. Cutaneous Adnexal Tumors. Philadelphia, PA: Lippincott Williams & Wilkins; 2012.

Singh RS, Grayson W, Redston M, et al. Site and tumor type predicts DNA mismatch repair status in cutaneous sebaceous neoplasia. Am J Surg Pathol. 2008;32:936–942.

Broekaert SM, Flux K, Kyrpychova L, et al. Squared-off nuclei and “applique” pattern as a histopathological clue to periocular sebaceous carcinoma: a clinicopathological study of 50 neoplasms from 46 patients. Am J Dermatopathol. 2017;39:275–278.

Wiedemeyer K, Kyrpychova L, Isikci OT, et al. Sebaceous neoplasms with rippled, labyrinthine/sinusoidal, petaloid, and carcinoid-like patterns: a study of 57 cases validating their occurrence as a morphological spectrum and showing No significant association with muir-torre syndrome or DNA mismatch repair protein deficiency. Am J Dermatopathol. 2018;40:479–485.

Kazakov DV, Kutzner H, Rutten A, et al. Carcinoid-like pattern in sebaceous neoplasms: another distinctive, previously unrecognized pattern in extraocular sebaceous carcinoma and sebaceoma. Am J Dermatopathol. 2005;27:195–203.

Kacerovska D, Drlik L, Slezakova L, et al. Cutaneous sebaceous lesions in a patient with MUTYH-associated polyposis mimicking muir-torre syndrome. Am J Dermatopathol. 2016;38:915–923.

Kazakov DV, Kutzner H, Spagnolo DV, et al. Discordant architectural and cytological features in cutaneous sebaceous neoplasms-a classification dilemma: report of 5 cases. Am J Dermatopathol. 2009;31:31–36.

Kazakov DV, Calonje E, Zelger B, et al. Sebaceous carcinoma arising in nevus sebaceus of Jadassohn: a clinicopathological study of five cases. Am J Dermatopathol. 2007;29:242–248.

Abbott JJ, Hernandez-Rios P, Amirkhan RH, et al. Cystic sebaceous neoplasms in Muir-Torre syndrome. Arch Pathol Lab Med. 2003;127:614–617.

Bourlond F, Velter C, Cribier B. Clinicopathological study of 47 cases of sebaceoma. Ann Dermatol Venereol. 2016;143:814–824.

Curry ML, Eng W, Lund K, et al. Muir-Torre syndrome: role of the dermatopathologist in diagnosis. Am J Dermatopathol. 2004;26:217–221.

Kruse R, Rutten A, Hosseiny-Malayeri HR, et al. Second hit in sebaceous tumors from Muir-Torre patients with germline mutations in MSH2: allele loss is not the preferred mode of inactivation. J Invest Dermatol. 2001;116:463–465.

Kruse R, Rutten A, Lamberti C, et al. Muir-Torre phenotype has a frequency of DNA mismatch-repair-gene mutations similar to that in hereditary nonpolyposis colorectal cancer families defined by the Amsterdam criteria. Am J Hum Genet. 1998;63:63–70.

Misago N, Narisawa Y. Sebaceous neoplasms in Muir-Torre syndrome. Am J Dermatopathol. 2000;22:155–161.

Roberts ME, Riegert-Johnson DL, Thomas BC, et al. Screening for Muir-Torre syndrome using mismatch repair protein immunohistochemistry of sebaceous neoplasms. J Genet Couns. 2013;22:393–405.

Everett JN, Raymond VM, Dandapani M, et al. Screening for germline mismatch repair mutations following diagnosis of sebaceous neoplasm. JAMA Dermatol. 2014;150:1315–1321.

Hampel H, Frankel WL, Martin E, et al. Feasibility of screening for Lynch syndrome among patients with colorectal cancer. J Clin Oncol. 2008;26:5783–5788.

Gudgeon JM, Williams JL, Burt RW, et al. Lynch syndrome screening implementation: business analysis by a healthcare system. Am J Manag Care. 2011;17:e288–300.

Castillejo A, Vargas G, Castillejo MI, et al. Prevalence of germline MUTYH mutations among Lynch-like syndrome patients. Eur J Cancer. 2014;50:2241–2250.

Rodriguez-Soler M, Perez-Carbonell L, Guarinos C, et al. Risk of cancer in cases of suspected lynch syndrome without germline mutation. Gastroenterology. 2013,144:926–932 e921; quiz e913-924.

Perez-Carbonell L, Ruiz-Ponte C, Guarinos C, et al. Comparison between universal molecular screening for Lynch syndrome and revised Bethesda guidelines in a large population-based cohort of patients with colorectal cancer. Gut. 2012;61:865–872.