Wang B, Sarma DP (2007). Sebaceous carcinoma and mismatch repair gene expression. The Internet J Dermatol 6(1). Indexed by Google Scholar.


Sebaceous Carcinoma and Mismatch Repair Gene Expression

B Wang, D Sarma


B Wang, D Sarma. Sebaceous Carcinoma and Mismatch Repair Gene Expression. The Internet Journal of Dermatology. 2006 Volume 6 Number 1.


We present a case of an 81-year-old male with an asymptomatic skin nodule on his left upper cheek.


An 81-year-old male presents with an asymptomatic skin nodule on his left upper cheek. An excisional biopsy specimen (Fig.1) shows a well-circumscribed neoplasm in the dermis with central necrosis and peripheral chronic inflammatory cell infiltrate. The organoid neoplasm is composed of somewhat palisading or ribbon-like atypical basaloid cells and abnormal clear cells with multivesicular and vacuolated cytoplasm. The basaloid cells have enlarged hyperchromatic nuclei, prominent cherry-red nucleoli, basophilic cytoplasm, and brisk mitotic figures with scattered apoptotic bodies. The clear cells exhibit nuclear pleomorphism with prominent nucleoli with sebaceous differentiation (Fig. 2). The well-demarcated growth pattern of this sebaceous carcinoma is classified as Grade I tumor according to the WHO Classification (1). Immunohistochemical studies show that the tumor  cells strongly positive for androgen receptor (AR) (Fig.3), a diagnostic finding in sebaceous neoplasm. The tumor cells also express mismatch repair gene MLH-1 and PMS-2 (Fig. 4), but they are non-immunoreactive to MSH-2 and MSH-6 (Fig. 5), which may indicate microsatellite  instability.







Sebaceous carcinoma is a rare malignant skin appendage tumor occurring in the eyelids (75%) and extraocular (25%) locations. It occurs predominantly in female (2:1 female versus male ratio) at an average age of 65 years (2). The tumor usually presents as a slowly growing, firm, and painless nodule or mass. It can be locally aggressive with 20-25% distant metastasis.

Certain sebaceous carcinomas are now known to be associated with Muir-Torre syndrome and hereditary non- polyposis colorectal cancer (HNPCC) or Lynch syndrome through sharing of germ-line mutations in Mismatch repair genes. Such tumors demonstrate microsatellite instability at DNA level (3, 4). Muir-Torre syndrome is an autosomal dominant disorder with variable penetrance that consists of  at least one sebaceous gland tumor (adenoma, epithelioma,  or carcinoma) and a minimum of one internal malignancy such as colorectal carcinoma, genitourinary neoplasm or breast carcinoma. In a subgroup of Muir-Torre syndrome patients, the patients have germline DNA mismatch-repair (MMR) defect(s) and microsatellite instability, which is identical to the DNA defect of hereditary non-ployposis colorectal cancer (HNPCC) or Lynch syndrome. Therefore, Muir-Torre syndrome has been postulated as a variant of HNPCC or Lynch syndrome. Approximately 80% sebaceous gland malignancies show a loss of mismatch repair proteins (either MLH-1 or MSH-2) or microsatellite instability (3,  4).

In our patient, the sebaceous carcinoma cells have lost immunoreactivity of MSH-2 and MSH-6, which may  suggest microsatellite instability. MSH-2 gene defect is commonly present in sebaceous carcinoma associated with Muir-Torre syndrome. However, the loss of MSH-6 is rarely seen in this malignancy. The mismatch repair gene defect or microsatellite instability is a strong risk factor for visceral neoplasms. Additional clinical investigation may be required for appropriate management of such patients.


Deba P Sarma, M.D. Department of Pathology Creighton University Medical School Omaha, Nebraska 68131 E-mail:


  1. LeBoit PE, Burg G, Weedon D, Sarasin A. Pathology and genetics of skin tumours. World Health Organization Classification of Tumours. 2006, 161-162.
  2. Wang B, Sarma, DP. Sebaceous Carcinoma with Apocrine Differentiation. The Internal Journal of Dermatology. 2006. 4(2).
  3. Ponti G, Losi L, Pedroni M, Lucci-Cordisco E, Di Gregorio C, Pellacani G, Seidenari S. Value of MLH1 and MSH2 mutations in the appearance of Muir-Torre syndrome phenotype in HNPCC patients presenting sebaceous gland tumors or keratoacanthomas. J Invest Dermatol. 2006 Oct; 126(10): 2302-7.
  4. Popnikolov NK, Gatalica Z, Colome-Grimmer MI, Sanchez RL. Loss of mismatch repair proteins in sebaceous gland tumors. J Cuban Pathol. 2003 Mar; 30(3): 178-84.

Author Information

Bo Wang, M.D., Department of Pathology, Creighton University Medical  School

Deba P. Sarma, M.D., Department of Pathology, Creighton University Medical  School


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