A 54-year-old woman presents for evaluation of an enlarging, firm yellow papule on her left cheek. A biopsy is performed and shows a well-circumscribed dermal tumor composed of lobules of sebocytes with peripheral basaloid cells and mature sebaceous differentiation. Mitotic figures are rare, and there is no necrosis. She has no known family history of skin cancer but reports that several relatives have had colon cancer in their 40s and 50s.
Which of the following genetic mutations is most likely associated with her condition?
A. PTCH1
B. MSH2
C. TP53
D. APC
E. BRAF
Rationale:
This patient presents with a sebaceous neoplasm, likely a sebaceous adenoma, and a strong personal and family history of colon cancer. This constellation raises concern for Muir-Torre syndrome which is a subtype of Lynch syndrome (hereditary nonpolyposis colorectal cancer). Recognizing the dermatologic manifestations such as sebaceous adenomas, sebaceous carcinomas, and keratoacanthomas can provide a crucial opportunity to identify internal malignancies early.
Correct answer: B. MSH2
Muir-Torre syndrome is caused by mutations in DNA mismatch repair (MMR) genes such as MSH2, MLH1, and MSH6. Identifying these patients allows for appropriate genetic counseling, cancer surveillance, and possible early detection of life-threatening cancers.
Incorrect Answers:
A. PTCH1 is mutated in basal cell carcinoma syndrome (Gorlin syndrome), which presents with numerous basal cell carcinomas, jaw cysts, palmar pits, and skeletal abnormalities.
C. TP53 mutations are seen in Li-Fraumeni syndrome, which predisposes to multiple malignancies like sarcomas, breast cancer, and brain tumors, but is not typically associated with sebaceous tumors or the cutaneous findings seen in our vignette.
D. APC mutations underlie familial adenomatous polyposis (FAP) which is associated with the development of hundreds of colonic polyps and early-onset colorectal cancer. Patients with FAP may have epidermoid cysts and fibromas but the condition is not associated with not sebaceous neoplasms.
E. BRAF mutations are commonly associated with melanoma as well as a variety of other cancers. They are not associated with Muir-Torre syndrome or sebaceous neoplasms.
Additional reading at Skin Cancer: A Comprehensive Guide Chapter 33: Syndromes Associated with Skin Cancers