Dermatology Question of the Week: Deductive Dermpath
Question:
A 55-year-old male comes to the office for a rapidly growing nodule on the cheek that is tender. Biopsy is performed showing the histopathology seen below. The cells are also found to stain positively with androgen receptor.
Which of the following correctly lists the gene(s) for the syndrome associated with this type of tumor?
Answer choices:
A. CYLD
B. FLCN (folliculin)
C. MLH1, MSH2, MSH6
D. PTCH
Rationale: The photograph above shows a basophilic lobular nodule with a proportion of clear cells, cytologic atypia, and mitoses consistent with a sebaceous carcinoma. Although there is no perfect stain to evaluate for sebaceous differentiation, androgen receptor, EMA, adipophilin, and factor XIIIa can be used to highlight sebaceous cells. Sebaceous carcinoma, particularly when not located periorbitally, can be associated with Muir-Torre syndrome of which cutaneous findings include increased sebaceous tumors, keratoacanthomas, and squamous cell carcinoma. Non-cutaneous malignancies include gastrointestinal, endometrial, ovarian, and urologic tumors. Screening patients for associated malignancies is critical and the Mayo Muir-Torre risk score algorithm can be a helpful tool to determine a patient's risk of having a germline mutation.
Correct answer:
C. MSH2, MSH6 and MLH1 are genes associated with Lynch syndrome/Muir Torre syndrome.
Incorrect answers:
A. CYLD gene mutations are seen in Brooke-Spiegler syndrome. Cutaneous findings include cylindromas, trichoepitheliomas, spiradenomas, and basal cell carcinomas. Extracutaneous findings include salivary and parotid gland tumors.
B. An autosomal dominant mutation in FLCN (folliculin) describes Birt-Hogg-Dube syndrome. Cutaneous findings include fibrofolliculomas, achrocordons, and trichodiscomas. Extracutaneous findings include renal cell carcinoma and spontaneous pneumothorax.
D. PTCH gene mutations are seen in basal cell nevus syndrome characterized by numerous early basal cell carcinomas, palmoplantar pits, keratocysts of the jaw, ovarian fibromas, calcification of the falx cerebri, and medulloblastomas.
Additional reading at Barnhill Dermatopathology Chapter 28: Tumors with Hair Follicle and Sebaceous Differentiation
I am a general dermatologist practicing at an academic medical center in Danville, PA. I see both adult and pediatric patients and also perform various surgical procedures. I have a special interest in Hidradenitis Suppurativa (HS) and am the founder of our HS specialty clinic where we treat patients medically and surgically (deroofing, excision, staged CO2 excision with marsupialization, Nd:YAG). I am actively involved in resident education and am passionate about medical education. Additional interests include autoimmune bullous disorders, dermatomyositis, and procedural dermatology.
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