An association between sebaceous carcinoma and microsatellite instability in immunosuppressed organ transplant recipients

Sebaceous carcinomas are rare cutaneous appendageal tumors that may occur s poradically or in association with an internal malignancy in Muir-Torre syn drome. In Muir-Torre syndrome microsatellite instability can often be demon strated in tumor DNA as a result of an inherited mutation in one of several known mismatch repair genes; however, the role of microsatellite instabili ty in sporadic sebaceous carcinomas has not been previously studied. In thi s report we describe the clinicopathologic characteristics of a series of u nselected sebaceous carcinomas and examine them for the presence of microsa tellite instability. Of 10 consecutive tumors identified over a 10 y period , only one was from a patient known to have Muir-Torre syndrome. Of the nin e presumed sporadic cases, five were from four renal transplant recipients and four from otherwise healthy individuals. Microsatellite instability was demonstrable in three cases: in the Muir-Torre syndrome-associated tumor a nd in two tumors from transplant patients. Microsatellite instability was s ubsequently also found in a sebaceous carcinoma from a further transplant p atient prospectively sought from another institution. The presence of micro satellite instability in post-transplant sebaceous carcinomas was associate d with loss of expression of the mismatch repair protein hMSH2. In summary, sebaceous gland carcinomas, while characteristic of Muir-Torre syndrome, a re commonly found outside this context. Among presumed sporadic cases, our data suggest they may be over-represented in immunosuppressed renal transpl ant recipients. The presence of microsatellite instability in transplant-as sociated lesions, together with loss of hMSH2 expression suggests that immu nosuppression might unmask a previously silent Muir-Torre syndrome phenotyp e in some cases. Alternatively, there is experimental evidence to suggest t hat immunosuppressive drugs, most plausibly azathioprine, could select for the emergence of a mutator phenotype and thus predispose to the development of sebaceous carcinomas. The role of mismatch repair defects in other post -transplant skin malignancies remains to be established.