Sebaceous
carcinomas are rare cutaneous appendageal
tumors that may occur sporadically or in association with an internal
malignancy in
Muir-Torre syndrome. In
Muir-Torre syndrome microsatellite instability can often be demonstrated in
tumor DNA as a result of an inherited mutation in one of several known mismatch repair genes; however, the role of
microsatellite instability in sporadic sebaceous
carcinomas has not been previously studied. In this report we describe the clinicopathologic characteristics of a series of unselected sebaceous
carcinomas and examine them for the presence of
microsatellite 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 nine 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 and in two
tumors from transplant patients.
Microsatellite instability was subsequently also found in a sebaceous
carcinoma from a further transplant patient prospectively sought from another institution. The presence of
microsatellite instability in post-transplant sebaceous
carcinomas was associated with loss of expression of the mismatch repair
protein hMSH2. In summary, sebaceous gland
carcinomas, while characteristic of
Muir-Torre syndrome, are commonly found outside this context. Among presumed sporadic cases, our data suggest they may be over-represented in immunosuppressed renal transplant recipients. The presence of
microsatellite instability in transplant-associated lesions, together with loss of hMSH2 expression suggests that immunosuppression might unmask a previously silent
Muir-Torre syndrome phenotype in some cases. Alternatively, there is experimental evidence to suggest that 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.