title: An association between sebaceous carcinoma and microsatellite instability in immunosuppressed organ transplant recipients.
abstract: 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.
authors.affiliation: Center for Cutaneous Research, St Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, 2 Newark Street, London E1 2AT, UK. caharwood@doctors.org.uk
authors.forename: C A
authors.initials: CA
authors.lastname: Harwood
authors.forename: V J
authors.initials: VJ
authors.lastname: Swale
authors.forename: V A
authors.initials: VA
authors.lastname: Bataille
authors.forename: A G
authors.initials: AG
authors.lastname: Quinn
authors.forename: L
authors.initials: L
authors.lastname: Ghali
authors.forename: S V
authors.initials: SV
authors.lastname: Patel
authors.forename: I
authors.initials: I
authors.lastname: Dove-Edwin
authors.forename: R
authors.initials: R
authors.lastname: Cerio
authors.forename: J M
authors.initials: JM
authors.lastname: McGregor
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D016377:Organ Transplantation; D012626:Sebaceous Gland Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D014181:Transplantation Immunology