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V J Swale

Publications and source records attributed to V J Swale.

7 recordsLinked to original sources
PubMed2001

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

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.

Aged↗
PubMed1999

Microsatellite instability in benign skin lesions in hereditary non-polyposis colorectal cancer syndrome.

The coexistence of cutaneous and extra-cutaneous malignancies within one family could be explained by shared genetic mechanisms such as common tumor suppressor gene mutations or oncogene activation, as well as mutations in DNA repair genes. Hereditary non-polyposis colorectal cancer syndrome (HNPCC) and its variant Muir-Torre syndrome (MTS) are caused by germline DNA mismatch repair gene mutations. Colonic and endometrial tumors from HNPCC patients exhibit microsatellite instability (MSI), as do sebaceous lesions in MTS. We recruited individuals from cancer prone families to determine if MSI is found in benign and malignant skin lesions and to assess whether MSI in the skin is predictive of genomic instability with susceptibility to tumors characteristic of HNPCC. One hundred and fifteen benign, dysplastic, and malignant skin lesions from 39 cancer prone families were analyzed. Thirteen benign skin lesions from three individuals belonging to two HNPCC pedigrees showed MSI. No mutations in hMSH2 and hMLH1 were found in two of the three individuals with RER + skin lesions. We found MSI in non-sebaceous non-dysplastic skin lesions in HNPCC pedigrees. MSI was not found in skin lesions within other family cancer syndromes. These results have important clinical implications as the detection of MSI in prevalent readily accessible skin lesions could form the basis of noninvasive screening for HNPCC families. It may also be a valuable tool in the search for new mismatch repair genes.

Adenoma↗
PubMed1998

Lichen planus pemphigoides: two case reports.

Lichen planus pemphigoides (LPP) is a rare condition with characteristic clinical, histological and immunopathological features, in which a lichenoid eruption is found in association with bullae on both involved and apparently normal skin. We present two patients to illustrate the diverse clinical manifestations of this disease.

Adult↗