ABSTRACT
BACKGROUND: Mal de Meleda (MDM) is a rare inherited autosomal recessive genodermatosis characterized by palmoplantar keratoderma (PPK) with transgrediens and caused by mutations in the SLURP1 gene. Uncommonly, cutaneous tumors have been found at PPK sites in MDM patients. OBJECTIVE: To study a Middle Eastern family with MDM with both PPK and skin tumors. METHODS: We studied a Middle Eastern (Palestinian) family with clinical features of MDM and cutaneous tumors. Histopathological analysis was performed on biopsies from skin lesions found in the affected individuals. Direct sequencing of SLURP1 was performed in MDM affected members. In silico analysis of publicly available datasets was used to survey SLURP1 mRNA levels in normal and malignant tissues. Statistical analysis was performed in the R statistical language. RESULTS: Affected members from the Middle Eastern family displayed severe forms of PPK consistent with MDM. Histopathological analysis of the skin lesions revealed that the examined affected members exhibited skin squamous cell carcinomas (SCCs) and melanoma. Sequence analysis revealed homozygous SLURP1 mutations (c.82delT) in the affected members. Following analysis of various publicly available expression datasets, SLURP1 mRNA levels were found to be markedly elevated in tissues of epithelial lineage, relative to tissues of other lineages, and significantly suppressed in malignant tumors of epithelial lineage relative to normal or their premalignant counterparts. There was significant decrease in SLURP-1 expression in melanomas versus melanocytic nevi as well as a highly significant decrease in SLURP-1 expression in metastatic melanomas as compared to primary melanoma. CONCLUSION: Our study underscores cases of Middle Eastern MDM with SLURP1 mutations and skin malignancies at PPK sites. Our findings also highlight a plausible epithelial lineage-specific tumor suppressor role for the SLURP1 gene, as well as a role in the development and metastasis of melanoma and thus a potential molecular signature for melanoma.
Subject(s)
Antigens, Ly/genetics , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/genetics , Keratoderma, Palmoplantar/genetics , Melanoma/genetics , Nevus, Pigmented/genetics , Skin Neoplasms/genetics , Urokinase-Type Plasminogen Activator/genetics , Adult , Biomarkers, Tumor/metabolism , Databases, Genetic , Epithelium/metabolism , Female , Gene Expression , Genes, Tumor Suppressor , Homozygote , Humans , Keratoderma, Palmoplantar/pathology , Male , Melanoma/pathology , Melanoma/secondary , Middle Aged , Mutation , Pedigree , RNA, Messenger/metabolism , Skin Neoplasms/pathologyABSTRACT
BACKGROUND: Idiopathic atrophoderma of Pasini and Pierini (IAPP) usually manifests as one or multiple depressed and hyperpigmented patches, with a predilection to the trunk. No diagnostic changes are usually seen on histology. Elastic stains often reveal no abnormalities. OBJECTIVE: To review our cases of IAPP, describe their clinical and histological findings and compare them with the literature. METHODS: Retrospective review of IAPP cases who presented to our institution between 1994 and 2006. RESULTS: From a total of 16 patients, only 19% displayed hyperpigmented lesions, while 81% had either hypopigmented (9/16) or skin-colored (4/16) lesions. The sites predominantly affected were the lower extremities (62.5%), followed by the upper extremities and trunk. Only in one patient was IAPP co-existent with morphea. Histology revealed no diagnostic abnormalities; however, elastic stains showed a spectrum of changes ranging from normal to severe diminution and fragmentation of elastic fiber network. CONCLUSIONS: Our study shows several new aspects of IAPP. Clinically, the lesions were most commonly hypopigmented and involved predominantly the extremities. Histologically, IAPP exhibited a spectrum of alterations in elastic fibers. The most prevalent form of IAPP in our country seems to be unassociated with morphea.
