ABSTRACT
BACKGROUND: We present a family consisting of a father and his two children with an exceptional phenotype of childhood renal cell carcinoma and brain tumors. Extensive genetic testing revealed two inherited tumor predisposition syndromes in all three family members: Birt-Hogg-Dubé syndrome and Li-Fraumeni syndrome. The corresponding genes (FLCN and TP53) are both located on the short arm of chromosome 17. METHODS: We describe the phenotype and performed single nucleotide polymorphism (SNP)-based loss of heterozygosity (LOH) analysis of the tumors. RESULTS: All examined tumors showed somatic loss of the wild-type alleles of both FLCN and TP53. CONCLUSIONS: We hypothesize that a synergistic effect of both mutations caused the unusual phenotype of childhood renal cell carcinoma in this family. This family emphasizes the importance of further genetic testing if a tumor develops at an unexpected young age in an inherited cancer predisposition syndrome.
Subject(s)
Brain Neoplasms , Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Tumor Suppressor Proteins/genetics , Genetic Predisposition to Disease , Germ Cells/metabolism , Germ Cells/pathology , Tumor Suppressor Protein p53/genetics , Proto-Oncogene Proteins/geneticsABSTRACT
Anisometric cell lipoma (ACL) and dysplastic lipoma (DL) are underrecognized subtypes of benign lipomatous tumors, with wide variation in cell size, microscopic fat necrosis, and no or mild nuclear changes (DL). ACL/DL appear more commonly in retinoblastoma patients, in whom an increased incidence of lipomas has been established. The occurrence of ACL/DL in retinoblastoma patients suggests that RB1 aberrations play a role in its pathogenesis, similar to spindle cell/pleomorphic lipoma. In this article, we present a patient with a history of retinoblastoma with multiple lipomas histologically consistent with ACL/DL. Analysis of the lipomas supports involvement of RB1 in the development of ACL/DL. Dysplastic changes were only seen in a single lipoma, which harbored an additional TP53 mutation. While providing further support for the occurrence of ACL/DL in retinoblastoma patients, we also suggest that DL is an ACL with TP53 mutation.
