Molecular analysis as a tool in the differential diagnosis of VHL disease-related tumors

• Published in: Diagnostic molecular pathology Vol. 14; no. 2; p. 115
• Main Authors: Gijtenbeek, Johanna, Jacobs, Bram, Boots-Sprenger, Sandra, Bonne, Anita, Lenders, Jacques, Küsters, Benno, Wesseling, Pieter, Jeuken, Judith
• Format: Journal Article
• Language: English
• Published: United States 01.06.2005
• Subjects: Adult; Carcinoma, Renal Cell - diagnosis; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; Chromosomal Instability; Diagnosis, Differential; DNA - genetics; Fatal Outcome; Germ-Line Mutation; Humans; Kidney Neoplasms - diagnosis; Kidney Neoplasms - genetics; Kidney Neoplasms - pathology; Loss of Heterozygosity; Male; Nucleic Acid Hybridization; Pheochromocytoma - diagnosis; Pheochromocytoma - genetics; Pheochromocytoma - pathology; Tumor Suppressor Proteins - genetics; Ubiquitin-Protein Ligases - genetics; von Hippel-Lindau Disease - complications; von Hippel-Lindau Disease - genetics; Von Hippel-Lindau Tumor Suppressor Protein
• ISSN: 1052-9551
• DOI: 10.1097/01.pas.0000155022.42944.73

Von Hippel-Lindau (VHL) disease is an autosomal dominant tumor syndrome, in which hemangioblastomas (HBs), clear cell renal cell carcinomas (RCCs), and pheochromocytomas are the most frequently encountered tumors. The differential diagnosis of dedifferentiated tumors in general can be difficult, as standard histologic and immunohistochemical investigations do not always allow a definitive diagnosis. We used molecular genetic analysis to resolve the differential diagnosis of sarcomatoid RCC versus pheochromocytoma of a (peri)renal tumor in a VHL patient. Germline mutation analysis identified the C407T mutation, which has been related to a VHL phenotype in which pheochromocytomas are rare. Chromosomal imbalances detected in the tumor by CGH showed a pattern typical for RCCs and not for pheochromocytomas. CGH analysis of the multiple tumors of this VHL patient revealed a comparable karyotype in the metastatic tumors and the (peri)renal tumor. Concordantly, although the germline mutation was detected in all analyzed tumors, LOH 3p was only detected in the (peri)renal mass and most metastases. Overall, based on all genetic data, this tumor corroborated a diagnosis of metastatic sarcomatoid RCC. In line with these observations is the immunopositivity for the RCC-specific RC38 detected in the (peri)renal mass and the metastases that was not detected in pheochromocytomas. The RCC specific marker G250 was uninformative as it stains positive in all types of VHL tumors. This case report illustrates the promising role of genetic analysis in the differential diagnosis of histologically dedifferentiated tumors.