Clinical Pathology: Genetic Testing

• Although the diagnosis of the renal tumors is based on their classic histologic characteristics, a small but significant percentage of tumors have ambiguous morphologic features, and approximately 5% are reported as “unclassified” because of the overlapping morphologic characteristics. Identification of the cytogenetic abnormalities can assist in the diagnosis and prognosis of renal epithelial tumors.

• The 5-year survival and disease-free progression of renal cell carcinomas (RCCs) varies by subtype: chromophobe RCC (100% and 94%), papillary RCC (86% and 88%), clear cell RCC (76% and 70%), and RCC unclassified (24% and 18%). Oncocytomas are benign neoplasms with very low risk of metastasis.

• Single-nucleotide polymorphism (SNP) and array comparative genomic hybridization (aCGH) arrays could resolve morphologically challenging renal tumors. These genomic methods are becoming the method of choice for comprehensive evaluation of chromosomal imbalances in RCC.

• Conventional cytogenetics is the method of choice when assessing for non-recurrent balanced translocations, such as those present in familial non–von Hippel-Lindau clear cell RCC. FISH can be used to detect the presence of recurrent chromosomal translocations, such as those present in pediatric tumors involving the Xp11.2 locus.

• Cytogenetic analysis does not provide distinction between papillary adenomas and low-grade RCCs because of overlapping combinations of numerical chromosome abnormalities. Tumor diameter remains an important diagnostic criterion.