Clear cell papillary renal cell carcinoma-like tumors in patients with von Hippel-Lindau disease are unrelated to sporadic clear cell papillary renal cell carcinoma

Am J Surg Pathol. 2013 Aug;37(8):1131-9. doi: 10.1097/PAS.0b013e318282dab8.

Abstract

Clear cell papillary renal cell carcinoma (CCPRCC) shares morphologic overlap with clear cell renal cell carcinoma, although it lacks chromosome 3p and VHL gene abnormalities. Rare cases have been reported in von Hippel-Lindau (VHL) patients (germline mutation of the VHL gene), the significance of which is uncertain. We analyzed morphologic, immunohistochemical, and molecular features in 14 CCPRCC-like tumors and 13 clear cell renal cell carcinomas from 12 patients with VHL disease. Gross appearance of CCPRCC-like tumors ranged from yellow-orange to tan, red-brown, or extensively cystic. Histologic features included: small papillary tufts (79%), branched tubules (71%), branched papillae (64%), flattened peripheral cysts (64%), and apically aligned nuclei (43%). Almost all CCPRCC-like tumors (82%) lacked the characteristic immunoprofile of sporadic CCPRCC (CK7, CAIX, CD10, AMACR), often showing diffuse CD10 labeling (64%), negative or focal CK7 reactivity (55%), or both (18%). Three tumors (27%) showed strong AMACR staining. Chromosome 3p deletion was often present (82%), similar to that observed in clear cell renal cell carcinomas (80%); no CCPRCC-like tumor had chromosome 7 or 17 abnormalities. In summary, tumors that histologically resemble CCPRCC sometimes occur in patients with VHL disease but usually lack the characteristic immunohistochemical and molecular profile, suggesting that they do not share the same pathogenesis.

Publication types

  • Comparative Study

MeSH terms

  • Antigens, Neoplasm / analysis
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / analysis
  • Carcinoma, Papillary / chemistry
  • Carcinoma, Papillary / genetics
  • Carcinoma, Papillary / pathology*
  • Carcinoma, Renal Cell / chemistry
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / pathology*
  • Chromosome Deletion
  • Chromosomes, Human, Pair 17
  • Chromosomes, Human, Pair 3
  • Chromosomes, Human, Pair 7
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Keratin-7 / analysis
  • Kidney Neoplasms / chemistry
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / pathology*
  • Male
  • Neprilysin / analysis
  • Racemases and Epimerases / analysis
  • Retrospective Studies
  • von Hippel-Lindau Disease / complications
  • von Hippel-Lindau Disease / genetics*

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • KRT7 protein, human
  • Keratin-7
  • Neprilysin
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases
  • Racemases and Epimerases
  • alpha-methylacyl-CoA racemase