Immunophenotypic and pathologic heterogeneity of unclassified renal cell carcinoma: a study of 300 cases

Hum Pathol. 2020 Aug:102:70-78. doi: 10.1016/j.humpath.2020.06.007. Epub 2020 Jun 30.


Renal cell carcinoma, unclassified (RCC-U), is a heterogenous group of tumors that do not fit in any of the recognized histologic types. Immunohistochemical studies are frequently used to characterize these tumors. Herein, we sought to investigate the immunophenotypes of 300 cases of RCC-U. The cases were morphologically classified into three groups: oncocytoma/chromophobe renal cell carcinoma-like, group 1; clear cell renal cell carcinoma-like, group 2; and others (ie, papillary renal cell carcinoma-like/collecting duct-like/pure sarcomatoid), group 3. The male-to-female ratio was 1.4. Most cases (168, 66%) were group 1. Group 3 was associated with larger tumor size, advanced stage, and frequent lymph node metastases. The most commonly used immunohistochemical stains were CK7 (n = 270; 89.5%), vimentin (n = 186, 82%), CD10 (n = 181; 59.9%), and AMACR (n = 162; 54%). Pancytokeratin (79/101; 78.2%) and PAX8 (54/61; 88.5%) were diffusely positive in most cases, followed by AMACR (69/117; 59%). CD117 was positive in 53 of 118 cases (45%). RCC-U is a morphologically and immunophenotypically heterogenous group of tumors, and comprehensive workup is needed before rendering the diagnosis.

Keywords: Differential diagnosis; Heterogeneity; Immunohistochemistry; Kidney; Unclassified renal cell carcinoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Carcinoma, Renal Cell / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • Kidney Neoplasms / pathology*
  • Male
  • Middle Aged
  • Young Adult


  • Biomarkers, Tumor