Non-Clear Cell Renal Cell Carcinoma - Pathology and Treatment Options

Oncol Res Treat. 2019;42(3):128-135. doi: 10.1159/000495366. Epub 2019 Feb 23.


Non-clear cell renal cell carcinomas (nccRCC) are rare diseases with heterogeneous histopathologically and genetically defined entities. The clinical data on optimal systemic treatments of nccRCC is rather limited. In this review, the current World Health Organization (WHO) classification of nccRCC based on histopathologic and genetic findings is reported. Regarding systemic treatment options, the most commonly used agents are mTOR inhibitors like everolimus or temsirolimus, or tyrosine kinase inhibitors like sunitinib. 2 small randomized clinical trials with nccRCC comparing sunitinib with everolimus revealed a trend towards a better progression-free survival (PFS) and overall survival (OS) in favor of sunitinib. In RCC with predominant sarcomatoid features, both chemotherapy and targeted agents are reported without any preference for outcome. For subsequent lines of therapy, some case reports describe promising effects of PD-1 or PD-L1 inhibitors in nccRCC including sarcomatoid subtype and Bellini duct carcinoma. Currently, nccRCCs are treated similarly to clear cell RCC or, whenever possible, within clinical trials. Clinical trials with immune checkpoint inhibitors are ongoing.

Keywords: Classification; Non-clear cell renal cell carcinoma; Pathology; Treatment.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology
  • Costimulatory and Inhibitory T-Cell Receptors / antagonists & inhibitors
  • Costimulatory and Inhibitory T-Cell Receptors / immunology
  • Humans
  • Kidney / immunology
  • Kidney / pathology*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Progression-Free Survival
  • Randomized Controlled Trials as Topic


  • Antineoplastic Agents, Immunological
  • Costimulatory and Inhibitory T-Cell Receptors