Renal Medullary Carcinoma: Establishing Standards in Practice

Abstract

Although renal medullary carcinoma (RMC) is a rare subtype of kidney cancer, it is particularly devastating in that it is nearly uniformly lethal. No established guidelines exist for the diagnosis and management of RMC. In April 2016, a panel of experts developed clinical guidelines on the basis of a literature review and consensus statements. The goal was to propose recommendations for standardized diagnostic and management approaches and to establish an international clinical registry and biorepository for RMC. Published data are limited to case reports and small retrospective reviews. The RMC Working Group prepared recommendations to inform providers and patients faced with a low level of medical evidence. The diagnosis of RMC should be considered in all patients younger than 50 years with poorly differentiated carcinoma that arises from the renal medulla. These patients should be tested for sickle cell hemoglobinopathies, and if positive, SMARCB1/INI1 loss should be confirmed by immunohistochemistry. The majority of patients with RMC are diagnosed with metastatic disease. Upfront radical nephrectomy should be considered in patients with good performance status and low metastatic burden or after response to systemic therapy. Currently, cytotoxic, platinum-based chemotherapy provides the best, albeit brief, palliative clinical benefit. Vascular endothelial growth factor-directed therapies and mammalian target of rapamycin inhibitors are ineffective in RMC as monotherapy. Therapeutic trials of novel agents are now available for RMC, and every effort should be made to enroll patients in clinical studies.

Fig 1.

(A) Pathologic representation of renal medullary carcinoma. Hematoxylin and eosin stain (magnification, ×200) shows markedly atypical cells arranged in nests and cords infiltrated by abundant neutrophils. (B) Renal medullary carcinoma. Immunohistochemical stain (magnification, ×100) shows SMARCB1/INI1 loss in tumor cells, whereas expression is retained in endothelial cells.

Fig 2.

Renal medullary carcinoma (RMC) treatment algorithm. This flowchart represents diagnostic criteria and considerations in treating patients with RMC. *If performance status and surgical planning permit consideration. †Treatment with vascular endothelial growth factor–directed therapies or mammalian target of rapamycin inhibitors is not beneficial; single-agent chemotherapy is not encouraged. RPLND, retroperitoneal lymph node dissection.