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.

Renal medullary carcinoma masquerading as renal infection: a case report

“…Renal medullary carcinoma is a rare and aggressive tumor and nearly uniformly lethal [1][2][3]. The disease occurs almost exclusively in adolescents and young adults with sickle cell hemoglobinopathies [4].…”

“…Renal medullary carcinoma is characterized by gross hematuria, abdominal or flank pain, and loss of weight, which may lead erroneously to a diagnosis of renal infections or abscess. Therefore, early diagnosis of renal medullary carcinoma requires a high level of suspicion [3,5]. It has been recommended that renal medullary carcinoma should be considered in patients less than 50 years of age with poorly differentiated carcinoma that arises from the renal medulla [3] and renal medullary carcinoma patients should be tested for sickle cell hemoglobinopathies.…”

“…Therefore, early diagnosis of renal medullary carcinoma requires a high level of suspicion [3,5]. It has been recommended that renal medullary carcinoma should be considered in patients less than 50 years of age with poorly differentiated carcinoma that arises from the renal medulla [3] and renal medullary carcinoma patients should be tested for sickle cell hemoglobinopathies. Rarely, renal medullary carcinoma may be concomitant with renal echinococcosis.…”

Renal medullary carcinomas depend uponSMARCB1loss and are sensitive to proteasome inhibition

“…Biochemically, re-expression of SMARCB1 in RMC leads to stabilization of the SWI/SNF complex in the same manner as for MRT. Diagnostically, patients with RMC are often misdiagnosed with renal cell carcinoma (RCC) due to the rarity of RMC, the lack of access to SMARCB1 histological stains and unknown sickle cell status (Beckermann et al, 2017). Although SMARCB1 is currently included in targeted sequencing efforts nationwide(“AACR Project GENIE: Powering Precision Medicine through an International Consortium,” 2017), our studies along with prior studies (Calderaro et al, 2016; Carlo et al, 2017) suggest that conventional target exome sequencing may fail to identify patients with RMC.…”

“…Due to the aggressive behavior of this disease and the small numbers of patients, no standard of care exists, and patients are generally treated with therapies including nephrectomy, chemotherapy and radiation therapy. Despite, this aggressive regimen, the mean overall survival rate is only 6-8 months (Alvarez et al, 2015; Beckermann et al, 2017; Ezekian et al, 2017; Iacovelli et al, 2015). Gene expression of tumor samples from patients with RMC indicates that this entity is distinct from renal cell carcinomas and urothelial carcinomas (Swartz et al, 2002; Yang et al, 2004).…”