Renal medullary carcinoma (RMC) is rare and highly malignant neoplasm with SMARCB1 (INI1) -deficiency. The existence without a concomitant hemoglobinopathy is a controversial subject, but many will refer to such cases as ‘RCC unclassified with medullary features. ^1-4

It is found not infrequently in patients of African descent. ^5,6 It occurs in approximately 1 in 20,000 individuals with sickle cell trait or other associated hemoglobinopathy. RMC is the third most common kidney malignancy among male adolescents and young adults. ⁷

Young male patient of African or Mediterranean descent, with hematuria and/or flank pain/ or palpable mass, and weight loss. ⁸

Poorly circumscribed white, tan fleshy mass that arises in the medulla and can extend into the cortex. Affects the right kidney more frequently than the left. ⁹

Tumors arises in the renal medulla and demonstrates and infiltrative growth pattern between non-neoplastic tubules in the cortex. ^4,10 A characteristic reticular or cribriform growth pattern with a striking desmoplastic stromal response and a robust mixed inflammatory infiltrate is typically present. Sickled red blood cells can be seen in vascular spaces in patients with sickle cell trait.

Tumors with SMARCB1 translocation were more likely to show reticular and cribriform pattern (64% vs 17%), whereas tumors with SMARCB1 homozygous loss were significantly enriched for a solid growth pattern

Loss of SMARCB1 (INI1)- protein expression (Fig.1) is key diagnostic feature of these tumors; a subset of cases with demonstrate aberrant expression of OCT3/4.

Fig.1. Renal meduallary carcinoma: the absence (loss) of SMARCB1 protein expression is clear in on the tumor cells, in contrast inflammatory, endothelial and stroma cells are positive

Very poor prognosis, because metastatic disease (liver, lungs, bone and adrenal glands) is not uncommon at the time of presentation. Resistant to conventional chemotherapy, and a fatal outcome occurs within a few months. ^8,9

Given the presence of SMARCB1 alterations ^11,12, many of the same therapies utilized for the management of other SMARCB1-deficient neoplasms may be utilized. ^13,14

The most common molecular alteration is an inactivating translocation of one SMARCB1 allele and deletion (-22,/del22q) of the second allele; less frequent are deletion of both SMARCB1 alleles, representing an important molecular mechanism in patients with sickle cell trait ^15-18; this is a relatively unique mechanism that has not been well described in other SMARCB1-deficient tumors. ^12,19

FISH analysis can detect alterations in SMARCB1 consisting mostly in inactivating translocation of one allele and deletion of the second one.

Recurrent focal copy number variations have been reports , i.e., focal amplification on chromosome 2p, in the 11q14.3 region. NOTHC2, large amplification of chromosome 8, monosomy of chromosomes 4 and 22, large deletions of chromosomes 15 and 16, and a focal deletion of chromosome 17p13.1 TP53¹⁸

Somatic mutation of SMARCB1 was detected uncommonly, as well as recurrent mutation.

By expression profiling, RMC is most closely related to collecting duct carcinoma (which lacks an association with sickle cell trait) and is clearly distinct from malignant rhabdoid tumor (MRT) arising in the kidney; the latter of which also demonstrates SMARCB1 inactivation. ¹⁸

An increasing number of SMARCB1-deficient neoplasms outside of the renal medullary carcinomas have been described. ^12,14,20-22