Renal medullary carcinoma (RMC) is rare and highly malignant neoplasm that most often occurs in teenagers or young adults with sickle cell trait or other associated hemoglobinopathy.  The existence of RMC without a concomitant hemoglobinopathy is a controversial subject, and most consider the latter an Unclassified RCC with Medullary Features and SMARCB1/INI1 loss.

African descent increases risk ^1,2. 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 ³.

Young male patient of African or Mediterranean descent, with hematuria and/or flank pain and/or a palpable mass, and weight loss ⁴.

Poorly circumscribed mass arises predominantly from the right kidney occupying most of the renal medulla with extension into the renal cortex ⁵.

A characteristic reticular or cribriform pattern with a striking desmoplastic stromal response and a robust mixed inflammatory infiltrate.

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

Loss of SMARCB1 protein expression (Fig. 1) is a key diagnostic feature of these tumors, Aberrant expression of OCT3/4 may also be present.  Secondary loss of SMARCB1 expression has been found in other RCC types ⁶.

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

The most common molecular alteration was inactivating translocation of one SMARCB1 allele and deletion (-22,/del22q) of the second allele.  Less frequent is  deletion of both SMARCB1 alleles, representing an important molecular mechanism in patients with sickle cell trait ^8,9,10,11; this is a relatively unique mechanism that has not been well described in other [[SMARCB1-deficient neoplasms]] ¹².
RMC also has recurrent focal copy number alterations in chromosomal fragile sites, such as amplifications (11q14.3, NOTCH2, chr.2) and deletions (chr.4 and 22), in addition to 22q11.23 loss.  Chromosome 8q gain was noted with significantly upregulated genes in that chromosome arm ¹¹.

SMARCB1 somatic mutations are detected uncommonly, as well as recurrent mutations.

By gene expression profiling, RMC may be closely related to collecting duct carcinoma, but is clearly distinct from malignant rhabdoid tumor of the kidney; the latter shares etiology of SMARCB1 inactivation ¹¹

SMARCB1 loss has also been identified in a variety of other malignant neoplasms ^13,14,15

Very poor prognosis; metastatic disease (liver, lungs, bone and adrenal glands) frequent at the time of presentation. Resistant to conventional chemotherapy, and a fatal outcome often occurs within a few months ^4,5.

Given the presence of SMARCB1 alterations, targeted therapies utilized for the management of other SMARCB1-deficient neoplasms may prove to be helpful/increase survival ⁷.