Rhabdoid Tumors of the Kidney
Rhabdoid tumors (RTs) are extremely aggressive malignancies that generally occur in infants and young children. The most common locations are the kidney and central nervous system (CNS) (atypical teratoid/rhabdoid tumor), although RTs can also arise in most soft tissue sites. Initially they were thought to be a rhabdomyosarcomatoid variant of Wilms tumor when they occurred in the kidney.
Histologically, the most distinctive features of rhabdoid tumors of the kidney (RTK) are rather large cells with large vesicular nuclei, a prominent single nucleolus, and in some cells, the presence of globular eosinophilic cytoplasmic inclusions. A distinct clinical presentation with fever, hematuria, young age (mean age 11 months), and high tumor stage at presentation suggests a diagnosis of RTK. Approximately two-thirds of patients will present with advanced stage. Bilateral cases have been reported. RTK tends to metastasize to the lungs and the brain. As many as 10% to 15% of patients with RTK also have CNS lesions. Relapses occur early (median time from diagnosis is 8 months).[15,17]
RTs in all anatomical locations have a common genetic abnormality-the mutation and/or deletion of the SMARCB1 (also called hSNF5 or INI1) gene located at chromosome 22q11. This gene encodes a component of the SWI/SNF chromatin remodeling complex that has an important role in transcriptional regulation.[18,19] Based on gene expression analysis in rhabdoid tumors, it is hypothesized that rhabdoid tumors arise within early progenitor cells during a critical developmental window in which loss of SMARCB1 directly results in repression of neural development, loss of cyclin-dependent kinase inhibition, and trithorax/polycomb dysregulation. Identical mutations may give rise to a brain or kidney tumor. Germline mutations of SMARCB1 have been documented for patients with one or more primary tumors of the brain and/or kidney, consistent with a genetic predisposition to the development of rhabdoid tumors.[21,22] Approximately 35% of patients with RTs have germline SMARCB1 alterations. In most cases, the mutations are de novo, and not inherited from a parent. Germline mosaicism has been suggested for several families with multiple affected siblings. It appears that those patients with germline mutations may have the worst prognosis.
Rhabdoid predisposition syndrome (RPS)
Early-onset, multifocal disease and familial cases strongly support the possibility of an RPS. This has been confirmed by the presence of constitutional mutations of SMARCB1 in rare familial cases and in a subset of patients with apparently sporadic RTs. In a cohort of 74 RTs, 60% of the tumors occurring before age 6 months were linked to the presence of a germline mutation. However, in this same series, tumors that occurred after age 2 years were also found to be associated with germline mutations (7 of 35 cases). Germline analysis is suggested for all individuals with RTs, whatever their ages. Genetic counseling is recommended given the low-but-actual risk of familial recurrence. In cases of mutations, parental screening should be considered, although such screening carries a low probability of positivity. Prenatal diagnosis is feasible and should be considered.