Renal rhabdoid tumour of the kidney (RT) is a rare and aggressive malignancy, mainly characterized by SMARCB1/INI1 somatic mutations. ^1,2 It belongs to to the family of SMARCB1-deficient neoplasms ³

2% of pediatric renal tumors, mainly occur in the first 2 years of life, with 60% in the 1 year. Male: female ratio is 1.5:1.^4,5 Rhabdoid tumor predisposition syndrome (RTPS) when the mutation occurs in the SMARCB1 gene, RTPS1 syndrome OMIM:609322. When the mutation occurs in a different SWI/SNF protein, brahma-related gene 1 (BRG1), encoded by the SMARCA4 gene, RTPS2 syndrome OMIM:613325. Children presenting with RTPS tend to develop tumors at a younger age, ⁶ and concurrent tumors in other organs, mainly brain. ⁷

Frequently hematuria or symptoms related to the metastases. Metastases earlier than in Wilms tumor, mainly in lungs, liver, and brain.  Highly aggressive clinical behavior with poor prognosis in most patients.

A generally a large, poorly circumscribed mass in the kidney with foci of hemorrhage and necrosis, often extending beyond the renal capsule.

Classic rhabdoid tumors show sheets of monomorphic cells with abundant cytoplasm, eccentric vesicular nuclei and prominent, eosinophilic nucleoli. Eosinophilic hyaline paranuclear intracytoplasmic inclusions are characteristic of rhabdoid cells.  Morphological variations include tumors with predominant small cell component and focal or absent inclusions; predominant myxoid stroma or a dominant lymphocytic infiltrate. Vascular invasion is easily recognizable. Necrosis and hemorrhage are frequent, and mitoses are easily detectable. ⁵

Vimentin (typical dot-like paranuclear staining), cytokeratin and EMA are positive. Loss of nuclear staining for INI1 consistent with the inactivation SMARCB1 tumor suppressor gene is an important diagnostic marker. ⁸

Renal rhabdoid tumors are currently treated according to specific rhabdoid tumor protocols, with intensified treatment in children under 18 months. Early complete resection is prognostically important. ⁴  Adverse prognostic factor is the younger age (9% OS in infants). ⁷  A promising therapeutic approach targets cyclin D1 and CDK4 counteracting the loss of the role of SWI/ SNF complex in RTs in the inhibition of cell cycle progression via repression of CCND1, which encodes cyclin D1, and activation of p16INK4A and p21CIP.  Other potential targets for future treatment strategies include: the mitotic regulator Aurora A kinase and the Sonic hedgehog pathway, which are activated by loss of SMARCB1, EZH2, CXCR4, IGF2, PD-1/PD-L1. ^4,9

•    The findings of consistent chromosome 22 abnormalities e.g. del(22)(q11.2)/monosomy 22/ 22q11.2 translocation,  in a series of malignant rhabdoid tumors, ultimately leaded to the identification of the SMARCB1 gene as a candidate gene for renal and extrarenal rhabdoid tumors ^10,11.   The SMARCB1 (aka INI1, BAF47 and hSNF5) gene maps at 22q11.23, encodes one core subunit of SWI/ SNF complex, and acts as tumor suppressor gene ¹².

•    Bi-allelic SMARCB1 inactivation resulting in complete loss of expression in 95% of renal rhabdoid tumor, with the rare exception in those tumors with loss of SMARCA4 at 19p13.2. ^12-14 The SMARCB1 biallelic inactivation results in a complete loss of function via a spectrum of events including, whole-gene deletions, large intragenic deletions/duplications, small out-of-frame intragenic deletion/insertion,  splice-site mutations and nonsense mutations. Missense mutations are rare.

•    Approximately 35% of newly diagnosed patients with rhabdoid tumor have an underlying genetic predisposition to tumors due to a germline alteration on SMARCB1, ¹⁵ or rarely, on SMARCA4. ¹⁶

SMARCB1/INI1 has also been implicated in the pathogenesis of several and varied additional tumors, all showing loss of INI1 protein expression, e.g. SMARCB1-deficient neoplasms, a tendency for rhabdoid cytomorphology, and sometimes other overlapping immunohistochemical and histologic findings. ^3,17-19