hSNF5/INI1-deficient tumours and rhabdoid tumours are convergent but not fully overlapping entities.

Rhabdoid tumours (RTs) are rare but highly aggressive tumours of childhood. Their rarity and their miscellaneous locations make the diagnosis particularly challenging for pathologists. Central nervous system and peripheral RTs have been associated with biallelic inactivation of the hSNF5/INI1/SMARCB1 (hSNF5/INI1) tumour suppressor gene. Immunohistochemistry (IHC) with a monoclonal anti-hSNF5/INI1 antibody has recently been proposed as an efficient diagnostic tool for RTs. We have conducted a retrospective study of 55 tumours referred to our institution with a suspicion of RT. This analysis included pathological review, IHC with anti-hSNF5/INI1 antibody, and molecular investigation using quantitative DNA fluorescent analysis and sequencing of the nine exons of hSNF5/INI1. The molecular lesion could be detected in 37 of the 39 cases exhibiting negative staining for hSNF5/INI1. In the two discrepant cases, the lack of detection of genetic abnormality was probably owing to the presence of a high number of non-tumour cells in the samples. This indicates that hSNF5/INI1 IHC is very sensitive and highly specific for the detection of hSNF5/INI1 loss-of-function. Among the 38 cases with typical RT histological features, six failed to exhibit hSNF5/INI1 mutation and stained positive for hSNF5/INI1. This strongly supports the evidence of a second genetic locus, distinct from hSNF5/INI1, associated with RT. Conversely, seven tumours with histological features poorly compatible with RT stained negative for hSNF5/INI1; they nevertheless exhibited an age of onset and a clinical behaviour similar to RT. This suggests that hSNF5/INI1 inactivation is not strictly limited to typical RT but characterizes a wider family of hSNF5/INI1-deficient tumours. Consequently, we believe that anti-hSNF5/INI1 IHC should be performed widely, even when the pathological characteristics are not typical. The molecular investigation should be performed in infants when a rhabdoid predisposition syndrome is suspected.