[1740] Uncommon Focal/Regional Heterozygous or Homozygous Deletion of SMARCB1 (hSNF5/INI1) Locus in Two Atypical Teratoid/Rhabdoid Tumors

Jo Elle G Peterson, Vidya Mehta, Carrie A Mohila, Adekunle M Adesina. Methodist Hospital, Houston, TX; Texas Children's Hospital, Baylor College of Medicine, Houston, TX

Background: Atypical teratoid/rhabdoid tumors (ATRTs) are high grade tumors with CNS and non-CNS presentations. They comprise 1-2% of pediatric brain tumors, occurring most often in infancy. While characteristic histology of ATRTs is rhabdoid cells with abundant eosinophilic cytoplasm, they vary in histologic appearance and can mimic many other malignancies. Inactivation of the hSNF5/INI1 (SMARCB1) tumor suppressor gene, a component of the SWI/SNF chromatin-remodeling complex, is the characteristic genetic alteration in > 95% of ATRTs. It is associated with loss of nuclear immunostaining for INI1 (BAF-47). Several cases have now been reported with alternative alterations in the SMARCA4 (BRG1) gene, another component of the SWI/SNF complex. We present two cases of ATRT with heterogeneous staining for INI1, with an uncommon pattern of focal/regional heterogeneous or homozygous deletion of the hSNF5/INI1 locus demonstrated by fluorescence in situ hybridization (FISH).
Design: The study group is comprised of 2 cases. The first is a 3-month old with a metastatic lesion of the lower lip received in consultation because of heterogenous staining for INI1. The second case is a large, complex solid and cystic, congenital right frontal lobe mass in a 5-day old twin. Tumor tissue was paraffin-embedded, formalin-fixed, and stained with H&E. Immunohistochemical staining for INI1 was performed using an anti-BAF-47 antibody. FISH was performed using a cocktail of hSNF5-specific locus probes with chromosome 22-specific reference probes.
Results: Both tumors contained regions of rhabdoid cells histologically characteristic for ATRTs. Both cases also showed heterogeneous immunostaining for INI1, with regions of tumor cells with intact nuclear positivity for INI1 interdigitating with and adjacent to regions with loss of nuclear INI1 staining. Repeat INI1 staining showed similar results. FISH demonstrated an uncommon pattern of focal/regional homozygous deletion of the hSNF5/INI1 locus in case 1, while case 2 showed regional heterozygous deletion of the hSNF5/INI1 locus.
Conclusions: These two cases show an unusual pattern of deletion of the SMARCB1 locus associated with a heterogeneous loss of nuclear INI1 immunostaining. We are not aware of a previous report of this observation. These cases represent the first report of inherent molecular heterogeneity for SMARCB1 deletion within tumors that otherwise have classic histologic features for ATRT.
Category: Neuropathology

Monday, March 4, 2013 8:30 AM

Proffered Papers: Section G1, Monday Morning


Close Window