Atypical Teratoid Rhabdoid Tumors in Adults: Report of Six Cases with Molecular Cytogenetics Analysis
L Neder, MR Ericson-Johnson, X Wang, A Tay, AM Oliveira, BW Scheithauer. Mayo Clinic, Rochester, MN
Background: Atypical Teratoid Rhabdoid Tumors (AT/RTs) are rare malignant embryonal tumors of the CNS most commonly found in young infancy and early childhood. Loss of INI1 protein expression is seen in almost all AT/RTs, and most tumors exhibit loss or mutations of the INI1 gene (hSNF5/SMARCB1) located on chromosome 22q11.2. AT/RT only rarely affects adults; isolated cases have been reported but none with molecular analysis. Herein, we report the clinicopathologic and molecular signature of six cases of adult AT/RTs.
Design: All six AR/RT specimens were obtained from the consultation files of one of us (BWS) or were operated at Mayo Clinic between 1998 and 2009. Immunohistochemistry analysis for INI1 expression was performed in all instances. Interphase molecular cytogenetic analysis was performed using a customer designed fluorescence in situ hybridization (FISH) probe spanning the SMARCB1/INI1 locus paired with a reference probe spanning the BCR locus. All analyses were done on 4µm paraffin-embedded sections according to a standardized protocol. Ten typical infantile AT/RT were used as positive controls, and three CNS PNETs and 1 normal cerebral cortex served as negative controls.
Results: The patients (five female, one male) were age 23 to 44 years (mean age, 32 ± 3 SD). Of the six tumors, three involved the cerebrum (frontal and temporal lobes) and three the pineal region. Histologically, they were composed variably of rhabdoid cells, epithelioid cells in ribbons and cords, and mesenchymal appearing spindle cells in a basophilic matrix. No tumors exhibited a PNET component. Molecular cytogenetic studies demonstrated deletions of the INI1 locus in four tumors: 2 homozygous and 2 heterozygous deletions. One tumor showed a molecular cytogenetic signature consistent with rearrangement of chromosome 22 between the INI1 and BCR loci, and the other a normal INI1 molecular cytogenetic signature.
Conclusions: Adult AT/RTs differ somewhat from those of childhood with respect to female predominance, supratentorial location, and morphology (absence PNET component). Our preliminary molecular cytogenetic data suggest that adult AT/RT shows similar mechanisms of INI1 inactivation when compared to their typical infantile form. Spport: CAPES (Proc. No. 1429-08/6) and Mayo Fundation.
Tuesday, March 23, 2010 2:00 PM
Platform Session: Section G, Tuesday Afternoon