Atypical Teratoid Rhabdoid Tumor: How Tumor Diagnostic Methods in the Laboratory Have Evolved over the Past 40 Years

Atypical Teratoid/Rhabdoid Tumor (AT/RT) is a highly aggressive neoplasm of the central nervous system (CNS), most commonly affecting infants and young children. Originally recognized as a distinct entity following cytogenetic identification of monosomy 22 in renal Rhabdoid Tumors, AT/RT now encompasses CNS tumors characterized by SMARCB1 (INI-1) or SMARCA4 (BRG-1) alterations within the SWI/SNF chromatin-remodeling complex. The integration of immunohistochemical markers with advanced molecular diagnostics—including next-generation sequencing, DNA methylation profiling, and gene enrichment analyses—has facilitated robust tumor classification and the identification of three molecular subgroups: TYR, SHH, and MYC. Despite its distinctive histopathologic features, AT/RT remains diagnostically challenging in adolescent and adult populations due to age-related bias and potential morphologic heterogeneity. Differential considerations, including epithelioid sarcoma, poorly differentiated chordoma, CRINET, choroid plexus carcinoma, and rare composite tumors, further complicate the diagnostic landscape. A comprehensive, multimodal diagnostic approach combining histologic, immunophenotypic, and molecular data is essential to accurately identify AT/RT and guide clinical management, particularly in diagnostically ambiguous or atypical cases.