Role of immunohistochemistry in the molecular classification of atypical teratoid/rhabdoid tumor

Atypical teratoid/rhabdoid tumors (ATRTs) are rare, aggressive Central nervous system (CNS) tumors in young children with poor prognosis. Molecular subgrouping (ATRT-TYR, ATRT-SHH, ATRT-MYC) is crucial for understanding biology, guiding treatment, and predicting outcomes. This study assesses immunohistochemistry (IHC) as a surrogate for molecular subgrouping and is the second study to analyze histomorphological patterns across subgroups.

The study analyzed 39 histopathologically confirmed ATRT cases over 15 years. Clinical and radiological data were obtained from case records, and H&E and IHC slides were reviewed. IHC markers-SOX-11 for ATRT-SHH, C-MYC for ATRT-MYC, and tyrosinase for ATRT-TYR-were used for molecular subgrouping. Subgrouping results were correlated with clinical, pathological, and survival data available in the literature.

The most common subgroup was ATRT-SHH (41%), followed by ATRT-MYC (33%) and ATRT-TYR (23%). ATRT-SHH predominantly occurred in children ≤ 3 years and showed diverse cell morphology. ATRT-MYC had the widest age range, including adults, and a higher supratentorial prevalence. ATRT-TYR was common in infants and predominantly infratentorial. Rhabdoid cells were the most common cell type, varying across subgroups. Survival analysis (on a limited follow-up cohort of n = 11) suggested ATRT-MYC may be the most aggressive subtype, although this finding is limited by sample size and heterogeneity of treatment.

Immunohistochemistry (IHC) based classification of ATRT aligned with known molecular and clinicopathological patterns. These alignment with known patterns suggests that the IHC-based classification can be used in routine practice as a cost-effective alternative method to methylation profiling.