Descriptive and molecular analysis of pineal parenchymal tumors with clinical correlation.

BACKGROUND: Pineal parenchymal body tumors are rare central nervous system tumors with a variety of presentations ranging from well-differentiated low-grade tumors to undifferentiated highly aggressive tumors. Recent molecular classification has described this heterogeneity, particularly among pineoblastomas (PB) and pineal parenchymal tumor of intermediate differentiation (PPTID). METHODS: Our study analyzed 49 patients with pineal parenchymal tumors, including PBs (n = 39), papillary tumors of the pineal region (n = 5), PPTID (n = 2), pineocytoma (n = 1), and trilateral retinoblastoma (n = 2). Descriptive analysis of patients’ characteristics was done in percentages and numbers. Overall survival (OS) and event-free survival (EFS) analysis were evaluated in relation to age and metastatic status for PB cases. Molecular classification was performed using the EPIC methylation array and analyzed by Heidelberg Classifier on 20 cases, of which sixteen were histopathologically diagnosed as PB. RESULTS: Among PBs, univariate analysis showed that age significantly impacted OS and EFS (p-value = 0.003 and 0.021, respectively), while metastatic status only impacted EFS (p-value = 0.032). In Multivariate analysis, only age was of significance on OS (p-value 0.028). The identified methylation groups were PB-miRNA-1 (n = 10), PB-RB1 (n = 1), retinoblastoma-MYCN activated (n = 1), PPTID KBTBD4-altered (n = 1), papillary tumor of the pineal region (n = 1), medulloblastoma (MB) WNT activated (n = 1), MB non-WNT/SHH (n = 1), CNS embryonal tumor with BRD4-LEUTX fusion (n = 1) and unclassified N/A (n = 3). CONCLUSION: Our data identified age as a prognostic factor affecting survival among our PB cohort. We also highlighted the heterogeneity of pineal parenchymal body tumors, necessitating molecular classification for accurate diagnosis and for developing tailored treatment strategies. We demonstrate the feasibility of identifying new entities and MBs within pineal body tumors, thereby supporting the growing evidence that MBs originate in the pineal region. CLINICAL TRIAL NUMBER: Not applicable.