Histopathology and Molecular Pathology of Pineal Region Tumors

Tumors of the pineal region are rare neoplasms accounting for only about 1% of all central nervous system tumors. This chapter details the histopathological features and molecular alterations of these tumors. The two most common types are germ cell tumors (GCTs) and pineal parenchymal tumors (PPTs). PPTs are a group of neoplasms that exhibit varying degrees of pinealocytic differentiation and diverse prognoses. They comprise well-differentiated low-grade pineocytomas, pineal parenchymal tumors of intermediate differentiation (PPTIDs), and poorly differentiated high-grade pineoblastomas (PBs). The molecular pathogenesis of PBs notably involves alterations in the microRNA biogenesis and retinoblastoma pathway. PPTIDs are characterized by small in-frame insertions in the KBTBD4 gene. Pineal GCTs are thought to originate from primordial germ cells that have overmigrated along the midline. They exhibit the same histopathological spectrum as their gonadal counterparts. Germinomas are the most frequent GCTs in the pineal region and frequently present mutations in the MAPK pathway. Papillary tumor of the pineal region is a specific type of ependymal tumor that primarily affects the pineal region and exhibits a loss of chromosome 10 in most cases.