Histopathology and molecular pathology of pediatric pineal parenchymal tumors

Childs Nerv Syst. 2023 Sep;39(9):2273-2284. doi: 10.1007/s00381-022-05637-x. Epub 2022 Aug 16.


Pineal parenchymal tumors in children are rare. They consist of two main types, pineoblastoma (PB) and pineal parenchymal tumor of intermediate differentiation (PPTID), which are World Health Organization (WHO) grade 4 and grade 2-3 respectively. PBs are divided into four distinct molecular groups: PB-miRNA1, PB-miRNA2, PB-RB1, and PB-MYC/FOXR2. PB-RB1 and PB-MYC/FOXR2 affect young children and are associated with a dismal prognosis. PB-miRNA1 and PB-miRNA2 groups affect older children and follow a more favorable course. They are characterized by mutually exclusive alterations in genes involved in miRNA biogenesis, including DICER1, DROSHA, and DGCR8. They may be sporadic or may represent one manifestation of DICER1 syndrome. PB-RB1 tumors show alterations in the RB1 gene and may develop in the setting of congenital retinoblastoma, a condition known as "trilateral retinoblastoma." In the pediatric population, PPTIDs typically affect adolescents. They are characterized by small in-frame insertions in the KBTBD4 gene which is involved in ubiquitination.

Keywords: DICER1 syndrome; Molecular pathology; Pediatric tumor; Pineal parenchymal tumor of intermediate differentiation; Pineoblastoma; Trilateral retinoblastoma.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Brain Neoplasms* / surgery
  • Child
  • Child, Preschool
  • DEAD-box RNA Helicases / genetics
  • Forkhead Transcription Factors
  • Humans
  • MicroRNAs* / genetics
  • Pathology, Molecular
  • Pineal Gland* / surgery
  • Pinealoma* / surgery
  • RNA-Binding Proteins
  • Retinal Neoplasms* / pathology
  • Retinoblastoma* / pathology
  • Ribonuclease III


  • MicroRNAs
  • RNA-Binding Proteins
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases
  • FOXR2 protein, human
  • Forkhead Transcription Factors