Pathology of Medulloblastomas in Children

Molecular/Genetic Pathology

  • Molecular variants with prognostic significance: Recent genomic studies have determined that medulloblastomas have distinct molecular variants based on immunohistochemical markers: DKK1 (WNT), SFRP1 (SHH), NPR3, and KCNA1.  These variants have important prognostic implications, as the progression-free and overall survival rates are dramatically different among subgroups (27).

Histopathology

  • W.H.O. Grade IV: Medulloblastomas are malignant tumors that are categorized as W.H.O. Grade IV (12).
  • Densely packed cells on low-power magnification: Medulloblastomas are composed of densely packed cells with hyperchromatic nuclei and scant cytoplasm (12).
Medulloblastoma on low-power magnification: The histopathology shows typical sheets of undifferentiated cells

 

  • Nuclear pleomorphism with rosettes on high power: Tumors have significant nuclear pleomorphism, high mitotic activity, and neuroblastic (Homer Wright) rosettes in fewer than 40% of cases.
Medulloblastoma on higher power magnification: This view of a medulloblastoma shows an area with neuroblastic (Homer Wright) rosettes

 

  • Immunohistochemistry: Medulloblastomas most commonly have neuronal differentiation, which is manifested by immunopositivity for neuronal markers such as synaptophysin.
Medulloblastoma stained for synaptophysin: Synaptophysin positivity in medulloblastoma shows as a brown staining of the cells

 

  • MIB-1 labeling index: The MIB-1 level is typically very high, reflecting significant cellular proliferation.
MIB-1 labeling stain of medulloblastoma: A high MIB-1 labeling index is apparent

 

  • Histologic variants: Histological subtypes have been described that have varying responses to treatments. They include desmoplastic/nodular medulloblastoma, medulloblastoma with extensive nodularity, anaplastic medulloblastoma, large cell medulloblastoma, myogenic differentiation (medullomyoblastoma), and melanocytic differentiation (melanocytic medulloblastoma) (12).