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).

 

• 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.

 

• Immunohistochemistry: Medulloblastomas most commonly have neuronal differentiation, which is manifested by immunopositivity for neuronal markers such as synaptophysin.

 

• MIB-1 labeling index: The MIB-1 level is typically very high, reflecting significant cellular proliferation.

 

• 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).