Pathology of Supratentorial Primitive Neuroectodermal Tumors in Children

Pathophysiology

• Large, solid tumors: Cerebral supratentorial PNETs are often large at the time of initial diagnosis. On gross examination they are solid with areas of hemorrhage, calcification, necrosis, and cysts. The solid component is usually pink-red, soft, gelatinous, and highly vascular.
• Demarcation variable: Supratentorial PNETs may be well demarcated or they may have indistinct borders from surrounding brain.
• Primitive with ability to differentiate:  Supratentorial PNETs may have differentiation along neuronal, astrocytic, ependymal, muscular, or melanotic cell lines. Tumors with neuronal differentiation may be called cerebral neuroblastomas. Tumors with ganglion cells can be called ganglioneuroblastomas. Rarely, they may have smooth or striated muscle. Infrequently, tumor cells are found to contain melanin.

Molecular/Genetic Pathology

• Not well studied: There are few cytogenetic and comparative genomic hybridization studies of supratentorial PNETs.
• Complex karyotypes: Supratentorial PNETs may show complex karyotypes with double minute structures and high-level copy number gains or amplifications (6).
• Different cytogenetics from medulloblastoma: Although medulloblastomas and supratentorial PNETs appear morphologically similar, they are different on the basis of cytogenetics. Specifically, the deletion of 17p and the gain of 17q, which are the most frequently described chromosomal aberrations in medulloblastomas, are rare in supratentorial PNETs; and the isochromosome 17q abnormality, which is found in 30–50% of medulloblastomas, has been reported in only one supratentorial PNET (7).

Histopathology

Histologically similar to medulloblastomas

• Sheets or cords of primitive neuroepithelial cells: Supratentorial PNETs have primitive, neuroepithelial cells in dense sheets or cords. These cells are undifferentiated or poorly differentiated and demonstrate a high nuclear-to-cytoplasmic ratio with small, round to oval basophilic nuclei that are rich in chromatin. There is usually marked nuclear pleomorphism with variable mitotic activity and karyorrhexis or apoptosis.
• Homer-Wright rosettes: There may be Homer-Wright rosettes, which are neuroblastic rosettes formed as a result of tumor cell nuclei arranged in a circular fashion about tangled cytoplasmic processes. There may also be ependymal canals or Flexner-Wintersteiner rosettes.
• Calcification, necrosis, hemorrhage, and/or cyst formation may occur.

Immunohistochemistry

 Immunohistochemistry can be useful in identifying the poorly differentiated component of neoplastic cells that constitute supratentorial PNETs.

• Neuronal markers: Tumor cells may express neuronal markers and be positive for synaptophysin, neuron-specific enolase (NSE), and neurofilament.
• GFAP: Cells may be positive for glial fibrillary acid protein (GFAP) if there is glial differentiation.
• High Ki67: Immunohistochemical stain for Ki67, which indicates cells in proliferation, is usually high and can range up to 90%.

Electronmicroscopy

The ultrastructural features of supratentorial PNETs highlight the primitive characteristics of this tumor.

• Rare organelles: There is usually a paucity of cytoplasmic organelles. The presence of dense-core vesicles is diagnostic of neuroblastoma. The appearance of growth cones containing arrays of microtubules suggests ganglionic differentiation. The presence of synapses is rare. Glial differentiation is manifested by the appearance of cytoplasmic glial filaments.