Extracerebellar primitive neuroectodermal tumors: A clinicopathologic study with bcl-2 and CD99 immunohistochemistry.

Supratentorial primitive neuroectodermal tumors (S-PNETs) are uncommon lesions that occur predominantly in children and are histologically identical to cerebellar medulloblastomas. Like their cerebellar counterparts, S-PNETs often show divergent differentiation along neuronal, glial, and mesenchymal lines. The relationship of S-PNETs to medulloblastoma and other embryonal neoplasms remains controversial, largely because the cell of origin and histogenesis of these lesions are incompletely understood. To clarify these issues, we examined eight S-PNETs with antibodies to bcl-2 (an antiapoptosis protooncogene that has been postulated to be a marker of neuronal differentiation) and CD99 (a glycoprotein present in most peripheral embryonal tumors). S-PNETs in eight patients (seven males and one female; age range, 2 months to 40 years) were studied. All lesions were composed predominantly of small round cells with deeply basophilic nuclei and minimal surrounding cytoplasm. Tumors in two patients demonstrated no evidence of differentiation, two tumors neuronal differentiation only, and four tumors both neuronal and glial differentiation. No tumors stained with CD99. Three tumors showed focal, strong cytoplasmic staining with bcl-2. The positive lesions included one tumor showing neuronal differentiation only and two tumors with both neuronal and astrocytic differentiation. Patients were treated with various combinations of radiation and chemotherapy; five patients died from their tumor a mean of 1.7 years after diagnosis, two patients were alive with residual disease at 3 months and 3 years, and one patient was alive without disease at 17 months. Our findings suggest that bcl-2 positivity may identify a subgroup of patients having inhibition of apoptosis as a pathogenetic mechanism; we were unable to show any definite relationship between bcl-2 staining and neuronal differentiation. Despite their morphologic similarity, supratentorial and peripheral embryonal tumors appear to be distinct pathogenetic lesions, as evidenced by their different staining patterns with CD99.