86 Controversies in Neuropathology

Neuro-Oncologist: “You’ve got to help me with this case. It was called PNET at one institution but malignant glioma at another. It’s a frontal lobe tumor in a 5-year-old.”

Pathologist: “Well, I see the problem. Take a look. It’s a highly cellular blue cell tumor all right. There’s focal necrosis with maybe some pseudopalisading, but not really. There’s mild nuclear pleo-morphism, and no vascular proliferation, and no neuronal or neu-roblastic features other than trapped cortical ganglion cells. It’s cer-tainly malignant, but I’m not sure I can tell you what it is. There’s some infiltration, and maybe a bit of perineuronal satellitosis, but I’m not sure that helps. Is the diagnosis of small cell malignant tumor good enough?”

Neuro-Oncologist: “No. If it’s PNET the whole neuraxis will be irradiated, but only the tumor area if it’s malignant glioma. Che-motherapy would not be the same either. Treatment protocols are very different. There’s no evidence of CSF dissemination so far in this case, but I’m concerned about under treatment if it’s PNET and I treat it like a malignant glioma.”

Pathologist: “I understand the protocol issue, but has it ever been established that supratentorial PNETs are more prone to CSF dis-semination than malignant gliomas?”

Neuro-Oncologist: “I guess the assumption has been that neur-axis radiation is standard for medulloblastomas and it should be for supratentorial PNETs as well, but I don’t know of any controlled study. In any case, I have little flexibility since neuraxis treatment is basically standard-of-care for PNET.” The parents are devastat-ed. They had a hope of cure with the original diagnosis of PNET, but now if it’s malignant glioma—, they know what that means. I thought it was easy to distinguish PNETs from malignant glio-mas.”

Pathologist: “Not really, at least not to me. There’s little agree-ment between pathologists. Some lean toward malignant glioma in this situation or just “malignant tumor, particularly if they’re more experienced in adult CNS tumors. Others are liberal with the diagnosis of PNET. A glioblastoma with features of the lesion as it occurs in adults is distinguished easily from a supratentorial neuroblastoma with Homer-Wright rosettes. A small cell tumor that is diffusely immunoreactive for synaptophysin would qualify readily as PNET as well. But it’s much different with lesions such as your case without specific histological or immunohistochemical features. I must say, that all of these pediatric malignant tumors

tend to overlap. No two cases seem exactly the same and they often don’t fall into established diagnostic categories. It’s hard to get trac-tion. I know it’s important to you, but it’s just not clear.”

Neuro-Oncologist: “Was immunohistochemistry done?”

Pathologist: “Several times. You can see this synaptophysin stain-ing here that is consistent with PNET, but it’s focal and could well be that of trapped cortex. GFAP staining is prominent as in these perivascular astrocytes overrun by the tumor. There’s reactivity over here too, but it’s hard to sure whether it’s of reactive astrocytes or tumor cells. Even if tumor cells were positive there’d be the difficult issue of small cell malignant glioma versus PNET with glial differ-entiation, and I have no idea how to distinguish these two.”

Neuro-Oncologist: “Can anything else be done?”

Pathologist: “Well, we could take tissue from the paraffin block and look for neuroblastic differentiation in the form of microtu-bules and neurosecretory granules, but I’m not optimistic that the findings would be definitive.”

Neuro-Oncologist: “What about molecular or cytogenetic fea-tures?”

Pathologist: “Sounds good, but there’s little known. There’s lots of papers about PNETs, but they basically all describe medullo-blastomas. Even if there were a large series of supratentorial tumors I’d be skeptical of the conclusions given the problem of defining PNET at the histological level. I mean, would the present case be included or not? In some problem cases, like yours, almost every tumor cell is immunoreactive for p53, but whether this favors gli-oma or PNET is unclear.”

Neuro-Oncologist: “How confusing. I had no idea. What do you suggest?”

Pathologist: “It won’t help you here but someone needs to iden-tify individual prognostic factors in pediatric small cell supratento-rial tumors, rather than evaluate outcome on the basis of tumors diagnosed by a priori definitions. The latter seem clear on paper but are hard to apply in practice. It would take large number of patients, and would be a HIPPA nightmare, but without such a study cases such as this will continue to be decided on an institu-tion-to-institution basis.”

Neuro-Oncologist: “Thanks. I guess.”

CONTROVERSIES IN NEUROPATHOLOGY

Supratentorial Primitive Neuroectodermal Tumor (sPNET)

Peter C. Burger, M.D.

Department of Pathology, Johns Hopkins University, Baltimore, Md.

Editor’s Note: Suptratentorial primitive neuroectodermal tumor is a controversial entity, one often difficult to differentiate from a high grade glioma. The following hypothetical dialogue between a Neuro-Oncologist and his Pathologist colleague illustrates some of the difficulties that arise in the diagnosis and treatment options for affected patients.