Final Diagnosis -- Glioblastoma (WHO grade IV) with primitive neuroectodermal tumor (PNET)-like component

DIAGNOSIS

Glioblastoma (WHO grade IV) with primitive neuroectodermal tumor (PNET)-like component.

DISCUSSION

Glioblastoma (WHO grade IV) is the most frequent primary brain tumor of adults, and exhibits a heterogeneous histologic spectrum (2). As an astrocytic neoplasm, it is expected to demonstrate morphologic and immunohistochemical features of glial and astrocytic differentiation, as typically evidenced by reactivity for S-100 protein and glial fibrillary acidic protein (GFAP).

Primitive neuroectodermal tumor (PNET), an aggressive neoplasm encountered more commonly in the pediatric population, constitutes essentially the supratentorial counterpart of medulloblastoma (5). Defined as a primitive, embryonal-type neoplasm, it is expected to demonstrate potential for divergent differentiation along glial, neuronal, and occasionally muscular or melanocytic lines; as such, while some degree of reactivity for glial markers are expected, expression of neuronal antigens, such as neurofilament, synaptophysin, and/or neuron-specific enolase should also be demonstrated. This tumor is exceedingly rare in the adult population, with documented experiences limited to mostly single case reports (3, 6, 10). When present, the entire neuraxis is at risk, with a relatively high propensity for cerebrospinal fluid (CSF) dissemination.

It is rare to encounter a brain tumor demonstrating both, PNET-like features and elements of more advanced glial, specifically astrocytic, differentiation. Although documented experiences with cases have been mostly limited to the occasional individual case reports in adults (1, 9) and children (4), tumors demonstrating such biphasic histology are being increasingly recognized and studied. The most recent and largest series studied 53 cases (8). Within this series, N-myc or c-myc gene amplification was observed in the primitive component in many cases (43%), while alterations typically associated with gliomas were observed in both, the gliomatous and the primitive neuroectodermal components, with 10q loss being the most common (10%).

A neoplasm with both, glial and primitive components poses an interesting question regarding its tumoral biology, specifically whether (i) the differentiated glial component arose from the primitive component, (ii) the primitive component reflects metaplasia or dedifferentiation of the glial component, or (iii) the two components reflect a "collision" phenomenon between two separate neoplastic clones. Evidence from the largest recent case series suggests that the primitive component likely arises from a pre-existing glioma, most often a secondary glioblastoma, and may represent a metaplastic phenomenon or expansion of a tumor progenitor cell clone (8). Interestingly, report has been made of a case of glioblastoma occurring 13 years after treatment for medulloblastoma (7). From this case, it is possible to postulate that the glioblastoma reflects differentiation of residual, multipotent cells of the medulloblastoma; alternatively, the glioblastoma may represent a radiation-induced neoplasm following therapy for medulloblastoma.

In the present case, following gross total resection, the patient was initiated on temozolomide and concurrent radiation. During the course of his treatment, the patient died approximately five weeks after initial diagnosis.

REFERENCES

1. Kandemir NO, Bahadir B, Gul S, Karadayi N, Ozdamar SO (2009). Glioblastoma with primitive neuroectodermal tumor-like features: case report. Turkish Neurosurgery 19(3):260-264.
2. Kleihues P, Burger PC, Aldape KD, Brat DJ, Biernat W, Bigner DD, Nakazato Y, Plate KH, Giangaspero F, von Deimling A, Ohgaki H, Cavenee WK (2007) Glioblastoma. In WHO Classification of Tumours of the Central Nervous System. D.N. Louis, H. Ohgaki, O.D. Wiestler, W.K. Cavenee, Editors. International Agency for Research on Cancer, 33-46.
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7. Pearl GS, Mirra SS, Miles ML (1980). Glioblastoma multiforme occurring 13 years after treatment of a medulloblastoma. Neurosurgery 6(5):546-551.
8. Perry A, Miller CR, Gujrati M, Scheithauer BW, Zambrano SC, Jost SC, Raghavan R, Qian J, Cochran EJ, Huse JT, Holland EC, Burger PC, Rosenblum MK (2009). Malignant gliomas with primitive neuroectodermal tumor-like components: a clinicopathologic and genetic study of 53 cases. Brain Pathology 19(1):81-90.
9. Prayson RA (2009). Lipomatous supratentorial primitive neuroectodermal tumor with glioblastomatous differentiation. Annals of Diagnostic Pathology 13:36-40.
10. Shingu T, Kagawa T, Kimura Y, Takada D, Moritake K, Hoshii Y (2005). Supratentorial primitive neuroectodermal tumor in an aged patient. Neurol Med Chir (Tokyo) 45:530-535.

Contributed by Brian H Le, MD and Matthew Sandusky, MD