81 YEAR‐OLD MALE WITH CONFUSION AND WEAKNESS

CLINICAL HISTORY

An 81 year‐old male with a clinical history of hypertension and hyperlipidemia presented with weakness, confusion, aphasia, and short‐term amnesia. Five months prior to presentation he had sustained a stroke involving the left middle cerebral artery. Current imaging by CT scan reveals worsening edema in the vascular territorial distribution of the left middle cerebral artery accompanied an ovoid, mass‐like lesion in the left temporal‐parietal region. Follow‐up MRI revealed, in the anterior aspect of the left temporal lobe and extending into the insula and basal ganglia, a 5.0 × 4.6 × 3.2 cm mass with serpiginous border enhancement. Foci devoid of enhancement were also observed, suggestive of necrosis. The patient subsequently underwent a craniotomy with attempt at gross total resection, yielding an approximate 20 mL aggregate of tissue.

MICROSCOPIC PATHOLOGY

Histologic examination of the tumor shows biphasic histology. The less dominant morphologic pattern consists of a hypercellular proliferation of pleomorphic cells, with occasional giant cells, present within a gliofibrillary background (figure 1). Foci of microvascular proliferation are observed (figure 2). Cellular elements within this component show reactivity for glial fibrillary acidic protein (GFAP), vimentin, and S‐100 protein.

Figure 1.

Figure 2.

The second, more prominent component is composed of cells with large nuclei, present within a background of extensive necrosis (figure 3). High power magnification is notable for nuclear molding and an elevated mitotic index (4, 5). Cellular constituents comprising this component show faint immunoreactivity for S‐100 and neurofilament, but more prominent reactivity for synaptophysin (figure 6), and neuron‐specific enolase (NSE) (figure 7).

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

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.

ABSTRACT

Glioblastoma, the most common primary brain tumor, is a highly infiltrative, malignant astrocytic neoplasm that demonstrates a wide spectrum of morphologic heterogeneity. Cases with a primitive neuroectodermal tumor (PNET)‐like component are rare, but are being increasingly recognized and studied. The primitive component typically shows immunohistochemical features that are indicative of potential for divergent differentiation along glial and neuronal pathways; when present, the entire neuraxis may be at risk for involvement, portending a particularly poor prognosis. Recently, data from the largest case series studying malignant gliomas with a PNET‐like component suggest that the primitive component likely arises from the malignant glial component. This report presents an example of glioblastoma with a prominent primitive neuroectodermal‐like component in an 81 year‐old male who, during the course of concurrent chemotherapy and radiation therapy, died five weeks following initial diagnosis.