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81 YEAR-OLD MALE WITH CONFUSION AND WEAKNESSBrian H. Le, M.D.1; Matthew Sandusky, M.D.2

1 Department of Pathology, Reading Hospital and Medical Center, West Reading, PA.2 Department of Diagnostic Imaging, Brown University, Providence, RI.

CLINICAL HISTORYAn 81 year-old male with a clinical history of hypertension andhyperlipidemia presented with weakness, confusion, aphasia, andshort-term amnesia. Five months prior to presentation he had sus-tained a stroke involving the left middle cerebral artery. Currentimaging by CT scan reveals worsening edema in the vascular ter-ritorial distribution of the left middle cerebral artery accompa-nied an ovoid, mass-like lesion in the left temporal-parietalregion. Follow-up MRI revealed, in the anterior aspect of the lefttemporal lobe and extending into the insula and basal ganglia, a5.0 ¥ 4.6 ¥ 3.2 cm mass with serpiginous border enhancement.Foci devoid of enhancement were also observed, suggestive ofnecrosis. The patient subsequently underwent a craniotomy withattempt at gross total resection, yielding an approximate 20 mLaggregate of tissue.

MICROSCOPIC PATHOLOGYHistologic examination of the tumor shows biphasic histology. Theless dominant morphologic pattern consists of a hypercellular pro-liferation of pleomorphic cells, with occasional giant cells, presentwithin a gliofibrillary background (figure 1). Foci of microvascularproliferation are observed (figure 2). Cellular elements within thiscomponent show reactivity for glial fibrillary acidic protein(GFAP), vimentin, and S-100 protein.

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

Figure 1.

doi:10.1111/j.1750-3639.2010.00404.x

867Brain Pathology 20 (2010) 867–870

© 2010 The Authors; Journal Compilation © 2010 International Society of Neuropathology

Figure 2.

Figure 3.

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868 Brain Pathology 20 (2010) 867–870

© 2010 The Authors; Journal Compilation © 2010 International Society of Neuropathology

Figure 4.

Figure 5.

Figure 6.

Figure 7.

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869Brain Pathology 20 (2010) 867–870

© 2010 The Authors; Journal Compilation © 2010 International Society of Neuropathology

DIAGNOSISGlioblastoma (WHO grade IV) with primitive neuroectodermaltumor (PNET)-like component.

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

Primitive neuroectodermal tumor (PNET), an aggressive neo-plasm encountered more commonly in the pediatric population,constitutes essentially the supratentorial counterpart of medullo-blastoma (5). Defined as a primitive, embryonal-type neoplasm, itis expected to demonstrate potential for divergent differentiationalong glial, neuronal, and occasionally muscular or melanocyticlines; as such, while some degree of reactivity for glial markers areexpected, expression of neuronal antigens, such as neurofilament,synaptophysin, and/or neuron-specific enolase should also be dem-onstrated. This tumor is exceedingly rare in the adult population,with documented experiences limited to mostly single casereports (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, specificallyastrocytic, differentiation. Although documented experiences withcases have been mostly limited to the occasional individual casereports in adults (1, 9) and children (4), tumors demonstrating suchbiphasic histology are being increasingly recognized and studied.The most recent and largest series studied 53 cases (8). Within thisseries, N-myc or c-myc gene amplification was observed in theprimitive component in many cases (43%), while alterations typi-cally associated with gliomas were observed in both, the glioma-tous and the primitive neuroectodermal components, with 10q lossbeing the most common (10%).

A neoplasm with both, glial and primitive components posesan interesting question regarding its tumoral biology, specificallywhether (i) the differentiated glial component arose from the primi-tive component, (ii) the primitive component reflects metaplasia ordedifferentiation of the glial component, or (iii) the two compo-nents reflect a “collision” phenomenon between two separate neo-plastic clones. Evidence from the largest recent case series suggeststhat the primitive component likely arises from a pre-existingglioma, most often a secondary glioblastoma, and may represent ametaplastic phenomenon or expansion of a tumor progenitor cellclone (8). Interestingly, report has been made of a case of glioblas-toma occurring 13 years after treatment for medulloblastoma (7).From this case, it is possible to postulate that the glioblastomareflects differentiation of residual, multipotent cells of the medullo-blastoma; alternatively, the glioblastoma may represent a radiation-induced neoplasm following therapy for medulloblastoma.

In the present case, following gross total resection, the patientwas initiated on temozolomide and concurrent radiation. Duringthe course of his treatment, the patient died approximately fiveweeks 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 ofTumours of the Central Nervous System. D.N. Louis, H. Ohgaki, O.D.Wiestler, W.K. Cavenee, Editors. International Agency for Researchon Cancer, 33–46.

3. Kouyialis AT, Boviatsis EI, Karampelas IK, Korfias S, KorkolopoulouP, Sakas DE (2005). Primitive supratentorial neuroectodermal tumorin an adult. Journal of Clinical Neuroscience 12(4):492–4925.

4. Kuhn SA, Hanisch U, Ebmeier K, Beetz C, Brodhun M, Reichart R,Ewald C, Deufel T, Kalff R (2007). A paediatric supratentorialprimitive neuroectodermal tumour associated with malignantastrocytic transformation and a clonal origin of both components.Neurosurg Rev 30:143–149.

5. McLendon RE, Judkins AR, Eberhart CG, Fuller GN, Sarkar C, NgH.-K (2007) Central nervous system primitive neuroectodermaltumours. In WHO Classification of Tumours of the Central NervousSystem. D.N. Louis, H. Ohgaki, O.D. Wiestler, W.K. Cavenee, Editors.International Agency for Research on Cancer, 141–143.

6. Ohba S, Yoshida K, Hirose Y, Ikeda E, Kawase T (2008). Asupratentorial primitive neuroectodermal tumor in an adult: a casereport and review of the literature. J Neurooncol 86:217–224.

7. Pearl GS, Mirra SS, Miles ML (1980). Glioblastoma multiformeoccurring 13 years after treatment of a medulloblastoma.Neurosurgery 6(5):546–551.

8. Perry A, Miller CR, Gujrati M, Scheithauer BW, Zambrano SC, JostSC, Raghavan R, Qian J, Cochran EJ, Huse JT, Holland EC, BurgerPC, Rosenblum MK (2009). Malignant gliomas with primitiveneuroectodermal tumor-like components: a clinicopathologic andgenetic study of 53 cases. Brain Pathology 19(1):81–90.

9. Prayson RA (2009). Lipomatous supratentorial primitiveneuroectodermal tumor with glioblastomatous differentiation. Annalsof 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 agedpatient. Neurol Med Chir (Tokyo) 45:530–535.

ABSTRACTGlioblastoma, the most common primary brain tumor, is a highlyinfiltrative, malignant astrocytic neoplasm that demonstrates awide spectrum of morphologic heterogeneity. Cases with a primi-tive neuroectodermal tumor (PNET)-like component are rare, butare being increasingly recognized and studied. The primitive com-ponent typically shows immunohistochemical features that areindicative of potential for divergent differentiation along glial andneuronal pathways; when present, the entire neuraxis may be atrisk for involvement, portending a particularly poor prognosis.Recently, data from the largest case series studying malignantgliomas with a PNET-like component suggest that the primitivecomponent likely arises from the malignant glial component. Thisreport presents an example of glioblastoma with a prominentprimitive neuroectodermal-like component in an 81 year-old malewho, during the course of concurrent chemotherapy and radiationtherapy, died five weeks following initial diagnosis.

Correspondence

870 Brain Pathology 20 (2010) 867–870

© 2010 The Authors; Journal Compilation © 2010 International Society of Neuropathology