doi:10.1111/j.1750-3639.2010.00404.
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CASE OF MONTH APRIL 2010 bpa_404
81 YEAR-OLD MALE WITH CONFUSION AND WEAKNESS
Brian 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 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 sus-
tained a stroke involving the left middle cerebral artery. Current
imaging 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-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.
Figure 1.
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867..870
MICROSCOPIC PATHOLOGY
Histologic examination of the tumor shows biphasic histology. The
less dominant morphologic pattern consists of a hypercellular pro-
liferation 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.
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 (figures 4 and 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).
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Figure 2.

Figure 3.

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 Correspondence

Figure 4. Figure 6.

Figure 5. Figure 7.

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Correspondence
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 mor-
phologic 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 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, 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 dem-
onstrated. 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 typi-
cally associated with gliomas were observed in both, the glioma-
tous 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 primi-
tive component, (ii) the primitive component reflects metaplasia or
dedifferentiation 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 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 glioblas-
toma 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 medullo-
blastoma; 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.
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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.
3. Kouyialis AT, Boviatsis EI, Karampelas IK, Korfias S, Korkolopoulou
P, Sakas DE (2005). Primitive supratentorial neuroectodermal tumor
in 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 supratentorial
primitive neuroectodermal tumour associated with malignant
astrocytic transformation and a clonal origin of both components.
Neurosurg Rev 30:143–149.
5. McLendon RE, Judkins AR, Eberhart CG, Fuller GN, Sarkar C, Ng
H.-K (2007) Central nervous system primitive neuroectodermal
tumours. 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, 141–143.
6. Ohba S, Yoshida K, Hirose Y, Ikeda E, Kawase T (2008). A
supratentorial primitive neuroectodermal tumor in an adult: a case
report and review of the literature. J Neurooncol 86:217–224.
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.
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 primi-
tive neuroectodermal tumor (PNET)-like component are rare, but
are being increasingly recognized and studied. The primitive com-
ponent 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.
Brain Pathology 20 (2010) 867–870