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Universitätsklinikum Düsseldorf

Institut für Neuropathologie
Direktor: Univ.-Prof. Dr. med. Guido Reifenberger

Patient: GHARAVI, Parham         born/age: 27.04.91/10vears NP-No.: 01/02
Clinic/Station:

Operation: Dec. 2000                       Received: 02.01.2002
Klinische Angaben: Attacks of absence in 1999. Diagnosis of epilepsy in October 1999.
Treatment with various anti-epileptic drugs. In October 2000 presentation with a more severe
seizure with marked confusion of speech. CT and MRI scans taken at that time revealed a
temporal, deep-seated tumor with infratentorial extension. The supratentorial tumor portion
was gross totally removed in December 2000 while the infratentorial tumor part remained.

MACROSCOPICAL EVALUATION:

For histopathological consultation, we received 4 H&E stained sections, 3 paraffin blocks and

wet tissue fixed in formalin.

HISTOPATHOLOGICAL EVALUATION:

I. Light Microscopy:

Tumor Tissue:

5 urn thick paraffin sections were cut from each of the 3 paraffin blocks and stained by H&E,
Masson trichrome stain, and silver impregnation according to Tibor-PAP. Histological
examination shows a solid, cellular glioma composed of pleomorphic astrocytic tumor cells.
In addition to bipolar and occasionally multipolar cells with eosinophilic cytoplasm, there are
pleomorphic mono- and multinuclear giant cells and many tumor cells with xanthomatous
cytoplasm. Nuclear atypia is marked. In some areas, tumor cell density is increased and one
can find a few mitotic figures. However, the overall mitotic index is relatively low. At several
places, eosinophilic protein droplets and occasional Rosenthal fiber-like processes are
present. In addition, a few microcalcifications are evident. Tumor vasculature is moderately
dense, without obvious microvascular proliferation. Focal perivascular lymphocytic infiltrates
are present. Necroses are absent. Reticulin stain shows dense network of reticulin fibers

between the tumor cells. In the tumor periphery, infiltration of the adjacent brain tissue,
including parts of the hippocampus, can be seen.

CSF Sample:

The H&E stained section labelled as CSF sample shows amorphous material and artefacts.
Tumor cells are not present.

II. Immunohistochemistry:

1. Glial fibrillary acidic protein (GFAP):

Strong immunoreactivity in a regionally variable fraction of tumor cells, including bipolar as
well as some pleomorphic elements.

2. CD34 (Q-bend):

In addition to staining of vascular endothelial cells, numerous tumor cells are strongly CD34-
positive. In the adjacent temporal cortex, one can recognize small clusters ofdysplastic
neural cells that are strongly CD34-positive.

3. Tumor suppressor protein p53(D07):

Weak to moderate immunoreactivity in a subset of tumor cells (about 10-20 %).

4. Macrophage-microglial marker CD68 (PGM1):

Glial tumor cells, including pleomorphic and xanthomatous elements, negative. Within the
tumor tissue, intermingled CD68-positive macrophages/microglial cells are present.

5. Proliferation-associated antigen Ki-67 (MiB1):

Most tumor areas demonstrate a low MiB1-labelling index (about 1%). Focal areas show a
slightly increased fraction of MiB1-positive cells, reaching approx. 5 % in circumscribed
tumor parts.

CRITICAL EVALUATION:

The tumor tissue received for consultation shows a cellular, pleomorphic astrocytic glioma
with the typical histological features of pleomorphic xanthoastrocytoma. In addition to cellular
pleomorphism, there are many tumor cells with lipidized (xanthomatous) cytoplasm, a dense
network of reticulin fibers between the tumor cells, focal lymphocytic infiltrates and
eosinophilic protein droplets. Immunohistochemical stainings confirm the diagnosis of
pleomorphic xanthoastrocytoma by demonstrating expression of GFAP in a fraction of tumor
cells. In addition, many tumor cells express the stem cell and endothelial cell marker CD34.
Although not yet published, we have found that CD34 is expressed in the vast majority of
pleomorphic xanthoastrocytomas, a pattern that is not typically seen in diffuse astrocytic
gliomas. With respect to histological grading, the current World Health Organization (WHO)
classification of tumors of the nervous system assigns the WHO grade II to pleomorphic
xanthoastrocytoma. The present tumor shows no histological features of anaplasia, in
particular necroses and microvaskular proliferation are absent. A few mitotic figures are
present in focal areas, which also show a slightly elevated MiB1-index reaching about 5 7o,
Nevertheless, these findings are not sufficient to qualify for a pleomorphic xanthoastrocytoma
with histological features of anaplasia.

Enclosed we are sending a copy of the chapter on pleomorphic xanthoastrocytoma in the
current WHO-classification as well as a copy of the paper by Dr. Gianinni and co-worker from
the Mayo Clinic in Rochester, who have reported on clinical pathological correlations in the
largest series of patients with pleomorphic xanthoastrocytoma.

CLASSIFICATION:

Pleomorphic xanthoastrocytoma (WHO grade II).

Encl.    4 H&E stained sections,

4 paraffin blocks retour,

2 photocopied articles

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