Brain Pathology Case of the Month - August 2005

Contributed by Wolf Mueller1, Ulrike Lass1, Julian Veelken2, Friedrich Reuter2, Andreas von Deimling1
  1 Institute for Neuropathology, Charité University Hospital, Berlin, Germany
  2 Department of Neurosurgery, Vivantes Hospital Neukölln, Berlin, Germany
Published on line in August 2005


In 1999, at the age of 41 this man developed focal seizures in his right arm. The neurological examination was otherwise normal. He was in good health and his medical history was devoid of underlying disease. Cranial MRI revealed a homogeneously contrast enhancing lesion with microcalcifications in the left frontal lobe (Figs. 1 and 2). One year later the patient decided to have stereotactic biopsy. Surgically induced artifacts and small sample size aggravated tumor classification at that time. Differential diagnoses included oligodendroglioma WHO II and diffuse astrocytoma WHO II. In January 2003, at the age of 45, the patients developed weakness in his right arm and seizure frequency increased despite medication. Tumor size had considerably increased. Surgery was offered and the patient decided to have the lesion removed through a left frontal craniotomy. The postoperative course, was unremarkable, the weakness of the right arm disappeared.


Histology revealed a moderately cellular infiltrative neoplasm and both cortical as well as subcortical involvement. The tumor cells had round and homogenous nuclei. Small groups of tumor cells with clear swollen cytoplasm and well defined plasma membranes were detected in paraffin-embedded sections throughout the tumor (Fig. 3). Other striking morphological features included intratumoral microcalcifications in snap-frozen specimen (Fig. 4), a network of branching capillaries without evidence of microvascular proliferation (Fig. 5), small nucleus-free areas of neuropil (Fig. 6) and perivascular pseudorosette formation of tumor cells (Fig. 7). Immunohistochemically the tumor cells were devoid of GFAP except for occasional entrapped reactive astrocytes (Fig. 8). A strong cytoplasmic expression of neuron specific enolase (Fig. 9) by the tumor cells was noted. Additionally, the nucleus-free "neuropil islands" demonstrated a fine granular expression of synaptophysin (Fig. 10).


PCR based loss of heterozygosity (LOH) analysis was performed. Multiple microsatellite polymorphic tetranucleotide markers on the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q) were used. All amplified products lied within the common region of deletion for oligodendrogliomas. Leukocyte DNA of the patient was available for analysis of the constitutional allele status. A loci was coined "informative" in case of heterozygosity for the investigated allele. LOH 1p and 19q for all informative loci was demonstrated. The figures 11 and 12 show representative examples of informative loci on 1p and 19q, respectively. Corresponding leukocyte DNA is paired with tumor DNA. In the tumor DNA one of the two alleles, constitutively present in the leukocyte DNA, is lost.


International Society of Neuropathology