21‐YEAR‐OLD WOMAN WITH A CYSTIC BRAIN LESION

CLINICAL HISTORY

A 21‐year‐old woman admitted to the hospital with severe headache. While driving, she suddenly could not feel the steering wheel in her right hand and experienced a feeling of getting lost. The symptoms subsided but followed by headache that gradually evolved into the worst headache in her life. Neurologic exam was normal and magnetic resonance imaging disclosed left parietal tumor with a large cystic component and enhancing mural nodule (Figure 1A). Differential diagnosis included ganglion cell tumor (GCT), pleomorphic xanthoastrocytoma (PXA) and pilocytic astrocytoma. The patient underwent left craniotomy with a complete resection of the tumor. Intraoperatively, the mass was intra‐axial and consisted of a white‐yellow firm 3 cm nodule located on a wall of a large cavity filled with an amber‐colored fluid. There was no association with leptomeninges.

Figure 1.

GROSS AND MICROSCOPIC DESCRIPTION

The biopsy specimen consisted of a solid yellow firm nodule, with an irregular granular surface and prominent superficial vasculature (Figure 1B). Microscopically, a non‐infiltrative tumor was predominantly composed of vaguely defined lobules of plump cells with vesicular nuclei, bearing prominent nucleoli and surrounded by an abundant amphophilic cytoplasm (Figure 2A–C). Rare binucleate forms were seen (Figure 2A,B). The lobules were separated by bundles of reticulin (Figure 2D). Many blood vessels were cuffed by mature lymphocytes (Figure 2A) and a few eosinophilic granular bodies were detected (Figure 2C). Scant parenchymal microcalcifications were accompanied by an incipient microcyst formation. There were no mitoses. No xanthic cells, prominent cytologic atypia or fascicular arrangements were detected. Strong and often perivascular “band‐like” staining for synaptophysin (Figure 2E) and rare cells, expressing neurofilament (not shown) were seen. Ki67 disclosed a few atypical nuclei and was in a range of 0.2%.

Figure 2.

DIAGNOSIS AND DISCUSSION

Diagnosis.  Gangliocytoma.

DISCUSSION

GCTs are rather common low grade neoplasms found in patients with epilepsy and representing up to 1.3% of brain tumors (5). Over 80% of tumors are discovered during the first three decades of life with a male‐to‐female ratio of 1.1:1–1.9:1 3, 7. Many of the tumors arise in the temporal lobe, but other sites are not spared (1). A classic cyst with an enhancing mural nodule appearance simplifies the diagnostic challenge (8), effectively limiting the differential diagnosis to such entities as pilocytic astrocytoma, PXA, hemangioblastoma, extraventricular neurocytoma and ependymoma. PXA and GCT share not only desmoplasia, but also a variable proportion of a neuronal component (2). PXA differs in having mostly fascicular architecture, presence of xanthic cells and extreme nuclear pleomorphism. The prognosis of GCT is generally favorable, except for a fraction of neoplasms featuring a component of frankly anaplastic astrocytes. Even in such cases the outlook mostly depends on the extent of surgical removal (6). Both neural and astrocytic components are clonal (9), but the histogenesis of GCT is unclear. Frequent association of GCT with focal microdysgenesis suggests a dysembryoplastic component (4).

CASE OF THE MONTH: ABSTRACTS

January 2006. Ceruloplasmin deficiency is an autosomal recessive disorder linked to a mutation of the ceruloplasmin gene located on chromosome 3, mainly described in Japanese patients. This first French case, a 65‐year‐old patient developed dementia, hallucinations and facial dyskinesia. MRI showed low signal intensity in the striatum, thalamus and dentate nuclei. Liver biopsy showed hemosiderosis. Laboratory investigations showed increased ferritin and undetectable ceruloplasmin in serum. Two brothers had similar findings. Postmortem showed diffuse hemosiderosis of heart, liver and lung. Gross examination of the brain showed rust‐brown discoloration and cavitation of the striatum, posterior thalamus and dentate nuclei in which there was massive iron deposition within neurons, glial cells and macrophages, and free in brain parenchyma. It was associated with necrosis, fibrosis, neuronal loss, frequent axonal swellings and intense astrocytic and macrophagic reaction including gemistocytic astrocytes, Alzheimer’s type II glia and Opalski cells. Iron deposits, neuronal damage and gliosis were also found in the cerebellar and, to a lesser extent, cerebral cortex. Although sharing common clinical, biological, and pathological features, this specific clinico‐pathological entity is clearly different from Wilson’s disease, pantothenate kinate‐associated neurodegeneration (Hallervorden–Spatz’s syndrome), and idiopathic hemochromatosis.

February 2006. A 44‐year‐old man with a 4‐year history of progressive neuropsychiatric symptoms, presented with increasing impairment of executive functions, delusions and mild cognitive decline. Over a 4‐month period progressive worsening in visuospatial skills and in short‐term memory was observed. EEG recording showed theta activity over the right frontotemporal region, whereas brain MRI demonstrated bilateral cortical atrophy. At the age of 48 years the patient had severe cognitive impairment, marked rigidity and hypokinesia; MR images showed diffuse cortical widening and hyperintense signal in caudate heads, putamina and cortical ribbon. The patient died at the age of 49 years. Sectioning of the brain revealed diffuse thinning of the cortical ribbon, marked ventricular enlargement and white matter atrophy. Microscopic examination showed severe neuronal depletion and intense gemistocytic astrocytosis in the neocortex and subiculum, while the hippocampus showed mild neuronal loss and spongiosis. Astrocytosis and spongiosis were also observed in the thalamus, striatum, brainstem nuclei and cerebellar cortex. In addition, round eosinophilic, Congo‐red positive plaques were seen in the cerebellum. Prion protein immunostaining disclosed widespread dot‐like and plaque‐like deposits, in addition to kuru‐type plaques. Molecular studies showed methionine/valine heterozygosity at the codon 129 of the prion protein gene, in the absence of mutations, and the presence of proteinase K‐resistant prion protein. In the setting of a dementing illness of long duration, only pathological and molecular studies can provide an unequivocal diagnosis of Creutzfeldt–Jakob disease.

March 2006. A 21‐year‐old woman presented with a partial complex seizure and progressively worsening headaches. MRI revealed a large cystic mass with an enhancing mural nodule located within the left parietal lobe. Excisional biopsy disclosed a non‐infiltrating tumor composed of lobules embedded in reticulin‐rich matrix. The tumor cells contained large vesicular nuclei with prominent nucleoli, and were surrounded by an abundant amphophilic cytoplasm. Eosinophilic granular bodies were noted, as well as perivascular lymphocytic cuffs. Strong immunoreactivity for synaptophysin was seen. The findings are characteristic of ganglion cell neoplasm. Most ganglion cell neoplasms contain a significant glial component (usually astrocytic) and are called gangliogliomas. However, in some cases there is minimal or no glial component identified and these tumors are then called gangliocytomas. The patient is symptom‐free 4 months after surgery.