23‐YEAR‐OLD MAN WITH A SUPERFICIAL CORTICAL BRAIN TUMOR

CLINICAL HISTORY

A 23‐year‐old male with no significant past history, presented with a tonic‐clonic generalized seizure. Physical and neurological examinations were normal. MRI of the brain showed a superficial cystic mass with a mural nodule in the right fronto‐parietal lobe. Patient underwent right frontal craniotomy with total resection of the tumor. The post‐operative course was uneventful.

MICROSCOPY PATHOLOGY

Microscopic examination disclosed a mass lesion composed of two, distinct in origin, cellular components. One was glial, mainly with elongated and spindle‐shaped astrocytes, with moderate pleomorphic nuclei (fig. 1a), displaying GFAP immunoreactivity (fig. 1b). The other, neuronal, was composed of mature, with middle pleomorphic nuclei, some times foamy, ganglion neoplastic cells, either intermixed with the glial component (Fig. 2) or clustering in nests (Fig. 3), showing immunoreactivity for neurofilaments (Fig. 4a) and synaptophysin (Fig. 4b). A dense, prominent, desmoplastic reticulin‐rich stroma, intermixed with the neoplastic cells was elicited (Fig. 4c). There was no striking nuclear atypia, no necrotic areas, and endothelial proliferation was mild. Mitotic figures were extremely rare, and the proliferation index (Mib‐1 immunoreactivity) was below 1%. Despite the presence of some foam cells, there were no true xanthomatous elements. The tumor was partially located in the subarachnoid space, displayed some mononuclear inflammatory perivascular infiltrates and, frequently, there was a clear‐cut interface between the tumor and the surrounding brain parenchyma where several microcalcifications (Fig. 4d) and Rosenthal fibers were elicited. A striking feature was the presence of a few cells containing brownish‐black pigment in the cytoplasm (Fig. 4e), (Fig. 4f). It stained black with Fontana‐Masson stain, bleached completely with potassium permanganate, and did not stain for iron (by Perl's stain), neuromelanin or lipofuscin (by periodic acid‐Schiff and long Ziehl Neelsen, acid‐fast, stains). What is your diagnosis?.

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DIAGNOSIS

Pigmented (melanin producing) desmoplastic ganglioglioma

DISCUSSION

This tumor disclosed all the classic microscopic features of a desmoplastic infantile ganglioglioma except the perivascular inflammatory infiltrate, which is much more common in pure gangliogliomas, and the pigment deposits which were shown to be melanin. Pigmented primary intracranial tumors other than meningeal melanocytomas and melanomas are rare. However, some pigmented neoplasms in the central nervous system (CNS), either neuroepithelial or non‐neuroepithelial ones, have been reported 4, 5, 8

The nature of these pigments has been shown to be either melanin, which derives from melanosomal activity, or neuromelanin, which results from catecholamine synthesis 2, 5; in some cases, lipofuscin, a pigment that is derived from oxidation of lipids or lipoprotein sources, has been shown in addition to neuromelanin. Melanosomal melanin and neuromelanin have distinctive ultrastructural features. Some authors suggested that neuromelanin is a melanized form of lipofuscin, because of their histochemical similarities (2). Pigments are normally found in certain parts of the CNS: melanin in meninges, fetal pineal gland and pigmented layer of retina; neuromelanin in substantia nigra and locus ceruleus; lipofuscin in precentral gyrus, nuclei of cranial nerves, red nucleus, part of thalamus, globus pallidus, inferior olives and dentate nucleus (2).

There are only three previous reports of pigmented ganglioglioma: one case of a melanotic ganglioglioma of the pineal region (4), another of a ganglioglioma of the temporal lobe with evidence of melanogenesis in neoplastic astrocytes (8), and, finally, a desmoplastic infantile ganglioglioma (1). This report addressed a 9‐month‐old boy with a temporo‐mesial mass, and in which the ultrastructural exam disclosed cells with melanosomes and premelanosomes. This enlarges the evidence that melanin production is not restricted to cells of neuronal crest derivation and that central neuroepithelial cells are also capable of melanogenesis 4, 5, 8.

The differential diagnoses to consider in this case are: the pleomorphic xanthoastrocytoma, with two pigmented cases reported previously 3, 7, the ganglioglioma, the desmoplastic infantile astrocytoma (9) and the desmoplastic infantile ganglioglioma. The first two are typically encountered in childhood, with involvement of the subarachnoid space and a history of seizures but, despite the coexistence of some similar microscopic features, these diagnoses were excluded by presence of ganglion cells. The diagnosis of desmoplastic ganglioglioma was made instead of ganglioglioma because of the prominent desmoplastic reticulin‐rich stroma.

The case reported has also the peculiar feature of being a desmoplastic non‐infantile ganglioglioma. Indeed, desmoplastic gangliogliomas are uncommon supratentorial brain tumors typically occurring in children below the age of 24 months, usually with good prognosis. Only 20 cases of non‐infantile desmoplastic gangliogliomas have been reported in the literature, none of them pigmented (6).

ABSTRACT

A 23‐year‐old male presented with a tonic‐clonic generalized seizure. Neuroradiological examination revealed a superficial cystic mass with a mural nodule in the right fronto‐parietal lobe. Histological and immunohistochemical examination were consistent with a pigmented (melanin producing) desmoplastic ganglioglioma. These tumors have been first described in childhood, one of them displaying melanin deposits. Only twenty cases of non‐infantile desmoplastic gangliogliomas have been reported in the literature, none of them pigmented. According to the clinical and histomorphology (including the desmoplastic component) features, the differential diagnosis should include the ganglioglioma, the xanthoastrocytoma pleomorphic (both tumors also with pigmented forms) and the superficial desmoplastic infantile astrocytoma.