FINAL DIAGNOSIS: Intrasellar glioneuronal hamartoma with GH-cell pituitary adenoma and schwannoma-like component.
Intrasellar gangliocytomas are well-differentiated lesions composed of neurons and, in most cases, neoplastic adenohypophyseal cells with low proliferative potential and a favorable prognosis, provided there is complete tumor resection. The morphologic characteristics of this rare entity, which has to be distinguished from hypothalamic neuronal hamartomas (4), have been reviewed recently (1, 3, 5).
The histological hallmark are islands of large ganglion-like cells resembling normal hypothalamic neurons and accompanying neuropil interspersed within the substance of a pituitary adenoma. Binucleate neurons are pathognomonic. The relative proportions of pituitary adenoma, ganglion-like cells, and particularly neuropil show considerable variations from one case to another. The ganglion-like cells stain with antibodies against hypothalamic releasing hormones, neuropeptides as well as other neuronal markers (3). Interestingly, some authors also detected ACTH or prolactin protein, both being pituitary hormones (5). Cytokeratin immunoreactivity was demonstrated in globular areas in the small adenoma-like cells suggesting fibrous bodies. Occasionally, neuron-like cells and processes (Fig. 2H; arrow) in the fibrillary areas of neuropil were also positive (1, 5). Ultrastructurally, the small adenoma-like cells exhibited features of sparsely granulated GH cell adenoma replete with fibrous bodies in most cases (1). The ganglion-like cells showed structural equivalents of Nissl substance, filamentous aggregates comparable to neurofilaments, and secretory granules. A few tumors included scattered cells with ambiguous features intermediate between pituitary adenoma and ganglion cells. In particular, the co-localization of neurofilament protein and cytokeratin immunoreactivity in structures interpreted as fibrous bodies or as neuropil stresses a close relation of both cell types (1). Unlike gangliogliomas, gangliocytomas contain either no glial elements, or only reactive astrocytes. More than 50% of the cases reported up to now occurred in the setting of acromegaly (2), with features of a classical GH-producing pituitary adenoma and GHRH expression (3). A quarter of all patients presented without any endocrine disorder; in single cases Cushing´s disease or a prolactinoma with galactorrhea was noticed.
In our patient schwannoma-like cells, an additional third component, represented a finding which has not yet been reported. The presence of GFAP-imunoreactivity in these spindle-cells may indicate astrocytic or pituicytic differentiation. However, morphology was not typical, and also the presence of a delicate reticulin-fiber network would be unusual. It could not be decided with certainty whether immunostaining for neurofilament and synaptophysin was localized to intermingling processes or co-localized with the spindle cells. In the latter case this would be a further indicator for the transitional character of this lesion.
The precise histogenetic origin of these lesions is still controversially discussed as is the neoplastic character. Thus, Horvath et al. (1) regarding the process as a hamartoma suggested the term "pituitary adenoma with neuronal choristoma". In contrast, emphasizing the neoplastic nature, Puchner et al. (3) and Towfighi et al. (5) recommended the term "gangliocytoma" and "mixed pituitary adenoma-gangliocytoma", respectively. In our case, the neuronal component resembled normal hypothalamic tissue, which was displaced, thus creating a hamartoma-like picture. In summary, three different hypotheses are currently discussed in the literature: I) The ganglion-like cells are of hypothalamic origin; an "initiating" factor(s) not yet defined may transform these neurons and adenohypophyseal cells into tumor cells; ganglionic-cell released GHRH "promotes" transformed pituitary cell proliferation (3); II) Conversion and transdifferentiation of sparsely granulated GH adenoma into neuronal elements (1); III) Both neuronal and adenohypophyseal elements originate from hypothetical embryonal rests (5).
Contributed by Volkmar H.J. Hans MD, Horst Urbach MD, Rudolf A. Kristof MD, Martina Deckert MD