Atypical Pituitary Adenoma With Neurocytic Transformation

Abstract

Here, we report an example of an atypical prolactin-producing pituitary adenoma showing clear morphologic and immunohistochemical evidence of neurocytic transformation. Its features support the concept that neoplastic neuroendocrine cells, in this case adenohypophyseal cells, are capable of neuronal differentiation and broaden the morphologic spectrum of such rare tumors. Our findings have implications with respect to the nosology of neuronal tumors of the adenohypophysis.

Characteristics of ganglion cells in pituitary gangliocytomas

“…The precise relationship between this adenoma subtype and the more frequent occurrence of accompanying neuronal cells remains enigmatic, as appropriately stressed by Scheithauer et al 7 The possibility of a transdifferentiation from normal or adenomatous pituitary epithelial cells to neuronal cells is suggested by many authors. 7,9,12,14,[20][21][22] In particular, the presence of numerous cells with morphological features intermediate between pituitary adenoma and neurons was pointed out by Horvath et al 14 A support to the hypothesis of transdifferentiation is given by in vitro investigations showing the possibility of neuronal differentiation from pituitary cells under the influence of specific factors added to the culture media. 23,24 Moreover, in an acromegalic female patient, Ikeda et al were successful in demonstrating a monoclonality of both adenoma and neuron-like cells by an X-chromosome inactivation method.…”

“…The possibility of a transdifferentiation from normal or adenomatous pituitary epithelial cells to neuronal cells is suggested by many authors . In particular, the presence of numerous cells with morphological features intermediate between pituitary adenoma and neurons was pointed out by Horvath et al .…”

“…The presence of ganglion cells in the sellar region, generally in association with a pituitary adenoma, mainly of GH type, is a rare, but intriguing finding that has occasionally been reported. 2,4,5,14 In the current WHO classification of tumors of the pituitary gland, lesions with these features are referred to as gangliocytomas, 4 alternatively named pituitary adenoma with neuronal choristoma, 14,18 adenohypophyseal neural choristoma, 17 pituitary adenoma with neuronal component, 7 pituitary adenoma with neuronal differentiation, 9 pituitary adenoma with neurocytic transformation 12 and pituitary adenoma with gangliocytic component. 15 In a limited number of the reported cases, immunohistochemical studies have highlighted a peculiar presence of cells with neuronal features simultaneously expressing cytokeratins in the cytoplasm (Table 1).…”

“…[2][3][4][5] Interestingly, in most cases these neuronal cells were found in the context of a pituitary adenoma, more frequently in growth hormone (GH)-or, less frequently adrenocorticotropic hormone (ACTH)-, prolactin (PRL)-producing, or non-functioning adenomas. 2,[6][7][8][9][10][11][12] Variable positivity for hypothalamic peptides or pituitary hormones has been found in this accompanying neuronal cell component. 2,7,[13][14][15][16][17] However, more interesting seems the presence of cytokeratin immunoreactivity in the neuronal cells that has been found in some of reported cases.…”

“…The immunohistochemical finding, in all cases, of cytokeratins in the cytoplasm of a proportion of ganglion cells in our opinion seems to support the hypothesis expressed by some authors that a differentiation of pituitary adenoma cells into neuronal cells may occur. [7][8][9]12,16,17,21…”