Immunocytochemistry of four mixed pituitary adenomas and intrasellar gangliocytomas associated with different clinical syndromes: Acromegaly, amenorrhea-galactorrhea, Cushing's disease and isolated tumoral syndrome

Abstract

Four tumors consisting of pituitary adenomatous cells (AD) intricated with ganglion cells (GC) were studied. Each case was associated with a different clinical syndrome: acromegaly, amenorrhea-galactorrhea, Cushing's disease and isolated tumoral syndrome with no hormonal hypersecretion. (a) In the case with acromegaly, immunoreactive growth hormone (IR-GH) was present in 80% of AD. IR-vasoactive intestinal peptide (VIP) was found in 5%-10% of AD and in few GC. Rare GC and processes showed IR-GH-releasing hormone (GRH), -somatostatin (SRIH), -gonadotropin-releasing hormone and -adrenocorticotropin-releasing hormone. (b) In the case with amenorrhea-galactorrhea, IR-prolactin (PRL) was seen in 90% of AD. IR-PRL and -VIP were present in rare GC. (c) In the case with Cushing's disease, 60% of AD and very few GC contained IR-adrenocorticotropin (ACTH) and beta-lipotropin. Rare GC processes contained IR-SRIH. (d) In the case without pituitary hormone hypersecretion, PRL was localized in rare AD and GC. Pituitary hormone and neuropeptides were never colocalized in the same cells. No case displayed IR-neurophysins or -thyroliberin. Pituitary hormones were localized by ultrastructural immunogold labeling. These findings show that: (i) in three cases, pituitary hormones (PRL and ACTH), and, in one case, VIP could be localized in both adenomatous and ganglion cells; (ii) the pituitary hormone-containing cells in the tumors could be related to the hypersecretory syndromes; (iii) intratumoral IR-VIP and -GRH might be involved in GH and PRL hypersecretion in the cases with acromegaly and amenorrhea-galactorrhea.

Ganglion cell tumours in the sella turcica in close morphological connection with pituitary adenomas

“…A close relationship between neurons and adenomatous GH cells was also confirmed by electron microscopy [3]. Moreover, pituitary hormones have been detected within the neuronal element of some gangliocytic pituitary lesions [25]. Towfighi et al [46] explained that the transformation of pituitary adenoma cells into mature ganglion cells was a result of their common origin from the same embryonic pituitary cell; their explanation rests on the fact that the cells exhibit features that place them on an intermediate developmental axis between neurons and adenohypophyseal cells.…”

“…They are composed of mature ganglion cells with or without a glial component. Gangliocytomas of the pituitary gland are exceptionally rare and usually coexist with a pituitary adenoma, most commonly a GH-secreting adenoma, with the clinical manifestation of acromegaly [4][5][6]12,17,23,27,32,35,39,44,46]; less often, they are associated with ACTH-producing adenomas, and present with Cushing's disease [25,36,40].…”

“…Such neoplasms occur without evidence of adjacent adenoma only occasionally. The majority of ganglion cell tumours appear in association with growth hormone-secreting pituitary adenoma presenting with acromegaly [2,[4][5][6]12,[17][18][19]23,25,32,38,40,42]. They appear less often with adrenocorticotropic hormone-producing adenomas with clinical presentation of Cushing's disease [25,36,40].…”

Ganglioglioma of the Neurohypophysis

“…Of gangliocytomas of the sella, entirely 65% are adenoma-associated, and 75% are endocrine-active [12]. The genesis of those in which a pituitary adenoma, typically a growth hormone and only rarely an adrenocorticotropin [13][14][15] or prolactin-producing adenoma [16][17][18], have invited two very different pathophysiologic explanations. One mechanism, the earliest proposed, suggested that the neuronal lesions, by producing hypothalamic releasing hormones, result in pituitary hyperplasia and promote adenomagenesis [12].…”

Ectopic Cushing’s Syndrome due to an Adrenal Ganglioneuroma

“…Interestingly, intrasellar gangliocytomas have been described to be associated with secreting pituitary tumors. They are able to synthesize hypothalamic and pituitary hormones [27,28,29]. Whether these very rare cases of ganglion cell proliferations and gland hyperplasia or adenoma can be compared remains to be established.…”