Abstract
Growth hormone (GH)-secreting pituitary neuroendocrine tumors (PitNET) arising from somatotrophs is the most common cause of acromegaly. It may rarely develop in the setting of a growth hormone-secreting PitNET associated with a neuronal tumor composed of neoplastic ganglion cells, the so-called mixed gangliocytoma somatotroph PitNET. We present a case of acromegaly which proved to be due to a mixed gangliocytoma somatotroph PitNET on pathology.A 58-year-old, healthy woman presented to the ER with a 3-day history of left-sided vision loss and worsening headache. MRI revealed 4.5×4.2×3.8 cm heterogeneously enhancing bilobed mass consistent with a pituitary PitNET with suprasellar extension causing compression of the optic chiasm, invasion into the left cavernous sinus and partial encasement of the left internal carotid artery. She had coarse facial features, wide feet, multiple skin tags, and a history of multiple colonic polyps. Biochemical work up revealed an IGF-I of 664 ng/ml (50-317), AM cortisol 19.7 mg/dl, ACTH 30 pg/ml, prolactin 15.5 ng/ml, FSH 35.6 mIU/ml, LH 11.3 mIU/ml, and FT4 0.7 ng/dl (0.70-1.48). She underwent endoscopic transsphenoidal resection of the tumor. Histopathology demonstrated mature ganglion cells with neuropil-like areas, intermixed with small cell components. The neuronal population was immunopositive for NeuN (Neuronal nuclei antibody), synaptophysin, and NF (Neurofilament). PitNET cells were positive for GH, prolactin, Pit- 1 transcription factor and the somatostatin 5 receptor, histological features consistent with mixed gangliocytoma and sparsely granulated somatotroph pitNET. Some ganglion cells also showed weak immunostaining with Pit-1. A 3-month follow-up MRI showed a residual 3 cm lesion. IGF-I improved but was still elevated at 456 ng/ml associated with a GH 2.9 ng/ml. Medical treatment with pasireotide was recommended, but the patient temporarily declined further treatment to explore other options with her Naturopath.Gangliocytomas are a rare, benign, slow-growing, differentiated form of neuroblastic tumors of sympathetic nerve fibers, largely extracranial and rarely present in the sellar region, most frequently in association with a PitNET, forming the so-called mixed gangliocytoma PitNET. Definitive diagnosis is established by histological and immunohistochemical studies. Though PitNET components of mixed gangliocytoma PitNET are known to frequently secrete an excess hormone, the ganglionic components also show immunoreactivity for hypothalamic releasing hormones along with other neuroendocrine markers. The histological origin of these mixed tumors is controversial, but the small population of ganglionic cells that express the acidophilic lineage transcription factor, Pit-1, favors the theory of transdedifferentiation of neuroendocrine cells into neuronal elements. Treatment of mixed gangliocytoma- PitNET is similar to other PitNETs and the presence of neural components does not modify aggressiveness or risk of recurrence after surgical resection, as gangliocytomas have a low proliferative index. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.