Abstract General Information

Title

A Mixed Gangliocytoma–Plurihormonal Tumor of PIT1-Lineage of the sellar region: Case Report and Review of the Literature

Case Presentation, Discussion, and Final Comments.

Case Presentation:
A 46-year-old male presented with acromegaly and progressive visual loss. The patient´s past medical history included morbid obesity, arterial hypertension, type 2 diabetes and hyperparathyroidism. Brain MRI disclosed an expansive sellar and suprasellar mass of 26 mm that compressed the optic chiasm. Next, the patient was submitted to an endonasal endoscopic transsphenoidal surgery for tumor resection. Histological examination revealed a pituitary neuroendocrine tumor (PitNET, “pituitary adenoma”) mostly composed of pleomorphic cells with large and chromophobic cytoplasm besides few tumor cells with eosinophilic cytoplasm. The neoplastic cells showed slightly hyperchromatic round nuclei and the chromatin was stippled. Noteworthy was the presence of some intermingled mature neuronal cells with evident ganglionar differentiation. Neither necrosis nor mitotic figures were seen. Also, normal pituitary and brain parenchyma were not observed in the sample. Reticulin stain showed loss of the usual acinar pattern. Immunohistochemistry study revealed diffuse nuclear positivity for PIT-1 and focal cytoplasmic positivity for GH, PRL and TSH in the neoplasm. The low molecular weight cytokeratin CAM5.2 was expressed in the majority of tumor cells and the Ki-67 labeling index was 2% in the hot spot. Other biomarkers (ACTH, LH, FSH, TSH, ER) were negative. Therefore, the final diagnosis was established as mixed gangliocytoma – plurihormonal tumor of PIT1-lineage. Nineteen months later, the patient was undergone to total thyroidectomy to remove a papillary thyroid carcinoma and 3 of 4 hyperplastic parathyroid glands. Mixed gangliocytomas – PitNETs are rare tumors in the hypothalamic/sellar region that are characterized by biphasic morphology, with neuroendocrine and gangliocytic components. In most cases, patients had acromegaly our, more rarely Cushing's disease and hyperprolactinemia. It is still controversial whether these tumors should be considered as derived from the hypothalamus or the pituitary gland. A proposed mechanism involves the production of GH-releasing hormone (GHRH) by the gangliocytic component, which promotes the growth of the entire tumor, including the neuroendocrine GH-secreting component. Herein, we are presenting a mixed gangliocytoma-pituitary PitNET, a rare neoplasm of uncertain origin with poorly understood pathogenesis. In the current case, the tumor exhibited PIT1-lineage differentiation and concomitant expression of GH, PRL and TSH.

Keywords

PIT1; pituitary adenoma; gangliocytoma; PitNET; plurihormonal adenoma; acromegaly