Discussion

Granular cell tumor of the neurohypophysis is a rare, generally slow-growing neoplasm arising from pituicytes of the posterior pituitary gland and pituitary stalk. In the current WHO classification, it belongs to the pituicyte tumor family together with conventional pituicytoma and spindle cell oncocytoma. These tumors share a common pituicytic lineage and characteristically express thyroid transcription factor-1 (TTF-1). Granular cell tumors of the neurohypophysis are considered low-grade neoplasms and usually behave in a benign fashion.

The tumor occurs predominantly in adults, most commonly in middle-aged patients, with a slight female predominance reported in larger series. It usually arises in the posterior pituitary, infundibulum, or suprasellar region. Small asymptomatic granular cell lesions may occasionally be encountered incidentally, whereas larger tumors produce symptoms through mass effect. Common clinical manifestations include visual disturbance, headache, and varying degrees of hypopituitarism. Hyperprolactinemia may occur as a consequence of compression of the pituitary stalk. Diabetes insipidus is relatively uncommon despite the neurohypophyseal origin of the tumor. Radiologically, the lesion is typically a well-circumscribed, solid sellar or suprasellar mass with contrast enhancement and may be difficult to distinguish preoperatively from a PitNET, meningioma, pituicytoma, or other sellar region tumor. Granular cell tumors have a particular tendency to present as predominantly suprasellar lesions.

Histopathologically, granular cell tumor is composed of sheets, nests, or fascicles of relatively uniform polygonal to occasionally spindle-shaped cells. The cells contain abundant eosinophilic granular cytoplasm and usually have small round to oval nuclei with inconspicuous nucleoli. The cytoplasmic granularity results from accumulation of numerous lysosomes and is typically strongly positive with periodic acid–Schiff (PAS) stain and resistant to diastase digestion. The tumor cells may be separated by delicate collagen fibers and variable vascularity. Nuclear pleomorphism may occasionally be present but usually does not indicate aggressive behavior. Mitotic figures are generally absent or very uncommon, and necrosis is not a typical feature.

The tumor cells characteristically show strong nuclear immunoreactivity for TTF-1, supporting their origin from pituicytes. S100 protein and vimentin are also frequently expressed. GFAP expression is variable and is often absent or only focally present. The tumor cells are negative for adenohypophyseal hormones and transcription factors associated with PitNET lineages. Cytokeratin is generally negative. The combination of typical granular morphology and nuclear TTF-1 expression is particularly useful for establishing the diagnosis.

Granular cell tumor of the neurohypophysis is morphologically related to other members of the pituicyte tumor family. Conventional pituicytoma is composed predominantly of bipolar spindle cells arranged in interlacing fascicles and lacks the prominent granular cytoplasm. Spindle cell oncocytoma consists of spindle to epithelioid cells with abundant eosinophilic oncocytic cytoplasm caused by accumulation of mitochondria. All of these tumors may express TTF-1, supporting their shared pituicytic origin. However, granular cell tumor is quite morphologically distinctive from the other two neurohypophyseal tumors.

Recognition of the pituicyte tumor family is particularly important because these lesions may be mistaken clinically and radiologically for the much more common PitNET. Cytoplasmic granularity can occur PitNET as a result of mitochondrial accumulation. However, cytoplasmic granules from mitochrondria are finer than those observed in granular cell tumor. TTF-1 expression and negative neuroendocrine markers (synaptophysin and chromogranin) should resolve this differentials. 

Complete surgical excision is generally curative. However, complete removal may be difficult because of the tumor's location, attachment to the pituitary stalk or hypothalamus, and occasionally prominent vascularity. Subtotally resected tumors may persist or recur, and clinical and radiologic follow-up is therefore appropriate. Overall, granular cell tumor of the neurohypophysis is a low-grade tumor with a favorable prognosis.

References

1. WHO Classification of Tumours Editorial Board. Endocrine and Neuroendocrine Tumours. WHO Classification of Tumours, 5th ed., Vol. 10. Lyon: International Agency for Research on Cancer; 2025.

2. Asa SL, Mete O, Perry A, Osamura RY. Overview of the 2022 WHO Classification of Pituitary Tumors. Endocr Pathol. 2022;33:6-26. 

3. Covington MF, Chin SS, Osborn AG. Pituicytoma, spindle cell oncocytoma, and granular cell tumor: clarification and meta-analysis of the world literature since 1893. AJNR Am J Neuroradiol. 2011;32:2067-2072.