An 57‐Year‐Old Female with Sudden onset of Transient Right Homonymous Hemianopsia

Clinical History and Neuroimaging

A 57 y/o female presented with sudden onset of transient right homonymous hemianopsia while driving. Later the same day she also reported a 3–4 h period of decreased cognitive ability, being unable to perform calculations. She was seen in the emergency room and underwent neuroimaging studies. MRI demonstrated a 25.9 × 23.6 × 21.3 mm round, slightly lobulated, mass within the suprasellar cistern with significant mass effect. A preoperative T1‐weighted sagittal image without contrast showed a suprasellar mass, isointense to the brain cortex with compression and superior displacement of the optic chiasm and floor of the third ventricle (Figure 1A). The inferior margin of the mass was in contact with the dorsum sella and posterior aspect of the diaphragm sella. No intrasellar extension was seen. The posterior margin extended into the region of interpeduncular cistern with associated splaying of the cerebral peduncle. T1‐weighted gadolinium‐enhanced sagittal images demonstrated homogenous enhancement. Normal pituitary gland is seen within the sella turcica, independent of the lesion. There is no enlargement of the sella turcica (Figure 1B) T2‐weighted coronal image shows low signal intensity of the mass (Figure 1C). The patient underwent a right fronto‐temporo‐parietal stereotactic craniotomy for resection of the lesion.

Figure 1.

 

Microscopic Pathology

Smear preparations reveal large epithelioid cells with generous cytoplasm which had a distinctly granular appearance (Figure 1C,1D). The nuclei were round and fairly uniform, often eccentrically placed, with a prominent nucleolus and dispersed chromatin. On routine histologic sections the specimen was moderately cellular with thin walled vessels (Figure 1F). The granular cytoplasmic content was readily evident (Figure 1G). No significant pleomorphism was seen and mitotic activity and necrosis were absent. Tumor cells displayed patchy but consistent immunoreactivity for S‐100 (Figure 1H), with focal mild positivity for Inhibin and CD68. TTF‐1 immunoreactivity was strong and readily seen in the vast majority of tumor cells (Figure 1I). What is your diagnosis?

Diagnosis

Granular cell tumor of the neurohypophysis.

Discussion

The histologic features described are classic for this tumor. The large epithelioid population, uniform, round nuclei and prominent nucleoli are typical. It is, however, the distinct granular morphology of the cytoplasm that confirms the diagnosis and contributes to its nomenclature. Additionally in this case, a focal spindle cell population distinct in appearance from the tumor cells was identified in close proximity. These cells also displayed strong immunoreactivity for GFAP and TTF‐1. This population was identified as a fragment of neurohypophysis and was morphologically different from the tumor.

Granular cell tumors (GCTs) are uncommon neoplasms that occur intracranially, in close association with the posterior pituitary or infundibulum. These tumors are asymptomatic by virtue of their frequently microscopic size and often are only discovered at autopsy. In a study examining 100 pituitary glands obtained at autopsy from asymptomatic individuals, identified 26 adenomas in the anterior pituitary and 9 granular cell tumors in the neurohypophysis 4. Despite the above data, there are a limited number of cases that grow large enough to become symptomatic, particularly in women (2:1 female: male) in their 4th–5th decades of life 2. Common presenting symptoms include visual deficits, headache, hyperprolactinemia and amenorrhea, with less than 5% presenting with diabetes insipidus. Symptoms are usually due to compression of structures adjacent to the pituitary as opposed to production of hormones by the tumor itself.

Granular cell tumors of the pituitary stalk are difficult to diagnose preoperatively. The presenting symptoms generally prompt neuroimaging studies. CT often shows a smooth, well‐defined, circumscribed hyperdense mass in the pituitary fossa. The majority of granular cell tumor features described on MRI are based on lesions that compromise the neurohypophysis 1. In our case the lack of expansion of the sella turcica and presence of normal enhancing pituitary tissue within the sella without continuity to the tumor limited the differential diagnosis. In many cases, however, the possibility of a neoplasm such as a macroadenoma originating from the anterior pituitary remains a confounding factor.

The location of the tumor, growth pattern and clinical presentation facilitate the diagnosis. Histologic phenotype, however, is typically very characteristic including sheets of large polygonal shaped cells often with eccentrically placed nuclei. The generous, eosinophilic cytoplasm displays a granular content that generally is coarse and easily recognized although in some cases this may be quite fine. Granules are PAS positive, diastase resistant. Nuclei are uniform, often eccentrically placed and have a finely stippled appearance. Mitotic activity is rare. A fine capillary network may be present. On ultrastructural examination, the granular component of GCTs is largely derived from lysosomes which explains the nonspecific staining seen with lysosomal markers such as CD68, alpha‐1‐antitrypsin, and so forth. Proliferative activity is low as determined by very low MIB‐1 immunolabeling and clinically by its typically indolent behavior. The immunophenotype of these lesions also includes nonspecific immunoreactivity for S‐100, Vimentin, CD68 and occasionally alpha‐1‐antitrypsin. Strong nuclear staining with TTF‐1 is consistently present and is regarded as a marker for cells of infundibular origin 3. Nonetheless, a number of other entities must also be considered in the differential diagnosis. These include other tumors also thought to be derived from pituicytes including “pituicytoma” and spindle cell oncocytoma, both of which are also TTF‐1 immunoreactivity. Pituicytoma is composed of more spindle cells, staining for Vimentin, S‐100 and focally for GFAP. Oncocytomas are bland, spindle cell to epithelioid neoplasms with uniform, oncocytic, eosinophilic cytoplasm. They are also Vimentin and S‐100 positive, supplemented with EMA immunoreactivity. The cytoplasmic content of these tumors differs from GCTs, in that the predominant element is an abundance of normal appearing mitochondria and lack the characteristic cytoplasmic granularity.

The etiology of GCTs remains unclear, but current knowledge points most likely to granular pituicytes. This theory is supported by the immunohistochemistry findings as well as immunoreactivity to TTF‐1, which is known to be characteristic of other pituicyte tumors. GCTs with a similar morphologic appearance occur in many different areas of the body, however, they most commonly localized in the head and neck region. The latter neoplasms, however, are believed to originate from Schwann cells 2.

GCTs are slow‐growing and can remain asymptomatic throughout one's life; however, once they reach a stage where they are diagnosed they progress fairly rapidly. Occasional examples of more aggressive biologic behavior with rapid growth have been reported. Conservative, non‐surgical treatment is known to be ineffective. Total resection should be attempted; however, GCTs are firm and vascular which sometimes results in subtotal resection. It is recommended that these patients undergo adjuvant radiation therapy.