Introduction

The neurohypophysis is composed of glial cells that have been termed pituicytes. These cellular elements give rise to two types of primary tumors: pilocytic astrocytomas (also called pituicytomas) and granular cell tumors (historically referred to as choristomas or myoblastomas ).

Subsequently, autopsy studies have demonstrated the common occurrence of these small neurohypophyseal tumors, ranging from 6.5 percent of 1364 routinely sliced pituitary stalks to 17 cases in 100 serially sectioned pituitary stalks. These incidental autopsy findings were referred to as tumorettes and did not occur in the first two decades of life but rather increased in frequency and number with age. These findings of the absence of congenital neuro­hypophyseal tumorettes strongly implied that the choristoma concept was invalid.

Other observers noted that the extracranial myoblastoma has histologic findings similar to those of the neurohypophyseal lesions, and thus the term myoblastoma of the neurohypophysis was coined. Extracranially, these tumors arise from a wide variety of tissues and organs (especially within the oral cavity), including gingiva, mucosa, larynx, tracheobronchial tree, esophagus, stomach, and small and large intestine, as well as bladder, uterus, genital mucosa, breast, skin, and even the eye. Peripherally, myoblastomas are now believed to originate from Schwann cells, thus being dissimilar to granular cell tumor progenitor cells.

For over 40 years, pituicytes have been proposed as the cell of origin for neurohypophyseal granular cell tumors. Takei et al. have subclassified pituicytes into five categories and have suggested that the granular type of pituicyte may be the specific cell of origin for these tumors. These granular cells may represent a transitional type of astrocyte in which the glial filaments have undergone partial or complete biodegeneration. Russell and Rubinstein, on the other hand, suggest that the negativity for gliofibrillary immunostains might be the consequence of the crowding of cell cytoplasm by the granular elements of these neoplasms. The enigmatic origin of these tumors unquestionably has contributed to the multiple terminology for this lesion.

About 35 clinically symptomatic cases of granular cell tumors have been reported in the literature. There has been a female predominance, with only 11 male cases recognized. Most cases present clinically during the fourth and fifth decades of life. Seventy-four percent of these patients have presented with visual field deficits or blindness, and headaches were noted in 12 cases (34 percent). Dementia, especially with recent memory loss, has also been reported commonly (23 percent). Sixty percent of endocrinologically evaluated patients presented with symptoms suggestive of adenohypophyseal dysfunction, including hypogonadism (six cases), hyperprolactinemia (one case), 7 hypothyroidism (six cases), and hypoadrenalism (eight cases). Interestingly, only two cases appear to have presented with diabetes insipidus, probably because the tumor rarely invades or destroys the hypothalamus. Although these lesions tend to be benign and grow slowly, the compression of the hypothalamus or pituitary obviously has caused destructive loss of adenohypophyseal function in a significant number of cases.

Radiologic Features

The radiologic findings of a suprasellar granular cell tumor are nonspecific. Modest enlargement of the sella turcica or, more commonly, a normal size sella, has been described. Neither calcification nor sellar erosion is present in these lesions. Angiography has demonstrated a mild suprasellar mass effect. and occasionally a definite tumor stain may be appreciated. The computed tomography (CT) scan often shows a highly dense and sharply demarcated lesion with diffuse intense contrast enhancement. The magnetic resonance imaging (MRI) scan shows the mass to be isointense on T1-weighted, proton density-weighted, and T2-weighted images, The normally bright posterior pituitary signal on T1-weighted images, presumably due to phospholipid vesicles in the neurohypophysis, appears to be diminished or lost with these tumors. The lesion is discrete from the pituitary and intimately associated with the hypothalamus; retrochiasmatically it compresses the mammilary bodies and the cerebral peduncles. After gadolinium administration, dense enhancement has been noted.

In the differential diagnosis of neurohypophyseal tumors, a wide variety of ganglion cell tumors must be considered. Some of these are primarily hamartomatous lesions, but others, such as gangliocytomas and gangliogliomas, may be growing more actively. Other lesions encountered in this area include teratomas, suprasellar germinomas, epidermoid cysts, craniopharyngiomas, and meningiomas. Occasionally, metastatic lesions such as breast carcinoma, multiple myeloma, or lymphoma may involve this area.

Surgical Management

The surgical approach to these lesions will vary, depending on the precise tumor location. In several cases with an enlarged sella turcica, the approach was by a trans-sphenoidal route. In each instance, the normal pituitary gland was encountered anteriorly and had to be resected or incised to permit access to the tumor mass. Although a few cases have been approached transcallosally, the most common approach seems to be subfrontal. These lesions are discrete, firm, and rarely invasive. They adhere tenaciously to the adjacent arteries and the optic chiasm. They have considerable vascularity and lack dural attachments or cystic components. The striking vascular characteristic of this tumor argues for haemostatic control via the transcranial approach.

Pathologic Studies

Light microscopy has demonstrated that granular cell tumors consist of plump granular eosinophilic cells with small oval nuclei. The cytoplasmic granules are periodic acid Schiff (PAS) positive, and in some cases they are positive for phosphotungstic acid hematoxylin (PTAH). Capillaries, some with sinusoidal channels. are fairly numerous throughout. Electron microscopic studies have demonstrated cytoplasmic inclusions corresponding to the granules seen on light microscopy. There are abundant cytoplasmic lysosomes, and a basement membrane is infrequently identified.

The immunocytochemical reaction pattern of these tumors has tended to be heterogeneous. Glial fibrillary acidic protein (GFAP) has been demonstrated diffusely in the cytoplasm of the granular cells but not within the granules or the cellular organelles. Immunohistochemical testing for S-100 protein has usually been positive, although not in all cases. On the other hand, such testing for neuron-specific enolase, myelin basic protein, keratin, vimentin, and desmin has been reported to be negative. Alpha-1 antitrypsin and anti-chymotrypsin, well known markers for histiocytes, have been demonstrated sporadically. Tests for peanut lectin (PNA), a protein which has recently been shown to bind intracytoplasmically to neurohypophyseal granular cells, are consistently positive; this appears to be a useful histochemical marker for granular cell tumors.

Prognosis

Several authors have discouraged radiation therapy, since the lesions do not appear to be particularly radiosensitive. Radiosurgery is possible in this area, but, at the present time, no such case has been reported. These tumors, even if not totally resected, seem to allow an extended postoperative life span without progressive symptoms. Most patients have developed hypopituitarism postoperatively. Preoperative visual deficits have resolved in several cases treated with microsurgery. On the other hand, patients blind preoperatively remained blind postoperatively. Headaches have not been a major problem, but some patients have had persistent cognitive defects despite decompression of the hypothalamic area. Even if the complete lesion cannot be extirpated safely, repeat surgical decompression may preserve normal neurological status in these patients for many years.