1.Concept
Concept: Pituitary cell tumor is a solid benign spindle-shaped astrocytic tumor originating from adult pituitary or pituitary stalk glial cells, which belongs to WHO grade I. The glial cells that make up the pituitary gland and pituitary stalk are divided into five types: major cells, dark cells, oncocytic cells, oncocytic cells and granular cells. This concept was first clearly proposed by Brat et al. in 2000 based on a report of 9 cases of pituitary cell tumors, and was finally recognized in the 2007 WHO classification of CNS tumors.
In the past, granular cell tumors, choristomas, pilocytic astrocytomas and granular cell myoblastomas were also included in pituitary cell tumors, as well as “posterior pituitary astrocytoma” and “funnel tumors” originating from the pituitary stalk. “The range of pituitary astrocytomas also includes posterior pituitary astrocytoma and infundibuloma, which originates in the pituitary stalk. Currently, pituitary astrocytoma is clearly defined as an astrocytic tumor distinct from these tumors, and the synonym “funnel tumor” is no longer used, nor is it confused with posterior pituitary astrocytoma. The WHO Working Group believes that the diagnostic term “pituitary cell tumor” can help to more clearly classify tumors originating from the pituitary gland and pituitary stalk.
2. Clinical features
To date, 26 cases of pituitary cell tumors have been pathologically confirmed and reported in the English literature, including one incidental finding at autopsy. The largest group of case reports came from Brat et al. in 2000 reporting 9 cases, followed by Figarella-Branger et al. in 2000 reporting 3 cases, and the rest were mostly 1~2 case reports. In China, since the first report of 2 cases of astrocytomas originating from the pituitary gland at Peking Union Medical College Hospital in 1993, there has been a gradual increase in similar reports. Although some of these tumors were suspected to be pituitary cell tumors, the final diagnosis could not be confirmed due to the lack of reliable pathological evidence. Pituitary cell tumors occur in adults, aged 26-83 years, with a significantly higher incidence in men than in women, with a ratio of 1.6:1.0, as described by Brat et al [3].
In 26 cases of pituitary cell tumors, the common preoperative signs and symptoms were visual and visual field impairment (19 cases), loss of libido (15 cases), headache (15 cases), and general malaise (12 cases); a few patients presented with memory loss, nausea, vertigo, psychiatric abnormalities, and urinary collapse; one case presented with tumor stroke. Endocrinological examination showed partial anterior pituitary hypoplasia in 10 cases, total anterior pituitary hypoplasia in 6 cases, mild to moderate increase in prolactin in 8 cases, mild increase in adrenocorticotropic hormone in 1 case, and breast development in 1 male patient. Interestingly, despite the origin of the tumor in the posterior pituitary lobe or pituitary stalk, only 1 of these patients presented with enuresis.
Most authors report that the tumor was well-defined and not invasive to surrounding structures. The signs and symptoms caused by pituitary cell tumors are secondary to the direct compression of surrounding structures by their occupying effect during growth, such as visual disturbances due to compression of the optic chiasm, hypopituitarism and headaches due to compression of the pituitary gland, hyperprolactinemia (with amenorrhea and decreased libido) secondary to impaired hypothalamic dopamine delivery due to compression of the funnel, and psychiatric symptoms due to hypothalamic compression.
3.Imaging features
The imaging of pituitary cell tumors is not specific. Because it originates from the posterior pituitary lobe or pituitary stalk, the tumor can be in the saddle, supra-saddle or both, but most of them show intra-saddle and supra-saddle masses, and a few of them are located in the saddle or supra-saddle. Only two cases were reported to be solely suprasellar, which may be related to its origin in the pituitary stalk [8, 10]. Most of the tumors were >1.5 cm in maximum diameter and resembled pituitary macroadenomas or giant adenomas; more than half of the 26 cases reported tumors >2 cm in diameter.
In these patients, five CT examinations were performed, showing an isodense, round-like solid mass with marked homogeneous enhancement, with no calcification, necrosis of tumor tissue, destruction of surrounding bone tissue, or irritative hyperplasia. one plain radiograph of the saddle area showed enlargement of the pterygoid saddle and thinning of the bone in the anterior and posterior bed processes and saddle base. On MRI, the tumor appeared as a solid mass with well-defined borders, with isosignal in T1 and mostly mild to moderate high signal in T2, except for one case reported by Shah et al. In addition, the proton image of one case also showed high signal. The majority of cases showed uniform and distinct gadolinium enhancement, and non-homogeneous enhancement and cystic changes were seen only in a few cases. No calcification or necrosis of the tumor tissue was observed on MRI, and only one case of hemorrhagic stroke occurred.
Thiryayi et al. noted that pituitary cell tumors show rapid homogeneous enhancement early in the MRI scan, and this enhancement feature suggests that the tumor has a very rich blood supply. Although the imaging features of pituitary cell tumors are nonspecific, Gibbs et al. suggested that MRI combined with cerebral angiography may provide valuable diagnostic clues. They reported a case in which a tumor fed by the superior and inferior pituitary arteries showed significant capillary staining on selective internal carotid angiography, and the staining effect persisted into the late capillary phase and venous phase, suggesting a very rich blood supply to the tumor.
In contrast to the results reported by Gibbs, Benveniste et al. reported that the tumor was not significantly stained on cerebral angiography and did not show abundant blood supply vessels around it. We believe that pituitary cell tumors are difficult to distinguish from pituitary adenomas in terms of CT density and MRI signal, but the enhancement of pituitary tumors tends to appear in late stages, whereas pituitary cell tumors are early and rapidly enhancing, and dynamic enhancement may be helpful to distinguish the two based on this feature. In addition, the absence of necrosis and cystic changes in pituitary cell tumors is an important feature that differs from pituitary macroadenomas and giant adenomas.
4. Pathological features
The diagnosis of pituitary cell tumors ultimately relies on their pathologic features. Intraoperatively, pituitary cell tumors are seen as well-defined solid masses with smooth surfaces that can reach several centimeters in diameter without infiltration, and those originating from the pituitary stalk are often adherent to the superior pituitary stalk and are not easily distinguishable [5], mostly pink in color, with a very rich blood supply; it has also been reported that no significant bleeding was seen during intraoperative resection of the tumor or that bleeding could be controlled. The tumor texture was hard and tough, but there were some individual reports of texture. Cystic degeneration is rare. Although the tumor is generally free, in the suprasellar space the tumor may be tightly adherent to surrounding structures such as the pituitary stalk, funnel, and optic cross.
Microscopically, the tumor is almost entirely composed of spindle-shaped or fat-circle shaped bipolar spindle cells arranged in glial fiber bundles or matrices, with abundant vascular network and cells containing richer eosinophilic cytoplasm with clear borders. The nuclei were medium-sized, round or elongated, with rare general heterogeneity and rare mitoses. Intercellular reticulin is absent around individual tumor cells. In contrast to hairy cell astrocytomas, pituitary cell tumors lack Rosenthal fibers and eosinophilic granular vesicles.
The majority of pituitary cell tumors are unresponsive to epithelial membrane antigen (EMA), and a few are only locally positive in the cytoplasm. Benveniste et al. concluded that strong S-100 and intermediate filament positivity are characteristic of pituitary cell tumors. The results of the study were positive for synaptophysin, neurofilaments, smooth muscle actin, neurofilament protein (NFP), somatostatin, carcinoembryonic antigen, type IV collagen, cytokeratin and chromoprotein, and negative for the melanoma marker HMB 45 and Melan-A.
In general, Ki-67-labeled MIB-1 was very low, ranging from 0.5% to 2.0%, with only one case of 5% reported by Figarella-Branger et al. In addition, immunostaining for various hormones secreted by the anterior pituitary gland was negative. The tumor cells were found to have scattered small bands of intermediate junctions but no bridging granule connections, abundant intermediate filaments and mitochondria in the cytoplasm, and sometimes the presence of secretory granules; they had tumor vascular basement membranes, but lacked the pericellular basement membranes characteristic of Schwann cell tumors and the interdigitated synaptic cell membranes apparent in meningiomas. Based on the above pathological features, we tentatively propose that the pathological diagnosis of pituitary cell tumor must meet at least the following conditions.
(i) spindle cell tumor with no or minimal nuclear anisotropy and mitotic phase;
(ii) Immunohistochemistry GFAP (+);
(iii) Immunohistochemistry S-100 (+) and Vimentin (+);
④MIB-1 labeling index was less than 2%. This is generally consistent with the pathological diagnostic criteria proposed by Brat et al.
5. Treatment and prognosis
Pituitary cell tumors are inert benign tumors with slow growth and long recurrence intervals reported in most of the literature. Surgical resection of the tumor is currently the main treatment. Ulm et al. reported two patients who underwent only subtotal resection of the tumor due to extensive intraoperative bleeding. Because of the rich blood flow of the tumor, uncontrollable bleeding is often encountered during the removal of the tumor, which leads to difficulty in removing the tumor and leaving it residual.
Among the 26 patients reported, only 10 cases achieved total tumor resection and the rest were subtotal or partial resection. At follow-up of 3 months to 11 years, those with total tumor resection had a good prognosis and none of them had recurrence [5]; although there were reports of no recurrence, those with subtotal resection often recurred 6 months to several years after surgery and had a higher recurrence rate. Of the 9 patients reported by Brat et al, 6 had total tumor resection and no recurrence at 13-99 months; 3 had subtotal resection, 2 of which had recurrence at 20 and 26 months postoperatively, respectively, and 1 had no recurrence at 8 months follow-up. 2 of the 3 patients reported by Figarella-Branger et al had total resection and 1 had subtotal resection, with no recurrence at 2-, 4-, and 12-year postoperative follow-up. No recurrence was observed at 2-, 4-, and 12-year postoperative follow-up. Postoperative fractionated radiotherapy and stereotactic radiotherapy are routinely recommended for subtotal resection patients.
In cases of total tumor resection, there is no data to support that radiotherapy is more beneficial to the patient. Although data are limited, Kowalski et al. concluded that adjuvant chemotherapy and radiotherapy have no clear efficacy. No reports of malignant transformation or tumor spread to the cerebrospinal cord have been seen. Based on the reports in the literature, we believe that: for patients whose tumors were not completely resected, postoperative adjuvant radiotherapy is necessary to prevent tumor recurrence; for patients whose tumors were completely resected, postoperative radiotherapy and chemotherapy are not necessary, but regular review of MRI is still necessary.
6.Outlook
In conclusion, pituitary cell tumor is a kind of rare benign pituitary tumor, which can be cured by total resection under the sarcoid eye. However, in clinical practice, it should be distinguished from pituitary adenoma, saddle meningioma, craniopharyngioma and pituitary hairy cell astrocytoma. The imaging performance is not specific, and pathological confirmation is needed to confirm the diagnosis. The tumor is rich in blood flow, and how to control bleeding and improve the total resection rate of the tumor during surgical treatment is an important issue that deserves further discussion; preoperative blood supply artery embolization may open a new path for total resection of pituitary cell tumor.