Pituicytoma is extremely rare and has a high misdiagnosis rate. Compared with pituitary adenoma and craniopharyngioma, pituicytoma is an antecedent. It is not possible to diagnose pituicytoma pre-operatively, however a degree of suspicion should be held in large sellar lesions certain features on imaging. However, the statistical analysis of a large sample may enable the preoperative diagnosis of pituicytoma and choice a more suitable surgical approach, as well as better preparation for difficult intraoperative bleeding.
Epidemiology and clinical characteristics
Pituicytoma, which is a low-grade neurogenic tumor (WHO I), is a very rare spindle-shaped astrocytic tumor that originates from the posterior lobe or stalk of the pituitary gland [9,10]. To date, only 4 articles have reported more than 6 cases of pituicytoma [11,12,13,14]. Thus, useful, detailed, and accurate information regarding the diagnosis and treatment of pituicytomas is difficult to obtain. The number of cases reported in this study is currently the largest number reported by a single center. From the case data we reported, we did not observe a significant gender difference, which was slightly different from the larger number of male patients reported in a previous study . Pituicytomas can occur at any age but are more common in middle-aged and elderly individuals . In our study, the average age of onset of patients was 49.27 years (range: 32 to 65 years). The clinical symptoms of pituicytomas vary due to the different sizes and locations of compression. Some of the adenopituitary insufficiency observed in the patients in this study without diabetes insipidus was due to the gradual, dorsal and nondestructive extension of the tumor at the lowest part of the pituitary stalk, which may cause vasopressin to leak into the systemic circulation before reaching the affected segment of the pituitary stalk, while the hypothalamic release of factors through the pituitary portal system is interrupted and tumor growth oppresses the optic nerve, resulting in visual field damage and pituitary compression. Similarly, tumor compression may cause hypopituitarism and headaches, and compression of the hypothalamus potentially causes mental symptoms [4,17,18]. Some patients also experience hyperprolactinemia due to secondary hyperprolactinemia caused by hypothalamic dopamine transport disorders induced by funnel compression , which was observed in patient 4, who had slightly increased prolactin levels before the operation. Most of the reported pituicytomas have clear boundaries, and a few have been reported to invade the cavernous sinus [20,21].
Pituicytomas are easily confused with other tumors in the sellar region, such as pituitary adenomas and craniopharyngiomas. Pituicytomas are mostly located in the suprasellar region. However, some are located in the sellar or the sellar-suprasellar region. Most pituicytomas are uniformly enhanced, some are inhomogeneous, and some cystic degeneration has been observed . MRI showed that the tumors were solid masses, and most of them had clear boundaries. It has been reported in the literature that pituicytomas are isointense on T1-weighted images and slightly hyperintense or isointense on T2-weighted images . In our patients, most pituicytomas showed isosignals on T1-weighted images and slightly hyperintense or isosignals on T2-weighted images. Some patients showed hyperintensity on T1-weighted and T2-weighted images. Some authors suggest that the early contrast enhancement of dynamic MRI or angiography should be used as a differential feature, which reflects the high vascularity of pituicytoma[24,25]. The empty shadow of vascular flow was observed on T1-weighted images from patient 1, indicating the abundant blood supply of the tumor. Although pituicytoma has no special imaging features, it displays no calcification on CT and can be distinguished from craniopharyngioma. Pituitary adenomas are homogeneously enhanced and easily invade the surrounding tissues, which enable them to be distinguished from pituicytomas. Pituicytomas are distinguished from other tumors in the sellar region based on these radiological characteristics. Notably, pituicytoma lacks calcification and rarely exhibits cystic changes, which help to distinguish it from ameloblastic craniopharyngiomas in the sellar region or suprasellar region.
The final diagnosis of pituicytoma depends on the pathological findings. During the operation, the boundary of the pituicytoma is clear, and most tumors are tough and smooth. A few reports have described a soft texture or cystic degeneration [7,26]. Most of the tumors are red or grayish red, with an abundant blood supply and no invasion of the surrounding tissue. The adhesion between the tumor originating from the pituitary stalk and the posterior pituitary lobe can be difficult to distinguish . Immunohistochemical staining showed that S-100 was strongly positive , GFAP was invisible or weakly positive [7,29], EMA was rarely positive, and TTF-1 positivity was helpful for the diagnosis of pituicytoma . In our 11 patients, S-100 immunoreactivity was strongly positive, consistent with the diagnosis of pituicytoma.
According to Brat et al., the diagnostic criteria for pituicytoma are spindle cell tumors, no or trace levels of nuclear atypia and mitotic phase. Immunohistochemical staining showed GFAP (+), S100 (+) and vimentin (+). Because pituicytomas originate from pituitary cells, TTF-1 has been widely used in the diagnosis of pituicytomas in recent years. Pituitary spindle cell oncocytoma and granulosa cell tumors are derivatives of pituicytoma. TTF-1 is also positive in spindle cell oncocytoma and granulosa cell tumors. The neurohypophysis is a periventricular organ. Interestingly, the endplate vascular organ in the anterior part of the third ventricle also expresses TTF-1. Chordate gliomas located in this region also express TTF-1 . The expression of TTF-1 in pituitary cytomas and chordate gliomas prompted the hypothesis that these tumors may belong to a series of lineage-related tumors in the basal forebrain . In general, all pituicytomas showed diffuse nuclear labeling for TTF-1 and positive expression of EMA, S100 and GFAP to varying degrees. These findings were similar to other reported cases of pituicytomas .
Treatments and outcomes
Currently, the pathogenesis of pituicytoma is still unknown. These tumors theoretically display benign biological behaviors with neither malignant histological features nor tumor-derived metastasis. Currently, the GTR of tumors is the primary treatment. The surgical approach includes transfrontotemporal craniotomy and a transnasal transsphenoidal approach. Compared with craniotomy, transsphenoidal surgery is minimally invasive and may reduce the risk of postoperative complications. The transsphenoidal approach includes the standard transsphenoidal approach and extended transsphenoidal approach. For giant pituicytomas invading the cavernous sinus, the extended transsphenoidal approach is adopted to achieve total resection. Most of the patients with poor preoperative vision experience varying degrees of clinical improvement after operation, and patients with poor vision undergo a craniotomy. However, the effect of the surgical approach on the GTR rate of pituicytomas must be further evaluated. Due to the rich blood supply of the tumor, uncontrollable bleeding is often encountered in the process of tumor resection, which leads to subtotal resection of the tumor [35,36,37]. However, angiographic studies are inevitably needed before a reoperation, and another goal is to exclude the existence of vascular iatrogenic lesions. In most reported studies, pituicytomas show inert growth and have a long recurrence cycle, and patients with subtotal resection are more likely to relapse [7,28,39]. However, cases of recurrence after GTR have still been reported [18,39]. In our study, we also confirmed the effect of the tumor resection extent on tumor progression. A retrospective analysis of previous patients found that sex is also one of the potential factors that affect tumor progression, but further verification is needed. Some authors suggest that stereotactic segmentation or conventional radiotherapy should be used systematically to control the residual tumor following subtotal resection of tumors, while others suggest that these treatments are limited to smaller tumors that do not affect visual acuity, but further data are needed to prove the effect. Recently, Mende et al indicated strong immunostaining for vascular endothelial growth factor receptor (VEGF-R) in a small series of patients with pituicytomas . Based on these results, anti-VEGF-R therapy (bevacizumab) and somatostatin analogs may be promising treatment options, although their use has not yet been approved.