Manifestation of a sellar hemangioblastoma due to pituitary apoplexy: a case report

Hemangioblastomas (HBLs) are benign, slowly growing and highly vascular tumors of the central nervous system (CNS), accounting for just 1% to 2.5% of all intracranial neoplasms, and 7% to 12% of primary tumors located in the posterior fossa [ 1]. In up to one in four cases of HBL there is an association with von Hippel-Lindau (VHL) disease [ 2], a rare autosomal dominant condition that predisposes patients to multisystemic neoplastic disorders such as HBLs of the CNS, retinal angiomas, renal cell carcinoma, pheochromocytomas, serous cystadenomas and neuroendocrine tumors of the pancreas. VHL-associated HBLs tend to occur in younger patients and are often multiple in occurrence [ 2– 4]. Sporadic HBLs, however, are mostly solitary lesions and predominantly found within the cerebellum or spinal cord. Supratentorial HBLs, which are more often associated with VHL disease [ 3, 4], are a rare entity with just over 100 reported cases to date [ 5]. HBLs originating from the sellar or suprasellar region are exceptional, especially in cases with no association with VHL disease.

We report here what is, to the best of our knowledge, the seventh sporadic case in the literature of sellar HBL, which presented with pituitary apoplexy. We also review the literature on cases of HBL within the sellar and suprasellar region.

An 80-year-old Caucasian woman was admitted to our hospital with a 12-year history of an endocrine inactive steady sellar mass lesion (13 mm in diameter; Figure 1A, B). Our patient had been previously asymptomatic with no pituitary hormone deficiency or visual impairments. Moreover, our patient had a medical history of good health with only minor health issues that included hypertension and osteoporosis. However, prior to hospital admission, she had recently experienced two severe headache attacks; the last episode was accompanied by nausea, vomiting and blurred vision. Hyponatremia (120 mEq/L) with low serum osmolality (247 mOsm/L) and highly elevated urine osmolality (695 mOsm/L) were detected. An endocrinological investigation revealed hypocortisolism with no other hormone disturbances. Fundoscopy showed no pathological findings. However, further ophthalmologic examination with Goldman perimetry confirmed a bitemporal hemianopsia accentuated on her right side. Her neurological examination results were otherwise normal. After substitution therapy with hydrocortisone, our patient rapidly improved and her headaches subsided.

Findings from a magnetic resonance imaging (MRI) scan were suggestive of an acute hemorrhage of the sellar process, consistent with pituitary apoplexy (Figure 1C-F). Except for an age-consistent vascular leukoencephalopathy, the diagnostic imaging showed no further pathological findings. Our tentative diagnosis at this point was a pituitary adenoma with pituitary apoplexy.

Due to these clinical and radiological findings, the decision was made to surgically remove the tumor. A gross total extirpation using a transnasal, transsphenoidal approach to the pituitary mass was successfully performed. Intraoperatively, the tumor appeared yellowish-brown, was relatively firm and was located within a sellar hematoma cavity, which was evacuated.

Postoperatively, our patient's visual field deficits improved markedly on clinical examination and Goldman perimetry confirmed a partial recovery of her bitemporal visual field deficits. Endocrinological studies showed panhypopituitarism with partial and transient diabetes insipidus. Our patient received substitution therapy with hydrocortisone, levothyroxine and transient therapy with desmopressin. Overall, our patient remained in good health with a satisfactory level of performance. A repeat MRI scan taken 16 months after surgery showed good chiasmatic decompression with no residual tumor mass (Figure 1G, H).

The resected tumor was examined with light microscopy, which revealed a small, well circumscribed, non-adenomatous tumor surrounded by slightly compressed remnants of adenohypophyseal parenchyma (Figure 2A-C). The tumor was richly vascularized with an observable reticular mesh of thin-walled capillaries interspersed with large epithelioid-looking cells (Figure 2D, E). Pale eosinophilic cytoplasm showed xanthomatous or vacuolar change (Figure 2F). Immunohistochemistry confirmed the expression of the endothelial-associated markers CD31 and CD34 in the intratumoral capillaries, although not in the stromal cells themselves. Conversely, the stromal cells were diffusely immunoreactive for vimentin, with a minority of cells also coexpressing S100 protein and epithelial membrane antigen (Figure 2G). No inflammatory infiltrate was detected except for the occasional mast cell (Figure 2H). Staining for cytokeratins tested negative, as did the Langerhans-cell-associated marker CD1a. Less than 1% of lesional cell nuclei were labeled with the cell proliferation-associated antigen Ki-67.

Given the above findings, we identified the tumor as an intrapituitary example of capillary hemangioblastoma (World Health Organization grade I). Since our patient displayed no clinical stigmata of VHL disease, genetic testing was not performed.

Based on previous studies, the occurrence of supratentorial HBLs is thought to be in the range of 2% to 8% of all HBLs [ 3, 4, 6], accounting for 116 reported cases from 1902 to 2004 [ 5]. Supratentorial tumors were mostly found in the frontal, parietal or temporal lobes [ 7].

No more than 27 reported cases to date (including our patient's case) describe HBLs originating in the sellar and suprasellar region (see [ 1] and references therein, and [ 2, 8– 11]) of which 18 were confirmed with histopathology (Table 1). Of the 27 cases, only seven (26%) were sporadic. In accordance with previous studies, the average age at presentation of patients with sporadic HBLs (52.4 years) was greater than patients affected with the VHL syndrome (35.8 years), excluding two cases with postmortem diagnosis (Table 1, cases 1 and 2) and one case not stating VHL association [ 10].

While information on clinical features is derived from reports of sellar and suprasellar HBLs causing symptoms generally related to mass effect, a long presymptomatic stage can be assumed. Of a total of 250 patients with VHL disease enrolled in a prospective study, eight incidentally discovered HBLs located in the pituitary stalk remained stable during a mean follow-up of 41.4 ± 14 months [ 8]. Also, in our patient's case, the sellar lesion, initially diagnosed as an incidental finding on MRI performed for an unrelated reason, remained stable for 12 years.

Overall, the unexpected nature and the unspecific presentation render an accurate preoperative diagnosis of sporadic HBLs challenging. In our patient, the apoplexy of a well known sellar mass suggested a pituitary macroadenoma; clinical apoplexy was observed in 0.6% to 9.0% of these cases [ 12]. The typical, albeit not pathognomonic, radiological feature of HBLs is that they can be identified as an enhancing lesion on T1-weighted MRI scans. This finding was lacking in our case due to acute hemorrhage of the lesion.

The main histological differential diagnosis of HBL, irrespective of location, is metastatic clear cell carcinoma. In our patient, lack of immunoreactivity for cytokeratins along with a negligibly low proliferation index allowed for this alternative to be confidently ruled out. In the peculiar context of intrapituitary occurrence, we also addressed the possibility of xanthomatous hypophysitis and Langerhans cell histiocytosis [ 13, 14]. The non-inflammatory character of the lesion in our case strongly argued against xanthomatous hypophysitis (or sellar xanthogranuloma). However, the circumscribed rather than infiltrative pattern of this solitary intrapituitary nodule, one devoid of CD1a immunoreactivity, was an intuitive obstacle against seriously considering Langerhans cell histiocytosis.

Supratentorial HBLs are rare, especially within the sellar region and without an association with VHL disease. However, our patient's case shows that intrasellar HBL must be considered in the differential diagnosis of pituitary apoplexy.

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.