Spindle Cell Oncocytoma of the Anterior Pituitary Presenting with an Acute Clinical Course Due To Intraventricular Hemorrhage. A Case Report and Review of Literature

Background

Primary tumors of the anterior pituitary, or adenohypophysis, account for between 10% and 15% of all intracranial tumors. The spectrum of tumors at this site includes the most common, the pituitary adenoma, followed by craniopharyngioma, meningioma, oncocytoma, pituitcytoma and granular cell tumor [1].

SCO of the adenohypophysis is a rare, benign, primary tumor in the sellar region, accounting for 0.1% 0.4% of all sellar tumors [2]. SCO was described as a new entity in 2002 by Roncaroli and colleagues and was classified as a distinct non-adenomatous sellar mass in the 2007 World Health Organization (WHO) classification [3,4].

Due to its rarity, little information is available regarding the imaging features and surgical characteristics of SCO. To our knowledge, there are only 34 cases reported to date (including our case). Most cases present with symptoms of slow onset that progress with as the tumor increases in size, resulting in compression of surrounding structures. Few cases presented with acute symptoms. Our case report is the first to describe a case presenting clinically with intratumoral bleeding and hemorrhage into the ventricles.

Case Report

A 56-year-old man presented to the emergency room (ER) with acute onset of a severe headache, vomiting, neck pain, back pain, and reduced level of consciousness. His son reported recently impaired visual acuity. On examination, the patient was stable and the Glasgow Coma Scale (GCS) score was 13/15 with no other neurological deficit. Following initial management in ER, the patient was sent for further investigations.

Magnetic resonance imaging (MRI) of the brain was performed using a 1.5 Tesla Siemens Avanto scanner. Multi-planar, multi-sequence images were obtained. Brain MRI showed a sellar and suprasellar macro-adenoma measuring 2.5×4.4×2.5 cm in its maximum anteroposterior, craniocaudal, and transverse dimensions, respectively, with intralesional bleeding, and intraventricular hemorrhage extending into the fourth ventricle. Mild ventricular system dilatation was also noted, with chiasmal and hypothalamic compression (Figures 1, 2).

The patient went for urgent sub-frontal craniotomy for tumor resection and placement of an external ventricular drain (EVD). Intra-operative tumor hypervascularity gave the macroscopic appearance of meningioma, and profuse bleeding limited the surgical resection. A sample of cerebrospinal fluid (CSF) was sent for analysis, and the tumor specimen was sent for histopathological examination and microbiological culture and sensitivity.

There were no significant abnormalities found on analysis of the CSF, Gram stain or culture and sensitivity. Light microscopy (Figure 3) with hematoxylin and eosin (H&E) staining showed interlacing fascicles of spindle cells, and epithelioid cells with eosinophilic cytoplasm containing numerous mitochondria (oncocytic change). The absence of cellular atypia, mitoses, invasion, and necrosis, together with a low cell proliferation rate on immunohistochemical staining with antibodies to Ki67 all supported the benign nature of the tumor. Immunohistochemical staining also showed that the tumor cells were uniformly positive for vimentin, S100, epithelial membrane antigen (EMA), and thyroid transcription factor-1 (TTF-1), and focally positive for glial fibrillary acidic protein (GFAP), and was negative for immunostaining with antibodies to CD34, smooth muscle actin (SMA), desmin, and pan-cytokeratin (CK).

Serological findings showed that the basal level of growth hormone (GH) was <0.10 ng/ml, morning cortisol level was 0.9 ug/dL, free triiodothyronine (T3) was 3.49 pmol/L, thyroid stimulating hormone (TSH) was 1.1819 uIU/mL, free thyroxine (T4) was 9.37 pmol/L, prolactin was 15.31 ng/mL, sodium (Na) was 131 mmol/L, and potassium (K) was 3.4 mmol/L.

The patient underwent good recovery with unchanged visual acuity but with a field defect in the left eye. He was referred for radiotherapy to control any residual tumor and showed no tumor recurrence at six-month follow-up.

Discussion

Spindle cell oncocytoma (SCO) is defined as an oncocytic, non-secreting, benign neoplasm of the adenohypophysis that presents in adults, with a mean age at presentation of 56 years [3,4]. These tumors may be indistinguishable macroscopically from a non-functioning pituitary adenoma and follow a benign clinical course, corresponding to World Health Organization (WHO) Grade 1 tumors of the central nervous system (CNS) [4].

Due to its benign clinical course and slow progression, review of the literature has shown that SCO usually presents with visual impairment (20 cases), which was the most common presenting symptom. Panhypopituitarism was the next most common symptom (15 cases) followed by headache (14 cases). Less commonly, SCO presented with vomiting, epistaxis, fatigue, syncope, polyuria, weight loss, oligomenorrhea, and amenorrhea (Table 1).

Abrupt neurologic deterioration may result from several etiologies associated with brain tumors, resulting in increased intracranial pressure (ICP). These causes include intracranial hemorrhage, infarction, cerebral edema, hydrocephalus, tissue necrosis, pituitary hemorrhage, and seizures. Pituitary infarction and/or subsequent hemorrhage occur mainly from the compression effects of the tumor mass on the hypophyseal arteries against the edges of the sellar diaphragm. The signs and symptoms of pituitary hemorrhage (apoplexy) include abrupt onset of headache, ophthalmoplegia, visual disturbances, and changes in mental status [5].

Although the radiological findings have been reported to be non-specific in the literature, the characteristics of magnetic resonance imaging (MRI) and the different patterns of contrast enhancement may help to recognize this rare tumor. In the recent publication from Hasiloglu and colleagues, they described the radiological findings of SCO, which include hypointense foci and linear signal-void areas on T1-weighted imaging and T2-weighted imaging [6]. On dynamic contrast-enhanced MRI (DCE-MRI) SCO shows intense contrast enhancement during the early stage of contrast administration (Hasiloglu’s sign) [6]. The difficulty in distinguishing SCO from other tumors such as pituitary adenoma is important, because this tumor, unlike pituitary adenoma, tends to be very vascular and prone to hemorrhage during surgical resection [7]. This property of SCO is important to recognize, as hemorrhage can lead to the need to stabilize the patient, abort or defer surgery, or to consider embolization of the tumor vasculature [8].

Conservative treatment of pituitary hemorrhage (apoplexy) is rarely associated with reversal of hypopituitarism and may worsen the condition [9]. Open trans sphenoidal decompression of the hemorrhagic pituitary adenoma is the favored treatment for pituitary hemorrhage [10]. Unlike the trans-frontal approach, no brain retraction is needed, and trans-sphenoidal decompression is better tolerated by severely ill patients. A craniotomy is reserved for patients with a non-aerated sphenoid sinus, a small sella with a large suprasellar mass, a narrow sellar diaphragm. with a dumb-bell shaped mass, or an associated intracerebral hematoma [11].

Alexendersecu and colleagues have proposed an explanation of why a minority of these tumors present with recurrence after an initial complete resection [12]. The expression of precursor neuronal immunomarkers, such as cytoplasmic pan-neuronal marker, SMI-311, expressed by the spindle cell component, nestin and CD44 expressed by the epithelioid or polygonal cells of the tumor, may indicate that SCO of the adenohypophysis has a neuronal origin [12].

There is little evidence in the literature for the sensitivity of SCO to radiotherapy. Four of five published cases of SCO that underwent radiation therapy recurred. Therefore, at this time, no recommendations can be made regarding the effectiveness of adjuvant radiotherapy for SCO, and the effectiveness of stereotactic radiosurgery for treatment of this tumor has not been described [13].

Conclusions

A case of spindle cell oncocytoma (SCO) of the anterior pituitary (adenohypophysis) is presented, which has the unusual feature of an acute presentation (pituitary apoplexy) due to the presence of the intraventricular hemorrhage associated with a large sellar and suprasellar tumor mass. Previously reported cases of SCO have been associated with hypervascularity, and problematic bleeding has been previously reported during surgical resection. Being aware of the possible diagnosis of SCO of the anterior pituitary is of clinical importance.

A review of the literature has shown that there is some evidence to suggest that different imaging patterns from dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) may be an aid to distinguishing SCO from other tumors of the adenohypophysis. However, SCO should be considered if peri-tumoral or intraventricular bleeding is present on initial imaging. In such cases, urgent surgery is indicated that should also include management of the effects of intraventricular hemorrhage.