Pituitary Spindle Cell Oncocytoma: More than a Grade 1 Tumor?

1. Introduction

Spindle cell oncocytomas (SCO) are rare non-neuroendocrine tumors arising from the pituicytes of the posterior pituitary gland. They were included in the World Health Organization (WHO) classification of central nervous system tumors in 2007 after being first described by Roncaroli et al. in 2002 [1,2].

SCOs were previously thought to stem from the adenohypophysis, however, more recent research has identified that SCOs are positive for thyroid transcription factor 1 (TTF1) which is only found in pituicytes and not in folliculostellate cells of the adenohypophysis [3]. In our search from 2002 to 2024, there have only been 98 cases published in literature which highlights the rarity of this type of tumor.

SCOs are often misdiagnosed as pituitary adenomas; yet are important to distinguish as they usually have higher vascularity as well as an increased tendency to invade the surrounding structures. This results in higher recurrence rate, thus requiring closer follow-ups [4]. If gross total resection (GTR) is not achieved, 50% of tumors show significant progression requiring extra treatment by two years and recurrence occurs in 20% of people and even distant metastasis has been reported [4].

Despite these factors, the WHO considers pituitary SCOs a grade 1 tumor with benign behavior [5]. Moreover, although this tumor is considered grade 1, it is important to understand these critical features as it guides treatment and follow up and will improve patient outcomes.

Due to the low incidence of this neoplasm, there is no definitive understanding of the unique clinical signs and symptoms, diagnostic imaging (DI), immunohistochemistry (IHC), and treatment. With this report and literature review we aim to provide further knowledge and understanding of these factors to improve the identification and treatment of individuals with SCO.

2. Case Presentation

We present the case of a 48-year-old female with a two-month history of persistent headaches, mental and physical fatigue, and light sensitivity. Her past medical history includes chronic migraines, fibromyalgia, psoriasis, anxiety, obesity, and obstructive sleep apnea. When looking back, the patient realized that her headache symptoms had changed from her normal migraine symptoms to more frequent albeit less severe frontal pain and aching in the previous months.

Given the persistence of the above-mentioned symptoms, she was investigated with a head computed tomography (CT) scan that showed a pituitary lesion with sellar and suprasellar extension. For further investigation, she underwent a brain magnetic resonance imaging (MRI) scan that demonstrated a homogenous mass in the pituitary gland (Figure 1). The MRI also showed that the mass was compressing the optic chiasm and was encasing both internal carotid arteries. These findings were thought to be compatible with pituitary macroadenoma.

On physical examination the patient had no cranial nerves deficits, pupils were equal, round, and reactive to light and accommodation. She did not have any focal motor or sensory deficit. She also underwent an ophthalmological assessment that ruled-out papilledema and confirmed normal bilateral visual fields. Lastly, a thorough endocrinological assessment was completed including a full hormonal panel that demonstrated only mild hyperprolactinemia.

Given the clinical and radiological findings, an elective surgical treatment was recommended and carried out using an endoscopic endonasal transsphenoidal approach. Intraoperatively, the tumor had the usual soft consistency, but it presented stronger adherence with what was thought to be the normal pituitary gland and therefore required extra-work to separate it. Although no major bleeding was identified, an unusual constant tumor oozing made the procedure more challenging. An apparent GTR of the tumor was achieved and confirmed by direct visualization of the suprasellar cistern coming down into the sella turcica. For this reason, no adjuvant radiotherapy was performed.

The patient had an uneventful postoperative period. She spent two days in the intensive care unit and was then transferred to the floor, low levels of cortisol and mild diabetes insipidus were diagnosed and treated medically. Post-operative CT ruled out intraoperative complications and confirmed decompression of the optic chiasm (Figure 2). She was discharged home on postoperative day seven, neurologically intact.

She was reassessed in follow up four weeks after surgery and no obvious focal deficits were identified. Her headache and light sensitivity had notably improved. A repeat MRI was completed three months postoperatively and it confirmed GTR of the SCO.

Microscopy examination of the specimen demonstrated fascicles of spindle cell tumor cells with eosinophilic cytoplasm and elongated nuclei showing moderate pleomorphism (Figure 3). Other areas of tumor cells showed more eosinophilic cytoplasm with clear borders and contained round to oval nuclei with mild pleomorphism. Granular cytoplasm was not seen; however, mitotic figures were present. No tumor necrosis was noted. The tumor cells were diffusely positive for TTF-1, S100, CD56, and synaptophysin (Figure 4).

3. Discussion

SCOs are very rare tumors of the posterior pituitary gland that originate from the pituicytes located in the neurohypophysis. They are called SCOs because their cells are spindle shaped under microscopic examination and contain many mitochondria in their cytoplasm [6]. Oncocytomas can occur in many different areas of the body, including kidney, breast, prostate gland, thyroid and salivary glands [6]. Although, they are often only called oncocytomas in these locations as they lack the spindle shaped cells, which are characteristic of the pituitary SCO [6,7].

Unfortunately, pituitary SCOs appear very similar to non-functioning pituitary adenomas on clinical presentation and diagnostic imaging. Yet, they require unique care because of two specific features: increased vascularity and increased fibrotic adherence to surrounding structures.

Of note, SCOs higher vascularization can cause significant intraoperative bleeding. Borges et al. report a case of recurrent subclinical intratumoral bleeding occurring in a recurrent SCO [8]. In the same manuscript, Borges reports that 29% of 28 case reports reviewed noted excessive intraoperative bleeding and 46% of cases noted the tumor to be highly vascular intraoperatively [8]. There were also three cases of spontaneous tumor hemorrhage.

Careful tumor dissection and strategic use of cottonoids with hemostatic agents is crucial when dealing with any tumor of the posterior pituitary gland, especially SCO.

In addition to that, SCOs have a significant risk of progression or recurrence because of the adherent nature of the tumor. In a study by Hasegawa et al., it was found that GTR was only achieved in 24% of cases mainly because of those tumor features [5]. These characteristics make recurrence of SCOs very likely, with 50% of tumors showing significant progression if GTR is not achieved and radiotherapy is not added [5].

There are also case reports of SCOs managed trans-cranially. In fact, in cases with extensive suprasellar extension, this approach may provide more intraoperative maneuverability to deal with excessive bleeding and better access to adherent areas of tumor.

In cases of recurrent tumor or growth of residual tumor after subtotal resection, patients should seek multidisciplinary management, with consideration given to both reoperation and possible radiation therapy.

The role of preoperative radiotherapy is still being debated; Hasegawa et al. found in their meta-analysis that preoperative radiotherapy did not have an impact on those who achieved GTR [5]. There was also no statistical difference between the non-GTR group that received preoperative radiotherapy and the non-GTR group that did not receive preoperative radiotherapy. However, in patients who do not achieve GTR, postoperative radiotherapy should be considered as it has shown promising results in controlling tumor progression [9].

In our review of literature (Table 1), we analyzed every case that has been reported in literature which now totals 98. We found the mean age to be fifty-seven and forty-seven patients were female and fifty-one were male. Of particular importance, we found that out of 98 cases of SCO, there was recurrence or tumor growth in almost 25% of patients, highlighting the importance of continued surveillance with these tumors. Also, recurrence was even found in cases that appeared to achieve GTR. Many of the reports noted how partial resection was all that could be achieved due to the highly vascular nature of the tumor.

Regarding the use of adjuvant radiotherapy, we found that 11 cases utilized radiotherapy postoperatively and nine of those cases had follow up information that showed no recurrence or progression. The remaining two cases had recurrence/progression which required further treatment. Five of the cases that utilized adjuvant radiotherapy were in the report by Akyoldasa et al. which showed all the tumors to be stable at 51 months, the average follow-up [10]. This information on radiotherapy after surgery shows that it has the potential to be very useful in achieving tumor stability and decreases the chances of progression and need for further operations.

Our case specifically highlights the importance of being aware of the high vascularity of these tumors due to their increased risk of bleeding during surgical resection. If a SCO is suspected/identified, measures can be put into place to prepare for increased bleeding, such as careful tumor dissection and strategic use of cottonoids with hemostatic agents in addition to blood products typed and matched if they are needed. Special consideration is also needed regarding the follow-up plan for patients with SCO due to their increased rate of recurrence.

4. Conclusions

SCOs are rare tumors of the posterior pituitary gland that have many unique features that require specific treatment and follow up. Although this tumor presents similarly to a pituitary adenoma there are marked differences in physical appearance of the tumor, IHC, and follow-up required. From a surgical perspective, the challenge is related to higher vascularity and stronger adherence to the surrounding structures. This makes the surgery itself more difficult and a GTR less likely, with higher recurrence rate.

To date, the use of radiotherapy has not been well established. Although our review only provides a small sample size of patients that received postoperative radiotherapy it did show promising results in those patients.

In our opinion, radiotherapy is definitely something that should be considered, especially when GTR is not achieved. In our case, a GTR was achieved thus we decided to proceed without radiotherapy and with closer follow up appointments to identify any early sign of recurrence.