Incidental High-Grade Sellar Solitary Fibrous Tumor Mimicking Non-Functioning Pituitary Adenoma: A Case Report and Literature Review

Introduction

Originally described by Stout and Murray in 1942, intracranial solitary fibrous tumors (SFT) are particularly rare tumors historically thought to originate from the pericytes layering dura mater capillaries [1]. The classification and cellular origin of central nervous system (CNS) SFT have been the subject of debate and evolved over decades [2–4]. Because of their presumed origin from the pericytes of meningeal capillaries and similar histological traits to meningiomas, SFTs have been mistakenly considered for years to originate from the meningothelial tissue [5,6]. In the 1980 World Health Organization (WHO) classification of CNS tumors (1st edition), SFTs were considered as a variant of meningiomas (“hemangiopericytic meningiomas” or “angioblastic meningioma”) [6]. Further immunohistochemical, genetic, and electron microscopy studies have established hemangiopericytoma (HPC) as a separate tumor entity [7,8]. As such, in the 1993 WHO classification of CNS tumors (2nd edition), HPCs were recognized as their own class within the mesenchymal-nonmeningothelial tumor category [2]. Since the 2021 CNS WHO classification, the historical term hemangiopericytoma has been retired, with the tumor now termed only SFT, to align with the soft tissue tumor subcategory of fibroblastic and myofibroblastic tumors [4,9]. Grading of these tumors has also evolved, though grading of CNS SFTs remains unique from their extracranial counterparts [10]. Presently, CNS SFTs are graded as CNS WHO grade 1, 2, and 3, with SFT grades 2 and 3 replacing the old nomenclature of hemangiopericytoma and anaplastic hemangiopericytoma, respectively (Table 1) [4,9,11]. Under the 2021 CNS WHO guidelines, grades are now reported using Arabic as opposed to Roman numerals [4]. In this manuscript, we retain references to older terminology and the Roman numeral classifications given that the described case and historical cases were reported under older classification schemes.

WHO grade II and III SFTs (SFT II/III) account for 0.4% of primary CNS tumors [12]. Approximately one-third of SFTs II/III occur in the head and neck [13]. Among the intracranial hemangiopericytomas, 60% occur in the skull base and 26% in the falx or parasagittal area [14, 15]. Hemangiopericytomas located in the sella turcica region are extremely rare. Considering also the current article, since the first case in 1983, only 23 case reports of sellar and/or suprasellar SFT II/III have been reported [16–38] (Table 2).

In the current report, the authors describe the case of a 62-year-old woman with encephalopathy and a sellar SFT presenting as a non-functioning pituitary mass. This is an uncommonly reported case of sellar WHO grade III SFT presenting as an incidentally detected tumor.

Case Report

A 62-year-old woman with encephalopathy and severe urosepsis was transferred from an outside hospital to Emory University Hospital (EUH) for neurosurgical evaluation of a sellar/suprasellar mass (Figure 1A, 1B). The mass was originally identified as an incidental finding on computed tomography (CT) of the head without intravenous contrast during another hospitalization for decreased alertness secondary to urosepsis 2.5 months prior.

At EUH, a magnetic resonance imaging (MRI) of the brain with and without contrast showed a complex heterogeneous solid and cystic 2.1×2.3×2.9 cm sellar mass with central T2-sequence hyperintensity and T1-sequence isointensity that extended rostrally into the suprasellar space with a mass effect upon the optic chiasm (Figure 1C). Because of the patient’s presenting encephalopathy, a review of systems to investigate for headache and vision changes was deferred. An endocrine workup was otherwise unremarkable, except for primary hypothyroidism secondary to a past surgical history of thyroidectomy, and a presumed diagnosis of non-functioning pituitary adenoma (NFPA) was made.

Consequently, a partial resection was recommended and performed through a trans-nasal trans-sphenoidal adenectomy. The gross morphologic presentation was of a highly vascular tumor infiltrating the dura, rather firm and adherent to the sella wall and undersurface of the suprasellar diaphragm. The tumor bleeding was brisk after resection. Specimens of a tan-to-red or pink-tan soft tissue were sent out for pathologic evaluation. The hematoxylin and eosin (H&E) stain revealed a markedly cellular mesenchymal neoplasm exhibiting morphology characteristic of a solitary fibrous tumor, with haphazardly arranged spindled to epithelioid cells set in a variably collagenized background aside dilated, tortuous vasculature (Figure 2A). High magnification images depicted 12 mitotic figures counted in 10 high-power fields, consistent with a high mitotic index and higher grade tumor (Figure 2B).

Immunohistochemistry (IHC) showed nuclear positivity for the Signal Transducer and Activator of Transcription 6 (STAT6) (Figure 2C), a reliable surrogate marker for the NFGI-A Binding Protein 2 (NAB2)-STAT6 fusion characteristic of SFT. Additional immunostains for cytokeratin AE1/3, Sry-related HMg-Box gene 10 (SOX10), synaptophysin, thyroid transcription factor 1 (TTF1), and somatostatin receptor 2A were negative. At EUH, the diagnosis and grading of this tumor type are governed by the CNS WHO guidelines, most recently revised in 2021 [4]. Per these guidelines, the pathological diagnosis was of an anaplastic hemangiopericytoma, WHO grade III (now regarded as an SFT).

Following surgery, the patient developed hypocortisolism requiring hormonal replacement with hydrocortisone. The follow-up MRI 5 days after surgery revealed a residual enhancing tumor extending along the posterior margin of the resection (Figure 3). Because of the final pathologic diagnosis, adjuvant treatment was initiated with proton therapy to the dose of 59.4 gray (Gy) given in 33 fractions (1.8 Gy/fraction) to the gross disease with a 3 mm clinical target volume margin. The residual tumor demonstrated shrinkage at follow-up one and a half years after proton therapy (Figure 4). Three years after proton therapy, there was no evidence of recurrent disease on serial imaging (Figure 5).

Discussion

This report describes a 63-year-old woman with encephalopathy secondary to urosepsis, incidentally found to have a sellar mass after imaging was ordered to investigate the altered mental status. The case illustrates that high-grade sellar SFTs can present without symptoms, as incidentalomas. In addition, the original working diagnosis was of an NFPA until pathology evaluation proved the SFT diagnosis. This case highlights that sellar SFTs can be misdiagnosed as NFPAs based on presentation and imaging findings. Pathological evaluation is essential for the final diagnosis. To expand on this clinical evidence that may guide clinical practice, the following is a comparison of the previously described case with the reported sellar and/or suprasellar SFTs II/III cases between 1983 and 2024, and an in-depth analysis of the epidemiological, clinicopathological, and radiological aspects of these cases and how they differ in management and prognosis from NFPAs.

SFT II/III incidence in 2016 was 0.060 per 100 000 individuals, with a slighter higher frequency in females (53.1%) than males (46.9%), and in the White population (81.3%) [39]. The mean age of onset is 55.1 years old [39]. Sellar and/or suprasellar SFT II/III reflects similar epidemiology, with 12 of 23 cases reported in the literature occurring in females (Table 2). Interestingly, the mean age of onset is nearly a decade earlier, at 48 years old (Table 2).

Clinically, sellar and/or suprasellar SFT II/III can present as asymptomatic incidentalomas, as in this reported, or with compression symptoms related to the tumor location (Table 2). Headache, visual field defects, and anterior hypopituitarism-related symptoms are frequent chief complaints (Table 2). Unsteady gait secondary to visual deficits is also possible [26,27]. Some cases of sellar and/or suprasellar SFT II/III present with mild prolactin (PRL) elevation, most likely secondary to pituitary stalk compression, and without overt clinical findings of hyperprolactinemia, as opposed to prolactinomas [18,19,29,34]. This presentation closely resembles NFPA, the most common sellar mass in adults [40, 41]. As such, almost all cases of sellar and/or suprasellar SFT II/III had a pre-biopsy working diagnosis of NFPA (Table 2). About 50% of sellar and/or suprasellar SFT II/III are reported to a physician after 1–3 months of developing symptoms, whereas a minority presented after 1 year of symptoms onset (Table 2). More rarely, intracranial SFT II/III presents with hypoglycemia [42]. This finding is thought to be a paraneoplastic syndrome related to the production and secretion of insulin-like growth factor [42]. A similar case has yet to be described for sellar and/or suprasellar SFT II/III.

On MRI, sellar and/or suprasellar SFT II/III morphology is of a lobulated, solid-cystic tumor with hypo-to-isointense signal intensity on T1-weighted imaging and iso-to-hyperintense signal intensity on T2-weighted imaging, with heterogeneous or homogeneous dense enhancement on contrast-enhanced MRI (Table 2). Heterogeneous contrast enhancement raises higher suspicion for an SFT compared to an NFPA [43]. SFT II/III shows enhancement from an early stage in dynamic MRI studies, unlike what is observed with pituitary adenomas [19]. Pituitary adenomas appear as relatively hypoenhancing (dark) lesions within an intensely enhancing pituitary gland 30–60 seconds after contrast injection [44], with peak enhancement of the pituitary adenomas after 60 seconds [45]. However, as dynamic MRI studies are not yet standard practice for managing sellar masses, distinguishing SFTs II/III from pituitary adenomas based solely on imaging remains challenging, and surgical biopsies are necessary for a definitive diagnosis [19].

Surgical reports of sellar and/or suprasellar SFTs II/III, including this case, describe a unifying and characteristic trait of a highly vascular tumor adherent to the surrounding dura that bleeds profusely after resection [18,19,23,26–28]. The bleeding is oftentimes uncontrolled and limits sellar mass excision [30,33,34]. These characteristics differentiate SFTs II/III from a typical pituitary adenoma. Neurosurgical gross morphology descriptions or imaging reveal that sellar and/or suprasellar SFTs II/III oftentimes displace or compress the optic pathways, with ~50% of sellar and/or suprasellar SFTs II/III cases described in the literature compressing the optic chiasm (Table 2). This finding correlates with visual disturbances being the most frequent chief concern at presentation (Table 2). Compression of the optic chiasm without associated symptoms, as demonstrated in this case, is also possible (Table 2). In a minority of cases, the pituitary gland is compressed, leading to hypopituitarism, the dural sinuses are invaded, with the cavernous and sphenoid sinuses being the most commonly involved, and the internal carotid or anterior cerebral arteries are encased (Table 2).

Sellar and/or suprasellar SFTs WHO grade II and III are equally reported in the literature (Table 2). Under current CNS WHO guidelines, CNS WHO grade 2 SFT displays a mitotic activity of ≥5/10 HPF and no tumor-type necrosis [4]. CNS WHO grade 3 SFT exhibits mitotic activity of ≥5/10 HPF as well as necrosis (Table 1) [3, 4, 10, 46]. One reported case of lipomatous sellar hemangiopericytoma presented also with mature adipose tissue scattered throughout the tumor section [23]. Noticeably, the 2020 WHO Classification of Soft Tissue Tumors categorizes fibroblastic and myofibroblastic tumors based on a clinicopathological grading in low-risk, intermediate-risk or high-risk tumors [47–49]. SFTs are classified as tumors of intermediate grade, with subcategories of “locally aggressive” and “rarely metastasizing” [47–49]. The WHO 2021 Classification of Tumors of the CNS does not follow the same risk classification-based framing for its grading criteria, grading SFTs as CNS WHO grades 1, 2, and 3 as described above [4,9,10].

The genetic hallmark of SFT at all anatomical sites is paracentric inversions at 12q13, fusing the NAB2 and STAT6 genes, with consequent nuclear expression of STAT6 [50,51]. CD34 also may be positive in SFT II/III [52]. Including the current case, sellar and/or suprasellar SFT II/III presents strong nuclear STAT6 expression and CD34 positivity on IHC [21,27]. Some cases of SFT II/III do not exhibit CD34 expression; for instance, the aforementioned case of sellar lipomatous hemangiopericytoma demonstrated negativity for CD34 on IHC [23].

Sellar and/or suprasellar SFTs II/III are generally managed with gross resection (Table 2), though a case of spontaneous resolution due to tumor necrosis has also been reported [32]. The highly vascular nature of this tumor is responsible for profuse bleeding on resection and, consequently, complete excision is challenging [30,33,34]. Moreover, SFTs II/III have a higher propensity than SFT I for recurrence, local invasion, and metastasis which sometimes occur years after the initial diagnosis [14,53,54]. For instance, a case of spinal metastases was reported 7 years after the initial diagnosis of a high-grade sellar solitary fibrous tumor [36]. Adjuvant radiotherapy (RT) or radiosurgery may be selected to treat residual SFT II/III after surgery and/or reduce the risk for recurrence (Table 2). Among the sellar SFT II/III cases reported in the literature, RT has been used at a dose range of 50–60 Gy in 25–33 fractions (Table 2). Four case reports described no evidence of tumor recurrence after RT treatment, highlighting the role of adjuvant RT in decreasing the risk for sellar and/or suprasellar SFT II/III recurrence [27,30,38,39]. In our case, proton therapy was given at the dose of 59.4 Gy in 33 fractions. A follow-up MRI one and a half years after proton therapy showed a decrease in the size of the sellar mass. Whereas surgery and adjuvant RT are the goal of care for adult intracranial SFT II/III, there is conflicting evidence for adjuvant radiation therapy in children [20]. Ghanci et al suggested a potential benefit to adjuvant radiation therapy below 50 Gy, though further investigations are needed [20].

SFTs II/III management differs from NFPA therapeutic approaches. NFPAs are typically monitored with MRI every 6 months, unless amenable to resection [55, 56]. Surgical intervention is warranted in cases of headache, visual disturbances, neurological deficits, hormonal deficiencies, and asymptomatic chiasmal compression [55–57]. Postsurgical RT is limited due to long-term side effects, and reserved for NFPAs with postoperative enlarging tumor remnants and in cases of cavernous sinus invasion not surgically resectable [55–57]. Therefore, obtaining an accurate and definitive diagnosis for sellar masses suspected to be neoplastic is crucial to defining treatment plans.

Conclusions

This is an uncommon case of sellar and/or suprasellar SFT WHO grade III that presented as an incidentaloma. Because only 22 cases of sellar SFT II/III have been described since 1983, these reports need to be documented. Our case highlights the importance of accurate histological evaluation of sellar masses. Sellar and suprasellar SFTs can present with clinical and imaging presentations overlapping those of pituitary adenomas. However, their management and prognosis may differ due to the potential for local invasion, metastasis and recurrence. Hence, it is crucial to include SFT among the pre-biopsy differential of sellar and/or suprasellar masses identified on imaging. Resection to the maximum extent, and pathologic confirmation guide the need for radiotherapy, imaging follow-up, and re-resection of these sellar tumors.