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. 2026 May 11;54:101259. doi: 10.1016/j.bbih.2026.101259

Sellar-parasellar Epstein-Barr virus associated smooth muscle tumour mimicking a pituitary adenoma: A case report

E Saravanakumar a,⁎, A Vastani b, A Merve c, R Nair b, JM Das b
PMCID: PMC13234261  PMID: 42253620

Abstract

Epstein-Barr virus-associated smooth muscle tumours (EBV-SMTs) are rare mesenchymal neoplasms. These tumours almost exclusively occur in immunocompromised individuals, with the three main causes being Human Immunodeficiency Virus (HIV), post-organ transplantation immunosuppressants and congenital immunodeficiency. We report the case of an intracranial Epstein-Barr virus-associated smooth muscle tumour in a 54-year-old male with a long-standing history of HIV and immunosuppression. This tumour originated in the sellar region and extended into the cavernous sinus. To the authors’ knowledge, this is the fourth reported case of a sellar EBV-SMT. Diagnosis is dependent on histopathological analysis and despite having an indolent course, EBV-SMTs with central nervous system invasion are likely to cause neurological deficits, which can hinder survival and quality of life.

Keywords: EBV-SMT, Epstein-Barr, HIV, Parasellar, Sellar, Intracranial

Highlights

  • •

    An Epstein-Barr virus-associated smooth muscle tumour (EBV-SMT) was found in the sella of a 54-year-old male.

  • •

    This is the fourth reported case of such location and tumour type and the first reported case not involving surgical resection.

  • •

    Central nervous system EBV-SMTs currently have no established treatment plan, due to their rarity.

1. Introduction

Epstein-Barr virus-associated smooth muscle tumours (EBV-SMTs) are rare mesenchymal tumours that almost exclusively occur in immunocompromised patients. Over 95% of patients with EBV-SMTs are immunocompromised. The most common causes of this are Human Immunodeficiency Virus (HIV) infection and immunosuppressants used in post-organ transplantation (Lau et al., 2021). Epstein-Barr virus is a double stranded DNA virus that infects over 90% of the world population at some point in their lifetime (Luzuriaga and Sullivan, 2010). It is the root cause of a variety of conditions, including infectious mononucleosis, lymphoproliferative disorders and epithelial tumours. EBV-SMTs can occur in a range of unusual locations, and those associated with HIV tend to occur in the gut, liver, skin, lungs, larynx, pharynx, adrenal glands and the central nervous system (CNS) (Hussein et al., 2014). There are roughly 30 reported cases of EBV-SMTs with solely intracranial CNS invasion in the literature, making it a rare complication of HIV (Lau et al., 2021; Yokoyama et al., 2020; Paez-Nova et al., 2021; Barrett et al., 2022; Alfalahi et al., 2024). EBV-SMTs often present with multiorgan involvement as a result of multiple infection sites as opposed to metastasis (Deyrup et al., 2006).

Here, we present the case of a 54-year-old adult male diagnosed with an Epstein-Barr virus-associated smooth muscle tumour originating in the sellar region with a background of HIV. Unlike leiomyosarcomas, which are rarer, more aggressive smooth muscle tumours, EBV-SMTs have a comparably indolent growth pattern. This is the fourth known case of a sellar EBV-SMT (Lau et al., 2022; Pitjadi and Grayson, 2019) and is presented to highlight the capabilities of an EBV-SMT to invade the central nervous system, as in this case, and cause neurological deficits which could impact overall survival and quality of life.

2. Case

A 54-year-old man was referred to the neurology outpatient department with subacute blurry vision followed by diplopia in the right eye. He had hepatitis B and thrombocytopenia alongside a seventeen-year history of HIV with immunosuppression, and a viral load of 3,970 copies per millilitre. This was due to non-adherence to antiretroviral medication. On examination, he was found to have HIV retinopathy changes, a subtle right-side ptosis and mild impairment in right eye adduction. He was diagnosed with a partial non-painful pupil sparing right-sided oculomotor nerve palsy.

CT cerebral angiography was performed at this stage to investigate whether a posterior communicating artery aneurysm was behind the oculomotor nerve palsy but appeared normal. On magnetic resonance imaging (MRI), a 10× 6 mm lesion in the sellar region, mistaken as a non-functioning pituitary microadenoma, was seen. This was later found to be an EBV-SMT. Blood results showed no evidence of pituitary hormone hyper or hyposecretion. He was managed conservatively and kept under surveillance at this stage.

Four months later, the patient presented with right-sided retro-orbital pain, a right abducens nerve palsy with left horizontal gaze-evoked nystagmus and a dilated reactive right pupil. The previous oculomotor nerve palsy had resolved, and pupils remained reactive. No limb weakness was noted, however, there was reduced V1-3 sensation in the right side of the face. A non-contrast MRI scan of the head showed a 9 mm right-sided cavernous sinus lesion, extending into the superior orbital fissure antero-posteriorly. The patient subsequently developed right-sided secondary cluster headaches, which responded well to high flow oxygen and sumatriptan.

Four months after this, the patient developed a complete right-sided ptosis, partial left ptosis and recurring severe retro-orbital eye pain attacks. On contrast MRI imaging of the brain, there was interval enlargement and dorsal extension of the solid, T2 hypointense cavernous sinus lesion. Mild-moderate increased perineural cerebrospinal fluid space enlargement around the right optic nerve was also noted. Within the subsequent year, on surveillance, the lesion measured 15mm transversely and 27mm antero-posteriorly (Fig. 1). A new separate lesion was imaged on MRI located in the floor of the right temporal fossa. This appeared to be dural-based, attached to the skull with possible bony involvement.

Fig. 1.

Fig. 1

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Lesion Imaging: (A) Contrast T1-weighted MRI scan, axial view of the right-sided sellar lesion extending into the right-side cavernous sinus. (B) Contrast T1-weighted MRI scan, coronal view showing lateral extension of the right-sided sellar lesion. (C) Contrast T1-weighted MRI scan, sagittal view showing antero-posterior extension of the right-sided sellar region.

Since the sellar lesion was expanding and a new lesion started appearing, his scans were discussed in the skull base multidisciplinary team meeting and it was advised to perform a diagnostic biopsy of the larger sellar-parasellar lesion. Under the ear, nose and throat (ENT) surgical team, the patient underwent an exploration under anaesthetic of the right nasal cavity with sphenoidotomy. A pulsatile mass with a widespread doppler signal was found. The tumour was deemed unsafe to biopsy due to the high risk of internal carotid artery injury and on-table mortality. The planned biopsy was aborted, and he was referred to the neurosurgical team.

Subsequently he underwent a neuronavigation-guided endoscopic endonasal trans-sphenoidal approach via the right nostril for biopsy one month later. Upon opening the dura, a firm, dull white lesion was found, and multiple biopsies were taken from the sella.

The pathological (histological, immunohistochemistry and molecular) analysis of the tumour found it to be an EBV-associated smooth muscle tumour (Fig. 2) (Watanabe et al., 2020).

Fig. 2.

Fig. 2

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Tumour pathology: (A) Histologically this is a cellular tumour comprising spindle shaped neoplastic cells displaying moderate cytological atypia, with occasional mitoses. (B) Immunohistochemistry demonstrated tumour cells diffusely positive for smooth muscle actin (SMA), and negative for glial (GFAP) or neural (S100) markers (not shown). (C) There was moderate Ki67 proliferation index, estimated at 8-10%. The tumour cells showed diffuse positivity for Ebstein Barr Virus (EBV) staining (not shown). Based on the combined findings, the conclusion by the soft tissue/sarcoma specialist histopathologists is an EBV-associated smooth muscle tumour. (D) The methylation array analysis on sarcoma classifier v12.3 returned the tumour classification of Leiomyosarcoma with a high calibrated score of more than 0.9. The copy number plot showed no significant chromosomal alterations. Further, the DNA and RNA next generation sequencing (NGS) showed no actionable gene variants or relevant gene fusions. Abbreviations: SMA – Smooth Muscle Actin; Ki67 – immunohistochemistry marker for cell proliferation. Magnification: A-C scale bar = 250 μm.

Symptoms continued to worsen over the following three months with complete ophthalmoplegia in the right eye and reduced sensation in V1 and V2 area of the face. He was further discussed in a neuro-oncology multidisciplinary team meeting and given the fact that both lesions were continuing to increase, a six-week course of radiotherapy was suggested. There was no follow up surgery. Surgical resection was not opted for due to the location and extension of the tumour into the cavernous sinus and his persistent thrombocytopenia status. Three months after the start of his radiotherapy course, the patient passed away due to unrelated causes.

3. Discussion

Epstein-Barr virus-associated smooth muscle tumours belong to a rare subset of spindle cell tumours. There are three major known subtypes of EBV-SMT: Human immunodeficiency virus associated (HIV-SMT), post-transplantation associated (PTSMT), and congenital immunodeficiency associated (CI-SMT) (Hussein et al., 2014). These are based on the most common causes of EBV-SMTs. Out of the reported EBV-SMTs with CNS invasion, HIV is the most common cause, accounting for 63% of these tumours (Lau et al., 2021). The exact prevalence of EBV-SMTs in the HIV-infected population is not known but estimated to be less than 1-5%, making this a rare complication of HIV (Hussein et al., 2014). From the limited available literature, EBV-SMTs are 60% more likely to occur in females, with a median age of 35 years (Willeke et al., 2020). Out of the limited cases reported on EBV-SMTs, CNS invasion is the highest reported location (Purgina et al., 2011).

There are two main hypotheses surrounding how the Epstein-Barr virus enters and causes tumorigenesis in smooth muscle cells. The first involves CD21, a receptor found on smooth muscle cells. EBV can bind to these receptors, thus providing a potential entryway for EBV into these cells (McClain et al., 1995). The presence of CD21, has not been found on all EBV-SMTs, however, and attempts to highlight the presence of CD21 on post-transplantation EBV-SMTs are yet to succeed (Lee et al., 1995). Therefore, this is unlikely to be the sole path of entry. The expression of CD21 has also been found to be higher in the cells of smooth muscle tumours in AIDS patients when compared to smooth muscle tumours in those without AIDS (McClain et al., 1995). This could signify an amplification of the receptor for EBV in AIDS patients on smooth muscle cells. The second proposed theory arises from the presence of lymphocytes intratumorally in EBV-SMTs. This theory suggests that prior to tumorigenesis there is a fusion event between EBV-infected B lymphocytes and potentially smooth muscle cells (Bayliss and Wolf, 1980). An increase in the copies of genes involved in viral infection response was found in EBV-SMTs, indicating this immune-response environment may have triggered tumour transformation (Wah et al., 2023). However, this theory is also disputed. One study found that most of the lymphocytes were CD3+ and CD8+, and negative for the EBV-encoded small RNAs (EBER), so may have been present as part of the immune response as opposed to tumorigenesis (Soares et al., 2019). Following the entry of EBV into the smooth muscle cells, the agreed hypothesis on proliferation is where EBV-LMP2A initiates the reactivation of the Akt/mammalian target of rapamycin (mTOR) signalling pathway which leads to the overexpression of the MCY. This is what drives cellular proliferation and, in turn, tumorigenesis (Ong et al., 2009).

The diagnosis of an EBV-SMT can only be made upon histopathological analysis. Due to their rarity, they are often misdiagnosed as meningiomas, based on radiological imaging. Computer-topography imaging would show both a meningioma and an EBV-SMT to be iso-attenuating and dural based. T1 imaging would show hypo to isointense lesions and T2 would show iso to hyperintense lesions (Smith et al., 2014). In our patient, the initial leading differential diagnosis was deemed to be a non-functioning pituitary adenoma. There are some aspects of this case which point towards an alternate diagnosis, such as the rapid growth and invasion of the tumour into the cavernous sinus and beyond. A significant growth rate is yet to be defined and tends to vary depending on patient and tumour-specific characteristics (Raverot et al., 2018). However, it has been said that non-functioning pituitary adenomas become less likely where volumetric growth rates are beyond 1.00cm3/year (Hwang et al., 2019).

The cavernous sinus area has been reported as the most common intracranial location for EBV-SMTs (Lau et al., 2021). It has been postulated that this is due to the hypervascularity of the cavernous sinus, providing a source of vascular smooth cells for an EBV-SMT (Yokoyama et al., 2020). In our case, the tumour originated in the sellar region, which is also known for its hypervascularity. Therefore, the vascular smooth cells in the sella could also provide a source of origin for the EBV-SMT. Two of the three previous pituitary cases did not provide clinical presentations or treatment follow-up (Pitjadi and Grayson, 2019). Similarities between our case and Lau et al.‘s (2022) are that a third nerve palsy occurred in both patients (Lau et al., 2022). However, there was no evidence of hormone hypersecretion in our case whilst Lau et al. (2022) reported hyperprolactinaemia causing secondary amenorrhea, where management involved a biopsy followed by surgical debulking.

There is currently no fixed treatment for CNS EBV-SMTs. One systematic review reported that treatment for all EBV-SMTs with CNS invasion involved surgery (Lau et al., 2021). Those with intracranial CNS involvement only had an increased survival with total surgical resection when compared to sub-total resection (Lau et al., 2021). Boosting immunity through increasing antiviral treatment in HIV/AIDS and adjusting immunosuppressant medication post-transplantation patients is also an integral part of treatment (Hussein et al., 2014). The aforementioned, mTOR pathway believed to be involved in the pathogenesis of EBV-SMTs is being investigated for targeted therapy. Sirolimus, an mTOR inhibitor, has been reported to control disease and regression in EBV-SMT (Toh et al., 2006). A 1-year survival rate of 76% and 5-year survival rate of 60% has been determined for EBV-SMTs with CNS invasion (Lau et al., 2021), highlighting the indolent nature of a CNS EBV-SMTs.

4. Conclusion

This is a rare case of an Epstein-Barr virus-associated smooth muscle tumour originating in the sellar region. Having been mistaken for a pituitary adenoma, this case highlights the importance of patient immunocompetency status when looking at intracranial lesions. Despite no fixed regulations surrounding treatment, improving immunity and surgical resection are key considerations alongside adjuvant therapies. The differential diagnosis of an intracranial lesion in a HIV positive patient should include an Epstein-Barr virus-associated smooth muscle tumour with further therapeutic and diagnostic research needed to improve clinical management of these tumours.

CRediT authorship contribution statement

E. Saravanakumar: Conceptualization, Writing – original draft, Writing – review & editing. A. Vastani: Supervision, Writing – review & editing. A. Merve: Writing – original draft. R. Nair: Supervision. J.M. Das: Conceptualization, Supervision, Writing – review & editing.

Declaration of competing interest

The authors declare that there is no known conflict of financial or personal interests that could have appeared to influence the work reported in this case report titled ‘Sellar-parasellar Epstein-Barr virus associated smooth muscle tumour mimicking a pituitary adenoma: a case report’ written by Elakya Saravanakumar et al.

Acknowledgements

Acknowledgements to Dr Fernanda Amary and Dr Roberto Tirabosco from RNOH pathology team for their specialist sarcoma pathology review/opinion.

Contributor Information

E. Saravanakumar, Email: elakya.saravanakumar22@imperial.ac.uk.

A. Vastani, Email: a.vastani@nhs.net.

A. Merve, Email: amerve@nhs.net.

R. Nair, Email: ramesh.nair@nhs.net.

J.M. Das, Email: joe.mariadas@nhs.net.

Data availability

No data was used for the research described in the article.

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Data Availability Statement

No data was used for the research described in the article.

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