Solitary thoracic Epstein-Barr virus–associated smooth muscle tumor presenting after kidney transplant: illustrative case

Abstract

BACKGROUND

Epstein-Barr virus–associated smooth muscle tumors (EBV-SMTs) are rare neoplasms that primarily occur in the setting of immunosuppression from HIV/AIDS, solid organ transplant, or congenital/primary immunodeficiencies. The majority of posttransplant patients present with multifocal disease; however, solitary spine tumors can occur at initial presentation.

OBSERVATIONS

The authors present the case of a solitary spinal EBV-SMT presenting 1 year after a renal transplant.

LESSONS

Although EBV-SMTs are a rare entity, they should be considered in the differential diagnosis of solitary spine tumors in immunocompromised or immunosuppressed patients.

https://thejns.org/doi/10.3171/CASE25754

Epstein-Barr virus (EBV)–associated smooth muscle tumors (SMTs) are rare neoplasms that primarily occur in immunocompromised individuals.^1,2 EBV-SMTs can present as solitary or multiple tumors, most commonly occurring in the liver, lungs, adrenal glands, kidney, and CNS.³ EBV-SMT pathogenesis is attributed to EBV-encoded proto-oncogenes, which inhibit apoptosis, enable immune evasion, and enhance cellular proliferation.⁴ Histological features include relatively monomorphic spindled nuclei, chronic inflammatory infiltrates, hemangiopericytoma-like vasculature, and variable immunoreactivity for smooth muscle actin (SMA), h-caldesmon, and desmin.⁵ In situ hybridization is the gold standard for diagnosing EBV-SMTs by identifying EBV RNA within tumor cells.⁶ Molecular techniques such as polymerase chain reaction can also be utilized to support a diagnosis by identifying EBV DNA in tumor cells or serum.

EBV-SMTs occur due to EBV infection in the setting of T-lymphocyte suppression and are exclusively reported in immunosuppressed patients.^7–12 Adult EBV-SMTs mostly occur in the setting of acquired immunodeficiency due to HIV infection or posttransplant immunosuppression, while in children, they also occur due to primary immunodeficiency.^13,14 In the setting of posttransplant immunosuppression, the majority of EBV-SMTs occur in the liver, lungs, or gastrointestinal tract.¹⁵ Spinal EBV-SMTs are exceptionally uncommon in posttransplant patients, with only 4 cases previously reported in the literature (Table 1).^16,17 In all 4 cases, tumors occurred at multiple discrete sites throughout the body. We describe the case of a 43-year-old male who presented with thoracic numbness, back pain, and lower extremity weakness 1 year after a kidney transplant for end-stage renal disease (ESRD). He was found to have a solitary T6 epidural mass diagnosed as an EBV-SMT. This case highlights the importance of considering EBV-SMTs in the differential diagnosis for spine tumors in immunosuppressed patients.

TABLE 1.

Literature review of previously reported cases of spinal EBV-SMTs in patients after kidney transplant

Authors & Year	No. of Cases	Age (yrs), Sex	Locations	Multiplicity	Tissue Diagnosis	Presenting Sx	Primary Tx	Adjuvant Tx	Complications	Initial Immunosuppression	Change to Immunosuppression	Outcome
Lau et al., 202216	1	27, F	Liver, pituitary lesion w/ bilat cavernous sinus invasion, bladder, C5 vertebral lesion	Yes	EBV-SMT	Lymphadenopathy, amenorrhea, incomplete 3rd nerve palsy, lt superior temporal quadrantanopia, pathological Fx due to vertebral lesion	C5 corpectomy, bilat neck dissection	NR	None	Kidney transplant, immunosuppressive regimen not defined	Not specified	NR
Tan et al., 201317	1/3	NR	Airway w/ multiple pulmonary lesions & an extradural lesion at T5–6	Yes	EBV-SMT	NR	Partial resection & discontinuation of azathioprine	None	NR	Kidney transplant on cyclosporine, prednisolone, azathioprine	Continued low-dose cyclosporine & prednisone	Died of sepsis at 42 mos
	2/3	NR	Pulmonary, liver & spine	Yes	EBV-SMT	NR	Discontinued azathioprine	None	NR	Kidney transplant on cyclosporine, prednisolone, azathioprine	Continued low-dose cyclosporine & prednisone	Alive at 9 yrs
	3/3	NR	Rt femur, spine	Yes	EBV-SMT	NR	Partial resection (unclear which lesion)	None	NR	Not on immunosuppressants	NA	Died of cardiac cause at 7 mos
Present case	1	43, M	T5–7 extradural lesion	No	EBV-SMT	BLE & abdominal numbness, BLE weakness, gait instability	T6 laminectomy & lt transforaminal approach for gross-total resection w/ T5–7 pedicle screw fixation	None	None	Kidney transplant on MMF, tacrolimus, prednisone	Discontinued MMF; tacrolimus dose lowered; started low-dose sirolimus & continued prednisone	Full strength in BLE, improved gait

BLE = bilateral lower extremities; Fx = fracture; NA = not applicable; NR = not reported; Sx = symptoms; Tx = treatment.

Illustrative Case

A 43-year-old male patient presented to the emergency department with 6 weeks of progressive bilateral lower extremity and abdominal numbness and approximately 1 week of bilateral lower extremity weakness and gait instability requiring a walker. Of note, the patient had presented to the emergency department 1 week prior with lower extremity and abdominal cramps, which were attributed to recent initiation of calcitriol and cholecalciferol. His past medical history included hypertension, gastritis, and ESRD for which he had undergone a renal transplant 1 year prior to the current presentation and was taking mycophenolate (MMF), tacrolimus, and prednisone. Neurological examination was notable for a T6 sensory level and bilateral lower extremity spasticity.

MRI of the thoracic spine demonstrated an enhancing extradural mass in the spinal canal spanning T5–7, compressing the spinal cord and extending through an enlarged left T6 neural foramen (Fig. 1A and D). CT of the chest/abdomen/pelvis was performed as part of a metastatic workup, which did not demonstrate any additional soft tissue or bony lesions. A dedicated CT scan of the thoracic spine was also obtained to better visualize the patient’s bony anatomy, which showed a noncalcified mass and dilated left neural foramen due to the tumor (Fig. 1E and F).

FIG. 1.

Preoperative T1-weighted postcontrast sagittal (A) and axial (B) MR images. Preoperative T2-weighted sagittal (C) and axial (D) MR images showing a T2 hyperintense, contrast-enhancing mass in the spinal canal spanning T5–7, compressing the spinal cord and extending through an enlarged left T6 neural foramen. Preoperative sagittal (E) and axial (F) CT scans of the thoracic spine demonstrating a noncalcified mass with dilation of the left T6 neural foramen (arrow).

The patient underwent a T6 laminectomy and left transforaminal approach for complete resection of the lesion, with T5–7 pedicle screw fixation. Biopsy was considered but not pursued in this case as the patient was experiencing worsening neurological symptoms from progressive spinal cord compression. Intraoperatively, the tumor was found to be an encapsulated, purely extradural lesion with areas of capsule adhesion to the dura and epidural soft tissues. Postoperative MRI revealed complete resection of the lesion (Fig. 2). Histopathological examination revealed a spindle cell neoplasm with nuclear hyperchromasia, mild nuclear pleomorphism, and focally increased mitotic activity (Fig. 3A). The tumor cells were positive for SMA (Fig. 3B) and EBV-encoding small RNA (EBER) (Fig. 3C) and demonstrated focally elevated Ki-67 (Fig. 3D). This combination of histological and immunophenotypic features was supportive of a final diagnosis of EBV-SMT The patient tolerated the procedure well, with significant improvement in his presenting symptoms postoperatively. Owing to EBV-SMTs occurring in the setting of T-lymphocyte suppression, the patient’s immunosuppression regimen was reduced by discontinuing his MMF and lowering his dose of tacrolimus to 1 mg daily. To avoid graft rejection, he was subsequently started on low-dose sirolimus of 1 mg daily and prednisone 5 mg daily. Medical management of the patient’s immunosuppression was led by our institution’s transplant nephrology team, who continue to closely monitor the patient’s kidney health, which has remained stable, every 3 months.

FIG. 2.

Immediate postoperative T1-weighted postcontrast sagittal (A) and axial (B) MR images at T6. Postoperative T2-weighted sagittal (C) and axial (D) MR images at T6 demonstrating complete resection with reduction of mass effect on the spinal cord.

FIG. 3.

Hematoxylyn and eosin–stained section showing a cellular proliferation of plump spindled to epithelioid cells with marked nuclear atypia and focally brisk mitotic activity (A). The tumor cells were positive for SMA (B) and EBER (C), and Ki-67 demonstrated focal labeling in up to 10% of tumor cell nuclei (D).

Adjuvant radiation therapy was initially considered; however, with the histology demonstrating a more benign EBV-SMT rather than a malignant EBV-leiomyosarcoma, the decision was made to defer radiation therapy until there was evidence of radiographic progression. The patient’s thoracic spine has been closely monitored with repeat thoracic MRI studies with and without contrast every 3 months, which have remained stable for 1 year (Fig. 4). The current plan is to continue with repeat MRI studies of the thoracic spine every 3 months. At 1 year, the patient has had marked neurological recovery, regaining full strength in his lower extremities, ambulating independently, and experiencing only mild residual back numbness.

FIG. 4.

One-year postoperative T1-weighted postcontrast sagittal (A) and axial (B) MR images demonstrating mild residual tumor versus mild dural thickening that indents the ventral aspect of the spinal cord. Postoperative T2-weighted sagittal (C) and axial (D) MR images with no cord signal change.

Informed Consent

The necessary informed consent was obtained in this study.

Discussion

Observations

EBV-SMTs are a rare manifestation of immunosuppression in patients who have received a solid organ transplant. Treatment of these tumors in posttransplant patients involves resection followed by a reduction in immunosuppression. This follows a similar approach to individuals with untreated HIV/AIDS, where the majority of tumors are treated with resection and optimization of antiretroviral therapy.^6,7,10,18 Additionally, there may be a role for radiotherapy in the treatment of residual tumor after partial resection, or in patients who are poor surgical candidates.^9,11 At this time, there is no evidence supporting a role for systemic chemotherapy in the treatment of EBV-SMTs.¹⁹ Additionally, many chemotherapeutic agents are nephrotoxic and should ideally be avoided in the setting of a recent kidney transplant.

All 4 previously reported patients with posttransplant EBV-SMTs in the spine presented with multifocal disease of the liver, brain, femur, or lungs. Thus, CT of the chest, abdomen, and pelvis with contrast should be performed in the initial evaluation of a patient presenting with a spine lesion as their initial presentation. Additionally, MRI of the brain with and without contrast may also be considered to assess for intracranial disease. Because of EBV infection resulting in the widespread expression of proto-oncogenes, multifocal disease is presumed to be the result of discrete primary tumors rather than metastatic spread.^13,14,20,21 Thus, in posttransplant patients with solitary or multifocal disease, reduction of immunosuppression under the guidance of the transplant surgery team is critical to reduce the risk of tumor recurrence and promote regression of any additional asymptomatic tumors.

In patients with surgically resected spine tumors, it is currently unclear how frequently they should be monitored for disease recurrence and how comprehensive surveillance imaging needs to be. In our case, initial imaging at diagnosis involved an MRI study of the entire spine. We elected to only surveil the patient’s thoracic spine with repeat MRI, as new separate lesions are less likely to develop in the setting of reduced immunosuppression. Given the difficulty in determining whether posttransplant EBV-SMTs represent reactivated or new EBV infections, the benefit of additional treatments such as EBV prophylaxis is uncertain. EBV prophylaxis is a controversial area in the management of other EBV-associated posttransplant neoplasias such as posttransplant lymphoproliferative disorder, with some studies showing benefit for a subset of patients, while others show no benefit.^22,23 Further research is necessary to better define the natural history of these tumors, risk-stratify posttransplant patients at risk of developing EBV-SMTs, and manage patients in whom they occur.

Lessons

EBV-SMTs should be considered in the differential diagnosis of immunocompromised or immunosuppressed patients presenting with a solitary spine tumor. Resection is the gold standard for the treatment and diagnosis of these rare tumors, followed by a reduction in immunosuppression. Because of the majority of spine tumors presenting in the setting of multifocal disease, abdominal or thoracic imaging should also be considered to assess for additional primary tumors. In immunosuppressed patients, multidisciplinary care should be initiated early to optimize the patient’s immune status after tumor resection to reduce the risk of disease recurrence or progression of any additional lesions.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Pickles, Zsigray, Arnold. Acquisition of data: Pickles, Zsigray, Smith, McMullen. Analysis and interpretation of data: all authors. Drafting the article: Pickles, Zsigray. Critically revising the article: Pickles, Zsigray, Smith, Arnold. Reviewed submitted version of manuscript: Pickles, Zsigray, Smith, Arnold. Approved the final version of the manuscript on behalf of all authors: Pickles. Statistical analysis: Pickles. Administrative/technical/material support: Zsigray. Study supervision: Arnold.

Correspondence

Andrew C. Pickles: Loyola University Chicago Stritch School of Medicine, Maywood, IL. apickles@luc.edu.