EBV-positive primary CNS lymphoma restricted to the conus medullaris in an immunocompetent host

PRACTICAL IMPLICATIONS

Although a rare occurrence, EBV-positive primary CNS lymphoma may occur anywhere in the CNS as well as in immunocompetent patients.

Primary CNS lymphoma (PCNSL) is a rare extranodal non-Hodgkin's lymphoma, constituting 1% of all human lymphomas.¹ PCNSL isolated to the spinal cord with no systemic involvement occurs in 1%–3.3% of all PCNSL cases.² Only 46 cases of intramedullary spinal cord PCNSL have been reported in case reports and series. According to Guzey et al.,³ only 4 of these cases reported lesions isolated to the conus medullaris.

Epstein–Barr virus (EBV) positive (EBV+) PCNSL is a hallmark malignancy in immunocompromised individuals, including patients with AIDS or who underwent a transplant. Few studies report an association of EBV in the pathogenesis of PCNSL in immunocompetent patients.⁴ Herein, we report a case of an intramedullary EBV+ PCNSL isolated to the conus medullaris with no evidence of immunodeficiency.

Case

A 58-year-old Hispanic woman with type 2 diabetes mellitus presented to an outside emergency department with urinary retention and saddle anesthesia. A Foley catheter was placed with no further workup. The urinary retention and the saddle anesthesia worsened over the next 2 weeks, and she presented to our hospital. No lower extremity weakness or back pain was initially evident, but she later developed lower extremity weakness leading to walker dependence. Lumbar MRI revealed an enhancing 3.9 × 0.8 × 0.8 cm lesion in the conus medullaris extending to the filum terminale (figure). Brain, cervical, and thoracic MRI revealed no additional lesions. Differential diagnoses included myxopapillary ependymoma, astrocytoma, and lymphoma. The patient underwent L1–L2 laminectomy with gross total resection of the intramedullary tumor and several specimens sent for pathology. Progression of cord compression symptoms warranted total resection regardless of pathology.

Figure. MRI.

Serial MRI of an Epstein–Barr virus (EBV)-positive primary CNS lymphoma (PCNSL) isolated to the conus medullaris: (A) T2 and (B) T1 post contrast images at initial presentation; (C) T1 post contrast image after surgical resection; (D) T2 image at 1 month after surgery, (E) after completion of chemotherapy, (F) and at 8 months after diagnosis and 4 months after completion of radiotherapy.

Pathology revealed an EBV+ atypical lymphohistiocytic infiltrate consistent with a diffuse large B cell lymphoma. Histologic analysis revealed small mature lymphocytes and atypical lymphoid cells in an angiocentric distribution. In situ immunohistochemistry revealed cells bright for PAX-5+, partially bright for CD20⁺, EBER+, CD79⁺, CD30⁺, CD45⁺, and MUM-1+. Features of grade 3 lymphomatoid granulomatosis were present. FISH showed C-MYC+ (50%) with no MYC rearrangement. Ki-67 proliferation index was 60%.

PET scan demonstrated no residual or extracranial disease. Bone marrow biopsy revealed normocellular marrow for age with trilineage hematopoiesis and complete maturation of all cell lines. HIV was negative, and serum EBV was positive at <100 cells/μL. CSF revealed no malignant cells by cytology or flow cytometry.

The patient received intrathecal methotrexate 9 days postoperatively. Four cycles of chemotherapy (rituximab IV 375 mg/m² on day 1, methotrexate IV 3.5 gm/m² on day 2, and cytarabine IV 2 gm/m² daily on days 1–3) at 3-week intervals were planned. Acute-on-chronic renal failure developed after the first cycle, and allopurinol was discontinued due to drug-induced rash. Chemotherapy was discontinued after the second cycle due to renal insufficiency, pancytopenia, and fatigue. After confirmed complete response on MRI, she received consolidative intensity-modulated radiotherapy to 45 Gy in 25 fractions without complications. Post-treatment MRIs demonstrated stable-to-improved fluid-attenuated inversion recovery signal in the spinal cord with no recurrent or residual tumor at 10 months from initial diagnosis.

Saddle anesthesia resolved with improvement in urinary incontinence. At last follow-up, the patient reported only intermittent and occasional use of a urinary catheter. The bowel incontinence persisted without change in sphincteric dysfunction. Her bilateral lower extremity weakness improved, resulting in stable gait without assistive device.

Discussion

EBV+ PCNSL is rare with most documented cases arising intracranially in immunocompromised patients. Four cases of PCNSL isolated to the conus medullaris have been reported so far.³ An EBV+ PCNSL isolated to the conus medullaris in an immune-competent patient has been rarely reported.

The rarity of PCNSL limits development of phase 3 clinical trials and evidence-based standardized therapy. Multiagent systemic therapy including high-dose methotrexate (HD-MTX) is generally recommended. The addition of rituximab to HD-MTX and cytarabine showed higher overall response rates and progression-free survival rates by 21% and 13%, respectively, compared to HD-MTX plus cytarabine.⁵ Most of the implemented therapeutic approaches use combined modality therapy, particularly in patients <60 years old.⁶

One promising investigational approach for EBV+ PCNSL involves EBV-specific chimeric antigen receptor T-cell (CAR-T) infusions. Cytotoxic T lymphocytes (CTLs) are harvested from autologous peripheral blood undergo in vitro generation of EBV specificity.⁷ The use of CAR-T cells as well as donor-derived CTLs, comprise a promising immunotherapeutic approach for the treatment of hematologic and lymphoproliferative disorders. Novel immunotherapeutic approaches may improve outcomes or serve as a viable salvage regimen following first-line therapy.

Appendix. Author contributions

Study funding

No targeted funding reported.

Disclosure

The authors report no disclosures relevant to the manuscript. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.