Despite initiation of high-dose oral dexamethasone to reduce cerebral edema and mass effect during the preoperative period, the patient’s neurological status continued to decline. He was subsequently admitted to the neurosurgical ward and transitioned to intravenous corticosteroid therapy. Nevertheless, his condition progressively deteriorated, prompting the decision for semi-urgent surgical intervention.

A right temporal craniotomy was fashioned to achieve broad exposure of the lesion and adjacent healthy brain parenchyma. Intraoperative frozen section analysis was suggestive of a lymphoproliferative process. Definitive histopathological evaluation, including immunohistochemistry, confirmed the diagnosis of primary central nervous system T-cell lymphoma (4, 5).

Given the patient’s poor clinical response to corticosteroids and existing literature suggesting a potential benefit of gross total resection (GTR) in selected cases, a complete supramarginal excision of the mass was undertaken (3, 6). The patient experienced marked postoperative neurological improvement and was subsequently referred to hematology/oncology for further management based on the definitive pathological diagnosis.

Three weeks postoperatively, the patient was admitted to the hematology-oncology unit and initiated on the AspaMetDex chemotherapy regimen (pegaspargase, methotrexate, and dexamethasone). During treatment, the patient developed acute kidney injury (AKI), which was managed conservatively with intravenous hydration, and hypofibrinogenemia, successfully corrected with fibrinogen supplementation. The regimen was otherwise well tolerated, and the patient was discharged in stable condition after a 2-week hospital stay.

Follow-up brain MRI at three months postoperatively showed no evidence of tumor progression or recurrence, either at the resection site or elsewhere in the central nervous system.

A visual timeline of the key clinical events from symptom onset through 3-month follow-up is presented in Table 1 .

Microscopic examination of the resected specimen revealed a dense infiltrate of large atypical lymphoid cells with irregular nuclear contours, prominent nucleoli, and areas of necrosis. A striking feature was the angiocentric and angioinvasive pattern of infiltration, with tumor cells arranged concentrically around leptomeningeal blood vessels, accompanied by fibrinoid vascular necrosis.

Immunohistochemical analysis demonstrated strong membranous and cytoplasmic expression of CD3, confirming T-cell lineage. CD2 was moderately expressed, while CD4 was globally negative and CD8 was positive in only approximately 15% of the neoplastic cells. The tumor showed a cytotoxic immunophenotype, with strong expression of TIA-1 and Granzyme B, whereas Perforin was negative. CD56 and T-cell receptor gamma-delta (TCRγδ) were not expressed. The Ki-67 proliferation index was greater than 95%, indicating a highly proliferative tumor.

In situ hybridization for Epstein-Barr virus–encoded RNA (EBER) revealed strong and diffuse nuclear positivity in virtually all tumor cells, confirming EBV association. This case is not classified as a large T-cell lymphoma due to the uniform EBER positivity, cytotoxic immunophenotype, and characteristic angiocentric necrosis, findings consistent with an EBV-positive extranodal T-cell lymphoma.

Furthermore, this case does not meet criteria for a T follicular helper (TFH) phenotype lymphoma, as the neoplastic cells lack expression of defining TFH markers such as PD-1, ICOS, and BCL6, and do not exhibit a TFH-associated immunophenotype.

These morphological and immunophenotypic features support a diagnosis of extranodal EBV-positive peripheral T-cell lymphoma, presenting as a primary central nervous system (CNS) lymphoma, in accordance with the 2022 WHO classification (ICD-O 9702/3).

EBV serology demonstrated positive viral capsid antigen (VCA) IgG and Epstein–Barr nuclear antigen (EBNA) IgG, with negative VCA IgM, consistent with prior EBV infection. This serological profile, which reflects past exposure, is the most common pattern observed in immunocompetent adults and is typical even in cases of EBV-associated lymphomas.

A review of the published literature reveals several case reports and small series that collectively underscore the heterogeneity and clinical challenges of managing PCNS-TCL. Table 2 summarizes key characteristics from selected cases, including patient demographics, lesion location, immunocompetence status, interventions, histology, corticosteroid response, imaging features, and outcomes.

Notably, gross total resection (GTR) was performed in a minority of cases—primarily in younger patients with solitary, accessible lesions—such as in the reports by Kawamura et al. and Goldbrunner et al. (12, 13), both involving adolescent males. Despite surgical intervention, these patients had poor survival, highlighting the aggressive biology of certain T-cell subtypes like Ki-1 (CD30+) lymphoma. On the other hand, Takeshita et al. reported a favorable 24-month outcome in a middle-aged male treated with biopsy and chemoradiotherapy alone, suggesting that multimodal therapy remains the cornerstone of treatment when feasible.

The table also emphasizes the variability in imaging findings and corticosteroid responsiveness, with several entries lacking detailed documentation. However, poor steroid responsiveness—similar to our case—is recurrently noted in cases with aggressive phenotypes and EBV association. Notably, Kang et al. (6) described a case of primary CNS NK/T-cell lymphoma, a subtype that is by definition associated with EBV positivity according to the 2022 WHO classification. Although EBER status was not explicitly stated in their report, the diagnosis of NK/T-cell lymphoma implies clonal EBV infection, as EBV is a defining feature of this entity. This makes their case, alongside ours, one of the very few reported instances of EBV-positive PCNS-TCL in the literature.

Together, these cases, although limited by heterogeneity and incomplete data, suggest that individualized management based on lesion accessibility, histologic subtype, and EBV status is critical. Our case adds to this evolving body of literature by demonstrating a rare EBV-positive T-cell phenotype with favorable early postoperative recovery following GTR, reinforcing the potential role of surgery in selected scenarios.

Prognostically, PCNS-TCL appears to have a less favorable outcome compared to its B-cell counterpart, with reported median overall survival ranging from 12 to 25 months, depending on treatment and patient factors (1, 14–16). Factors influencing prognosis in PCNS-TCL include patient age, performance status, extent of CNS involvement, treatment responsiveness, and EBV status. As shown in the largest series to date by Shenkier et al., performance status and the use of methotrexate-based regimens are independently associated with improved survival, reinforcing their central role in management despite the lack of EBV-specific treatment protocols.

More specifically Epstein–Barr virus (EBV) positivity in peripheral T-cell lymphomas, with CNS involvement, is increasingly recognized as a marker of aggressive disease biology and poor prognosis. According to the 5th edition of the WHO classification (2022), EBV-positive peripheral T-cell lymphoma (ICD-O 9702/3) constitutes a distinct clinicopathologic entity, often associated with rapid progression, extranodal involvement, and resistance to standard chemotherapy regimens such as CHOP. Alaggio et al. provide the updated WHO framework that formally distinguishes EBV-positive peripheral T-cell lymphomas, including γδ variants, emphasizing their aggressive behavior and extranodal predilection (17). In particular, CNS involvement further compounds the adverse outlook, with reported median overall survival frequently less than 12 months despite aggressive therapy (12, 18). The presence of EBV within tumor cells, confirmed by EBER in situ hybridization, may prompt consideration of alternative treatment strategies, including high-dose methotrexate-based regimens for CNS penetration, L-asparaginase–containing protocols (e.g., SMILE), or even early consolidation with autologous stem cell transplantation. In select cases, investigational therapies targeting immune checkpoint pathways (e.g., PD-1 inhibitors) have been explored, given the frequent expression of PD-L1 in EBV-positive lymphomas (19). These findings highlight the importance of establishing EBV status not only for diagnostic classification but also for prognostic stratification and potential modification of management.

Strengths:

This case contributes to the scarce literature on EBV-positive primary CNS T-cell lymphoma (PCNS-TCL) in immunocompetent patients, offering a detailed diagnostic and therapeutic account aligned with current WHO classification. It highlights the potential role of gross total resection (GTR) in corticosteroid-refractory cases with solitary, accessible lesions, supporting the value of individualized, multidisciplinary management.

Limitations:

The rarity of EBV-positive PCNS-TCL limits generalizability, and current management strategies are based on heterogeneous, low-level evidence. While GTR led to clinical improvement here, its broader role remains unclear due to the absence of prospective data. Similarly, the optimal systemic treatment for EBV-driven CNS T-cell lymphomas remains undefined, underscoring the need for more robust clinical evidence.