Synchronous Central Nervous System and Systemic Involvement in CD30-Positive Diffuse Large B Cell Lymphoma: A Rare Presentation Treated with Alternating R-CHOP plus HD-MTX and R-HIDAC plus HD-MTX

Introduction/Background/Significance: Diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin lymphoma, accounting for 30–40% of cases. It is an aggressive malignancy that often presents at an advanced stage and may involve extranodal sites. However, central nervous system (CNS) involvement at initial diagnosis remains rare, occurring in approximately 5% of cases. CNS disease is clinically significant due to its poor prognosis, limited treatment options, and the challenge posed by the blood-brain barrier, which restricts systemic drug penetration. Early identification of neurological symptoms—such as headaches, cognitive or visual changes, and behavioral alterations—is critical for timely diagnosis and tailored management. Recognizing CNS involvement at presentation may guide more aggressive treatment approaches and improve outcomes in this high-risk subset.

Materials and Methods/Case Presentation/Objective: We report the case of a 54-year-old hypertensive female with a 6-month history of generalized lymphadenopathy, back pain, and weight loss. She developed intermittent headaches two months before admission, prompting further evaluation. Cranial MRI revealed a 2.0 × 2.7 × 2.0 cm extra-axial, avidly enhancing infratentorial mass in the left paracavernous region. Systemic imaging showed widespread lymphadenopathy. Cerebrospinal fluid cytology was negative for malignancy. Excisional biopsy of a cervical lymph node demonstrated strong CD20, negative CD3, and partial CD30 positivity, consistent with CD30-positive DLBCL. She was initiated on an alternating chemotherapy regimen of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) with high-dose methotrexate (HD-MTX) and R-HIDAC (rituximab and high-dose cytarabine) with HD-MTX. The patient completed six cycles of treatment without major complications. Post-treatment PET-CT confirmed complete metabolic remission.

Results/Description/Main Outcome Measures: Synchronous CNS and systemic involvement in DLBCL is infrequently observed but associated with poor prognosis. Retrospective studies suggest median survival of 6 months in such cases, particularly when CNS disease arises at relapse. Optimal management remains undefined due to the rarity of this presentation and limited prospective data. The MARIETTA trial established MATRix (rituximab, methotrexate, cytarabine, and thiotepa) followed by RICE (rituximab, ifosfamide, carboplatin, and etoposide), and autologous stem cell transplant as an effective regimen, achieving comparable outcomes to non-CNS DLBCL. However, drug availability, patient frailty, and limited access to bone marrow transplant often limit its applicability. For resource-limited settings, alternatives such as R-CHOP plus HD-MTX and R-HIDAC plus HD-MTX have demonstrated acceptable survival outcomes. In our patient, this alternating regimen was chosen due to tolerability and accessibility. Despite the risk of toxicity, careful hydration, leucovorin rescue, and supportive care minimized adverse effects. CD30 expression was noted but brentuximab vedotin was not used due to its poor CNS penetration. The prognostic value of CD30 in DLBCL remains unclear, with conflicting data in the literature regarding its correlation with survival.

Conclusions: This case highlights the importance of early neurologic assessment in patients with systemic DLBCL, as subtle symptoms like intermittent headaches may signal CNS involvement. An alternating chemotherapy regimen of R-CHOP plus HD-MTX and R-HIDAC plus HD-MTX offers a practical and tolerable treatment approach in frail patients or resource-limited environments. Prompt diagnosis, CNS-directed therapy, and multidisciplinary coordination are key to improving outcomes in patients with synchronous CNS and systemic DLBCL.