Primary Testicular DLBCL with CNS Prophylaxis Using M-R-CHOP: A Case Report
Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is a rare extranodal lymphoma accounting for 1-2% of all non-Hodgkin lymphomas (NHL) and approximately 5% of testicular neoplasms. It carries a high risk of central nervous system (CNS) relapse, necessitating CNS-directed prophylaxis in addition to standard chemoimmunotherapy. Optimal integration of high-dose methotrexate (HD-MTX) with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) remains an area of active investigation.
Materials and Methods/Case Presentation/Objective:
A 36-year-old male with a history of thyroid cancer status post thyroidectomy and inflammatory bowel disease (IBD) on a ustekinumab biosimilar presented with painful testicular swelling and rupture. Cross-sectional imaging revealed testicular enlargement, an adrenal mass, and retroperitoneal lymphadenopathy. Adrenal biopsy confirmed high-grade B-cell lymphoma consistent with DLBCL, staged as IIE. MRI of the brain and spine and cerebrospinal fluid (CSF) cytology via lumbar puncture were negative for CNS involvement.
Given the high CNS relapse risk associated with testicular involvement, the patient was initiated on M-R-CHOP - an interdigitated regimen of HD-MTX with R-CHOP - administered on an inpatient basis. Each cycle included HD-MTX on day 1 with leucovorin rescue, urine alkalinization, and serial methotrexate level monitoring until clearance (0.1 µmol/L), followed by R-CHOP on day 2. Granulocyte colony-stimulating factor (G-CSF) was administered in the outpatient setting after each cycle.
The patient tolerated four cycles of M-R-CHOP with manageable toxicities, including chemotherapy-induced peripheral neuropathy (upper extremity paresthesias attributed to vincristine), electrolyte derangements (hypocalcemia, hypokalemia) requiring repletion, transient lower extremity edema related to intravenous hydration, and hiccups likely secondary to corticosteroid therapy. Renal function remained stable throughout treatment. Interim positron emission tomography-computed tomography (PET-CT) after cycle 3 demonstrated complete metabolic response (CMR).
Results/Description/Main Outcome Measure(s):
This case illustrates the feasibility and tolerability of interdigitated M-R-CHOP for stage IIE PT-DLBCL in a young patient with significant comorbidities, including concurrent immunosuppression for IBD. PT-DLBCL is associated with CNS relapse rates of 15-35%, and incorporation of HD-MTX into frontline therapy has been shown to reduce this risk. HD-MTX administration requires careful inpatient monitoring of drug clearance, renal function, and urine alkalinization to prevent crystal nephropathy. The concurrent use of a ustekinumab biosimilar raises considerations regarding cumulative immunosuppression and infection risk, though no infectious complications were observed. Clinical suspicion should remain high when young adults present with testicular swelling, as early diagnosis enables timely initiation of CNS-directed therapy. Continued surveillance for late CNS relapses and contralateral testicular involvement is essential during follow-up.
Conclusion(s).:
Interdigitated M-R-CHOP is a feasible CNS-directed strategy in PT-DLBCL, achieving early CMR with acceptable toxicity. This case highlights the importance of multidisciplinary coordination for the administration and management of inpatient HD-MTX and treatment-related complications in patients with complex comorbidities.
Trademarked Items:
References: 1. itolo et al. (IELSG-10 trial) - The landmark international phase II trial of 53 patients with stage I-II PT-DLBCL treated with R-CHOP-21, intrathecal methotrexate, and contralateral testis irradiation. It demonstrated a 5-year PFS of 74%, OS of 85%, and a 5-year CNS relapse rate of 6%, establishing the current standard of care for PT-DLBCL. 
