Abstract
Background: Marginal zone lymphoma (MZL) is a heterogeneous disease accounting for 7% of non-Hodgkin lymphomas. The lack of a standard first-line treatment and the toxicity associated with current systemic therapies have prompted the investigation of novel therapeutic approaches. Emerging evidence suggested favorable efficacy and tolerability of orelabrutinib-containing regimens in the first-line setting for MZL.
Aim and Methods: Herein, we report the diagnosis, treatment, and subsequent outcome of a rare case of MZL with multiple extranodal involvement and central nervous system (CNS) involvement.
Case: A 77-year-old female presented to the Department of Neurology in June 2024 with bilateral eyelid ptosis persisting for over 2 months. Cranial MRI revealed lacunar infarctions in the bilateral basal ganglia, periventricular area, centrum semiovale, and frontal lobe, accompanied by partial softening. Electromyography showed no evidence of peripheral nerve impairment in the extremities. The patient was ultimately diagnosed with mild generalized myasthenia gravis and initiated on oral tacrolimus therapy; however, no significant improvement in bilateral eyelid ptosis was observed. Additionally, she experienced intermittent head stuffiness and headache, without associated fever, nausea, or vomiting. The patient subsequently sought further medical evaluation, during which relevant investigations were performed. Computed tomography (CT) detected multiple lymph node shadows in the bilateral cervical regions, mediastinum, and bilateral axillae, with some being enlarged (the largest measuring approximately 2.4 x 1.2 cm). A left cervical lymph node biopsy was performed, and based on the immunohistochemical results, the patient was diagnosed with MZL. Given the prominent symptoms of head stuffiness and headache, a lumbar puncture was performed. Routine CSF examination showed an elevated white blood cell count (22x10⁶/L), while other cellular counts and CSF biochemical parameters were within normal ranges. The CSF flow cytometry analysis showed approximately 54% monoclonal B-cell infiltration. Bone marrow flow cytometry revealed 70% monoclonal B-cell. Bone marrow biopsy indicated grade 2 myelofibrosis (MF-2). Based on these findings, the patient was definitively diagnosed with stage IV MZL, with involvement of the bone marrow, meninges, bilateral cervical regions, mediastinum, bilateral axillae, abdominal cavity, and retroperitoneal lymph nodes. The patient subsequently received two cycles of CD20 monoclonal antibody in combination with the miniCHOP regimen, along with four intrathecal injections. Following treatment, CSF normalized, blood cell counts returned to normal ranges, and CT demonstrated a partial response (PR). However, the patient was unable to tolerate this therapeutic regimen. Subsequently, the patient received orelabrutinib monotherapy for one year, with complete resolution of headache symptoms, achieving CR as confirmed by CT, with minimal residual disease (MRD) negativity confirmed by peripheral blood flow cytometry.
Conclusion: This case describes a rare instance of MZL with multiple extranodal involvement and CNS invasion. Its diagnostic process, therapeutic course, and outcomes carry significant reference value for the clinical management of MZL with CNS involvement. Regarding treatment, the R-miniCHOP regimen partially controlled systemic lesions, while intrathecal injections were administered to specifically clear CNS lesions. Subsequent treatment with orelabrutinib deepened the depth of remission, achieving CR and MRD negativity. Owing to its favorable CNS penetration and sustained antitumor activity, this agent effectively prevents CNS recurrence. The patient maintained a sustained CR with this regimen, suggesting that for elderly patients with MZL involving the CNS, individualized combination therapy (systemic plus local) followed by targeted maintenance or sequential targeted therapy can achieve deep remission while ensuring safety. This case provides practical evidence for therapeutic strategies in similar scenarios and highlights the need for further exploration of long-term maintenance regimens to consolidate efficacy.
