Marginal zone lymphoma presenting with chylous ascites: A rare clinical manifestation and successful treatment with orelabrutinib–rituximab

Abstract

Marginal zone lymphoma is the second most common subtype of indolent non-Hodgkin lymphoma. Its clinical manifestations are heterogeneous and largely determined by the involved site. Chylous ascites, as the initial presentation of marginal zone lymphoma, is extremely rare. We report a 79-year-old man who presented with rapidly progressive abdominal distension due to high-volume chylous ascites. Flow cytometry of the ascitic fluid revealed a monoclonal lambda-restricted B-cell population consistent with low-grade B-cell lymphoma. Bone marrow biopsy confirmed splenic marginal zone lymphoma. Initial rituximab monotherapy was ineffective; however, combination therapy with orelabrutinib and rituximab led to complete resolution of ascites after two cycles and marked disease control. At 6-month follow-up, the patient remained in remission. Clinicians should consider lymphoma in the differential diagnosis of unexplained chylous ascites. Prompt etiologic treatment can result in favorable outcomes even in elderly patients with advanced disease.

Introduction

Chylous ascites is an uncommon form of ascites characterized by the accumulation of triglyceride-rich, milky peritoneal fluid due to disruption or obstruction of the lymphatic system. ¹ . The etiologies include traumatic injury, malignancy, infection, and congenital lymphatic anomalies. Lymphoma is the most frequently reported malignant cause, typically due to lymphatic obstruction by bulky lymphadenopathy or direct lymphatic invasion. ²

Marginal zone lymphomas (MZLs) encompass three main subtypes: extranodal MZL of mucosa-associated lymphoid tissue (lymphoma), nodal MZL, and splenic MZL (SMZL)—which was the final diagnosis in our case.^3–5 These are indolent B-cell neoplasms with variable clinical courses. ⁵ Chylous ascites/Chylothorax as an initial manifestation is extremely rare across all MZL subtypes, and to our knowledge, only one case of MZL presenting with Chylothorax exists in the literature. ⁶ A comprehensive review of the literature revealed no previously reported case of SMZL presenting with chylous ascites as the initial manifestation. Therefore, the present report appears to be the first documented instance, highlighting an exceptionally rare and novel clinical presentation.

We present a case of SMZL in an elderly man whose first clinical sign was massive chylous ascites, successfully treated with an orelabrutinib–rituximab regimen after failure of rituximab monotherapy.

Case presentation

A 79-year-old man presented in November 2024 with progressive abdominal distension, bilateral lower limb edema, fatigue, and an 8% unintentional weight loss over 2 months. His past medical history included type 2 diabetes, coronary artery disease, and hypertension, he did not consume alcohol or smoke.

Abdominal ultrasound revealed ascites (maximum depth 77 mm), splenomegaly, and gallbladder polyps. Physical examination confirmed tense ascites (grade III) and pitting leg edema without jaundice, stigmata of chronic liver disease, lymphadenopathy, or hepatomegaly.

Hemoglobin 13.6 g/dL; leukocytes 7.69 × 10³/µL (63% neutrophils, 30% lymphocytes); platelets 219 × 10³/µL; serum albumin 34.4 g/L; normal liver and renal function tests. Lactate dehydrogenase was elevated at 370 IU/L (normal 135–225). Viral serology for hepatitis B, hepatitis C, and HIV was negative.

Contrast-enhanced computed tomography (CT) of the abdomen and pelvis demonstrated large-volume ascites and small scattered abdominal lymph nodes without bulky adenopathy (Figure 1(a)).

Figure 1.

(a) Coronal CT showing large-volume peritoneal effusion and small abdominal lymph nodes. (b) A light pink and milky ascitic fluid obtained via paracentesis. (c) Flow cytometry identified a monoclonal lambda-restricted B-cell population.

Diagnostic paracentesis yielded light pink, milky fluid characteristic of chylous ascites (Figure 1(b)) with triglycerides 2298 mg/dL, albumin 1.1 g/dL, and 1461 leukocytes/µL (79% mononuclear cells). Cytology was negative for malignant cells, but flow cytometry identified a monoclonal lambda-restricted B-cell population (Figure 1(c); 92.6% of total cells) expressing CD19, CD20, and CD79b, negative for CD5, CD10, CD23, CD200, CD103, and CD38.

Splenic biopsy was considered but deemed contraindicated due to the high risk of procedure-related hemorrhage and potential for splenic rupture, particularly in the setting of splenomegaly. ⁷ Bone marrow aspiration and trephine biopsy revealed 40% cellularity with nodular and intrasinusoidal infiltration by small mature B lymphocytes. Immunohistochemistry showed positivity for CD19, CD20, CD22, and PAX5, and negativity for CD5, CD10, SOX11, CD103, CD25, CD123, CD11c, CD38, CD138, IgM, and IgD. Ki-67 proliferation index was <5% (Figure 2(a)). Findings were consistent with SMZL.

Figure 2.

(a) Bone marrow biopsy showing small lymphoid cell proliferation with intrasinusoidal infiltration. (b) Follow-up abdominal CT after six OR cycles demonstrating complete resolution of ascites.

Treatment and outcome: The patient initially received one cycle of rituximab monotherapy (day 1) without clinical improvement after 3 weeks. He was then commenced on OR (orelabrutinib 150 mg daily plus rituximab 375 mg/m² administered every 21 days). After two cycles (6 weeks), the ascites resolved completely, and the drainage catheter was removed. Following six cycles, repeat CT showed no ascites or lymphadenopathy (Figure 2(b)), and bone marrow examination revealed only 6% residual monoclonal B cells. Orelabrutinib maintenance was continued. The treatment course was uneventful, and the OR regimen was well-tolerated without any adverse events or the need for dose adjustment. At 6-month follow-up, the patient remained asymptomatic with no evidence of relapse.

Discussion

Chylous ascites results from the disruption or obstruction of lymphatic flow, leading to leakage of chyle into the peritoneal cavity. ⁸ In malignancies, the most common mechanisms include obstruction of the cisterna chyli or thoracic duct by tumor masses or direct infiltration of lymphatic vessels. ⁹ In our patient, the absence of bulky lymphadenopathy suggests that microscopic lymphatic involvement or splenic hilum compression may have contributed.

SMZL accounts for <2% of all lymphoid malignancies and usually presents with splenomegaly, bone marrow infiltration, and circulating villous lymphocytes.^5,10 Peripheral lymphadenopathy is uncommon, as in this case. Diagnosis often relies on bone marrow histology when a splenic biopsy is contraindicated. ¹¹

According to NCCN guidelines, asymptomatic SMZL patients can be managed with observation, but symptomatic patients—including those with cytopenia, massive splenomegaly, or constitutional symptoms—require treatment. Rituximab monotherapy is a standard first-line option in hepatitis C-negative patients. However, our patient’s lack of response prompted the use of orelabrutinib, a highly selective Bruton’s tyrosine kinase inhibitor (BTKi) approved in China for relapsed/refractory MZL.^12,13 Emerging evidence supports the use of BTKis in combination with anti-CD20 antibodies to achieve deeper and more durable remissions in high-risk MZL. ¹⁴ It is noteworthy that orelabrutinib is currently approved for the treatment of certain B-cell malignancies in China (adult patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma who have received at least one prior therapy. MZL who have received at least one prior therapy), but its regulatory approval in other major regions (e.g., the United States and European Union) is still under evaluation in clinical trials. ¹⁵ However, the findings from this report should be considered its limitations, including its nature as a single case study and the relatively short follow-up duration of 6 months. Longer-term observation is needed to fully assess the durability of the response.

This context is important for the international readership regarding the current global accessibility of this agent. This case expands the current clinical understanding by demonstrating the remarkable efficacy and tolerability of a BTKi-based combination regimen as an early therapeutic intervention for symptomatic rituximab-refractory SMZL in an elderly patient. It suggests that targeted therapy can achieve rapid control of severe complications like chylous ascites, potentially altering the disease course even in a demographically high-risk population where aggressive chemotherapy is often not feasible.

Nutritional support is essential in managing chylous ascites, including high-protein, low-fat diets enriched with medium-chain triglycerides to reduce lymph production.^2,16 In refractory cases, total parenteral nutrition or pharmacologic agents such as somatostatin analogs (e.g., octreotide) may be used to reduce chyle production by decreasing splanchnic blood flow and intestinal lipid absorption.^2,17

Our case demonstrates that targeted therapy against the underlying lymphoma can result in rapid and complete resolution of chylous ascites, even in elderly patients with advanced-stage disease.

Conclusion

Chylous ascites as the initial manifestation of SMZL is exceptionally rare and may delay diagnosis. Histopathologic confirmation is crucial, and management should focus on treating the underlying malignancy. Orelabrutinib in combination with rituximab represents an effective and well-tolerated option for refractory symptomatic MZL. Early recognition and intervention can lead to favorable outcomes.

Supplemental Material

sj-docx-1-sco-10.1177_2050313X251412734 – Supplemental material for Marginal zone lymphoma presenting with chylous ascites: A rare clinical manifestation and successful treatment with orelabrutinib–rituximab

Supplemental material, sj-docx-1-sco-10.1177_2050313X251412734 for Marginal zone lymphoma presenting with chylous ascites: A rare clinical manifestation and successful treatment with orelabrutinib–rituximab by Jie Wu, Feng-jing Wang, Zhi-dong Jia, Yang-qiu Li and Li-ye Zhong in SAGE Open Medical Case Reports