A 57-year-old man presented to the gastroenterology department of our hospital with refractory ascites for two years. He had no history of metabolic syndrome or alcohol consumption. He had a history of hypertension, hypothyroidism, and chronic nephritis, who was treated with nifedipine tablets and thyroxine tablets. He denied any fever, chest pain, rashes, oral ulcers, arthralgias and visual changes, and had no recent travel and no sick contacts. In the past two years, he has been treated in the gastroenterology department of many hospitals for ascites, and has undergone blood tests, ascites test, gastroscopy, colonoscopy, abdominal enhanced CT, etc. However, there was no clear diagnosis. The patients received oral or intravenous furosemide, oral spironolactone, and abdominal puncture drainage to resolve ascites in many hospitals, but the results were not satisfactory. The physical examination included a poor general condition, palpable lymph nodes in both sides of the neck and groin with a larger diameter of about 1 cm, abdominal distension, no tenderness and rebound pain, positive mobile dullness, mild edema of both lower limbs, enlarged spleen which lower edge is 3 fingers under the ribs. The blood routine showed that white blood cells were 4.44 × 109/L, hemoglobin was 111.0 g/L, and platelets were 93.0 × 109/L. Urine protein was weakly positive, urine pentaprotein test showed that microalbumin was 82.40 mg/L (reference value 0–30 mg/L), immunoglobulin IgG was 33.40 mg/L (reference value 0–8.5 mg/L), transferrin was 3.29 mg/L (reference value 0–2.2 mg/L), α1-microglobulin was 54.20 mg/L (reference value 0–12 mg/L), β2-microglobulin was 0.19 mg/L (reference value 0–0.22 mg/L). Other positive laboratory indicators included uric acid 520 μmol/L, albumin 36.6 g/L, and erythrocyte sedimentation rate (ESR) 26.0 mm/h. Serum thyroid stimulating hormone (TSH) was 5.5400 mIU/L, serum free thyroxine (FT4) was 14.81 pmol/L, serum free triiodothyronine (FT3) was 1.74pmol/L, which was a slight decrease. Stool routine, urea nitrogen, creatinine, C-reactive protein (CRP), liver function, serum vitamin B12, IgG4, folic acid, hepatitis virus (A, B, C, D, E), tumor markers (CA125, CA199, CEA, AFP, PSA), brain natriuretic peptide (BNP), and tuberculosis detection (PPD test, T-spot), as well as other autoimmunity makers containing antinuclear antibody (ANA), anti-neutrophil cytoplasmic antibodies (ANCA), and rheumatoid factors were all unremarkable. The patient’s HIV, EBV, CMV or Toxoplasma was negative. HHV8 and IL-6 were not detected. The gastroscope showed superficial gastritis, and the colonoscopy showed no obvious abnormalities. The echocardiogram showed a little pericardial effusion. The enhanced CT of the chest and abdomen depicted pneumonia, bilateral pleural effusion, and abdominal effusion. We performed abdominal paracentesis for this patient. The ascites was yellow and clear, the nucleated cell count was 40 × 106/L, the mononuclear cells accounted for 80.6%, and the multinucleated cells accounted for 19.4%. The Rivalta test was negative. The content of adenosine deaminase (ADA) in ascites was 2.6 U/L (reference value 0–25U/L), lactate dehydrogenase (LDH) was 74 IU/L (reference value 120–250 IU/L), albumin was 15.7 g/L, CA125 in ascites was 542 ng/mL (reference value 0–7 ng/mL), CEA, APF, and CA199 were normal. No malignant cells and tubercle bacilli were found in multiple tests of ascites. Serum ascitic albumin gradient (SAAG) was 20.9 g/L. The patient had ascites, which should be polyserositis to be precise, superficial lymphadenopathy, enlarged spleen, hypothyroidism. We made differential diagnosis based on available data. The causes of ascites may be the following: liver cirrhosis, tuberculosis, tumor, rheumatism, endocrine, cardiac insufficiency, and nephritis. SAAG remains the most sensitive and specific marker for the differentiation of ascites due to portal hypertension from ascites due to other causes. The SAAG of the patient was greater than 11 g/L, however, there were no history of hepatitis, no esophageal/gastric varices under gastroscope, and no typical CT images of liver cirrhosis. We did not perform HVPG measurement and liver stiffness measurement, nor did we perform liver biopsy to rule out other rare causes of portal hypertension. We comprehensively considered and ruled out liver cirrhosis, which should be reported to a certain extent as a limitation of case reporting. He had no history or exposure of tuberculosis infection, no fever, no night sweats, negative tuberculosis test (PPD, T-spot), normal ADA in ascites, and no tuberculosis bacilli have been detected in ascites. So tuberculosis infection was also ruled out. The patient had a small amount of urine protein, mild hypothyroidism, normal rheumatism indicators, and no manifestation of cardiac insufficiency, so it was necessary to focus on tumors or other rare causes. After communicating with the patient and obtaining his consent, we gave him an in-depth comprehensive examination including bone marrow testing, PET-CT, and lymph node biopsy. PET-CT reported that his bilateral neck, axillary, retroperitoneum and groin had enlarged lymph nodes with a slight increase in FDG metabolism. Combined with the medical history, it was considered to be consistent with the metabolic changes of indolent lymphoma by the medical technicians. Bone marrow cytology indicated that bone marrow cells proliferated actively, granulocyte proliferation was obviously active with nucleus shifted to the right, erythroid proliferation was active, platelets were aggregated and distributed, and primitive cells accounted for about 1.0% of nuclear cells. The immunophenotyping of bone marrow lymphoma showed that the proportion of myeloid blasts was not high, with normal phenotype, the proportion of lymphocytes was not high, there were no abnormal monoclonal cells and no abnormal plasma cells. Was this patient with lymphoma? We were in confusion. Fortunately, the right neck lymph node biopsy pathology gave us the answer. Pathological examination of the lymph nodes showed that the lymph follicles increased, the germinal center was atrophied, the inter-follicular and paracortical areas showed vascular hyperplasia, and the mantle area was obviously hyperplasia with onion-skin-like change. Onion-skin-like appearance was a typical pathological manifestation of CD. The immunohistochemical results were: CD3 (paracortical cells +), CD5 (paracortical cells +), CD20 (germinal center cells +), PAX5 (germinal center cells +), CD21 (follicular dendrites +), CD34 (Vascular +), Bcl-2 (mantle area +), SOX11 (−), Cyclin D1 (−), Ki-67 (+, about 10%). Finally, the patient was diagnosed with CD. We recommended him use CHOP chemotherapy, but he refused and chose oral thalidomide, the patient had poor compliance and refused to use steroid therapy. Three months later, his symptoms did not improve significantly. Due to economic reasons, he still refused chemotherapy and chose oral diuretics to relieve ascites.