In June 2021, a 64-year-old male patient was admitted to the Department of Respiratory Medicine of our hospital and complained of chest tightness and shortness of breath for more than 20 days. The chest CT showed that lymph nodes were partially enlarged in the right lower lung hilar, bilateral axillar, and retroperitoneal. In addition, there was a large amount of effusion in the left pleural cavity. Physical examination revealed multiple superficial lymph node enlargements throughout the body, breath sounds could not be heard on the left side, and did not reveal hepatomegaly or splenomegaly. Thoracentesis and drainage were performed in the Department of Respiratory Medicine. The patient's chest tightness and shortness of breath improved significantly. The tuberculosis test was negative. The hemoglobin level was decreased at 95g/L, leukocytes at 8.84x109/L, and platelets at 258x109/L. The color of the pleural effusion was red. A laboratory examination of the pleural effusion was as follows, monocytes at 96%, nucleated cell count at 2100x106/L, erythrocytes at 40-50/HF, ADA at 11.4U/L, glucose at 8.26mmol/L, and total protein at 47.8g/L. Biochemical showed an elevated globulin at 62.4g/L, albumin at 27.2g/L, lactate dehydrogenase(LDH) at 147.2U/L, beta2 microglobulin at 4mg/L, and an elevated monoclonal IgM at 55.6g/L. A right supraclavicular lymph node biopsy was performed on day 5 of hospitalization. Combined with immunochemical staining and HE staining, histopathological revealed that this case is a B-cell lymphoma. Immunohistochemical results were as follows: LCA (+), CD20 (+), S100 (-), actin (-), SMA (-), Ki-67 (20% +), HMB45 (-), CD31 (+), kappa (plasma cell +), lambda (-), CD79alpha (+), CD5 (-), CD3 (background cell +), CD10 (-), CD21 (FDC +), CD23 (FDC+), CD38 (+), CD138 (+), CD43 (+), CyclinD1 (-), Bcl-2 (+), Bcl-6 (30% +), MUM1 (+), PAX5 (+), c-Myc (-), CD19 (+). Immunophenotyping was incomplete, and genetic testing was not done. Due to doubts about the immunohistochemical results and difficulties in distinguishing which subtype of B-cell lymphoma, the patient went to Ruijin Hospital, Shanghai Jiaotong University School of Medicine for an axillary lymph node biopsy in August 2021. An immunohistochemistry analysis were as follows: CD20 (+), CD79a (+), CD19 (+), CD22 (+), BCL-2 (+), IgD (+), CD23 (+), Ki67 (2% +), CD37 (50% +), CD10 (-), BCL-6 (-), C-myc (-), MUM-1 (-), Kappa (-), Lambda (-), CD30 (-), CD38 (-), CD3 (-), CD5 (-), CyclinD1 (-), PD-1 (-), CD138 (-), CD21 (+). Epstein-Barr virus-encoded small RNA in situ hybridization (EBER-ISH) was negative. The somatic mutation of MYD88L265P and CXCR4 were negative. Combined with the patient's lymph node biopsies immunohistochemistry and clinical presentation, the patient was finally diagnosed with monoclonal IgM elevated NMZL. But the patient refused chemotherapy for personal reasons. In September 2021, the patient was transferred to the local hospital with a recurrence of chest tightness and shortness of breath. CT examination suggested a large amount of effusion in the left pleural cavity, and thoracentesis and drainage were performed again.
In October 2021, the patient was transferred to our hospital for further treatment. Flow cytometry of bone marrow showed that lymphocytes occupied about 12.7% of nuclear cells, of which CD19+ cells occupied about 6.2% of nuclear cells, expressing HLA-DR, CD19, CD20, cKappa, FMC-7, and CD38, and negative for CD5, CD10. There were no abnormalities in the chromosome examination. Referring to the 2014 Lugano staging, this patient was in stage IV group B. The patient chose chemotherapy of rituximab and lenalidomide. The patient developed a widespread rash with pruritus after taking lenalidomide and was considered to be allergic to it, which improved after discontinuation of the drug and anti-allergic treatment.
The patient developed shortness of breath and facial swelling during hospitalization, and the ultrasound examination of the chest cavity indicated a large amount of pleural effusion on the left side again. Thoracentesis drainage was performed for the third time, and the the color of pleural effusion was yellow. A flow cytometric analysis of the pleural effusion indicated abnormal monoclonal B cells, which expressed HLA-DR, CD19, CD20, CD22, cKappa, and were negative for CD5, CD10, and FMC-7. The flow cytometry indicated that pleural effusion may be associated with invasion of the pleura. Because of the patient's allergy to lenalidomide, the patient received the BR (rituximab 600mg d1, bendamustine 150mg d2-3) chemotherapy regimen in November and December separately. The patient underwent chills, vomiting, and diarrhea during rituximab treatment and improved with symptomatic supportive treatment.
Shortly after the second BR chemotherapy treatment, the patient was readmitted to our hospital with chest tightness and shortness of breath. Ultrasound examination showed a large pleural effusion on the left side, and ultrasound-guided thoracentesis was performed for the fourth time to drain the cavity. The pleural effusion color was milky white, and the Levantine test showed positive. 84% were mononuclear cells, and the nucleated cell count was up to 645x106/L. The level of total protein was at 49.5 g/L, LDH at 110.2 U/L, and glucose at 7.25 mmol/L. The chyle test of pleural effusion was positive. The somatic mutation of MYD88L265P of pleural effusion was negative. Immunophenotyping of the pleural effusion suggested that lymphocytes occupied about 71.3% of the nucleated cells, with CD19+ cells occupying about 1% of the nucleated cells, expressing HLA-DR, CD19, CD20, CD22, and Kappa. Considering that the patient developed a severe allergic reaction to rituximab, we adjusted to GB (Obinutuzumab 1000mg d1, Bendamustine 150mg d2-3) chemotherapy regimen in January 2022. One month later, the patient's chest ultrasound showed a significant reduction of pleural effusion in the left side of the chest cavity. The patient received another two cycles of treatment. In April 2022, pleural effusion could not be detected by ultrasound. The patient performed GB chemotherapy for the fourth course. The patient did not experience drug-related allergies or reignition of pleural effusion. Most importantly, the globulin and IgM gradually decreased to normal. The patient is currently in follow-up and maintaining remission. The patient is currently on maintenance therapy with the GB regimen. No further pleural effusion was observed on repeat chest CT ( Figure 1A . The treatment timeline of this patient.  Figure 1B  The decreasing trend of globulin and IgM in this patient during the inpatient and outpatient follow-up period from June 2021 to April 2022.  Figure 2A  In June 2021, CT suggested enlarged lymph nodes in the right hilar lung.  Figures 2B, C  In February and March 2022, CT suggested a gradual decrease in pleural effusion.  Figures 2D, E  In June 2021, a chest ultrasound suggested a large pleural effusion.  Figures 2F, G  No pleural effusion was detected by chest ultrasound in April 2022).