Beyond the Bone: When Multiple Myeloma Takes an Unexpected Turn

Introduction/Background/Significance: Multiple myeloma (MM) is a malignant plasma cell disorder that primarily affects the bone marrow, leading to hematologic complications, bone destruction, and end-organ dysfunction. True myelomatous pleural effusion (MPE) is extremely rare, occurring in less than 1% of cases, and is confirmed by malignant plasma cells in pleural fluid cytology or biopsy. Differentiating MPE from more common secondary causes of pleural effusion is crucial, as MPE carries a poor prognosis with median survival of less than four months. We present a case of a 78-year-old male with a history of MM who developed MPE.

Materials and Methods/Case Presentation/Objective: A 78-year-old male with a history of non-Hodgkin's lymphoma and multiple myeloma presented with acute hypoxic respiratory failure and found to have large left pleural effusion. Thoracentesis drained 2L of yellow cloudy fluid. Analysis showed an exudative effusion with a pH of 7.3, total protein of 4.1 g/dL, glucose of 105 mg/dL, lactate dehydrogenase (LDH) of 265 U/L. and a macrophage-predominant cell count of 93%. Serum protein was 5.3 g/dL, and serum LDH was 433 U/L.

Results/Description/Main Outcome Measures: Given the patient's underlying malignancy, there was suspicion for MPE. Cytological analysis showed CD138 positivity and clonal lambda light chain, confirming MPE. The patient was initially started on empiric doxycycline and cefepime to cover for infectious effusion, which was later discontinued after fluid analysis confirmed MPE. The patient's oxygen requirements improved after thoracentesis, and he did not develop a recurrent effusion during his hospital course.

Upon discharge, the patient and his oncologist decided to pursue bi-specific T-cell therapy with Teclistamab and he was hospitalized for the “ramp-up" phase at a different center.

Conclusions: This case underscores the clinical importance of recognizing myelomatous pleural effusion (MPE) as a rare but serious complication of multiple myeloma, as it significantly influences management and prognosis. Pathologic features of MPE include clonal plasma cells with aggressive markers such as CMYC/P53 overexpression, high Ki-67, and genomic alterations like RAS mutations and MYC rearrangements. Diagnosis is confirmed through cytology and immunostaining (e.g., CD138, MUM1, and light chain restriction), as demonstrated in our case. Prognosis is poor, with median survival reported as low as 32 days to 4 months, and significantly worse than other extramedullary manifestations (i.e soft-tissue plasmacytomas). Although treatment options are limited and largely palliative, early diagnosis may help tailor management strategies and inform prognosis. This case also emphasizes the urgent need for further research into targeted therapies, such as bortezomib, which may hold future promise in treating MPE.