Discussion:
This case illustrates an aggressive form of multiple myeloma that presented with both plasmacytic ascites and pleural effusion in the late stages of disease. The incidence of extra-medullary involvement in MM is about 7%, and that of malignant effusions is 1-2% which is usually associated with a poor prognosis. [9] [10] [11] Classic presenting symptoms and signs of MM include anemia, bone pain, renal failure, infections, and hypercalcemia. Effusions due to MM commonly occur due to secondary involvement of other organs like heart and kidney. Malignant ascites can occasionally be a presenting feature in MM, but myelomatous pleural effusion rarely manifests at initial diagnosis. [11] [12] [13] Four out of seven cases of MM with a malignant effusion that were reported by Gochhaitt et al presented with pleural effusion during their treatment with no other sites of involvement. All the four MM cases were first recognized based on the typical clinical presentation of hypercalcemia–renal function–anemia–bone lesion (CRAB). [10] Mitra et al reported case of an elderly male who was evaluated for ascites with abdominal pain and distension with high total protein but normal bilirubin and liver enzymes. Computed tomography (CT) scan of the abdomen revealed multiple peritoneal nodules, mesenteric and omental thickening. Both this and another MM patient reported by Abdulsamad et al presented with ascites at initial diagnosis unlike our patient who suffered from multiple relapses over 7 to 8 years and ultimately developed extra-osseous complications at an advanced stage of MM. [7, 8]
The body cavities are not unusual sites of metastasis, but the pathophysiology of their involvement is poorly understood. A pleural or peritoneal biopsy may show extensive plasma cell infiltration, but it is not necessary for diagnosis. [12] [13] The diagnosis of plasmacytic effusion can be confirmed based on detection of atypical plasma cells on fluid cytological analysis derived via paracentesis and/or thoracocentesis supplemented by immunofixation of proteins and identification of cytoplasmic immunoglobin, kappa or lambda light chains, and high CD38 and/or CD138 expression on their immunophenotypic analysis. [12] [14] An abdominal paracentesis in the case reported by Mitra did not reveal any significant findings. Histopathological examination of centrifuged peritoneal deposits showed CD138 positive plasma cells on immunohistochemistry. Serum electrophoresis confirmed the presence of IgG heavy chains and lambda light chains that led to the diagnosis of MM, IgG lambda, ISS Stage III. Similar findings were noted on flow cytometric immunophenotyping in the four patients described by Gochhaitt et al. [10] In one patient as described by Stoos-Veic et al, a diagnosis of myelomatous ascites was confirmed by flow cytometry immunophenotyping and presence of IgG kappa light chains on ascitic fluid immuno-electrophoresis. [15] Ghorbel et al described a case of an adult female diagnosed with MM Stage IIIa based on a serum electrophoresis, imaging, and bone marrow aspiration. Her clinical presentation was typical with worsening bone pain and classic fatigue but in about five months of treatment initiation, new respiratory symptoms led to the diagnosis of myelomatous pleural effusion based on a chest X-ray, thoracentesis, and a pleural biopsy. [16]
To help rule out secondary causes of effusion in MM such as infections, secondary tumors, renal or heart failure, ascitic fluid can be examined to calculate the serum ascites albumin gradient (SAAG) ratio, pleural fluid for pleural fluid/serum lactate dehydrogenase (LDH) ratio, adenosine deaminase (ADA) and glucose levels, and both for cell counts and cultures. [13] [17] Imaging modalities like skeletal survey, PET-CT scan and MRI are also commonly used to corroborate a diagnosis of MM bone disease and extra-medullary MM. [18] Alegre et al documented a disease presentation of similar nature as our patient, i.e., development of features of extramedullary MM in the form of ascites and pleural effusion later in the disease course. After remaining asymptomatic with a stage IA IgG multiple myeloma for 8 years after induction treatment, she abruptly presented with moderate ascites, unexplained fever, and pancytopenia due to bone marrow infiltration. A paracentesis demonstrated 93% atypical plasma cells on fluid cytology and monoclonal cytoplasmic kappa light chains on immunohistochemistry. [19]
Finally, myelomatous effusions seems to predict poor outcomes with short time to demise in the relapsed and refractory setting [15] [16] [19] [20] [21] it is important to recognize this entity as it might help differentiate infectious etiologies versus disease relapses in MM patients.