A Breathless Dilemma: Myelomatous Pleural Effusion

A 66 year old Caucasian woman presented to the emergency department with three week history of progressive shortness of breath and fatigue. Her past medical history was significant for IgA light chain multiple myeloma and hyperparathyroidism for which she had underwent Para-thyroidectomy. She had undergone multiple chemotherapy regimens including bortezomib, carfilzomib, Cytoxan, thalidomide and lenalilomide with failure to respond. At presentation, she was afebrile, heart rate of 120 beats/min, respiratory rate of 38 breaths/min, oxygen saturation of 95% on 55% venti mask and blood pressure of 120/80 mmHg.


Introduction
Pleural effusions in haematological malignancies are not uncommon. However, myelomatous pleural effusions (MPE) which are effusions directly related to infiltration of the pleura by plasma cells, are extremely rare. Herein we report a case of pleural effusion in patient with multiple myeloma.

Presentation
A 66 year old Caucasian woman presented to the emergency department with three week history of progressive shortness of breath and fatigue. Her past medical history was significant for IgA light chain multiple myeloma and hyperparathyroidism for which she had underwent Para-thyroidectomy. She had undergone multiple chemotherapy regimens including bortezomib, carfilzomib, Cytoxan, thalidomide and lenalilomide with failure to respond. At presentation, she was afebrile, heart rate of 120 beats/min, respiratory rate of 38 breaths/min, oxygen saturation of 95% on 55% venti mask and blood pressure of 120/80 mmHg.
Her physical examination was remarkable for stony dullness and reduced breath sounds on the right side of the chest. Initial laboratory investigations were significant for white cell count of 1 x 103 cells/mm 3 , hemoglobin 6.0 g/dl, and creatinine of 8.12 mg/dl and BUN 100 mg/dl. Chest X-ray demonstrated complete opacification of the right lung with mediastinal shift to the left ( Figure 1). She underwent ultrasound guided thoracentesis and 1.7 L of serous fluid was removed. Pleural fluid analysis revealed white cells of 575/uL with 56% atypical cells, exudative fluid as per Lights criteria.
On detailed cytological analysis, these atypical cells were single enlarged cells with eccentric nuclei, and were immunoreactive to CD138 supporting plasma cell differentiation ( Figure 2). Hence, the diagnosis made as large right true MPE. She was treated with haemodialysis and plasmapheresis for renal failure due to myeloma kidney. Recurrent pleural fluid accumulation was treated with pigtail catheter and this relieved her shortness of breath.

Discussion
Pleural effusions of true hematologic origin are rare occasional findings at some hematologic diseases. It was described in patient with chronic lymphocytic leukemia and was confirmed by lymphoma cells without Richter transformation at a high concentration [1]. Primary effusion lymphoma as a rare type of non-Hodgkin lymphoma was observed in herpes virus-8-positive but interestingly immunocompetent HIV negative patient [2]. Extramedullary hematopoietic effusion was described by Sekiguchi et al. [3] in 54-year-old man with follicular lymphoma; pleural effusion aspirate and a biopsied specimen obtained via thoracoscopy revealed megakaryocytes and immature myeloid cells in addition to lymphoma cells. Pleural effusion was observed in Multicentric Castleman's disease, a polyclonal lymphoproliferative disorder that manifests as marked hyper-γ-globulinemia, severe inflammation, anemia, and thrombocytosis [4]. Yamada et al. reported pleural effusion as initial presentation of MALT lymphoma and was associated with elevated CA125 [5].
True myelomatous pleural effusions (MPE) are very uncommon, with fewer than 100 cases reported in literature [6][7][8][9][10][11][12]. The diagnosis is usually confirmed by cytologic identification of malignant plasma cells and high levels of a monoclonal protein in the pleural fluid and histological study of pleural biopsy [13,14] At the time of diagnosis of MPE, patients also frequently have elevated serum β2-microglobulin, anemia, elevated serum lactate dehydrogenase, and elevated creatinine levels. Of various subtypes the incidence of MPE has been found remarkably high with IgD myeloma subtype [13]. However, other case studies suggest that majority of MPE take place in patients with the most abundant, IgG myeloma. Case reviews also show that MPE occurs equally among both genders, is typically hemorrhagic and occurs more commonly on the left [15][16][17].
Role of flow cytometry of pleural fluid has also been studied as a potentially useful and simple tool diagnosis (positive for CD56, CD38 and CD138, while negative for CD19), however it is not a standard method for diagnosis [18]. Elevated ADA activity in the pleural fluid (which can exceed the upper limits for tuberculous pleural effusions) could be helpful for detecting MPE at early stage [13].

Management
Various chemotherapies used in treatment include vincristine, adriamycin, cyclophosphamide, bortezomib with/without steroids combination. Low dose bortezomib has shown partial response in malignant pleural effusion in few cases; however this was followed by early relapse later in disease course [19]. Intrapleural injections of different chemotherapeutic agents like adriamycin and interferon were proposed [20,21]. Unfortunately, the outcome of these patients has not been favorable and they are usually found resistant to multiple chemotherapies. The median survival can vary between months to years. Timely etiological diagnosis and appropriate treatment is pivotal in overall prognosis in these patients.