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"textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Multiple myeloma (MM) is a malignant clonal proliferation of plasma cells in the bone marrow, which is typically accompanied by the secretion of monoclonal immunoglobulins detectable in serum and urine (M-component). MM represents approximately 10–15% of hematological malignancies.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">1</span></a> The median age at MM diagnosis is approximately 70 years, and 2 of every 3 patients are men.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> Although the proliferation of plasma cells in most patients with MM is limited to the bone marrow, the hematogenous dissemination of these cells can cause the infiltration of distant sites, a condition known as extramedullary myeloma. Approximately 6–8% of patients with MM have extramedullary disease at the time of diagnosis if the initial staging includes computed tomography and positron emission tomography (CT-PET).<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">3</span></a> During the course of the disease, extramedullary involvement can develop in 15–30% of patients with the disease.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">3</span></a> The diagnosis of extramedullary myeloma is associated with an adverse prognosis, particularly when it is part of a recurrence of MM.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Myelomatous pleural effusion (MPE) is a type of extramedullary involvement of MM. MPE is a rare cause of pleural effusion (PE), which, in a Spanish series, represented only 0.6% of 840 malignant PEs.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">4</span></a> Moreover, MPE is not the most common etiology of PE in patients with MM. In a retrospective study of 575 patients with MM, 80 (14%) developed PE in the chest radiography (bilateral in 61% of cases) during the development of the disease.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">5</span></a> The most common cause of PE was pneumonia (20 cases; 25%), followed by PE reactive to various processes (15; 18.8%), heart failure (9; 11.2%) and hypoalbuminemia (9; 11.2%). Only 7 patients (8.8%) had an MPE, which entailed poorer survival compared with those who had PE from other causes. Only 32 (40%) patients with PE underwent diagnostic thoracentesis or pleural biopsy to determine its etiology, while 22 (27.5%) patients did not undergo additional tests, mainly because the cause of the PE was considered obvious from a clinical viewpoint. This study reinforced the idea that etiologies foreign to the myelomatous infiltration of the pleura, such as parapneumonic PE, heart failure, renal failure and amyloidosis, should be initially considered for all patients with MM who develop PE. Amyloidosis can cause PE by cardiac (heart failure), renal (nephrotic syndrome and hypoalbuminemia), hepatic (ascites) or pleuropulmonary involvement. The broad etiological spectrum of PE in MM requires at least one diagnostic thoracentesis and, based on the results, an imaging test (CT-PET or CT).</p><p id="par0015" class="elsevierStylePara elsevierViewall">MPE can be explained by the pleural infiltration of plasma cells from the bloodstream (hematogenous dissemination), lymph nodes (lymphatic dissemination) or contiguous plasmacytoma in the ribs or vertebras.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">6</span></a> Given the rarity of this condition, the article by Riveiro <span class="elsevierStyleItalic">et al.</span> published in this edition of <span class="elsevierStyleSmallCaps">Revista Clínica Española</span> is timely and provides data of unquestionable clinical importance.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">7</span></a> The authors performed a systematic review of individual cases and small retrospective series that included 153 patients with MPE reported in the medical literature up to December 2016. The diagnosis of MPE preceded or was simultaneous to that of MM in only 26% of the cases, which mimics the behavior of breast cancers, where most patients who develop malignant PE have a previous history of the tumor.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">8</span></a> Given that these were already known relapses in patients with MM, the MPEs were typically associated with the signs and symptoms of the underlying hematologic disease (bone pain, osteolytic lesions, anemia and renal failure). Similar to that reported for malignant PEs,<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">9,10</span></a> MPE was typically unilateral (approximately two-thirds of cases), large or massive in half of the cases, with the presence of nodules or pleural thickening in 45% of cases. In addition, the general appearance of the fluid (hematologic in 55% of cases) and its biochemical analysis (95% of exudates, predominantly mononuclear cells in approximately 80% of cases) accurately reflect the general characteristics of a malignant PE.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">11</span></a> As with other hematological malignancies (lymphomas),<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">12</span></a> MPE frequently (65%) presented increased pleural adenosine deaminase levels above the diagnostic cutoff for tuberculosis (>35<span class="elsevierStyleHsp" style=""></span>U/L).</p><p id="par0020" class="elsevierStylePara elsevierViewall">The monoclonal immunoglobulin in most MPEs has classically been considered the IgA subtype,<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">13</span></a> although this fact is not recorded in the systematic review by Riveiro <span class="elsevierStyleItalic">et al.</span><a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">7</span></a> The diagnosis of MPE is typically performed by demonstrating the presence of tumor plasma cells or M-component in pleural fluid; alternatively, pleural biopsy may be performed. In questionable cases, flow cytometry helps identify the immunophenotype of the neoplastic plasma cells as opposed to the immunophenotype of the reactive cells. In the last decade, the median survival for MM has doubled (from 4 to 8 years) with the introduction of new drugs.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">14</span></a> For patients with extramedullary myeloma, however, survival is shorter than 6 months.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">3</span></a> Due to the poor prognosis and rate with which MPEs are symptomatic, there is a surprising lack of patients who undergo definitive pleural procedures, such as pleurodesis and the insertion of a tunneled pleural catheter (TPC), in the previously mentioned systematic review.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">7</span></a> In our opinion, TPC is a good therapeutic option, as showed by a multicenter study of 91 patients with hematological diseases (which included 12 patients with MM) who were undergoing active chemotherapy, whose PE was handled with this procedure.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">15</span></a> The patients carried the TPC for a mean duration of 3 months, and the risk of infection (7.7%) did not differ significantly from that reported in patients with solid malignancies treated in the same manner.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">16</span></a> Studies such as the one by Riveiro <span class="elsevierStyleItalic">et al.</span> are important, to say the least, for raising awareness among clinicians of the need for performing studies that strengthen the evidence on the diagnostic and therapeutic aspects of uncommon diseases.</p></span>"
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