multiple myeloma ( mm ) is a common disease , accounting for 10% of hematologic malignancies . pleural effusions occur in up to 6% of patients with mm [ 1 , 2 ] but rarely as a result of primary myelomatous infiltration or pleural involvement [ 2 , 3 , 4 ] . most pleural effusions in mm are secondary to heart failure from amyloidosis , nephrotic or nephritic syndrome , pulmonary embolism , lymphatic obstruction , hypoalbuminemia or infections [ 3 , 5 , 6 ] . myelomatous pleural effusion ( mpe ) is a rare entity , occurring in only about 1% of mm pleural effusions [ 1 , 2 , 3 , 4 , 5 ] with < 100 having been reported . mpe is usually a sign of advanced disease [ 1 , 2 , 7 ] and the reported median survival time is < 4 months . diagnosis is based on criteria proposed by the international myeloma working group , and includes monoclonal protein detection by pleural fluid protein electrophoresis , presence of atypical plasma cells in the effusion or histological confirmation by pleural biopsy [ 3 , 7 ] . the most frequently used study is pleural cytology [ 1 , 2 , 9 , 10 , 11 ] , which establishes diagnosis in > 90% of cases   and has been considered the best method , although electrophoresis confirmation is sometimes advocated for [ 7 , 12 ] . a general male predominance has been found [ 1 , 2 ] , and associated pleural or chest wall plasmacytomas are usually present [ 1 , 4 ] . although its development in advanced disease is more common [ 2 , 3 , 4 , 6 , 7 , 9 ] , less frequently it is the initial presenting feature of mm [ 1 , 5 ] . a higher prevalence of igg and iga was found in different series [ 1 , 2 , 4 ] , while light chain type is uncommon [ 2 , 4 ] except in mpe as initial presentation . ferritin is irregularly used as a tumor marker and has recently been explored as a prognostic factor   in mm , as it can reliably represent the inflammatory and oxidant pathways that play a significant role in plasma cell malignancies . we describe a case in which mpe presented with extremely high ferritin levels , reflecting the potential value of ferritin as an mm marker . a 40-year - old male was admitted to our institution for acute hypoxic respiratory failure for 3 days . seven months prior to admission , he had been diagnosed with mm stage iii ( according to the international staging system ) . at that time , records showed a bone marrow ( bm ) biopsy consistent with plasma cell myeloma : hypercellular marrow ( 90% ) with residual trilineage hematopoiesis and increased immature morphology plasma cell infiltrate involving 6070% of cellularity . flow cytometry of bm specimen showed a clonal population of plasma cells ( 27% ) with an immunophenotype positive for cd138 , cd38 and cd56 markers . cytogenetics displayed complex abnormalities consisting of monosomy 13 , trisomy 3 and 9 and 1p deletion . serum protein electrophoresis showed a monoclonal iga lambda paraprotein and urine protein electrophoresis revealed a monoclonal lambda light chain ( bence - jones protein ) . imaging studies revealed widespread lytic lesions in the calvarium , bilateral humerus , pelvis and spine , as well as a 5.8  3.8 cm right 5th lateral rib plasmacytoma . at the time of the initial diagnosis , he showed high disease activity with a baseline 2-microglobulin level of 6.2 mg / l and a serum ferritin level of 728 ng / ml . he was also found to have compromised kidney function consistent with stage iii chronic kidney disease from light chain nephropathy , but no major hepatic , pulmonary or coagulation abnormalities were found . he failed treatment with vincristine , cyclophosphamide , and methylprednisolone as well as bortezomib , cyclophosphamide , and solu - medrol , but remarkably responded to a modified phase ii study regimen with bortezomid , bendamustine , and dexamethasone for refractory mm . after ruling out pulmonary embolism with a ventilation / perfusion scan and heart failure with a normal brain natriuretic peptide level and left ventricular function on the echocardiogram , infectious causes were considered , despite normal body temperature , as chest imaging showed bilateral ground - glass opacities with superimposed interlobular septal thickening and intralobular reticular thickening ( fig . he received empiric broad - spectrum antibiotics , including coverage for atypical bacteria and pneumocystis jiroveci . bronchoalveolar lavage with methenamine silver stain for fungal and p. jiroveci - like organisms was negative , as were immunohistochemical studies for cytomegalovirus and herpes simplex virus . special stains including congo red and periodic acid - schiff stain were negative for amyloidosis and pulmonary alveolar proteinosis , respectively . after a brief initial response to supportive respiratory measures and empiric antimicrobial therapy , he developed multisystemic organ failure , including lactic acidosis , acute liver failure with metabolic encephalopathy , acute kidney injury and worsening pancytopenia dependent on blood and platelet transfusions . the workup revealed active myelomatous disease with rising serum iga and 2-microglobulin levels to 8.6 mg / l . remarkably , a serum ferritin level of 11,598.5 ng / ml was found and concern for hemophagocytic lymphohistiocytosis ( hlh ) led to empiric treatment with high doses of dexamethasone and an urgent bm biopsy , which showed atypical plasma cells comprising 90% of the marrow cellularity but no evidence of hemophagocytosis or increased blasts . sequential chest imaging showed a timely correlation between his acute clinical decline and the acute development of a large right pleural effusion . thoracentesis revealed a heavily blood stain exudate ( ph 7.38 , protein 6.9 g / dl , lactate dehydrogenase 1,543 iu / l , white blood cell count of 4,610/l with 94% lymphoid cells ) , with negative fungal and bacterial cultures . 2 ) and immunostaining confirmed mm involving pleural effusion [ cd138- and cd38-positive ( fig . high - dose steroids were continued and the effusion was drained ; however , multisystemic organ failure prevented the initiation of intravenous chemotherapy . despite aggressive supportive measures , he developed disseminated intravascular coagulation , required endotracheal intubation , vasopressor support , and finally perished soon after the diagnosis . mpe is extremely rare , with a recent series reporting only 64 cases from relevant sources in the english literature since 2000 . we present a case of mpe associated with hyperferritinemia and severe multiorgan failure , a clinical course resembling catastrophic inflammatory conditions such as hlh that has not been described in mpe before . given its infrequency , a high suspicion is needed for diagnosis . only about 1% of pleural effusions in mm patients will be attributed to myelomatous involvement [ 1 , 2 , 3 , 4 , 5 ] , but unless the clinical presentation is obvious and rules it out , we believe mpe should always be considered in mm patients presenting with pleural effusions . this is important because mpe represents an aggressive clinical progression of mm , and a recent series reported a median survival of 2.8 months despite aggressive local and systemic treatment . as in our case , the diagnosis is most likely revealed by pleural cytology [ 1 , 2 , 5 ] . protein electrophoresis is another option , by itself or as a confirmation to cytology , but is unreliable since most effusions are hemorrhagic . pleural biopsies are less commonly used due to their inconvenience   and a lower diagnostic yield given the patchy pleural involvement in mm . some risk factors for developing mpe in mm were found in our patient and are consistent with the review of other reported cases and series . these include its occurrence in the late stage of mm [ 2 , 4 , 7 ] , association with high - risk cytogenetics , such as deletion 13 chromosomal abnormality [ 1 , 2 ] and usual coexistence of chest wall plasmacytomas [ 1 , 4 ] . the mm subtype does not seem to be a risk factor given that igg was most common in 2 series with a total of 28 patients [ 1 , 4 ] , while iga was predominant in a 19-patient single - institution series   and overall all types have been reported in at least 1 case [ 7 , 8 , 9 ] . except in mpe as initial presentation of mm , where it constituted 24% of the cases , light chain type seems to be very uncommon [ 2 , 4 ] . as the majority of the literature on this topic is from single reported cases and small series , the relationship between tests or treatment and prognosis is not known ; however , as prognosis is known to be poor , palliation is considered the mainstay of treatment and includes chemotherapy and pleurodesis . there is no chemotherapeutic regimen of choice since a wide variety has been used over time and no meaningful comparisons can be made [ 1 , 2 , 4 ] . recent studies suggest that the inflammatory and oxidant pathways play a significant role in the pathogenesis of plasma cell malignancies , and ferritin levels can be a reliable indicator of these processes in carcinogenesis . therefore , ferritin has been used as a marker in mm and other hematologic malignancies [ 10 , 11 ] . studies show that ferritin levels are an independent predictor of mortality in newly diagnosed mm , that higher ferritin levels are present in recurrent mm compared to patients in remission   and that ferritin has a prognostic value in mm patients undergoing autologous transplantation [ 13 , 14 ] . this evidence has been proposed to reflect a correlation between ferritin levels and disease activity , tumor load and malignant potential . our case is the first report that links mpe to extreme levels of hyperferritinemia , which are usually present only in medical conditions associated with severe inflammatory states such as hlh and septic shock where ferritin is thought to have a pathogenic role leading to a cytokine storm and catastrophic clinical outcomes known as the hyperferritinemic syndrome . it is known that hematologic malignancies and sepsis can lead to hlh , but this was ruled out in our patient . unfortunately , ferritin levels have not been reported in previous mpe cases , and it is unknown if this finding is an isolated coincidence or if it has been missed in previous reports . we believe mpe could represent or be part of an extreme manifestation of myeloma disease activity leading to a severe inflammatory cascade with subsequent multiorgan failure . we recommend investigating ferritin levels in patients with mpe to better determine its relationship with pathogenic inflammatory states such as hlh . this relationship could certainly explain the poor prognosis and severe clinical complications seen with mpe . written informed consent for personal clinical and imaging information was obtained from the patient before publication of this case report and its accompanying images . a copy of the written consent is available for review from the editor - in - chief of this journal . the authors declare that there is no conflict of interest regarding the publication of this paper .
myelomatous involvement of pleural effusions developing in patients with multiple myeloma is extremely rare and only a few cases have been reported so far . 
 it is thought to represent an aggressive clinical progression of disease and is usually associated with severe complications , poor prognosis and high mortality . 
 ferritin is a marker of inflammatory pathways that plays a significant role in plasma cell malignancies and has been studied as a prognostic factor for multiple myeloma . in severe inflammatory states such as septic shock or hemophagocytic lymphohistiocytosis , extreme levels of ferritin are thought to precipitate a cytokine storm associated with poor clinical outcomes . 
 we present a case of myelomatous pleural effusion associated with extreme levels of ferritin and explore the possibility of a connection between this rare entity and other severe inflammatory states , which could account for its ominous outcomes and poor prognosis .