Myelomatous pleural effusion in a patient with plasmablastic myeloma: A case report

Myelomatous pleural effusion is an unusual clinical condition associated with poor outcomes. We report a case with myelomatous pleural effusion upon the presentation of the disease. The patient had multiple risk factors for inferior prognosis of multiple myeloma, including old age, immunoglobulin D (IgD) isotype, high lactate dehydrogenase, C‐reactive protein, β2‐microglogulin levels, and a high myeloma cell burden in the bone marrow. The myeloma cells in both bone marrow and pleural effusion had characteristic features of plasmablasts, including gigantic size, large and eccentrically placed nuclei, fine cytoplasm, and prominent nucleoli. Immunophenotypical analysis showed the plasmablastic cells in the pleural effusion were positive for surface CD38, cytoplasmic immunoglobulin, both κ and λ light chains but negative for surface CD19 or CD79a. Our experience suggests that the diagnosis of myelomatous pleural effusion should be made with clinical alertness and careful cytological examination, preferably supplemented by immunophenotypical analysis. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Cytological diagnosis of malignant pleural effusion in myeloma

The cytological examination of pleural fluid established the malignant etiology of the effusion in two patients with multiple myeloma. In contrast to patients with lymphoma, mediastinal lymph node enlargement in myeloma is an uncommon factor in fluid formation. As in patients with metastatic carcinoma, pleural and underlying lung involvement by myeloma is the main cause of pleural effusion. The two cases in this report, and similar cases in the literature, probably represent distal dissemination from skeletal multiple myeloma.     

Amylase-producing multiple myeloma.

We managed a case of amylase-producing multiple myeloma with extensive extramedullary spread. We reviewed five cases of amylase-producing multiple myeloma, including this case. This type of multiple myeloma has shown unique clinicopathologic features. (1) A distinct elevation of the serum amylase activity was demonstrated in all five patients. The amylase isozyme was of the S type without exception. (2) Extensive extramedullary spread with extramedullary tumors and/or myelomatous pleural effusions or ascites was seen in all five patients during the course of illness. (3) In three of four cases in which it was mentioned, extensive destruction of multiple bones was demonstrated roentgenographically. (4) In four patients, excepting one with a solitary bone lesion, the survival from the initial therapy was shorter than 1 year. (5) Myeloma cell lines were established in three cases. A common feature of these three cell lines was a translocation of chromosome 1, which supplied the amylase gene. This finding may be pathogenetically related to this entity.     

Early peripheral lymph node involvement of human herpesvirus 8-associated, body cavity-based lymphoma in a human immunodeficiency virus-negative patient

Human herpesvirus 8 (HHV-8), or Kaposi sarcoma-associated herpesvirus, is a gamma herpesvirus first detected in a specimen of Kaposi sarcoma from a human immunodeficiency virus (HIV)-positive patient. Human herpesvirus 8 is also found in an unusual clinicopathologic form of body cavity-based B-cell lymphoma, which has been named primary effusion lymphoma (PEL) and occurs primarily in HIV-positive patients. PEL is characterized by the formation of lymphomatous effusions, without obvious lymphadenopathy, tumor masses, or bone marrow involvement. Only a few cases of PEL in HIV-seronegative patients have been reported. We describe a case of an HHV-8-associated lymphoma, with ascites, pleural effusion, and axillary lymphadenopathy in an HIV-negative patient. The patient was a 68-year-old Jewish man of North African extraction, with a previous history of coronary bypass surgery and multiple blood transfusions. The pleural fluid contained large atypical lymphoid cells and was suggestive of lymphoma but could not provide a conclusive diagnosis of PEL. The lymph node contained groups of large anaplastic lymphoid cells. Polymerase chain reaction for HHV-8 performed on the lymph node specimen was positive, establishing the diagnosis of PEL. Polymerase chain reaction for Epstein-Barr virus was negative. Results of a gallium scan were normal. The patient did not respond to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine sulfate, and prednisone and progressively developed, massive intra-abdominal solid tumor formation. To our knowledge, this is the first report of a case of PEL that demonstrates peripheral lymph node involvement at diagnosis and the first report of PEL in an Israeli patient.     

Cytology and flow cytometry of malignant effusions of multiple myeloma

Identifying malignant plasma cells in body fluids from multiple myeloma patients is important for therapeutic and prognostic considerations. This can be difficult when plasma cells are mature in appearance or low in number. We examined the cytological and flow cytometric findings of myelomatous pleural and pericardial effusions from 8 patients with advanced multiple myeloma. Cytoplasmic immunoglobulin light chain excess vs. DNA ploidy in the plasma-cell population was evaluated by flow cytometry (FCM). The cytology smears of one pericardial and 14 pleural effusions from the 8 patients were reviewed. Screening Papanicolaou-stained smears facilitated the detection of malignant nuclear features; however, morphology of plasma cells was best seen in Diff-Quik-stained smears. Low cellularity and inadequate air-drying of smears accounted for the false-negative cytology seen in two fluids from a single patient. A malignant plasma cell population was identified in 9 of 10 fluids submitted for FCM, including the two fluids with negative cytology. The false-negative FCM was from a suboptimal specimen with high background staining. Six fluids had an aneuploid DNA content, and four were diploid. A combination of Papanicolaou- and Diff-Quik-stained smears is recommended for the evaluation of plasma cells in effusions from patients with multiple myeloma. Cytology and flow cytometry confirmed malignancy in 87% and 90% of fluids evaluated, respectively; all cases were diagnosed by either one or both methods. Our results suggest that FCM and cytology of serous effusions in multiple myeloma patients are complementary and should be used in difficult cases. Diagn. Cytopathol. 2000;22:147-151.     

胸水多项肿瘤标志物检测的临床价值

目的:通过对胸水中多项肿瘤标志物的联合检测来鉴别癌性、结核性胸水,以提高癌性胸水诊断的阳性率。方法:采用多肿瘤标志物蛋白芯片诊断系统,检测60例癌性胸水和30例结核性胸水中的12种常见肿瘤标志物。结果:癌性胸水组中CEA、NSE、SF、CA125四项肿瘤标志物均值数、阳性率均显著高于结核性胸水组。四种指标联检对癌性胸水的诊断阳性率可达96 7%。结论:胸水CEA、NSE、SF、CA125联检对鉴别良恶性胸水有重要价值,且可显著提高癌性胸水的阳性诊断率。     

Elevated IL-5 levels in pleural fluid of patients with paragonimiasis westermani

To investigate the pathogenic mechanisms of eosinophilic pleural effusion in patients with paragonimiasis, we measured the levels of IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) in pleural effusions. Samples were obtained from 11 patients with Paragonimus westermani infection. In addition, samples from 12 patients with pleural transudates, 16 with tuberculous pleurisy, seven with empyema and 20 with lung cancer were also examined. Eosinophilia was remarkable in peripheral blood (range 4-34%, median 23.4%) and pleural fluid (range 0-95%, median 71%) of paragonimiasis patients. IL-5 concentrations in pleural effusions of paragonimiasis were markedly higher than those in other groups. Although marked elevation of GM-CSF and IFN-gamma levels was observed in pleural effusion of empyema and tuberculosis patients, it was marginal in the pleural effusion of paragonimiasis patients. In paragonimiasis patients, IL-5 levels in the pleural effusion correlated well with the percentage of eosinophils in peripheral blood and pleural fluid. Such a correlation was not observed between GM-CSF levels in pleural effusion and percentages of eosinophils in pleural fluid or peripheral blood. Our findings suggest that in paragonimiasis IL-5 in the local inflammatory site is particularly important in mediating eosinophilia in peripheral blood and pleural effusion.     

Beta 2 microglobulin in pleural effusions

Beta 2 microglobulin (beta 2m) concentrations in serum and pleural fluid from 64 patients with pleural effusion were studied. The level of beta 2m in pleural fluid was generally twice that in serum. The ratio of pleural fluid beta 2m to serum beta 2m in patients groups defined according to the final diagnosis showed an interestingly high value in tuberculous pleuritis and in patients with rheumatoid arthritis with pleural effusion. There was a positive correlation between the beta 2m and lysozyme contents in pleural fluid, suggesting local and simultaneous activation of different cell lines when the pleura is involved. We suggest that pleural fluid and concomitant serum beta 2m measurements should be taken into consideration when pleural effusion of tuberculous origin is suspected. Furthermore, beta 2m determination might help to differentiate between rheumatoid pleural fluid and pleural involvement due to the other systemic diseases.     

Primary systemic amyloidosis leading to advanced renal and cardiac involvement in a 30-year old man

The case of a 30-year-old man with primary systemic amyloidosis is reported. Three months prior to admission the patient developed fever, night sweats, dyspnea, and bilateral ankle swelling. Recurrent left-sided pleural effusion led to further investigation when massive proteinuria with free monoclonal lambda chains in the urine became evident. Abdominal subcutaneous fat aspiration and renal biopsy confirmed the diagnosis of amyloidosis. Bone marrow biopsy and bone scan did not reveal multiple myeloma. Echocardiography showed a sparkling texture of the interventricular septum. Pulsed-wave Doppler recording of the left ventricular inflow profile showed the pattern of advanced cardiac amyloidosis consistent with markedly impaired diastolic heart function. Electrocardiogram-gated magnetic resonance imaging was carried out for noninvasive evaluation of cardiac function. The patient was started on repeated courses of melphalan, prednisone, and colchicine therapy. Despite increasing deterioration of renal function the therapy was tolerated quite well, and the patient is still alive 10 months after initial diagnosis. Although very rare in this age, primary systemic amyloidosis should be considered as a cause of pleural effusion, proteinuria, and congestive heart failure and should lead to further investigation.Abbreviations AL primary systemic amyloidosis - SAA serum amyloid A Correspondence to: I. Spyridopoulos     

Diagnostic utility of pleural fluid IFN-gamma in tuberculosis pleural effusion.

Pleural fluid interferon-gamma (IFN-gamma) levels are increased in patients with tuberculosis (TB) pleural effusion. Recent studies from the west have found that estimation of pleural fluid IFN-gamma levels is an excellent diagnostic strategy for these patients. The diagnostic utility of pleural effusion IFN-gamma level estimation has not been evaluated in patients from developing countries, however. This work was carried out to study the diagnostic utility of IFN-gamma level estimation in patients with TB pleural effusion and to define the best cutoff of IFN-gamma for diagnosis TB pleural effusion. We studied 101 patients with pleural effusion. Of these, 64 were found to have a TB etiology, established by means of various conventional modalities. Measurement of pleural fluid IFN-gamma levels was done by ELISA technique. The median value of pleural fluid IFN-gamma levels in patients with TB (1480 pg/ml, range 3-14,000 pg/ml) was significantly higher (p < 0.001) compared with the non-TB group (3 pg/ml, range 0-900 pg/ml). The receiver operator characteristic (ROC) curve for IFN-gamma showed an area under the curve (AUC) value of 0.954, and the best cutoff was computed to be 138 pg/ml. Using this cutoff for IFN-gamma levels in pleural fluid for the diagnosis of TB, sensitivity, specificity, negative predictive value, and positive predictive value were found to be 90.2%, 97.3%, 85.7%, and 98.3%, respectively. Estimation of IFN-gamma levels in pleural fluid is a useful diagnostic modality for TB pleural effusion. A cutoff of 138 pg/ml provides the best sensitivity and specificity for diagnosis of TB.     

Hemothorax with high number of eosinophils following warfarin overdose

Some drugs are known to induce pleural effusion. Drug-induced pleural effusion is often associated with pleural fluid eosinophilia. Anticoagulant therapy may induce pleural effusion by at least two different mechanisms: bleeding complication (haemothorax) and allergic or toxic reaction. Authors describe 76-yr-old male with warfarin-induced pleural effusion. Since INR was 15.5, and the value of pleural effusion Hct exceeded significantly 50% of Hct value in blood, spontaneous haemothorax due to warfarin overdose was diagnosed. Pleural fluid analysis revealed relatively high percentage of eosinophils (13%), but it was probably secondary to the presence of numerous red blood cells in the effusion. The authors discuss different mechanisms of drug-induced pleural effusion, with special attention to eosinophilic pleural effusion and review the literature on the spontaneous haemothorax as a complication of anticoagulant therapy.     

The diagnostic value of the adenosine deaminase activity in the pleural fluid of renal transplant patients with tuberculous pleural effusion

The assessment of the adenosine deaminase activity (ADA) in the pleural effusion is used for the diagnosis of tuberculous pleural effusion (TPE). To examine whether the procedure can be applied to immunocompromised patients, we analyzed the ADA activity in the pleural fluid of renal transplant recipients. We studied 23 renal transplant patients with TPE (21 men and 2 women; the mean age, 33 years). They were treated at the Yonsei University Hospital between January 1985 and December 2001. Patients with granuloma in the pleural biopsy specimen or positive for Mycobacterium tuberculosis in the pleural fluid culture were recruited. The ADA activity in the pleural effusion of 23 renal transplant patients with TPE was compared with 23 immunocompetent patients with TPE. The mean ADA activity was 69.5 +/- 4.6 in renal transplant patients and 65.0 +/- 4.9 U/L in immunocompetent patients. Applying the 40 U/L cut-off point, the positivity of ADA was 91.3% in renal transplant patients, and 86.9% in immunocompetent patients. We thus concluded that the measurement of ADA in the pleural fluid is a useful means in the diagnosis of TPE in renal transplant patients.     

A case of leukemic pleural infiltration in atypical chronic myeloid leukemia

Pleural effusion in chronic myeloid leukemia (CML) is poorly understood and rarely reported in the literature. When the pleural effusion is caused by leukemic pleural infiltration, the differential white blood cell count of the effusion is identical to that of the peripheral blood, and the fluid cytology reveals leukemic blasts. We report here a case of bilateral pleural involvement of atypical CML in an 83-yr old male diagnosed with pancreatic cancer with abdominal wall metastasis and incidental peripheral leukocytosis. Based on bone marrow examination, chromosome analysis and polymerase chain reaction he was diagnosed with Philadelphia chromosome negative, BCR/ABL gene rearrangement negative CML. Following 3 months of treatment with gemcitabine for pancreatic cancer, he developed bilateral pleural effusions. All stages of granulocytes and a few blasts were present in both the pleural fluid and a peripheral blood smear. After treatment with hydroxyurea and pleurodesis, the pleural effusion resolved.     

Cytology and clinical features of myelomatous pleural effusion: Three case reports and a review of the literature

The purpose of this study was to report the clinical features, laboratory findings, and cytomorphology, and prognosis of three patients with myelomatous pleural effusion (MPE). The literature pertaining to MPE was reviewed. The three cases and literature review suggest that MPE is rare and often associated with a poor prognosis. The correct diagnosis depends on the aggressive clinical characteristics, laboratory findings, and chromosomal abnormalities, but routine pathological examination of the pleural effusion has low sensitivity. Cell blocks stained with hematoxylin & eosin and by immunohistochemistry revealed that abnormal proliferation of plasma cells and light chain restrictive expression in MPE may be helpful for improving the detection rate of MPE.     

Digital chest radiography with storage phosphor systems: Potential masking of bilateral pleural effusions

A photostimulable storage phosphor (PSP) computed radiography imaging system was analyzed for its potential to mask pleural effusion during normal image processing. This phenomenon has been observed in several clinical cases in our hospital. To better understand the relationship between pleural effusion and the PSP radiograph appearance, portable radiographs of an athropomorphic chest phantom were acquired with the PSP system in conditions simulating various quantities and distributions of pleural fluid. It was observed that the optical density of the film in one hemithorax was significantly influenced by whether or not fluid was present in the opposite hemithorax. This optical density dependence was determined to be a system-induced effect that results from the image processing (histogram analysis) technique used by the PSP system during image plate readout. It is important to recognize that the PSP system's normal optical density (sensitivity) adjustment can obscure the presence of bilateral pleural fluid accumulation, particularly if the opposite hemithorax contains fluid in an equal or greater amount.     

Bilateral pleurisy revealing a myelome with free light chains complicated with an osseous amylose

The osseous amyloidosis associated with a pleural effusion in a myeloma is a rare situation. We report a case of an association of these three disease entities for discussion. A 75-year-old man was admitted for chest pain and dyspnea with left sacred bone pain. The radiological assessment reported pleurisy and bilateral lytic images of the sacrum with soft tissue invasion, the biochemical tests showed a lambda free light chain myeloma and bone biopsy reported amyloidosis. The occurrence of systemic amyloidosis in myeloma is well documented, but the osseous location is rare and rarely revealed. Pleural effusion is a known complication of myeloma but is exceptionally revealing; it is usually seen in the myeloma IgG and IgA but very rarely in free light chain myeloma. We reported here a case that represents an exceptional situation of complications of light chains myeloma to remember their possible occurrence and to insist for the clinician sensitizing to carry out investigations on time and avoid complications or at minimum to retard them.     

Fine-needle aspiration of malignant mesothelioma with unusual morphologic features: a case report

Malignant mesothelioma is an aggressive neoplasm linked to asbestos exposure. Most mesothelioma patients present with pleural effusion and the fluid is typically sent for cytological examination. Therefore, cytopathologists are most familiar with features of mesothelioma in fluid preparations. We present here a case of malignant mesothelioma with unusual cytological features diagnosed on FNA. The diagnosis was confirmed by immuno-histochemical and electron microscopic studies. In addition, we compare the cytomorphological features observed in malignant effusion versus fine-needle aspiration.     

Myelomatous involvement of the dura mater: a rare complication of multiple myeloma

A case of myelomatous involvement of the dura mater is reported. The patient presented with blurring of vision in the right visual field and left sided facial numbness. A magnetic resonance imaging scan of the head revealed extensive infiltration of the dura mater. Cerebrospinal fluid (CSF) analysis showed no plasmacytosis and although there was a raised CSF protein concentration, no paraprotein band was detected, despite the presence of serum paraprotein. The infiltration of the dura mater is likely to have arisen by spread from contiguous bone lesions, contrasting with the pattern of spread seen in myelomatous involvement of the leptomeninges, which probably occurs through haematogenous seeding of the meninges. Leptomeningeal involvement is associated with a very poor prognosis; however, this patient had a favourable response to combined chemotherapy and cranial radiotherapy, suggesting that myelomatous involvement of the dura mater should be considered as a distinct complication of myeloma.     

Role of the Neutrophil-Lymphocyte Ratio in the Differential Diagnosis of Exudative Pleural Effusion

OBJECTIVES:Pleural effusion is a common diagnostic and clinical problem. The differential diagnosis of pleural effusion may be difficult and may require several procedures, including invasive ones. Certain studies have investigated biochemical parameters to facilitate the diagnosis of exudative pleural effusion; however, it remains a challenging problem in clinical practice. We aimed to investigate the potential role of the neutrophil-lymphocyte ratio, which can be easily obtained by determining the cell count of the pleural fluid, in the differential diagnosis of exudative pleural effusion.METHODS:Records from patients who underwent thoracentesis and pleural fluid analysis between May 1, 2013, and March 1, 2015, were obtained from the electronic database of our hospital. The patients who met the inclusion criteria were divided into five groups according to their diagnosis: malignant pleural effusion, para-malignant pleural effusion, para-pneumonic effusion, tuberculosis-related effusion or other. The neutrophil-lymphocyte ratio value was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. The patient groups were compared according to the given parameter.RESULTS:A total of 465 patients who met the inclusion criteria among 1616 patients with exudative pleural effusion were included in the study. The mean neutrophil-lymphocyte ratio value was significantly lower in tuberculosis-related pleural effusion compared to malignant, para-pneumonic and para-malignant effusions (p=0.001, p=0.001, p=0.012, respectively). The areas under the curve for tuberculosis pleurisy compared to malignant, para-pneumonic and para-malignant effusions were 0.38, 0.36, and 0.37, respectively. Lower cut-off values had higher sensitivity but lower specificity for tuberculosis pleurisy, while higher cut-off values had higher specificity but lower sensitivity for this condition.CONCLUSION:The pleural fluid neutrophil-lymphocyte ratio, which is an inexpensive, reproducible, and easily calculated hematological parameter, may facilitate the differential diagnosis of pleural effusion.     

Human placenta-derived adherent cells prevent bone loss, stimulate bone formation, and suppress growth of multiple myeloma in bone

Human placenta has emerged as a valuable source of transplantable cells of mesenchymal and hematopoietic origin for multiple cytotherapeutic purposes, including enhanced engraftment of hematopoietic stem cells, modulation of inflammation, bone repair, and cancer. Placenta-derived adherent cells (PDACs) are mesenchymal-like stem cells isolated from postpartum human placenta. Multiple myeloma is closely associated with induction of bone disease and large lytic lesions, which are often not repaired and are usually the sites of relapses. We evaluated the antimyeloma therapeutic potential, in vivo survival, and trafficking of PDACs in the severe combined immunodeficiency (SCID)-rab model of medullary myeloma-associated bone loss. Intrabone injection of PDACs into nonmyelomatous and myelomatous implanted bone in SCID-rab mice promoted bone formation by stimulating endogenous osteoblastogenesis, and most PDACs disappeared from bone within 4 weeks. PDACs inhibitory effects on myeloma bone disease and tumor growth were dose-dependent and comparable with those of fetal human mesenchymal stem cells (MSCs). Intrabone, but not subcutaneous, engraftment of PDACs inhibited bone disease and tumor growth in SCID-rab mice. Intratumor injection of PDACs had no effect on subcutaneous growth of myeloma cells. A small number of intravenously injected PDACs trafficked into myelomatous bone. Myeloma cell growth rate in vitro was lower in coculture with PDACs than with MSCs from human fetal bone or myeloma patients. PDACs also promoted apoptosis in osteoclast precursors and inhibited their differentiation. This study suggests that altering the bone marrow microenvironment with PDAC cytotherapy attenuates growth of myeloma and that PDAC cytotherapy is a promising therapeutic approach for myeloma osteolysis.