Pleural Biopsy Specimens Research Articles

Evaluation of real-time polymerase chain reaction, interferon-gamma, adenosine deaminase, and immunoglobulin A for the efficient diagnosis of pleural tuberculosis

Pleural tuberculosis (TB) is a diagnostic challenge because of its non-specific clinical presentation and paucibacillary nature. Conventional diagnosis methods have limitations. We evaluated the real-time polymerase chain reaction (PCR), interferon-gamma (IFN-γ), adenosine deaminase (ADA), and immunoglobulin A (IgA). We assessed 204 cases: 50 were confirmed pleural TB, 104 were probable pleural TB, and 50 formed the non-TB group. IFN-γ and IgA were measured by enzyme-linked immunosorbent assay and ADA was measured by colorimetric assay. Real-time PCR was carried out using the 16S rRNA sequence, pleural biopsy specimens were submitted to histopathologic examination, pleural fluid culture was undertaken using Lowenstein-Jensen and MGIT-BACTEC, and pleural fluid smears were stained with auramine O. For confirmed and probable pleural TB cases, the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was highest for IFN-γ (0.994 and 0.963, respectively), followed by ADA (0.989 and 0.945, respectively), real-time PCR (0.898 and 0.784, respectively), and IgA (0.817 and 0.784, respectively). For confirmed and probable pleural TB cases, IFN-γ showed the highest sensitivity (98% and 76.9%, respectively), followed by ADA (92% and 73%, respectively), real-time PCR (80% and 57.7%, respectively), and IgA (70% and 57.7%, respectively). With regard to combined positivity, the combination of 'either real-time PCR or IFN-γ' showed the highest sensitivity: 100% in confirmed pleural TB and 96.2% in probable pleural TB. IFN-γ showed the highest sensitivity as an individual diagnostic test. When a combination of tests was used, positivity of 'either IFN-γ or real-time PCR' appeared valuable for the diagnosis of pleural TB.

Miyelomatöz Plevral Efüzyon: Multipl Miyelomda Nadir Bir Tutulum

Multiple myeloma is a neoplastic disorder caused by the proliferation of a single plasma cell clone and is associated with the production of monoclonal immunoglobulin. Multiple myeloma rarely involves the pleura, and this involvement indicates an unfavorable prognosis. We report a 53-year-old man with multiple myeloma and a myelomatous right-sided pleural effusion with elevated adenosine deaminase (ADA) activity. The diagnosis was made by examination of the pleural fluid cytology and pleural biopsy specimen. Systemic chemotherapy was administered to the patient, and pleuredesis was performed. However, the patient died 3.5 months after the diagnosis. Increased ADA activity may be observed in myelomatous pleural effusion, and it may mimic tuberculous pleuritis.

Primary Cardiac Angiosarcoma of the Right Auricle with Difficult-to-Treat Bilateral Pleural Effusion

A 70-year-old woman was admitted to our hospital with pleuritis and pericarditis. Cytological examination of pleural and pericardial effusion, and pleural biopsy specimens under thoracoscopy revealed no specific pathological findings. The pleural effusion was drained continuously; however, she died of circulatory insufficiency at day 45 from admission. At autopsy, a fragile hemorrhagic mass arising from the right auricle had invaded bilateral pleura and the pericardium directly without distant metastasis. Immunohistochemical staining showed that the tumor cells expressed endothelial markers such as CD31 and CD34 antibodies, and factor VIII-related protein. These findings supported the diagnosis of a poorly differentiated angiosarcoma.

IgG4-Related Pleural Disease Diagnosed by a Re-Evaluation of Chronic Bilateral Pleuritis in a Patient Who Experienced Occasional Acute Left Bacterial Pleuritis

A 78-year-old man with cryptogenic chronic bilateral lymphoplasmacytic pleuritis, diagnosed based on left parietal pleural biopsy specimens obtained by pleuroscopy, developed acute left bacterial pleuritis. The left pleural effusion was neutrophil dominant, however, the right pleural effusion showed lymphoplasmacytic infiltration. Laboratory examinations revealed that his serum IgG4 concentration was increased, with a higher level of IgG4 in the right pleural effusion. Re-evaluation of the previous biopsy specimens using an immunostaining method revealed numerous IgG4-positive plasma cell infiltrations with IgG4-positive/IgG-positive plasma cells at 85.4%. Accordingly, the new diagnosis of this patient was considered to be chronic bilateral IgG4-related pleuritis.

Malignant mesothelioma with prominent adenomatoid features: a clinicopathologic and immunohistochemical study of 10 cases

The clinicopathologic and immunohistochemical features of 10 cases of pleural malignant mesothelioma with predominantly adenomatoid growth pattern are described to determine the clinical, histologic, and behavioral features of these tumors and to highlight the importance of separating this unusual pattern from the benign adenomatoid tumor. Seventy-seven cases of pleural biopsy and extrapleural pneumonectomy specimens for malignant mesothelioma were examined to identify the specific type of histologic growth pattern exhibited by the tumors. The 10 cases herein described were identified as an unusual histopathologic subset of these tumors. Nine patients were men and one was a woman with an age range of 56 to 82 years (mean, 68.5 years). The main presenting symptoms included cough, dyspnea, and chest pain. The typical features of pleural malignant mesothelioma were noted both radiologically and macroscopically. The tumors were characterized by diffuse pleural thickening with confluent nodular patches of tumor obliterating the pleural space. Histologically, a distinct morphology was observed composed of small tubular spaces lined by epithelioid cells, reminiscent of adenomatoid tumors of the genital tract. Immunohistochemical studies confirmed the mesothelial nature of the tumors. Clinical follow-up in 7 of 7 patients demonstrated a mean survival of 10 months from time of diagnosis. Adenomatoid mesothelioma is an unusual variant of epithelioid malignant mesothelioma that histologically may mimic a range of other tumors, including benign adenomatoid tumors and metastases of adenocarcinoma to the pleura. The clinical presentation, infiltrative growth, distinct histologic features, cytologic atypia and immunohistochemical profile all serve to differentiate adenomatoid malignant mesothelioma from other infiltrative processes involving the pleura.

Using a whole-blood interferon-γ assay to improve diagnosis of tuberculous pleural effusion: Figure 1–

To the Editors: Tuberculous pleural effusion (TBPE) is treatable and curable, and hence it is important to establish the diagnosis and initiate treatment early. However, its diagnosis is not straightforward and depends on the demonstration of Mycobacterium tuberculosis in the pleural fluid or pleural biopsy specimen, or demonstration of caseating granulomas in the pleura. Due to the paucibacillary nature of this condition, sensitivity of pleural fluid smear for acid-fast bacilli is very low (0–1%) 1. Culture is relatively sensitive (12–50%) 2, but is time-consuming and requires standardised laboratories. The sensitivity of pleural biopsy ranges 39–80% 1, 3, 4 but this technique is invasive. Current diagnostic options have several merits as well as limitations. Although no single test from the available battery may be completely accurate, an optimum combination of some of these tests may improve the diagnostic information 5–7. We conducted this study to identify such a combination of tests for accurate diagnosis of TBPE. Specifically, we addressed two research questions. 1) What is the comparative diagnostic accuracy of the following five tests for the diagnosis of TBPE: the whole blood QuantiFERON®-TB Gold In-Tube assay (QFT-GIT) (Cellestis Ltd, Carnegie, Australia), adenosine deaminase (ADA) in pleural fluid, tuberculin sensitivity test (TST), PCR for mycobacteria and the lymphocyte/neutrophil ratio (L/N ratio) in pleural fluid? 2) Which strategy used to combine the results from these five tests can be most accurate in the diagnosis of TBPE? This study included 151 consecutive patients (102 in the development sample and 49 in the validation sample) with exudative pleural effusion (defined using Light's criteria 8) presenting at the Dept of Tuberculosis and Respiratory Diseases (Ganesh Shankar Vidyarthi Memorial Medical College (GSVMMC), Kanpur, India) between January 2006 and February 2007. Exclusion criteria were: age <18 yrs, pregnancy, positive HIV serology, …

Assessment of the N-PCR Assay in Diagnosis of Pleural Tuberculosis: Detection of M.tuberculosis in Pleural Fluid and Sputum Collected in Tandem

BackgroundThe nonspecific clinical presentation and paucibacillary nature of tuberculous pleuritis remains a challenge for diagnosis. Diagnosis of tuberculous pleural effusion depends on the demonstration of the presence of tubercle bacilli in the sputum, pleural fluid, or pleural biopsy specimen, or demonstration of granuloma in pleura by histological examination. We examined the clinical utility of the diagnosis of pleural tuberculosis using the in house N-PCR assay, AFB smear microscopy and culture. Besides pleural fluid the inclusion of sputum in the efficacy of diagnosis of pleural tuberculosis was scrutinized.Methodology/Principal FindingsPleural fluid and sputum samples of 58 tuberculous and 42 non-tuberculous pleural effusion patients were processed for AFB smear microscopy, culture and the N-PCR assay. Mycobacteria were detected exclusively in tuberculous pleural effusion samples. None of the non-tuberculous pleural effusion samples were positive for mycobacteria. Comparative analysis showed that the N-PCR assay had the highest sensitivity. Inclusion of sputum along with pleural fluid increased N-PCR sensitivity from 51.7 to 70.6% (p<0.0001).This improved sensitivity was reflected in AFB smear microscopy and isolation by culture. The sensitivity enhanced on inclusion of sputum from 3.4 (p = 0.50) to 10.3% (p = 0.038) for AFB smear microscopy and for isolation of mycobacteria from 10.3(p = 0.03) to 22.4% (p = 0.0005). Thirteen isolates were obtained from 58 pleural tuberculosis patients. Eleven mycobacterial isolates were identified as M.tuberculosis and two as M.fortuitum and M.chelonae. Complete concordance was seen between the biochemical identification of isolates and the N-PCR identification of mycobacterial species prior to isolation.Conclusions/SignificanceTo the best of our knowledge this is the first PCR based report on utility of sputum for diagnosis of pleural tuberculosis. The present study demonstrates that a combination of pleural fluid with sputum sample and N-PCR improved the diagnosis of pleural tuberculosis.

Trends in Pleural Biopsies Between 1996 and 2006 at a Tertiary Medical Center

IntroductionTo determine the cause of an exudative pleural effusion, clinicians may choose one of the three types of pleural biopsies—blind, image-guided, or surgical biopsies—depending on the extent of pleural involvement and the available expertise and technology. The purpose of this study was to examine the trends in the type of pleural biopsies performed between 1996 and 2006 and to assess the diagnostic sensitivity of the 3 aforementioned types of pleural biopsy. MethodsThis was a retrospective study of all patients who underwent a pleural biopsy at a large teaching hospital between January 1, 1996, and December 31, 2006. Patients were identified by reviewing databases for surgical pathology and hospital discharge. The final diagnosis was determined by conducting a detailed chart review. We examined the trend in pleural biopsies from 1996 and 2006. We also compared the disease-specific sensitivity of blind, image-guided and surgical biopsies. ResultsOf the 174 pleural biopsy specimens identified, 103 (59.1%) were blind, 38 (21.8%) were image guided (ultrasound and computed tomography), and 33 (18.9%) were surgical (video-assisted thoracoscopic surgery and open surgical). The proportion of blind pleural biopsies performed declined from 77.7% in 1996 to 26.6% in 2006 (P<0.0001). During the same period, the proportion of image-guided biopsy rose from 7.4% to 53.3% (P<0.001). The sensitivity of blind, image-guided and surgical biopsy was 42%, 78.7%, and 92.8%, respectively. ConclusionsThe number ofblind pleural biopsies performed by pulmonary fellows declined substantially between 1996 and 2006, with an increasing trend toward image-guided biopsy.

Plasma cell myeloma presenting with diffuse pleural involvement: a hitherto unreported pattern of a new mesothelioma mimicker

We described 2 cases of plasmacytoma presenting with a preponderant involvement of the pleural membranes simulating clinically, radiologically, and on gross pathologic inspection a primary mesothelioma. The patients were an 80-year-old man and a 45-year-old woman. In both cases, the clinical presentation was that of a serosal tumor, including effusions and pleural thickening. In the former, the serosal infiltration raised the suspicion of mesothelioma reinforced by history of occupational exposure to asbestos. Patient general condition deteriorated rapidly. Postmortem examination revealed unilateral encasing of the lung within a thick, irregular neoplastic rind. In addition, tumoral involvement was seen in the homolateral third rib and the clavicle. Histologic examination of pleural masses demonstrated diffuse infiltration by highly atypical, pleomorphic plasma cells with kappa chain restriction. In the second case, clinical presentation was also suspicious of mesothelioma. Nonetheless, a pleural biopsy specimen showed irregular sheets of plasma cells showing kappa light chain restriction. A bone marrow aspirate was also positive for abnormal plasma cell infiltrates. Despite chemotherapy, the patient died 4 months after presentation. Although rarely, it seems that plasmacytoma may present with an exclusive or preponderant pleural involvement; and it may therefore be added to the list of pseudomesotheliomatous tumors.

Direct comparison of the diagnostic yield of ultrasound-assisted Abrams and Tru-Cut needle biopsies for pleural tuberculosis

BackgroundTuberculous pleuritis remains the commonest cause of exudative effusions in areas with a high prevalence of tuberculosis and histological and/or microbiological confirmation on pleural tissue is the gold standard for...

Amyloidosis presenting as bilateral transudative pleural effusions with normal cardiac investigations: a case report

A 66-year-old man with a diagnosis of monoclonal gammopathy of unknown significance was referred for investigation of bilateral transudative pleural effusions by the cardiology team. Echocardiography, myocardial perfusion scanning and left heart catheterisation were all normal or non diagnostic. Given significant occupational asbestos exposure in his twenties he underwent thoracoscopic pleural biopsy. This showed fibrous inflammation only. He subsequently developed proteinuria and peripheral oedema. Reanalysis of the pleural biopsy specimen for amyloidosis was positive. Pleural disease is an uncommon presentation of systemic amyloidosis. The aetiology of the pleural effusions is unclear and is not simply a consequence of cardiac or renal impairment.

Pleural Fluid Interferon-Gamma (IFN-γ) Measurement as a Diagnostic Tool in Tuberculous Pleurisy

Introduction: Tuberculosis is one of the most common causes of pleural effusion (PE). However, the diagnosis of tuberculous pleurisy still remains difficult. Since M. tuberculosis isolation rates in tuberculous effusions are relatively low the histological and microbiological studies of pleural biopsy samples are usually required to confirm the diagnosis. Several biological markers have been proposed to enhance the effectiveness of diagnosing patients with tuberculous pleurisy. The study was undertaken to evaluate the diagnostic accuracy of pleural fluid IFN-γ concentration in differentiation between tuberculous pleural effusion (TPE) and non-tuberculous pleural effusion (nTPE). Material and methods: 94 patients (50 M and 44 F, mean age 59 ± 18, range 18–95 years) with PE were studied. All subjects underwent diagnostic thoracenthesis and extensive laboratory pleural fluid evaluation. Tuberculous pleural effusion was diagnosed in: (1) patients with positive pleural fluid or pleural biopsy culture and (2) patients with granulomas in the pleural biopsy specimen, after exclusion of other granulomatous diseases. IFN-γ level in pleural fluid was measured with commercially available immunoenzymatic assay (Quantikine Human IFN-γ Immunoassay, R&amp;D Systems, USA). Results: Tuberculous pleural effusion was diagnosed in 28 pts. The non-tuberculous pleural effusion group consisted of 66 pts, including 35 with malignant PE, 20 with parapneumonic effusion or pleural empyema, 5 with pleural transudates due to heart failure, and 6 with miscellaneous causes of PE. The mean concentration of IFN-γ was significantly higher in TPE than in nTPE (614.1 ± 324.5 vs. 15.1 ± 36.0 pg/ml, p &lt; 0.0001). At the cut-off value of 100 pg/ml the sensitivity and specificity of the test were 100% and 98.5% respectively. Conclusions: The pleural fluid concentration of IFN-γ was found to be highly sensitive and specific marker of tuberculous pleurisy.

Mycobacterium avium Pleuritis in a Non-Immunocompromised Patient

Nontuberculous mycobacterium infection is rarely accompanied by pleural involvement. We describe a very rare occurrence of Mycobacterium (M) avium pleuritis with pleural effusion in a non-compromised 73-year-old woman patient who had been treated for sick sinus syndrome. She was admitted to our hospital with general malaise and left pleural effusion. To establish a definitive diagnosis, a biopsy specimen was obtained from the left parietal pleura by video-assisted thoracoscopic surgery. The pleural biopsy specimen revealed only diffuse lymphoid cell infiltration and neoplastic or granulomatous lesions were absent. Culture of the pleural biopsy specimen revealed M. avium, indicating that the pleuritis was caused by this organism. A course of anti-tubercular agents (rifampin, ethambutol and streptomycin sulfate) and clarithromycin gradually resolved the pleural effusion.

EVALUATION OF THE USEFULNESS OF PHAGE AMPLIFICATION TECHNOLOGY IN THE DIAGNOSIS OF PATIENTS WITH PAUCIBACILLARY TUBERCULOSIS

The present study was undertaken to assess the performance of the Fast Plaque TB™ (FPTB) test in the diagnostically difficult group of paucibacillary tuberculosis (TB) and to compare its results with the conventional bacteriological methods. The study was conducted on a total of 139 patients, who were negative for TB in sputum-smear examination. Bronchoalveolar lavage (BAL) or pleural biopsy specimens collected from these patients were subjected to smear examination, LJ culture and FPTB test. The smear, culture and the FPTB positivity rates were compared between patients with pulmonary and pleuro-pulmonary involvement. The FPTB test was found to register an overall sensitivity of 58.8% and specificity of 97.9%. The positive and negative predictive values of the test were 98.1 and 56.5, respectively. Among patients with paucibacillary TB, on head-to-head comparison, we found that the sensitivity and specificity values of the FPTB test were marginally better than smear-microscopy and inferior to culture on LJ media.

Evaluation of the usefulness of phage amplification technology in the diagnosis of patients with paucibacillary tuberculosis

The present study was undertaken to assess the performance of the Fast Plaque TB(TM) (FPTB) test in the diagnostically difficult group of paucibacillary tuberculosis (TB) and to compare its results with the conventional bacteriological methods. The study was conducted on a total of 139 patients, who were negative for TB in sputum-smear examination. Bronchoalveolar lavage (BAL) or pleural biopsy specimens collected from these patients were subjected to smear examination, LJ culture and FPTB test. The smear, culture and the FPTB positivity rates were compared between patients with pulmonary and pleuro-pulmonary involvement. The FPTB test was found to register an overall sensitivity of 58.8% and specificity of 97.9%. The positive and negative predictive values of the test were 98.1 and 56.5, respectively. Among patients with paucibacillary TB, on head-to-head comparison, we found that the sensitivity and specificity values of the FPTB test were marginally better than smear-microscopy and inferior to culture on LJ media.

T(14;18)(q32;q21)-bearing pleural MALT lymphoma with IgM paraproteinemia: Value of detection of specific cytogenetic abnormalities in the differential diagnosis of MALT lymphoma and lymphoplasmacytic lymphoma

A 67-year-old woman presented with a pleural effusion and a tumor in the right pleural wall. Histological examination of thoracoscopic tumor and pleural biopsy specimens showed infiltration by medium sized cells, some of which showed plasmacytoid differentiation. In view of the presence of IgM paraproteinemia and bone marrow involvement by lymphoma cells, the patient was diagnosed tentatively as having lymphoplasmacytic lymphoma (LPL). However, chromosomal analysis of the cells in the pleural fluid detected t(14;18)(q32;q21), while fluorescence in situ hybridization was positive for 11% of the MALT1 split signal. Because of the presence of characteristic genetic abnormalities and notable extranodal involvement, the patient was diagnosed as having MALT lymphoma. She was treated with three courses of cladribine and rituximab, and achieved complete regression of the tumor. In this case the detection of t(14;18)(q32;q21) involving IGH and MALT1 was useful for the differential diagnosis of LPL and MALT lymphoma.

Diagnosis and Treatment of Tuberculous Pleural Effusion in 2006

Tuberculous (TB) pleural effusion occurs in approximately 5% of patients withMycobacterium tuberculosisinfection. The HIV pandemic has been associated with a doubling of the incidence of extrapulmonary TB, which has resulted in increased recognition of TB pleural effusions even in developed nations. Recent studies have provided insights into the immunopathogenesis of pleural TB, including memory T-cell homing and chemokine activation. The definitive diagnosis of TB pleural effusions depends on the demonstration of acid-fast bacilli in the sputum, pleural fluid, or pleural biopsy specimens. The diagnosis can be established in a majority of patients from the clinical features, pleural fluid examination, including cytology, biochemistry, and bacteriology, and pleural biopsy. Measurement of adenosine deaminase and interferon-γ in the pleural fluid and polymerase chain reaction forM tuberculosishas gained wide acceptance in the diagnosis of TB pleural effusions. Although promising, these tests require further evaluation before their routine use can be recommended. The treatment of TB pleural effusions in patients with HIV/AIDS is essentially similar to that in HIV-negative patients. At present, evidence regarding the use of corticosteroids in the treatment of TB pleural effusion is not clear-cut.

Five-Month-Old Infant With a Unilateral Pleural Effusion

Five-Month-Old Infant With a Unilateral Pleural Effusion

Bone or pleura? Primary pleural osteosarcoma

Clinical Summary A 76-year-old nonsmoking ex-Royal Navy engineer had a 2-month history of progressive breathlessness and recurrent right-sided bloody effusion. The chest computed tomographic scan showed striking pleural calcification of variable thickness encasing the right lung and a large pleural effusion (Figure 1, A and B). We did not recognize the appearances. Our differential diagnosis included old trauma and tuberculosis, but there was no history of either. Immunohistochemistry of pleural needle biopsy specimens raised suspicion of malignant pleural mesothelioma. He came to us for surgical biopsy. We performed a short (3-cm) rib resection and took a full-thickness pleural biopsy specimen through the bed of the rib. Not to our surprise, pleurodesis was ineffective. The pleural specimen was so bony that the pathologist initially mistook it for rib. On histologic review the diagnosis of primary pleural osteosarcoma was made (Figure 2). He was referred for specialist oncologic management.

Diagnostic Value of Procalcitonin and C-Reactive Protein in Differentiation of Pleural Effusions

Background: Malignancies are a common and important causes of exudative pleural effusions. Several tumor markers have been studied because the pleural fluid cytology and pleural biopsy specimens do not provide a diagnosis in a high percentage of malignant effusions. In an attempt to overcome this limitation, procalcitonin and C-reactive protein (CRP) in pleural effusions and serum, which are known to be inflammation markers, were measured to determine if they can differentiate an exudate from trasndate as well as the diverse causes of exudative pleural effusion. Methods: 178 consecutive patients with pleural effusion (malignant 57, tuberculous 51, parapneumonic 31, empyema 5, miscellaneous benign 7, transudative 27)were studied prospectively. The standard parameters of pleural effusion and measured serum and pleural procalcitonin were examined using in immunoluminometric assay. The level of CRP in serum and pleural fluid was determined by turbidimetric immunoassay. Results: The pleural procalcitonin levels in the exudate were significantly higher than those in the transudate, and , respectively (p=0.007). The pleural CRP levels were significantly higher in the exudate than the transudate, and , respectively (p and , respectively (p=0.032). The pleural CRP levels were significantly higher in the benign effusion than in the malignant effusion, and , respectively (p and , respectively (p=0.008). Conclusion: Measuring the level of procalcitonin and CRP in the pleural fluid is helpful for differentiating between transudates and exudates. In addition, it is useful for differentiating between benign and malignant pleural effusions.