A clinicopathological study of tuberculous pleural effusion in a tertiary care hospital


Context: Tuberculosis is a major contributor of exudative pleural effusion which is the second most common extra-pulmonary manifestation of tuberculosis following tubercular lymphadenitis. Aims: To re-evaluate the time tested and easily available investigation of closed pleural biopsy and its relation with pleural fluid adenosine deaminase (ADA) level and cytological findings in the clinically suspected cases of tuberculous pleural effusion. Materials and Methods: A total of 44 cases of suspected tubercular pleural effusion were selected from the indoor ward of a tertiary care hospital, over a period of 13 months. Apart from the relevant history taking and clinical examination, thorough investigations were done in each case to prove the etiological diagnosis, which comprised of routine hemogram, bleeding time, clotting time, Mantoux test, sputum microscopy, enzyme-linked immunosorbent assay (ELISA) for HIV, chest X-ray, examination of pleural fluid including ADA estimation, culture for Mycobacterium tuberculosis (BACTEC), and finally, pleural biopsy by Abram’s needle. Results: A total of 65.8% cases of tuberculous pleural effusion were diagnosed by pleural biopsy results. Second biopsy attempts improved the diagnostic ability by 18.4%. The highest incidence was observed in the 11-20 years age group (36.8%). Chest pain (86.8%) was the predominant symptom. Positive Tuberculin skin test was observed in 89.5% cases. Pleural fluid analysis showed a predominance of lymphocytes in all the cases, with 97.3% patients having ADA levels > 70 U/L. There was no major complication of pleural biopsy. Conclusions: Pleural biopsy is a very important tool for diagnosing tuberculous pleural effusion without any major complication. ADA values > 70 U/L are highly suggestive of tubercular etiology and correlated well with histopathological findings of pleural biopsy.

Keywords: Adenosine deaminase, pleural biopsy, pleural effusion, tuberculosis

How to cite this article:
Basu A, Chakrabarti I, Ghosh N, Chakraborty S. A clinicopathological study of tuberculous pleural effusion in a tertiary care hospital. Ann Trop Med Public Health 2012;5:168-72
How to cite this URL:
Basu A, Chakrabarti I, Ghosh N, Chakraborty S. A clinicopathological study of tuberculous pleural effusion in a tertiary care hospital. Ann Trop Med Public Health [serial online] 2012 [cited 2021 Mar 4];5:168-72. Available from: https://www.atmph.org/text.asp?2012/5/3/168/98606

Pleural effusion is an excessive accumulation of fluid in the pleural cavity which, in normal condition, contains a relatively small amount of fluid-approximately 10 ml on each side. [1] Caused by a misbalance between fluid production and fluid removal, it is often the first manifestation of a cardiac or pulmonary disease. Pleural effusion is not a disease by itself; rather it is a sign of an underlying disorder. So the need arises to arrive at a specific etiological diagnosis whenever there is a pleural effusion. As per Light, [2] 99% of pleural effusion could be classified into two general categories-transudative and exudative. If the effusion is transudative, systemic causes like congestive heart failure or a hypoalbuminemic state should be searched for. On the other hand, exudative effusion is principally caused by a local pleuro-pulmonary disease process like infection, malignancy, pulmonary thromboembolism, local trauma etc. Tuberculosis is the single most frequent cause of death by an infectious agent, worldwide. [3] Among the extra-pulmonary presentations, pleural tuberculosis is second in frequency after tubercular lymphadenitis. [4] In many areas of the world, including India, tuberculosis remains the most important cause of pleural effusion in the absence of demonstrable pulmonary disease. [5],[6],[7] Administration of anti-tubercular drugs for suspected tuberculous pleural effusion is often empirical. In young adults, the mere presence of straw colored pleural fluid with the presence of fever is often an enough indication for starting anti-tubercular drug. Tubercular bacilli are rarely positive in pleural fluid smear or culture. Newer investigation modalities like adenosine deaminase (ADA) level in pleural fluid are of much help, but it is not available everywhere. Also, it is costly, and not suitable for drug sensitivity testing. So, the time honored test of pleural biopsy is still of very much use. Ideally, pleural biopsy should be done in all the cases of pleural effusion, where the etiology is unknown. Standing the test of time, needle biopsy of pleura is able to establish a positive diagnosis in 50-80% of cases of tuberculous pleural effusion, [8],[9],[10],[11],[12],[13],[14],[15] and the yield increases when multiple biopsies are taken. [16] A definite diagnosis of tuberculous pleural effusion can be made only when tuberculosis bacillus is found either in the smear or culture of pleural fluid material or pleural tissue. But granuloma in the parietal pleura in pleural biopsy specimen is also a conclusive evidence of tuberculous pleuritis. [17],[18] So, we conducted a study, to re-evaluate the time tested and easily available investigation of closed pleural biopsy, and to ascertain its relation with pleural fluid ADA level and cytological findings in the clinically suspected cases of tuberculous pleural effusion.

Materials and Methods

The study was an institution-based, prospective study which was undertaken after obtaining ethical clearance. The study population comprised of 44 patients with exudative pleural effusion who were clinically and radiologically suspected of suffering from tuberculous effusion. A thorough clinical examination and relevant history was taken, according to the planned schedule. Careful clinical examinations of the respiratory system were done in each case. Other systemic examinations were done to detect whether other systems or organs were involved or not. Gynecological examinations were done for the female patients. Chest X-ray (postero-anterior and lateral view), hemoglobin level, total leukocyte count, differential leukocyte count, erythrocyte sedimentation rate (E.S.R. by Westergren’s method), platelet count, bleeding time (by Duke’s method), clotting time (by Sabraze’s capillary tube method), and enzyme-linked immunosorbent assay (ELISA) for HIV were done in all cases. Tuberculin skin test was done by using 5 ITU PPD (International Tuberculin Unit. purified protein derivative). Examinations of sputum for presence of Acid Fast Bacilli for three consecutive days by using the conventional Ziehl- Neelsen stain for Acid Fast Bacilli (AFB), and detection of malignant cells by Papanicolaou stain were done in all cases.

Depending on the radiological amount of pleural fluid present, patients were divided in to three groups. [19] To confirm and to identify the subjects of this study, thoracocentesis was performed by standard technique [5] in all the cases of suspected tuberculous effusion. It was not done when the effusion was very small, i.e. in lateral decubitus chest radiograph, where the distance between outer border of lung and the inner border chest wall was less than 10 mm. [20] The pleural fluid was collected in separate vials for biochemical (protein, sugar), cytological (cell count, cell type), and microbiological examinations (Gram stain and Conventional Ziehl-Neelsen stain for Acid Fast Bacilli). Culture for Mycobacterium tuberculosis was done by rapid culture method (BACTEC) in all cases. The ADA level was measured by colorimetric method as described by Giuseppe Giutsi and Galanti. [21] The advantage of this method is that it is of low cost, simple in technique, and rapid. Pleural biopsy was performed using the Abram’s needle [5] and the material was processed, sectioned, and stained with Hematoxylin and Eosin (H and E) stain and Zeihl- Neelsen stain. [22] All the relevant findings were noted and analyzed.


For the present study, 44 cases of suspected tubercular pleural effusion were selected from the indoor ward of a tertiary care hospital, over a period of 13 months, from December 2004 to December 2005. With the help of biopsy procedure, which was repeated on 20 occasions, 25 cases were diagnosed as tubercular pleuritis and 2 cases were found to have metastatic deposit of squamous cell carcinoma in the pleura. Pleural tissue was within normal limits in one occasion and the rest 16 cases showed histopathological features of non-specific chronic pleuritis. These 17 cases, which were not diagnosed by pleural biopsy alone, were further investigated and put on anti-tubercular drug (ATD) empirically. By these methods, diagnosis of tuberculosis was done in 13 more cases. Remaining four cases did not respond to ATD and remained as undiagnosed cases. Thus, the whole series was broadly divided into three groups depending on the etiology of the pleural effusion. The three groups were tubercular group, neoplastic group, and undiagnosed group [Table 1]. As this study is primarily concerned with the histopathological findings in closed pleural biopsy specimens in cases of tubercular pleural effusion, only those cases with final diagnosis of tubercular pleural effusion were taken into account while analyzing the final data, and the cases which were either undiagnosed or diagnosed as malignant pleural effusion, were discarded from the analysis. The mean age was 26.89 years. The highest incidence was observed in the 11-20 years age group (36.8%), followed closely by the 21-30 years age group (34.2%). Out of 38 cases, 11 cases were female (28.9%) and 27 cases were male (71.1%). A total of 24 came from rural areas (63.16%) and 14 cases came from urban areas (36.84%). Fourteen cases gave a history of contact with tuberculous patients (36.8%), and among these 14 cases, three patients had history of prior suffering from pulmonary tuberculosis that was fully treated with anti-tubercular drugs. Seventeen among 27 male cases were smokers (62.96%), and 2 among 11 female cases were smokers (18.18%). The three most common complaints in this series were chest pain (86.8%), dyspnea (81.6%), and fever (68.4%). Hemoptysis was found in none of the 38 cases [Table 2]. Discrete, small, mobile cervical lymph nodes were found in three cases. All of them were male, and their age was below 20 years. The lymph nodes were too small to undergo fine-needle aspiration cytology (FNAC). The nodes resolved with anti-tubercular drugs. Tachycardia (44.7% of cases) and tachypnea (50 % of cases) were quite common among the pleural effusion cases. The mean hemoglobin concentration was 9.95 gm/dl. The mean ESR was 71.63 mm in the first hour, and maximum number of cases was found (76.3%) in the 51-100 mm group. None of the cases were leukopenic, and only three of them were having leukocytosis. The differential count showed that all of them had predominance of neutrophils. Platelet counts were adequate in all of the cases, and both bleeding time and clotting time were within normal limits in all of them. Only after obtaining normal results in these tests, the patients were subjected to pleural biopsy. Tuberculin skin test was performed in all the cases and positive results (induration more than 10 mm in diameter) were found in 34 cases (89.5%). Only four cases had negative tuberculin skin test result. In 4 out of 38 cases, sputum examination showed presence of Acid Fast Bacilli, the positivity was 10.5%. None of the 38 cases showed presence of atypical cells on Hematoxylin and Eosin staining. This test was reactive in only one case with CD4 count, 273. The sputum examination, in this case, showed presence of AFB also in sputum. There was no case of encysted pleural effusion on chest X-ray. No other significant radiological finding (e.g. Rib erosion, diaphragmatic palsy, and space occupying lesion) was noted in any of the cases. In all the cases, shifting of mediastinum was opposite to the side of the pleural involvement. Those four cases with sputum positivity for AFB showed radiological finding typical of tubercular lung parenchymal lesion in the post-aspiration chest X-rays. The degree and laterality of effusion are summarized in [Table 3]. Amber colored pleural fluid was aspirated in 32 cases (84.2%), and in rest of the cases, the pleural fluid was hemorrhagic in color (15.8%). The color of the fluid was not related to the degree of the effusion. The mean cell count was 764.5 per cu mm. The minimum and maximum cell counts were 430 and 1380 per cu mm, respectively. All the cases show lymphocyte predominance in their pleural fluid and most of them (89.5%) had differential lymphocyte count of more than 75%. Zeihl-Neelsen stain of pleural tissue showed AFB in only three occasions. Gram’s staining failed to detect any microorganism in any of the cases. All the cases were tested for glucose and protein level estimation in their pleural fluid. All the cases had protein level of more than 3 gm/dl in pleural fluid. The mean level of protein was 4.64 gm/dl of pleural fluid. Sugar level was lower in all the cases. The mean sugar concentration was 57.89 mg/dl of pleural fluid. The mean ADA level was 100.05 U/L in pleural fluid. Only one patient had ADA level below 70 U/L. The minimum and maximum ADA levels were 68 U/L and 144 U/L, respectively [Table 4]. The pleural biopsy done by Abram’s needle had to be repeated in 18 cases within a gap of 3 to 14 days, either due to inadequate material yield or due to non-specific finding. Twenty five out of 38 tubercular pleural effusion cases (65.8%) were diagnosed by positive pleural biopsy results [Figure 1]. Second biopsy attempts, in cases of non-specific findings on first biopsy material, helped to diagnose 7 out of 38 cases (18.4%). Thirteen out of 38 cases (34.2%) of tubercular pleural effusion did not show positive histological finding on closed pleural biopsy material [Table 5]. None of the cases in this series had any major complication, except five cases, who had small pneumothorax detected in post aspiration chest X-rays.

Table 1: Final subdivisions of cases according to etiology

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Table 2: Incidence of different chest symptoms

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Table 3: Chest X-ray findings

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Table 4: Adenosine deaminase level in pleural fluid

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Table 5: Final pleural biopsy results in 38 cases

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Figure 1: Photomicrograph of pleural biopsy showing presence of caseous necrosis (black arrow) and Langhan’s giant cell (black arrowhead) (H and E, X100)

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The mean age was 26.89 years and the majority of the patients (71%) were in the age range of 11 to 30 years. The study conducted by Mestitz et al[23] reported that the predominant age group for tubercular pleural effusion was 18 to 25 years. A total of 36.8% gave a positive history of contact with tubercular patients, and 7.9% of the cases had a prior history of suffering from pulmonary tubercular disease. The findings are consistent with Sibley. [24] In our series, most of the patients came with chest pain (86.8%), dyspnea (81.6%), and fever (68.4%). Other symptoms like loss of appetite (60.5%), cough (44.7%), and weight loss (34.2%) were less in frequency. The frequency of different symptoms in this study was more or less similar to the findings of Bhadada. [25] He found that the most common symptoms in cases of pleural effusion were chest pain (60%), dyspnea (73%), fever (76.6%), and cough (70%). The increased respiratory rate was not proportional to the degree of pleural effusion, though all of the cases with massive pleural effusion had increased respiratory rates. The increased respiratory rate was not proportional to the degree of pleural effusion, though all of the cases with massive pleural effusion had increased respiratory rates. The mean ESR was elevated in the examined subjects – 71.63 mm in the first hour, but it was not very specific. Roper and Waring [26] opined that ESR was of no help in differential diagnosis of pleural effusion. Leukocytosis was found in seven cases (18.4%), and all of them had neutrophilia. Thirty four had (89.5%) positive tuberculin skin test, of which, four had negative result. Ideally, all tubercular pleural effusions should be positive to tuberculin skin test, but negative result does not rule out the diagnosis. In a study by Villegas, et al. in 2000, PPD was positive in 70.6% of the patients with tubercular pleural effusion. [27] A total of 10.5% cases had positive sputum smear examination for AFB and all of them had negative pleural biopsy report. All the four cases showed radiological evidence of lung parenchymal tubercular infiltration in the post aspiration skiagrams. All the cases in this study had predominantly lymphocytic pleural effusion, and 89.5% of them had lymphocyte more than 75% in their pleural fluid. According to Light, [5] in tubercular pleural effusion, the pleural fluid lymphocyte is usually more than 50%. Occasional mesothelial cells were found in 28.9% of cases, and in no case, it was more than 3%. So, in pleural effusion, mesothelial cells of more than 5% strongly argue against a tubercular etiology. [28],[29] The mean value of ADA level in this series was 100.05 U/L. Only 1 out of 38 cases had pleural fluid ADA level less than 70 U/L, and 17 cases (44.7%) had ADA level greater than 100 U/L. Various authors have reported that the ADA level was significantly higher in cases of tubercular pleural effusion. [30],[31] The reported values were in the range from 70 to 137 U/L. Adequate tissue material was obtained in 36 cases (94.74%) on first pleural biopsy attempt and it reached 100% value on second attempt. Scerbo, et al.[32] and Mungall et al[33] noted similar kind of findings. The positive biopsy diagnosis of tubercular pleuritis was made in 25 cases (65.8%) out of 38 cases of tubercular effusion. The second attempt increased the diagnostic yield by 38.9%. The positive biopsy finding was defined as the presence of caseating epithelioid cell granuloma with Langhan’s type of foreign body giant cell. However, the absence of caseation did not rule out the diagnosis. Though similar type of findings could be found in some other conditions as well (e.g. fungal infection), but they are so rare in occurrence that in all practical cases, this finding is enough to be synonymous with tubercular granuloma. [5] There has been multiple reports about following-up the cases with pleural biopsy report of non-specific pleuritis. In the series by Onadeko, et al. it was reported that 54% of cases with chronic non-specific pleuritis were finally diagnosed as tubercular pleuritis. [34] In India also, there are various study reports regarding diagnostic yield of pleural biopsy. Maldhure et al. in the year of 1994, published a study report on comparative efficacy of pleural biopsy and increased pleural fluid ADA level in 83 cases of suspected tubercular pleural effusion. The pleural biopsy report was consistent with tuberculosis in 67.07% cases. [35] In a review of 14 papers from 1958 to 1985, encompassing a total of 2893 pleural biopsies, the diagnostic yield was 75% with tubercular pleurisy. [36] Three cases (7.8%) showed AFB on tissue biopsy which is much lower than 25.8 % as detected by Valdes et al[37]


Pleural biopsy is a very important diagnostic tool in under-resourced centers for a definite diagnosis of tuberculous etiology, which is very common cause of exudative pleural effusions in a developing country like India and also to rule out the other causes. It has high positive diagnostic value and low complication rate. ADA values > 70 U/L are highly suggestive of tubercular etiology and correlated well with histopathological findings of pleural biopsy.

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1755-6783.98606


[Figure 1]


[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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