|Year : 2017 | Volume
| Issue : 1 | Page : 257-261
Demographic, clinical, biochemical, radiological and etiological characteristics of malignant pleural effusions from Eastern India
K Saha1, MK Maikap2, A Maji2, M Moitra3, D Jash2
1 Department of Pulmonary Medicine, Burdwan Medical College, Burdwan, India
2 Department of Pulmonary Medicine, NRS Medical College and Hospital, Shealdah, Kolkata, India
3 Department of Turberculosis and Chest Medicine, KPC Medical College and Hospital, Jadavpur, West Bengal, India
|Date of Web Publication||1-Dec-2017|
Dr. K Saha
Department of Pulmonary Medicine, Burdwan Medical College, Burdwan
Source of Support: None, Conflict of Interest: None
CONTEXT: There are very limited data regarding clinical, radiological and etiological aspects of malignant pleural effusion (MPE) from Eastern India. AIMS: To review natural history, clinical features, radiological features and etiology of MPEs. SETTING AND DESIGN: Hospital based cross-sectional descriptive study. MATERIALS AND METHODS: We had reviewed166 diagnosed cases of MPEsregarding demography; clinical, radiological and biochemical characteristics, diagnostic modalities and etiologies. RESULTS: Out of 166 patients, 72.89% were males and 27.11% were females. Mean age of presentation among males was 64.3 ± 12.7 and among females was 52.5 ± 14.8. Most common presenting symptom was dry cough (87.9%) and most common presenting sign was clubbing (54.5%). Massive effusion was found in 45.78% of cases. Pleural fluid macroscopic appearance was haemorrhagic in 54.82% of cases. Mean adenosine deaminase activity in MPE was 24.05 U/L. Mean pleural fluid/serum protein ratio was 0.65, mean pleural fluid/serum lactate dehydrogenase ratio was 1.01. Most of the cases (84.94%) were diagnosed by pleural fluid cytology for malignant cells. Primary cancer was diagnosed in 136 (81.93%) cases; among which 121 (88.97%) cases were lung cancers, among which adenocarcinoma (52.89%) was the most common histology. CONCLUSIONS: Pleural fluid cytologies for malignant cells are usually sufficient to diagnose MPE in nearly 85% of cases and in remaining cases if thoracoscopyis not available, blind pleural biopsy can be helpful. The most common primary in cases of MPE is lung cancer with adenocarcinoma being the commonest culprit.
Keywords: Lung cancer, malignant pleural effusion, pleural biopsy, pleural fluid cytology
|How to cite this article:|
Saha K, Maikap M K, Maji A, Moitra M, Jash D. Demographic, clinical, biochemical, radiological and etiological characteristics of malignant pleural effusions from Eastern India. Indian J Cancer 2017;54:257-61
|How to cite this URL:|
Saha K, Maikap M K, Maji A, Moitra M, Jash D. Demographic, clinical, biochemical, radiological and etiological characteristics of malignant pleural effusions from Eastern India. Indian J Cancer [serial online] 2017 [cited 2020 Apr 5];54:257-61. Available from: http://www.indianjcancer.com/text.asp?2017/54/1/257/219575
| » Introduction|| |
Malignant disease involving the pleura is the second most common cause of exudative pleural effusion next to tubercular and parapneumonic effusions. Malignant pleural effusion (MPE) is an important clinical entity because sometimes it may be the first manifestation of an underlying malignancy. It has varied modes of presentation. Common cancers which metastasize to the pleura are lung cancer, breast cancer, lymphoma, ovarian cancer, testicular cancer, gastro-intestinal malignancy. Diagnosis of MPE and finding out the primary malignancy is a challenge to the clinicians because in spite of extensive diagnostic work-up, in many cases the primary remains undetected. There is no study, until now conducted on MPE from eastern part of India. Therefore we intended to study the diagnosed cases of MPEs with emphasis on clinical, radiological and etiological diversities and comparative yield of common diagnostic procedures that help us to include those diagnosed cases of MPEs.
| » Material and Methods|| |
This study was a hospital based descriptive cross-sectional study performed at the Pulmonary Medicine department in two medical college of Kolkata, India from January 2010 to January 2012. All patients with exudative pleural effusions were enrolled for the study and only data of patients with positive pleural tissue biopsy for malignancy or presence of malignant cells in pleural fluid were analyzed.
Written informed consent was obtained from the patient. Before requesting consent, the individual was explained in an understandable language about the aimsfor the study, the methods of conduct, expected duration of subject participation, benefits, extent of investigators responsibility, provision of medical services, the right to refuse to participate and withdraw from the study without affecting further medical care.
Detailed history, thorough physical examination, radiological findings, biochemical findings were recorded in the proforma. Pleural aspiration and biopsy were performed for all patients of exudative pleural effusions after obtaining the written consent. Macroscopic findings, cytological, microbiological and biochemical analysis of pleural fluid were performed for all patients. To look for primary required investigations like fibre optic bronchoscopy (FOB), radiology guided fine needle aspiration cytology (FNAC) or biopsy, mammography, lymph node biopsies, etc., according to patient's clinical findings were also performed.
History taking: Symptoms such as the history of fever, cough, sputum, haemoptysis, dyspnoea, chest pain, weight loss, losses of appetite were recorded and analyzed. Detail history of smoking was recorded. Furthermore, history of pleural fluid aspiration in detail was taken.
Physicalexaminations: Patient's general conditions such as cachexia, body weight, breathlessness, fever were noted. Physical signs such as cervical or scalene lymph node enlargement, clubbing, superior venacava (SVC) obstruction were also recorded. Thorough respiratory system examination was done to find out features of collapse, consolidation and pleural effusion. Breast and careful pelvic examination in female and testicular examination, in particular, was done in male.
Radiologicalexaminations: Chest X-ray (CXR) postero-anterior (PA) view and computed tomography (CT) scan of thorax were taken, if necessary. The amount of fluid, the side involved, hilar and/or mediastinum lymphadenopathy, parenchymal involvement, cavitation, collapse and any other radiographic abnormalities were noted.
Pleural fluid aspiration
Macroscopic appearance of pleural fluid: Macroscopic appearance of pleural aspirates was recorded.
Cytology, celltypes and cell counts: Differential white cell counts of pleural fluid were recorded and calculated as a percentage. The actual number of cells was not counted. Pleural fluid cytology for malignant cells is particularly sought. We excluded patients with pleural fluid cytology report showing atypical cells with pleural biopsy negative for malignant cells.
Biochemistry of pleural fluid: Determination of pleural fluid total protein concentration (g/l), lactate dehydrogenase (LDH) (U/L), and sugar (mg/dl) were performed. To differentiate transudate from exudate, the ratio of pleural fluid and serum protein; the ratio of pleural fluid and serum LDH were calculated. Pleural fluid adenosine deaminase level was measures by Giusti and Galanti method.
Pleural biopsy: All patients were subjected to thoracentesis and closed pleural biopsy using Abram's needle after obtaining a written consent. It is a blind procedure.
Lymphnode FNAC: Fine needle aspiration was done from clinically palpable node and sent for cytological examination.
FNAC was also done from palpable breast lumps. CT guided FNAC was also done from detected lung masses. Fibre-optic bronchoscopy,(FOB) ultrasonography (USG) guided true-cut biopsy, CT abdomen, endoscopy, colonoscopy, magnetic resonance imaging (MRI) were done in selected cases.
| » Results|| |
In this one year study, 468 cases of exudative pleural effusions were primarily enrolled and among them 166 (35.47%) cases turned out to MPE. We had analyzed the clinical, radiological and biochemical data of those166 cases of MPE. 121 cases (72.89%) were male and 45 cases (27.11%) cases were female. Most of them were between 50 and 70 years of age (youngest was 14 years old and oldest was 78 years old) with mean 58.4 ± 13.6 [Figure 1]. Mean age of presentation among male patient was 64.3 ± 12.7 and among female patients was 52.5 ± 14.8. Only 31 patients (18.67%) were ≤40 years of age. Among the male patients 91 (75.2%) were smoker and 5 (11.11%) female patients were smoker. History of repetitive pleural fluid aspiration was found in 76 cases (45.78%).
Dry cough (87.9%) and chest pain (81.8%) were the two predominant symptoms [Figure 2]. On physical examination the most common finding was clubbing (54.5%). Other findings were pallor (30.3%), cervical lymphadenopathy (27.3%), palpable liver (21.2%) and ascites (15.2%) etc.[Figure 3]. Trachea was shifted towards the side of effusion in 65 (39.16%) cases, towards the opposite side in 61 (36.75%) cases and no shifting occurs in 40 (24.09%) cases [Table 1].
|Figure 2: Percentage of presenting symptoms in patients with malignant pleural effusion, other than signs of pleural effusion|
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|Figure 3: Percentage frequencies of physical signs in patients with malignant pleural effusion|
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Ninty (54.22%) patients had right sided pleural effusion, 71 (42.77%) had left sided pleural effusions and 5 (3.01%) presented with bilateral pleural effusion in this study [Table 2]. Seventy six (45.78%) cases had massive effusions [Table 1]. Massive effusion was defined by involvement of more than 2/3rd of the hemithorax.
|Table 2: Diagnostic positivity of pleural fluid cytology for malignant cell and blind pleural biopsy in patients with malignant pleural effusion|
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Pleural fluid macroscopic appearance was haemorrhagic in 91 cases (54.82%) and straw coloured in 75 cases (45.18%). All the cases were exudative with mean the pleural fluid protein/serum protein ratio 0.65 ± 0.08 and the mean pleural fluid LDH/serum LDH ratio 1.01 ± 0.3. The mean value of pleural fluid glucose was 38.75 mg/dl. Mean adenosine deaminase (ADA) activity in the pleural fluid was 24.05 U/L with a SD of 9.57 with highest and lowest value being 39 and 3 U/L. The most predominant cell was lymphocytes (mean ± SD of 49.97 ± 8.35%) followed by mononuclear cells (mean ± SD of 34.15 ± 7.36%).
In our hospital, we sent the pleural fluid for malignant cells and did a blind pleural biopsy by using Abram's pleural biopsy needle simultaneously during aspiration of pleural fluid. If pleural fluid for malignant cells report came as negative, then we always sent it for the 2nd time and 3rd time, if second report was negative. In our study, we found that a total of 141 (84.94%) cases was diagnosed by pleural fluid cytology; among them 91 (64.54%) cases had a positive report on the first occasions, 35 (24.82%) cases were positive on second occasion and 15 (10.64%) were positive in third occasion [Table 2]. There were 34 patients (7.27%) among 468 exudative pleural effusions in whom the pleural fluid cytology report showed atypical cells but no malignant cells after repeated aspirations. Among these, 4 patients showed malignancy in pleural biopsy. Remaining 30 patients were referred for thoracoscopic pleural biopsy to reach etiological diagnosis. Diagnosis was established by closed pleural biopsy in 68 cases (40.96%); out of these in 25 (15.06%) cases pleural fluid cytology for malignant cells was negative but pleural biopsy confirmed the diagnosis of MPE.
Forty-five cases had cervical lymphadenopathy and we did lymph node fine-needle aspiration cytology (FNAC) from all of them. Diagnosis was established in 35 cases (77.77%) and 10 (22.23%) cases revealed reactive hyperplasia. We examined the breast in each MPE cases in female and palpable mass was detected in 10 cases and FNAC from those masses in all the cases revealed intraductal carcinoma of breast.
On CXR mass lesion was detected in 85 cases (51.2%). CT scan revealed lung mass in 90 (54.2%) cases and CT-guided FNAC from lung mass established diagnosis in 80 cases (88.89%). We did FOB in 40 (24.09%) cases with clinicalsuspicion of malignancy but CXR and CT thorax failed to detect any mass lesions. FOB revealed intrabronchial growth in 25 (62.5%) cases and abnormal mucosa without any visible growth in 6 (15%) cases; from which biopsy was taken, and diagnosis was established. In 10 cases where CT showed a lung mass but CT-guided FNAC failed to bring diagnosis, we did USG guided true-cut biopsy and diagnosis of primary lung cancer was established in all 10 cases [Figure 4].
Five cases of Non-Hodgkin's lymphoma were diagnosed on the basis of lymphnode biopsy and immunohistochemistry. We ultimately found the primary in 136 (81.93%) cases; among which 121 (88.97%) cases were lung cancers, 5 (3.67%) were Non-Hodgkin's lymphoma and 10 (7.35%) were intraductal breast carcinoma [Figure 5]. Among the lung cancers 64 (52.89%) were adenocarcinoma, 36 (29.75%) were squamous-cell carcinoma and 21 (17.36%) were small cell carcinoma of lung. We did not find the primary site in 30 (18.07%) cases inspite of all possible investigations like CT abdomen and pelvis, upper GI endoscopy, colonoscopy, mammography of breast, MRI of brain, bone scan in our set up. We did all these investigations guided by the history given by the patients. The greatest drawback of our study is that we could not do thoracoscopy because of lack of facility in our set up.
|Figure 5: Histopathological diagnosis of primary sites in patients with malignant pleural effusion|
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| » Discussion|| |
MPEs are most commonly associated with cancer of the breast, lung, gastrointestinal tract, ovary, and with lymphomas. The mechanisms that cause the effusions include increased capillary permeability, decreased oncotic pressure due to hypoalbuminemia, increased negative pressure in the pleural space as a result of atelectasis, obstruction of pleural lymphatic vessels.
Clinical history is an important clue for the diagnosis of MPE. History of recurrent pleural fluid aspiration followed by rapid re-accumulation in an aged patient, particularly in smokers is typically suggestive of MPE. In our study history of repetitive aspiration was found in 76 cases (45.78%) and mean age was 58.4 years with 75.2% male smoker which is significant.
Dyspnea and cough were significant symptoms in one recent study. An old study in 1977 also showed that dyspnea occurred in more than 50% cases. Another study showed that MPE are more likely to have dull chest pain (34% vs. 11%), whereas patients with benign diseases are more likely to have pleuritic chest pain (51% vs. 24%). In our study, dry cough, dull chest pain, dyspnea, weight loss all was significant symptoms though the dry cough was the most common symptoms followed by chest pain and dyspnea. Hoarseness of voice in pleural effusion is particularly suggestive of MPE which we found in our study in 9% cases.
Next best thing in the assessment of cases of MPE is detailed physical examination. On general survey like one recent study, we also found that cachexia was the most common finding, though next most common finding in our study was clubbing in contrary to their study. Massive pleural effusion with central trachea or same sided tracheal shifting is a clue forthe diagnosis of MPE in clinical practice. This occurs due to underlying collapse of the lung due to intrabronchial growth. We in our study found same sided shift in 39.16% cases and central trachea in 24.09%cases constituting a total about 63.25% which is significant. Massive effusion occurs frequently in malignancy. In the way back to 1972 Maher et al. showed 67% of massive pleural effusion was due to malignancy. In a more recent study in 2003 it was again shown by Porcel et al. In our study we found it occurs in 45.78% cases. Bilateral effusion due to malignancy is rare. In our study, we found only 3.01% of cases with bilateral effusion, which is again consistent with our contemporaries. In all cases of suspected MPE breast examination should be done in female and testicular examination should be done in male as after lung carcinoma breast cancer is the second most common cause of MPE in female and genito-urinary cancers constitutes a significant proportion in both male and female.
Macroscopic appearance of pleural fluid has a clue to diagnosis as tumor (both primary pleuro-parenchymal as well as metastasis) is the most common cause of haemorrhagic effusion. In our study also 54.82% had haemorrhagic effusion. The pleural fluid from MPE is almost always an exudate. According to the tests first proposed by Light et al.; the fluid is considered exudates if any of the three criterion apply (i) ratio of pleural fluid to serum protein greater than 0.5, (ii) ratio of pleural fluid to serumLDH greater than 0.6, (iii) pleural fluid LDH greater than two-thirds of the upper limits of normal serum value.
In our study, mean value of pleural fluid to serum protein ratio and pleural fluid to LDH were 0.65 and 1.01 simultaneously. The pleural fluid glucose level in MPE is usually below 60 mg/dl as shown in their study by Martinez-Moragon et al. In our study also meanpleural fluid glucose was 38.75 ± 16.67. A low pleural fluid glucose level in association with MPE indicates that the patient has a high tumor burden in the pleural space. Pleural fluid ADA is elevated, particularly in tuberculosis. In two separate studies conducted by Lee et al. and Jimenez et al. showed that only 2% patients without tuberculosis had pleural fluid ADA level above 40 U/L including 3 cases of lymphoma, parapneumonic effusions each and 2 cases of bronchogenic carcinoma., In our study, we found all our cases having pleural fluid ADA level below 40 U/L with mean24.05 ± 9.57. Light et al., in their study showed that in MPE pleural fluid predominant cells were lymphocytes (45%) and mononuclear cells (40%). In our study also predominant cells were lymphocytes and mononuclear cells.
The easiest way to establish the diagnosis of pleural malignancy is with pleural fluid cytology. The percentage of cases in which cytologic study of the pleural fluid establishes the diagnosis of a MPE ranges from 40% to 87%. In our study also 84.94% cases were diagnosed by pleural fluid cytology for malignant cells and among them 64.54% were diagnosed after first pleural fluid specimen examination.
Blind needle biopsy of the pleura can establish the diagnosis of a MPE. The percentage of positive pleural biopsies in patients with MPE ranges from 39% to 75%. In our study the diagnosis was made by blind pleural biopsy in 40.96% cases. One major limitation of our study is the inability to perform a thoracoscopic pleural biopsy. Thoracoscopy will establish the diagnosis of malignancy in approximately 90% of patients with malignancy.,
Radiology has an immense role in the etiological diagnosis of MPE. Almost all patients with effusions secondary to bronchogenic carcinoma have radiographically demonstrable pulmonary abnormalities besides the effusion. In our study, CXR detected mass lesions in 70.24% cases among all diagnosed cases of bronchogenic carcinoma while CT thorax detected 74.38% cases. CT scan of thorax besides detecting lung mass helped in the evaluation of MPE in many ways. Yilmaz et al. reported four findings that were suggestive of MPE;.they were (a) pleural nodularity, (b) pleural rind, (c) mediastinal pleural involvement and (d) pleural thickening greater than 1 cm. CT scan in our study guided us to do FNAC and establish the diagnosis in 66.12% cases of total diagnosed lung cancer.
At the end, we found lung cancer was the most common cause of MPE of them adenocarcinoma was the most common. In most series, lung cancer is the most common cause of MPE. Pleural effusions occur in all cell types, but appear to be most frequent with adenocarcinoma. Though our contemporaries found metastatic large cell carcinoma to be thecommonest histologically identified cell type. In our study, breast cancer was found to be the second most common after lung cancer, which is consistent with most literatures. The incidence of MPE in Hodgkin's lymphoma is 7-21% and in non-Hodgkin's lymphoma it is 6-50%. Though in our study all were non-Hodgkin's lymphoma.
In spite of all these effortless investigations possible in our set up no primary site was found in 18.07% cases in comparison to only 6% in their study by Anderson etal. This discrepancy may be attributed to unavailability of thoracoscopy, mediastinoscopy, positron emission tomography scan etc., This is a majordraw back of our study.
| » Conclusion|| |
Pleural fluid cytology for malignant cells usually sufficient to diagnose MPE in nearly 85% of cases and in remaining cases if thoracoscopy not available blind pleural biopsy can be helpful. The most common primary in cases of MPE is lung cancer with adenocarcinoma being the commonest culprit.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]