THE SIGNIFICANCE OF CYTOLOGICAL EXAMINATION OF THE PLEURAL FLUID IN THE DIAGNOSIS OF PLEURAL EFFUSION IN NIGERIANS* B. O. Onadeko

Department of Medicine and T, A. Junaid and E, I, Odor

Department of Pathology, University College Hospital, Ibadan, Nigeria. Summary C Y T O L O G I C A L examination of the pleural fluid in 216 Nigerian patients with pleural effusion was carried out. The types of cells found were described. Their occurrence and frequency were correlated with the cause of the effusion. It was observed that lymphocytes predominated in the pleural fluid in 60% of all the cases. The commonest cause of lymphocytic effusion was tuberculosis, occurring in 76% of lymphocytic effusions. Lymphocytic effusion was due to neoplasm and pneumonia in a small proportion of cases. Eosinophils amounting to more than 5% of the total leucocyte count were found in association with a number of diseases causing pleural effusion and the significance of pleural fluid eosinophilia is discussed. Malignant cells were found in 22% of malignanL effusions. The common neoplasms responsible were carcinoma of the breast and bronchus. Introduction The cytological examination of pleural fluid has aroused the interest of several workers over the years (Foord et al, 1929; Scott and Finland, 1934; Wihman, 1948; Saphir, 1949; Spriggs and Boddington, 1960; Hinson, 1961 ). The first major work on cellular constituents was done by Widal and Ravault (1900), although as early as 1867, Lucke and Klebs re* This paper forms pa~t of the study for the degree of M.D. awarded by the University of Dublin to B. O. Onadeko in 1977.

ported the presence of tumour cells in exudates. Examination of pleural fluid for malignant cells is important in effusions occurring in persons of middle age or older whether the effusion be haemorrhagic or otherwise as this may be the only means of establishing a certain diagnosis in some cases (Luallen and Carr, 1955). The predominating type of cell found in an effusion may be helpful. Lymphocytes have been reported to predominate in tuberculous pleural effusion (Paddock, 1940; Close, 1946; Mestitz and Pollard, 1959). Lymphocytes may also predominate in malignant effusions (Berliner, 1941 ). Pleural effusion occurs commonly in Nigerians (Lucas and Mainwaring, 1963; Afonja and Sofowora, 1972; Elegbeleye, 1975; Onadeko, 1977). These reports concentrated mainly on the clinical features and management of effusion. No mention was made concerning the detailed cytological analysis of the fluid. In the last three years (1974-1976), a detailed prospective study of pleural effusion was undertaken at the University College Hospital (UCH), Ibadan, to determine the incidence and clinical patterns of the condition. This report on cytological examination of the pleural fluid forms part of the study and its findings are presented. Ma~erlaJs and Methods The pleural fluids of 216 patients were examined. Smears made from the cen-

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trifuged deposit were stained using the modified May- Gr~inwald - Giemsa and standard Papanicolaou methods for the examination of inflammatory and malignant cells. These routine stains were supplemented with PAS-Alcian blue and methyl green-pyronin when necessary. Total and differential white cell counts were carried out. The diagnosis of the cause of the pleural effusion was made from the clinical features and diagnostic aids such as biopsy of the pleura, lymph nodes or liver and microbiological examination of the fluid and sputum for tubercle bacilli.

TABLE II Causes of a predominantly lymphocytic pleural fluid. Causes

No. of cases

Tuberculosis 100 Neoplasm 10 Lymphoproliferative disorders 6 Congestive cardiac failure 6 Pneumonia 5 Other inflammatory disorders 2 Constrictive pericarditis 1 Nephrotic syndrome 1 Total 131

% 76.3 7.6 4,6 4.6 3.8 1.5 0.75 0.75 100

Results

Cyto/ogica/ findings : The cytological analysis of 216 fluids is shown in Table I. Lymphocytes predominated (i.e., more than 70% of the total white cell count) in 131 (60%) of cases. Polymorphonuclear leucocytes (polymorphs) predominated in 49 (22%) of cases. There was a mixture of lymphocytes and polymorphs in 21 (10%) of cases. Eosinophils were found in more than 5% of total white cell count in 12 (6%) of cases. There was a mixture of lymphocytes and lymphoblasts in 3 (1.4%) of cases. Lymphocytes: Table II shows the causes of pleural effusion with a predominant lymphocytic cytology. It was observed that tuberculosis was the com-

monest cause, being responsible in 100 (76%) of cases (Fig. 1). Neoplasm was responsible in 10 (8%) of cases. Diseases of the iymphoproliferative tissue such as Hodgkin's disease and lymphoma were responsible in 6 (4.6%) of cases. Heart failure and pneumonia were responsible in 6 (4.6%) and 5 (4%) of cases respectively.

Polymorphs (Table III): These predominated in the pleural fluid in 22% of 216 cases. It was observed that pneumonia and other acute inflammatory disorders were responsible in 31 (71%) cases. This was followed by tuberculosis in 10 (20%) cases. The only case in

TABLE I Cytology of pleural fluid in 216 cases. Causes Predominantly lymphocytes Predominantly polymorphs Polymorphs plus lymphocytes Eosinophils plus other inflammatory cells Lymphocytes + lymphoblasts Total Malignant cells in addition to other inflammatory cells Mesotheli~l cells in addition to other inflammatory cells

No. of cases

__

131 49 21

60.6 22.7

12 3 216

5.6 1.4 100

9

i

P

~

,,

10 25

Fig. 1 - - S h o w s a case of tuberculous pleural effusion with numerous lymphocytes in the pleural fluid. May GrOnwald-Giemsa. (X 700).

PLEURAL FLUID CYTOLOGY IN NIGERIANS TABLE III Causes of pleural fluid with a predominance of polymorphs. Causes

No. of cases

%

Acute inflammatory disorders (pneumonia, abscesses, etc.) Tuberculosis

35 10

71.4 20.4

Neoplasm Pulmonary infarction Congestive cardiac failure Total

2 1 1 49

4.1 2.05 2.05 100

this study with effusion due to pulmonary infarction had a predominance of polymorphs in the fluid.

Mixture of lymphocytes and polymorphs (Table IV): Both types of cells were found in proportions varying from 30% to 60%. Tuberculosis was responsible for this type of cytology in 11 (52%) cases, followed by pneumonia in 4 (19%). Other causes observed were heart failure, constrictive pericarditis, and neoplasm. TABLE IV Diseases causing a combination of polymorphs and lymphocytes in pleural fluid. Causes Tuberculosis Pneumonia Congestive cardiac failure Nephrotic syndrome Constrictive pericarditis Neoplasm Total

No. of cases

%

11 4 2 2 1 1 21

52.3 19.1 9.5 9.5 4.75 4.75 100

Eosinophils: Eosinophils amounted to 5% or more of the total leucocyte count in 12 cases (Table V). The major causes of the effusions in these cases were tuberculosis (33%) and pneumonia (33%). Other causes were neoplasm and abscesses. Blood eosinophils were not elevated in these cases.

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Mesothelial cells : The term 'mesothelial cells' is used to include all the large cells with round or oval nuclei and with truly basophilic cytoplasm. Mesothetial cells were found in the pleural fluid in 25 cases in this study (Table I). The cause of pleural effusion in these cases is shown in Table VI. Tuberculosis, pneumonia and neoplasm were responsible in 32%, 20% and 20% of cases respectively. Other causes observed were heart failure, cirrhosis of liver and nephrotic syndrome. TABLE V Diseases associated with eosinophils in the pleural fluid. Diseases

No. of cases

%

4 4 2 2 12

33.3 33.3 16.65 16.65 100

Tuberculosis Pneumonia Abscesses Neoplasm Total

Malignant cells (Table VII): These were found in the pleural fluid in 10 (22%) of the 45 cases of malignant effusion. In 7 cases, the pleural fluid was haemorrhagic and it was straw-coloured in the remaining 3. Malignant cells were found mainly in cases of carcinoma of the breast and carcinoma of bronchus. TABLE VI Diseases associated with mesothelial cells in the pleural fluid. Diseases Tuberculosis Pneumonia Neoplasm Congestive cardiac failure Others : Cirrhosis of liver 1 ) Chronic pancreatitis 1 ~" Nephrotic syndrome 2 Total

No. of cases

%

8 5 5 3

32 20 20 12

4

16

25

100

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TABLE VII Neoplastic diseases in which malignant cells are found in the pleural fluid. Neoplasm Carcinoma of breast Carcinoma of bronchus Carcinoma of ovary Pleural mesothelioma Total

No. of

cases

4 4 1 1 10

Fig. 2 shows malignant cells in the pleural fluid in a case of carcinoma of the bronchus. Discussion This study reveals that lymphocytes are the most commonly recognised inflammatory cells in the pleural fluid of Nigerian patients with pleural effusion. Tuberculosis was observed to be the commonest cause of a predominantly lymphocytic effusion. This finding is in agreement with those of other workers (Paddock, 1940; Close, 1946; Karron and Purves, 1947; Durrant and Rodgers, 1947; and Mestitz and Pollard, 1959). According to Forgacs (1957), a lymphocytic pleural effusion in tuberculin-positive young adults is likely to be a manifestation of tuberculosis. Mestitz and Pollard (1959) in their own conclusion, stressed that in a pleural effusion of recent onset,

Fig. 2 - - S h o w s malignant cells aggregated in clumps in the pleural fluid of a case of carcinoma of bronchus. Papanicolaou. (X 700).

where no antimicrobial therapy has been used, a lymphocyte count of 70% or more in the fluid is compatible with a tuberculous effusion. It was also observed from this study that 8% of effflusions in which lymphocytes predominated were neoplastic in origin. This finding was similar to those of Berliner (1941) and Yam (1967). Yam observed in his own study that 73% of lymphocytic effusions were due to tuberculosis, lymphoma and carcinoma. The predominance of lymphocy'3s in pneumonic effusion shown in this study is not unusual. Lymphocytes are known to predominate late in pneumonic effusions which have been treated with antibiotics (Scott and Finland, 1934; Forgacs, 1957). Polymorphs predominated in the pleural fluid, as expected, of cases of acute inflammatory disorders. This observation was also made in some cases of tuberculosis. It has been reported that polymorphs may predominate at the early stage of tuberculous effusion (Paddock, 1940; Hinson, 1961). A mixture of lymphocytes and polymorphs has been observed in tuberculous effusions (Close, 1946). A similar observation was made in this study. Eosinophils were found in fluids secondary to tuberculosis, pneumonia and abscesses. Pleural effusion, in which a high proportion of cells are eosinophils, is a widely recognised phenomenon (Campbell and Webb, 1964). Although this is an interesting laboratory finding it has no diagnostic significance (Robertson, 1954; Guhl, 1957; Javinen and Kahanpaa, 1959; Bower, 1967). Pleural fluid eosinophilia is found in fluids of relatively long duration and is secondary to many diseases like tuberculosis, pneumonia, cardiac failure, neoplasm and connective tissue diseases (Guhl, 1957). The significance of mesothelial cells in the pleural fluid of cases in this study is not known. Tuberculosis was the cause of the effusion in 32% of cases. This is surprising and is in contrast to the find-

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References ings of Widal and Ravault (1900), Koniger (1908), Zadek (1933), and Spriggs Afonja, A. O. and Sofowora, E. O. 1972. Empyema thoracis in Nigerians. Trop. Geog. Med. 24, 55. and Boddington (1960). They reported Berliner, K. 1941. Haemorrhagic pleural effusion. the absence or scarcity of mesothelial Analysis of 120 cases. Ann. Int. Med. 14, 2266. cells in tuberculous effusion. The smears G. 1967. Eosinophilic pleural effusion. made from pleural fluid in our cases were Bower, Amer. Rev. Resp. Dis. 95, 746. reexamined and the cells were confir- Campbell, G. D. and Webb, W. R. 1964. Eosinomed to be mesothelial cells, because it philic pleural effusion. Amer. Rev. Resp. Dis. has been reported that malignant cells 90, 94. may be confused with mesothelial cells Carr, D. T., Soule, E. H. and Ellis, F. H. 1964. Management of pieural effusion. Med. Clin. (Carr et al, 1964). North Amer. 48, 961. Examination of pleural fluid for malig- Childers, J. H. 1955. Cytologic studies on pleural nant calls has been of great value in and peritoneal fluids. Texas J. Med. 51,674. demonstrating the cause of pleural effus- Close, H. G. 1946. Tubercle bacilli in pleural effusion of young adults. Lancet i, 193. ion (Graham etal, 1933). Malignant cells Durrant, T. M. and Rodgers, L. R. 1947. Pleurisy were found in malignant effusion in this and empyema. Med. Clin. North Amer. 31, 1493. study in 22% of cases. Tinney and Olsen Elegbeleye, O. 1975. Pleural effusion in Nigerians. (1945) found them in 30% of cases, and Nig. Med. J. 5, 62. Robertson (1954) in 24% of cases, while Foord, A. G., Youngberg, G. E. and Wetmore, V. 1929. The chemistry and cytology of serous Berliner (1941) found malignant cells in fluids. J. Lab. Clin Med. 14, 417. 50% of haemorrhagic malignant effus- Forgacs, P. 1957. The treatment of tuberculous ions and in 52% of serous malignant pleurisy. Thorax. 12, 344. effusion, and Luallen and Carr (1955) in Graham, G. G., McDonald, J. R., Clagett, O. and Schmidt, H. W. 1933. Examination of pleural 59% of cases. The factors responsible fluid for carcinoma cells. J. Thorac. Surg. 25, for different rates being obtained in the 365. examination of pleural fluid for malignant Guhl, R. 1957. Uber. pleurale. Eosinophilic. Schweiz. Med. Wschr. 26, 834. Cited by Javinen cells have been discussed (Graham et al, and Kahanpaa (1959). 1933; Saphir, 1949; Childers, 1955). HowK. F. W. 1961. Examination of pleural ever, it is generally accepted that exam- Hinson, fluid. Practitioner, 186, 260. ination of multiple specimens of fluid Javinen, K. A. F. and Kahanpaa, A. 1959. Progwill increase the chance of finding malignosis in cases with eosinophilic pleural effusion. Acta. Med, Scand. 164, 245. nant cells in malignant effusions. In conclusion, the results of the cyto- Karron, I. G. and Purves, R. K. 1947. Tuberculous pleurisy with effusion. Amer. Rev. Tuberc. 56, logical analysis of the pleural fluid have 184. revealed that this examination may be Koniger, H. 1908. Diezytologische. Untesuchungs methode. Fischer. Jena. Cited by Scott and helpful in the diagnosis of the cause of Finland (1934). effusion. In a community like ours, where E. C. and Carr, D. T. 1955. Pleural effustuberculosis is still highly prevalent, a Luallen, ion. A study of 436 patients. New Eng. J. Med. predominant lymphocytic cytology of the 252, 81. pleural fluid in young adults and middle- Lucas, A. O. and Mainwaring, A. R. 1963. Pleural punch biopsy. West Afr. Med. J. 12, 106. aged persons with perhaps a positive tuberculin test, may be regarded as due Lucke, A. and Klebs, E. 1867. Cited by O. Saphir. (1949). to tuberculosis until proved otherwise. Mestitz, P. and Pollard, A, C. 1959. The diagnosis Similarly, examination of pleural fluid of tuberculous pleural effusion. Brit. J. Dis. Chest 53, 86. for malignant cells may be rewarding in the diagnosis of malignant effusion and Onadeko, B. O. 1977. A preliminary study of the pattern of pleural effusion in Africans. Nig. Med. should become a routine procedure in J. 7, 138. the investigation of patients with pleural Paddock, F. K. 1940. The diagnostic significance effusion. of serous fluids in disease. New Eng. J. Med. The authors are grateful to Mr. Ogunremi for the photomicrographs.

223, 1010. Robertson, R. F. 1954. Pleural eosinophilia, Brit. J. Tuberc. 48, 111.

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Saphir, O. 1949. Cytologic diagnosis of cancer from pleural and peritoneal fluids. Amer. J. Clin. Path. 19, 304. Scott, T. F. M. and Finland, M. 1934. The cytology of pleural effusions in pneumonia studied with a supravital technique. Amer. J. Med. Sci. 188, 322. Spriggs, A. I. and Boddington, M. M. 1960. Absence of mesothelial cells from tuberculous pleural effusions. Thorax. 15, 169. Tinney, W. S. and OIsen, A. M. 1945. The significance of fluid in the pleural space. A study

of 274 cases. Proc. Staff Meeting. Mayo Clinic. 20, 81. Widal, F. and Ravaults, P. 1900. Comptes. rend. soc. Biol. (Paris) 52, 648. Cited by Scott and Finland (1934). Wihman, G. 1948. A contribution to the knowledge of the cellular content in exudates and transudates. Acta. Med. Scand. Suppl. 205, 130, 1. Yam, L. T. 1967. Diagnostic significance of lymphocytes. Ann. Int. Med. 66, 972. Zadek, T. 1933. Cited by Scott and Finland (1934).

The significance of cytological examination of the pleural fluid in the diagnosis of pleural effusion in Nigerians.

THE SIGNIFICANCE OF CYTOLOGICAL EXAMINATION OF THE PLEURAL FLUID IN THE DIAGNOSIS OF PLEURAL EFFUSION IN NIGERIANS* B. O. Onadeko Department of Medic...
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