Thorax (1954), 9, 26.

MALIGNANT CELLS IN SEROUS EFFUSIONSCOMPLICATING BRONCHIAL CARCINOMA

BY

ARTHUR I. SPRIGGSFrom the Division ofLaboratories, United Oxford Hospitals

(RECEIVED FOR PUBLICATION AUGUST 25, 1953)

The object of this paper is to report on thecytological features of tumour cells which havebeen identified by a smear technique in 21 pleuralor peritoneal effusions complicating primary car-cinoma of the lung.There are already hundreds of cases reported

in the literature of the past 80 years in whichmalignant cells have been found in pleural orperitoneal fluid, and every clinical pathologist isfamiliar with the large aggregations of bizarrevacuolated cells which are especially common inmalignant ascites due to carcinoma of the ovary.This type of microscopical metastasis is parti-cularly well shown in sections of centrifuged sedi-ment, and the appearance of hollow acini leavesno doubt of the glandular origin of the tumour.

Malignant cells which are not of the adeno-carcinoma type are far less frequently recognized,and it is a surprising fact that hardly any attempthas so far been made to classify the different typesof cell shed into the serous cavities by differentvarieties of tumour. The reason for this gap inour knowledge is presumably the absence of anyagreed system of classification even of the benigncells of effusions; it is over 50 years since theintroduction by Widal and Ravaut (1900) of " cyto-diagnosis," and there is still no atlas or illustratedmonograph showing all the common types of cellencountered in effusions. Most textbooks ofclinical pathology have only a few lines explainingthat the identification of malignant cells is difficultand uncertain.The introduction of Dudgeon's (Dudgeon and

Wrigley, 1935) and Papanicolaou and Traut's(1943) wet-fixation techniques has resulted inonly a slight advance in our knowledge of thecytology of serous fluids. Malignant cells inpleural and peritoneal fluid seldom show the hyper-chromatism which is such a feature of squamouscarcinoma cells in vaginal and sputum smears, anddiagnosis has to depend on familiarity with allthe types of cell which occur in the serous cavities.

The Romanowsky stains which are found satis-factory in the study of blood and bone marrowcells give equally good cytological detail in thecells of effusions, and classification of these cellsusing any other technique causes confusion tothose who use orthodox haematological methods.One of the commonest causes of malignant

pleural effusion is anaplastic carcinoma of thelung of the small-celled variety, often known as" oat-cell carcinoma." Since this type of growthis particularly liable to dissemination over thepleura and pericardium, it is surprising to find thatthe metastasizing cells have hardly ever beendescribed from the sediment of a serous effusion.Almost all published records of malignant cellsin pleural effusions complicating primary car-cinoma of the lung have referred to adeno-carcinoma and not to the oat-cell variety.A search of the older literature has not

revealed any descriptions of oat-cells in pleuralfluid. There are some records of malignant cellsfound by the Widal technique (air-dried Roman-owsky-stained films), or by direct examination ofwet films, from cases classified as " endothelioma"(Fraenkel, 1892; Schulze-Vellinghausen, 1900;Meslay and Lorrain, 1903; Bloch, 1905; Erben,1906), as large round-cell sarcoma of the lung(Ravaut, 1901 ; Turton, 1905), or as primary car-cinoma of the lung or bronchus (Quincke, 1882;Schwalbe, 1891), but the reports are either veryincomplete, or else suggest adenocarcinoma orsquamous carcinoma rather than anaplastic car-cinoma of the oat-cell variety. Zadek (1933) pub-lished a coloured plate of a Romanowsky-stainedsmear of pleural fluid from a case of bronchialcarcinoma, but the cells labelled " Endothelien? Karzinomzellen" are almost certainly endo-thelial cells.

Quensel (1928a and b) examined a range ofpleural and peritoneal effusions by a wet-chambermethod, and published many beautiful photo-graphs of exudate cells including tumour cells. Of

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five cases due to bronchial carcinoma, he foundfour with collections of vacuolated cells of theadenocarcinoma type, and one with large pleo-morphic cells. There were no cases of oat-cellcarcinoma.Numerous workers have used the cell-block

technique by which sections are made of the centri-fuged deposit, but almost all of the publisheddescriptions and illustrations of positive findingsin bronchial carcinoma have shown the acinarformations of adenocarcinoma (Goldman, 1929;McDonald and Broders, 1939; Schlesinger, 1939;Wihman, 1948; Taylor and Thompson, 1949). Ina few cases there have been malignant cells ofsquamous origin (Marcuse and Coulter, 1948), orof doubtful or indeterminate type (Eisenberg,Wallerstein, and Plato, 1933; Foot, 1937), andmany others have given figures for "positives "and "negatives " without details; but the onlyacceptable report of oat-cells being found by thismethod is that of Wihman (1948), where the cellsoccurred in large aggregates.Among those who have used wet-fixed smears

(Dudgeon or Papanicolaou methods), only Bam-forth (1946) has given descriptions and illustrationsof the main varieties of malignant cells found inpleural effusions. Of 13 cases of bronchial car-cinoma in which malignant cells were found, 12showed cells of the adenocarcinoma type (whichBamforth calls "columnar ") and one showedtypical oat-cells of the same appearance as thosefound in sputum. He gives a drawing of these,apparently the first illustration in the literature ofoat-cells in a pleural fluid smear.

It has even been questioned whether the oat-cells of bronchial carcinoma are cytologically re-cognizable at all. Hauptmann (1948) made directsmears from tumours, using Romanowsky stainsas well as Papanicolaou's method, and consideredthe oat-cells to be indistinguishable from lympho-cytes.

In the course of systematic cytological examina-tions of pleural and peritoneal fluids, using a modi-fied Widal technique, I have found that effusionscomplicating anaplastic oat-cell bronchial car-cinoma do in fact often contain recognizablemalignant cells of a hitherto undescribed type.Although they do not look malignant to an eyetrained to expect large size, hyperchromasia, cyto-plasmic basophilia, prominent nucleoli, and bizarrevariations, they are none the less perfectly charac-teristic, and, once recognized, are not easily con-fused with any other type of cell. In particular,they bear no resemblance whatever to pleuralendothelial cells (Figs. 1 and 2). The cases to bedescribed illustrate this cell type, as well as the

other less common but better known types foundin effusions complicating adenocarcinoma andsquamous carcinoma of the bronchus.

MATERIALS AND METHODSOf the 21 cases to be described, 20 formed part of a

series of 270 cases of pleural or peritoneal effusionfluids from which were examined routinely in the clinicalpathological laboratory of the Radcliffe Infirmary,Oxford. One further case (Case 21) is included becauseit was possible to compare the cells of sputum andpleural exudates. The sputum of the other 20 caseswas not studied.The 20 cases to be described from the series all showed

clinical or histological as well as cytological evidenceof primary bronchial carcinoma. There were a further17 cases of pleural effusion considered to be due toprimary bronchial carcinoma in which no malignantcells were found. These will not be considered furtherexcept that they are included in the Table.

All of the effusions except one were aspirated duringlife from the pleural cavity. In Case 6 the fluid wasfrom the peritoneal cavity.

PREPARATION OF SMEARSMost textbooks of clinical pathology recommend

the technique of Widal and Ravaut (1900) for makingsmears of serous fluids. Smears made by this methodare slow to dry; the cells are shrunken, their nucleiappear pyknotic, and there is often background staining.We have used the following modification, which ensures,the quick drying essential for good Romanowskystaining.

Fluid is collected into l-oz. bottles containing 4 ml.of sterile 3.8%. sodium citrate solution. The examinationis carried out if possible on the day of collection.About 10 ml. of the fluid is centrifuged until the white

cells are deposited (five minutes at 1,500 r.p.m. is.sufficient).The supernatant fluid is poured off, and the tube is

held upside down so that no fluid runs back on to thedeposit.A flamed metal loop is introduced into the tube from

below, and a pinhead-sized portion of the deposit isremoved. A loopful is too mrruch, even when it canbe obtained.The material removed should be of a creamy con-

sistency. It is spread out rapidly on a slide with theloop, taking care that the loop does not go over thesame place twice. The smear should dry instantaneously.If the deposit contains fibrin, the fragment may bemore tenacious, and should be lightly drawn over thesurface of several slides, one or two of which may besatisfactorily quick drying.Smears made by this technique occupy only a small

area of the slide, for example, 1 cm.X 2 cm., but thecells lie close to one another and many thousands canbe rapidly examined.The air-dried smears are stained exactly as for blood

or marrow films. We have used the May-Griinwald-Giemsa combination, but Leishman's stain is also,

27

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satisfactory. It is desirable to mount the film with a

coverslip, so that it can be examined under a dry 4 mm.objective and is protected from dust.

RESULTSSummaries of the 21 cases in which malignant

cells were found are given in the Appendix. Therewere 37 cases in the consecutive series believed tohave primary bronchial carcinoma. These are

classified in the Appendix (see p. 32). Twenty(54%) had effusions containing cells interpreted as

malignant. In four cases (1, 2, 3, and 4) these cellswere similar to the adenocarcinoma cells whichare most commonly seen in malignant peritonitisin carcinoma of ovarian or alimentary origin; theyoccurred in clumps and showed marked vacuola-tion (Fig. 7). In Cases and 2 there was post-mortem or biopsy confirmation of adeno-carcinoma. In one case (Case 5) subsequentlyproved to have a squamous type of bronchialcarcinoma, the malignant cells were large, withprofuse cytoplasm, and lay separate from one

another (Fig. 8). In the remaining 15 cases, themalignant cells were of a type which I shallrefer to as the oat-cell. This name is not givenon account of any resemblance to oats, but be-cause these cells correspond to the oat-cells ofhistological sections. This correspondence was

demonstrated in eight cases; the remaining seven

died without biopsy or necropsy.

DESCRIPTION OF THE "OAT-CELLThe oat-cell is illustrated in Figs. 1, 2, 3, and 4.In examining a Romanowsky-stained smear, oat-

cells are not prominent, since they are not very

large, show little cytoplasmic basophilia, andseldom have distinct nucleoli; they may also occurin very small numbers. They can be picked outby their comparatively pale-staining nuclei andscanty cytoplasm. Although isolated examples are

seen, they commonly lie in small groups and occa-

sionally in clumps which are identifiable in sectionsof hardened deposit. The cell diameter is usuallyabout 15 ,u, but there is variation from case tocase, and also considerable variation in a singlesmear. In any group of these cells it is very com-

mon to see one or more very small cells, some-times inserted between several large ones. Dia-meters above 30 it are hardly ever seen.A very characteristic feature is the high ratio

of nucleus to cytoplasm. Since the cells usuallylie in small groups, the scarcity of cytoplasm pro-duces an appearance of flattened adjacent nuclearborders, and the nuclei often appear like unequalpieces in a mosaic, polygonal in shape and sepa-rated by narrow clefts. Only in the case of iso-

lated cells is a round or oval shape apparent, buteven here the nuclear borders are generally irre-gular. In Case 21 there were frequent forms inwhich one (or sometimes two) spherical nucleiwere partly surrounded by another crescenticnucleus in the same cell (Fig. 4).The nucleus shows a rather fine chromatin pat-

tern without any heavy areas or markings, butparts of it usually show fine parallel strands andthere are ill-defined paler areas and fenestrations.Nucleoli are not usually visible, but a few palelybasophilic areas can sometimes be distinguished.The cytoplasm exists as a thin basophilic rim.

It often appears of a rather smooth slate-blue orgrey. A few very clear, punched-out vacuoles notexceeding 3 t in diameter are often scatteredin the cells, and characteristically involve thenuclei as well as the cytoplasm: they are stainedby Sudan black.

Cells of this type are not often seen in mitosis,but in Case 16, where the cells were unusuallyabundant, mitotic figures could be found withoutdifficulty.

In Case 12 malignant cells were found showingmore cytoplasm than is usual in anaplastic lungcarcinoma. Post-mortem sections showed pleo-morphic cells with relatively abundant cytoplasm.The Table shows the cases of bronchial car-

cinoma classified according to cytological andhistological findings.

In one case (Case 21), which is not classifiedwith the others since it was not part of the con-secutive series, sputum was examined as well aspleural fluid. Oat cells were recognized in both,

TABLECOMPARISON OF CYTOLOGICAL AND HISTOLOGICALFINDINGS IN 37 CONSECUTIVE CASES OF BRONCHIAL

CARCINOMA WITH MALIGNANT EFFUSION

Cytological Findings

Histological C

Findings 0

Z u

Anaplastic and oat- 7cell carcinoma (Cases 6- 2 9

12)

Adenocarcinoma 1 1(Case 2)

Mixed oat-cell and 1 1 2adenocarcinoma (Case 13) (Case I)

Squamous carcinoma 1 1 2(Case 5)

No biopsy or necropsy 7 2 14 23(Cases 14- (Cases 3

20) and 4)

Total 15 4 1 17 37

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MALIGNANT CELLS IN SEROUS EFFUSIONS 29

FIG. l.-Case 19: Group of six oat-cells in pleural fluid. Theirnuclei are mutually compressed, giving the " mosaic " effect.(May-Grunwald-Giemsa.) x 1160.

Fio. 3.-Case 7: Pleural fluid. Almost all the nucleated cells in thisfield are " oat-cells." Tney are unusual in showing distinctnucleoli. Red cells and lymphocytes are also present. (May-Grilnwald-Giemsa.) x 1160.

FIG. 2.-Case 19: Pleural fluid. Most of the field is taken up by acluster of oat-cells. Eight nuclei of these cells are shown.Adherent to the lower right part of the cluster are an endothelialcell and a lymphocyte. Other endothelial cells, lymphocytesand polymorphs are shown in whole or in part. Note the dark-staining nuclei and basophilic cytoplasm of the endothelial cells,compared with the pale staining of the malignant cells. (Agfa-color- photograph of May-Grunwald-Giemsa film.) x 1460.

FIG. 4.-Case 21: Pleural fluid. Of the two central cells, the upperright is an endothelial cell; the lower left is an oat-cell showingtwo pale nuclei partly surrounded by a third crescentic one.(May-Grilnwald-Giemsa.) x 1460.

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RA- :

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FIG. 5.-Case 21: Sputum. Air-dried film stained with May-Gruinwald-Giemsa showing oat-cells. 550.

FIG. 7.-Case 4: Pleural fluid. All the cells shown are malignantcells of the adenocarcinoma type, separated from red cells byalbumin flotation. (May-Grunwald-Giemsa.) x 550.

FtC,. 6.-Case 21: Sputum. Papanicolaou-stained film, showingappearance of oat-cells by this method. The smaller size of thecells compared with Fig. 5 is due to the wet-fixation technique.x< 550.

FIG. 8.-Case 5: Pleural fluid. The two central cells are malignantcells from a squamous carcinoma. (Direct film of a haemor-rhagic fluid, stained May-Gruinwald-Giemsa. x 1160.

30

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4*

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and it was possible to compare the appearance ofthese cells in Papanicolaou preparations as wellas in air-dried May-Grunwald-Giemsa stainedfilms of the same sputum. By this means it couldbe shown that the oat-cells of pleural fluid, asseen by our technique, do in fact correspond withthe oat-cells of Papanicolaou preparations (Figs. 5and 6) as illustrated by the Vincent MemorialLaboratory, Boston (1950).

In the expectation that smears taken direct fromfresh anaplastic bronchial carcinomas would pre-sent the same appearance when stained by ourtechnique, I examined 11 lung tumours in thisway within an hour of operative removal. Mostof these were of squamous, large spheroidal, orglandular varieties, but two of them proved histo-logically to be typical oat-cell growths. Directsmears of material aspirated from these did notshow the same appearance as the oat-cells ofpleural fluid, the principal difference being theabsence of mutual distortion of nuclei. Thisdiscrepancy is probably explained by the fact thatthese cells were torn from their setting, whereasthe small metastases found in pleural fluid are seenentire, with their cytoplasm perfectly preserved.In the material aspirated from oat-cell tumours itis difficult to find a cell showing cytoplasm at all.I have to disagree with Hauptmann (1948), whofound the cells of oat-cell carcinoma indistinguish-able from lymphocytes; in the two growths whichI have examined the oat-cells were larger, hadan entirely different nuclear structure from that oflymphocytes, and usually lacked cytoplasm, whilelymphocytes always preserve a cytoplasmic rim.

DISCUSSIONAlthough primary carcinoma of the lung shows

a considerable range of histological types, severalof which may opcur in one tumour, it appzarsthat the metastases show more uniformity; thethree well-recognized types, squamous, oat-cell,and adenocarcinoma, are quite distinct whetherthey are observed in sputum or in serous fluids.SQUAMOUS CARCINOMA.-In the cytological

examination of sputum, squamous carcinoma isperhaps the most commonly recognized variety,and adenocarcinoma the least. Where pleuralfluid is concerned, on the other hand, squamouscarcinoma cells are only rarely seen; there is onlyone example in the present series (Case 5). Thebetter-differentiated types do not easily metas-tasize to the pleura, and there appears to be norecord in the literature of cornified cells beingfound in p'eural fluid. (The only two cases inwhich I have observed cornified cells in pleuralfluid were both of ruptured oesophagus, and the

c

cells concerned showed no evidence of malig-nancy.) In Case 5, the sole example in this seriesof a squamous carcinoma, the tumour was ratheranaplastic and a diagnosis of the type could hardlyhave been made on cytological evidence alone;the cells were isolated one from another, werelarge, and did not have the typical appearanceseither of the adenocarcinoma or of the oat-celltype (Fig. 8).ADENOCARCINOMA.-The present series includes

only four cases of adenocarcinoma thought to beprimary in the lung with malignant cells in pleuralfluid (Cases 1-4). Malignant acini are quitefrequently seen in pleural fluid, but in many casesthe involvement of the lung and pleura has beensecondary to an adenocarcinoma elsewhere;wherever the growth arose the metastatic cellshave the same characteristic features-aggregationin clumps, often of dozens or scores of cells (whichin sections appear as rosettes or hollow acinarformations), together with a tendency to giantvacuolation. Very large and bizarre individualcells, usually with enlarged nucleoli, may occurin the same field with large clumps or spheres ofregular, more or less uniform, cells which show noobvious malignant characteristics (Fig. 7). Thefour cases in this series do not show any featureswhich have not been noticed by previous authors.

OAT-CELL CARCINOMA.-From the frequentoccurrence of oat-cell carcinoma and the scarcityof descriptions in the literature of the oat-cells inmalignant effusions, one can only deduce thatthese cells are not being recognized when theyoccur. The cells which I have described in thispaper as oat-cells have been seen only in certaincases of carcinoma of the lung, all of which arenow dead from the disease (Cases 6-21), and inevery case where there has been a biopsy or anecropsy the primary growth has been found tobe of the oat-cell type. Apart from this evidencethe cells are recognizably the same as those whichhave been previously described from the bonemarrow in carcinomatosis secondary to bronchialcarcinoma, and from bronchial secretions; photo-graphs have been published by Rohr and Hegglin(1936), Rohr (1949), and Delarue and Orcel(1952) showing the round or polygonal nuclei withmutual compression and the narrow cytoplasmicborders. Furthermore, in Case 21 I have com-pared the malignant cells found in the sputumwith those of the pleural fluid, and found a closecorrespondence of appearances in air-driedRomanowsky-stained films; at the same time themalignant cells shown in Papanicolaou prepar-ations of the sputum were absolutely typical of the

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oat-cell type as figured by Bamforth (1946),Woolner and McDonald (1949), Vincent MemorialLaboratory, Boston (1950), and other authorities.To a pathologist who is familiar with the

benign cells of effusions, the oat-cells describedabove are sufficiently characteristic to allow of anunequivocal report of carcinoma even in caseswhere they lie separate from another and arepresent in small numbers. Since they occur mostfrequently in effusions complicating carcinoma ofthe lung, a provisional opinion of the primary siteis justified; it was possible in Case 6 to suggestthe lung as the primary site of the tumour fromthe examination of ascitic fluid. It is likely, how-ever, that similar cells can arise in tumours ofother sites; I have seen somewhat similar cells inan effusion due to a malignant synovioma, and themetastatic cells of sympathicoblastoma which aresometimes found in the bone-marrow are not veryunlike the oat-cells of pleural fluid. There isscope for much more extensive inquiry into thecytological features of all types of malignantmetastatic cells.

SUMMARYMalignant cells have been identified in 21 cases

of pleural and peritoneal effusion complicatingprimary carcinoma of the lung. In one case thecells were of squamous type, in four they weretypical of adenocarcinoma, and in 15 they wereof a type not previously described fromRomanowsky-stained films of serous fluids.Evidence is presented for regarding these as the" oat-cells " of anaplastic bronchial carcinoma. Ineight cases there was histological confirmation ofoat-cell carcinoma; the remaining seven died witha clinical diagnosis of primary carcinoma of thelung but were not subjected to necropsy.

I am grateful to Dr. A. H. T. Robb-Smith and toDr. R. G. Macfarlane for their advice and help; alsoto Dr. J. C. Sherris for correcting the manuscript. Mythanks are also due to all the colleagues who have sentmaterial.

REFERENCESBamforth, J. (1946). Thorax, 1, 118.Bloch, M. (1905). Les nioplasmes malins primitifs de la plevre.

Thesis, Paris.Delarue, J., and Orcel, L. (1952). Sem. Hdp. Paris, 28, 1014.Dudgeon, L. S., and Wrigley, C. H. (1935). J. Laryng., 50, 752.Eisenberg, A. A., Wallerstein, H., and Plato, A. (1933). J. Lab.

clin. Wfed., 19, 315.Erben, F. (1906). Z. Heilk., 27 (abt. intern. Med.), 3.Foot, N. C. (1937). Amer. J. Path., 13, 1.Fraenkel, A. (1892). Berl. klin. Wschr., 29, 497, 534.Goldman, A. (1929). Arch. Surg., 19, 1672.Hauptmann, E. (1948). Amer. J. Path., 24, 1199.McDonald, J. R., and Broders, A. C. (1939). Arch. Path., Chicago,

27, 53.Marcuse, P. M., and Coulter, W. W. (1948). Tex. St. J. Med., 43,

623.Meslay and Lorrain (1903). Bull. Soc. anat. Paris, 78, 88.Papanicolaou, G. N., and Traut, H. F. (1943). Diagnosis of Uterine

Cancer by the Vaginal Smear. Commonwealth Fund, New York.Quensel, U. (1928a). Acta med. scand., 68, 458.-- (1928b). Ibid., Suppl. 23.

Quincke, H. (1882). Dtsch. Arch. klin. Med., 30, 580.Ravaut, P. (1901). Le diagnostic de la nature des dpanchements

serofibrineux de la pl&vre (cytodiagnostic). Thesis, Paris.Rohr, K. (1949). Das menschliche Knochenmark, 2nd ed. Thieme,

Stuttgart.and Hegglin, R. (1936). Dtsch. Arch. klin. Med., 179, 61.

Schlesinger, M. J. (1939). Arch. Path., Chicago, 28, 283.Schulze-Vellinghausen, A. (1900). Munch. med. Wschr., 47, 647.Schwalbe, J. (1891). Dtsch. med. IVschr., 17, 1235.Taylor, H. E., and Thompson, W. J. (1949). Canad. med. Ass. J.,

61, 413.Turton, E. (1905). Practitioner, 74, 497.Vincent Memorial Laboratory, Boston (1950). The Cytologic Diag-

nosis of Cancer, compiled by Graham, R. M., MacKinney, D. C.,Rheault, M. H., Soule, M. H., Rudolf, K. A., Gray, E., Burke, A.,and Bradford, M. S. Saunders, Philadelphia and London.

Widal and Ravaut (1900). C.R. Soc. Biol. Paris, 52, 648.Wihman, G. (1948). Acta med. scand., Suppl. 205.Woolner, L. B., and McDonald, J. R. (1949). Surg. Gynec. Obstet.,

88, 273.Zadek, I. (1933). In Handbuch der allgemeinen Hamatologie, ed.

Hirschfeld, H., and Hittmair, A. Vol. I, p. 1373. Urban andSchwarzenberg, Berlin.

APPENDIXThe following table summarizes 21 cases of malignant

effusion complicating bronchial carcinoma, in whichmalignant cells were found in the fluid.

Case Sex Age Clinical and Pathological Description

1 M 148

2 M 54

3 M I 63

Left malignant pleural effusion. Twospecimens of fluid were examined,4 days apart. Both were heavilybloodstained. (1) N. 1, L. 96, M. 3%:(2) N. 1, L. 51, M. 44, EC. 3, Eos. 1%.Both showed clumps of large atypicalcells of adenocarcinoma type. Sec-tions of deposit showed ill-definedacini. Necropsy. - Bronchial car-cinoma of oat-celled variety withareas of adenocarcinoma

Left malignant pleural effusion. Biopsyof nodule in chest wall showed adeno-carcinoma. Three specimens of fluidwere examined; all deeply blood-stained, most of the white cells beinglymphocytes. In addition there wereclusters of malignant cells of adeno-carcinoma type

Clinically left bronchial carcinoma withmalignant pleural effusion. The fluidwas haemorrhagic; N. 13, L. 79,M. 5, Eos. 3%. There were collec-tions of adenocarcinoma cells, oftenmuch vacuolated; a few of thevacuoles gave a positive periodic acid-Schiff stain following salivary diges-tion, indicating mucus secretion. Diedwithout biopsy or necropsy

4 M 65 Clinical diagnosis left bronchial car-cinoma with pleural effusion. Thefluid was heavily blood-stained. N. 2,L. 58, M. 10, Eos. 29, B. 1%. Therewere collections of tumour cells ofadenocarcinoma type, and sections offixed deposit showed a few malignantacini. Died without biopsy or nec-ropsy

N =neutrophil, L =lymphocyte, M macrophage, EC =endothelialcell, Eos= eosinophil, B = basophil, P plasma cell, TC = tumour cell.

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Case Sex Age Clinical and Pathological Description Case

Large left pleural effusion. The fluidwas lightly bloodstained. Most of thewhite cells were lymphocytes andmacrophages, but tumour cells werealso frequent. These were large (upto 60 u in diameter in a few examples)and had profuse cytoplasm showingmarked fat vacuolation. Necropsyshowed gross pleural involvementfrom bronchial carcinoma. This wasof anaplastic squamous type

Long history of gastric ulcer. Admittedwith ascites. The fluid was almostclear, with a light deposit. L. 46,M. and EC. 49, TC. 5%. Thetumour cells were typical of theoat-cell variety of carcinoma, andoccurred in groups of up to severalhundred cells. Necropsy showed asmall bronchial carcinoma withmultiple secondaries and peritonealinvolvement. There was also alarge benign gastric ulcer. Histologi-cally the growth was an oat-cellcarcinoma

Mediastinal obstruction and right pleuraleffusion of almost clear, deep yellowfluid. Most of the white cells werelymphocytes; there were also typicaloat-cells isolated or in small clumps.Four specimens of fluid were exam-ined; three were as above, but thefourth, taken 3 weeks after the first,showed numerous pus cells and notumour cells. Necropsy showed rightbronchial carcinoma with massivepleural involvement; histologicallythe growth was of oat-cell type

Admitted 24 hours before death, with alarge left pleural effusion. The fluidcontained white cells with the follow-ing distribution: N. 3, L. 40, M. andEC. 57%. There were also veryoccasional oat-cells. Necropsy showeda bronchogenic carcinoma invadingthe pericardium and a left pleuraleffusion, but no macroscopic pleuralmetastases. Histologically this wasan oat-celled growth

Large right pleural effusion and medias-tinal obstruction. The fluid wasslightly bloodstained, with an averageto light deposit. N. 4, L. 92, M. 4%.There were also fairly frequent oat-cells. The patient died two days afteradmission, and necropsy showed anoat-celled bronchial carcinoma in-volving the pleura

Sex Agel Clinical and Pathological Description

10 F

11

12

M

M

49

32

53

13 M 57

141 M 39

15 M 67

Pleural effusion secondary to inoperablebronchial carcinoma. The fluid wasbloodstained. N. 13, L. 61, M. 25,B. 1%; also moderately frequentendothelial cells, and a few cellsconsidered most probably to be oat-cells. Bronchoscopic biopsy showedan oat-cell carcinoma

Bloodstained left pleural effusion tappedon the day before death. The fluidhad a heavy bloody deposit. N. 5,L. 83, M. and TC. 12%. The tumourcells were of the oat-cell type, occur-ring in clumps. Necropsy showedmassive pleural involvement from ananaplastic spheroidal-celled carcinoma

Pleural effusion tapped on the day beforedeath. The fluid was almost clear,pale pink, with a scanty deposit.Moderate numbers of red cells; N. 2,L. 76, M. 17, P. 5%. There were alsosmall numbers of cells resemblingoat-cells but with more profusecytoplasm and with larger nuclei thanis usual, and without mutual distor-tion of nuclei. Necropsy showedextensive pleural involvement froman anaplastic pleomorphic celledcarcinoma

Carcinoma of the lung with pleuraleffusion. The fluid was heavilybloodstained and contained clot.N. 5, L. 78, M. 12, B. 1, EC. 4°o.There were occasional groups of 2-4characteristic oat-cells. Bronchialbiopsy confirmed the diagnosis ofcarcinoma; the growth was of mixedadenocarcinoma and oat-celled types

Left pleural effusion with Homer'ssyndrome and mediastinal obstruc-tion. The pleural fluid was almostclear, yellow, with an average cellulardeposit. N. 15, L. 40, M. 32, EC. 13%.There were also frequent typical oat-cells. Bronchoscopy showed occlu-sion to the left main bronchus fromwithout. No biopsy was taken. Thepatient died at home and there wasno necropsy

Right pleural effusion and hard supra-clavicular lymph nodes. Two speci-mens of fluid were examined, 3 daysapart. Both were bloodstained. Thedifferential white cell counts were:(1) N. 19, L. 51, M. 29, B. 1%. Nomalignant cells seen. (2) N. 6, L. 57,M. 32, EC. 3, TC. 2%. Tumour cellsoccurred in groups of up to a dozen;they were ofoat-cell type. The patientdied two days later; there was nonecropsy

5 IF

6 1 M

56

46

7 M 149

8 M 160

589 1 F

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ARTHUR 1. SPRIGGS

Case Sex Age Clinical and Pathological Description

Pleural effusion overlying a consolidatedarea of lung. The fluid was slightlybloodstained and there was a fairlyheavy cellular deposit. N. 1, L. 28,M. 12, EC. 9, TC. 48. Cells in mitosis2%. The tumour cells occurred inclumps, large enough to be identifiedin sections of centrifuged deposit.They were typical examples of oat-cells. This patient died a few weekslater and was registered as a case ofcarcinoma of the lung. There wasno necropsy

Rccurrent right pleurisy of 1 year'sduration. Admitted with haemopty-sis and right pleural effusion. Whilein hospital he had a hemiplegic attack,clinically thought to be due to cerebralmetastases from bronchial carcinoma.Three specimens of the fluid wereexamined. All were bloodstained andshowed a high proportion of lympho-cytes; they also all contained oat-cells in small numbers. The patientdied outside 3 months later, and nonecropsy was performed

Haemoptysis, right laryngeal palsy andright pleural effusion. Hard lymphnodes in the right side of the neck andthe right axilla. Two specimens offluid were examined 2 days apart.(1) N. 10, L. 84, M. 2, EC. 3, P. 1%oand occasional cells suggestive ofmalignancy. (2) N. 12, L. 85, M. andEC. 3°% and moderate numbers oftumour cells of oat-cell type. Deathoccurred at home soon after discharge,and there was no necropsy

Case Sex Age Clinical and Pathological Description

19 t M 59

20 M 53

21 M 43

Carcinomatosis and leuco-erythroblasticanaemia. The supraclavicular lymphnodes were enlarged and there wasradiological evidence of compressionof the right main bronchus. Blood-stained pleural fluid was aspirated ontwo occasions 5 days apart. (1) N. 7,L. 35, M. 36, EC. 20, TC. 2% .

(2) N. 9, L. 55, M. 26, EC. 9, P. 1%.In both specimens there were frequenttumour cells of the oat-cell typeoccurring singly and in small collec-tions. The patient died a fortnightlater. There was no necropsy

Haemoptysis and left pulmonary col-lapse with overlying pleural eflusion.Bronchoscopy showed a carcinoma ofthe left main bronchus, but nobiopsy was taken. The fluid wasslightly turbid. L. 93, M. 7%; less than1% of neutrophils, plasma cells, andendothelial cells. There were alsofrequent oat-cells lying singly and ingroups. The patient died 6 monthslater. There was no necropsy

Right pleural effusion with hilar enlarge-ments, a palpable mass in the liver,and a collapsed 12th thoracic vertebra.Clinically a case of inoperable car-cinoma of the bronchus with meta-stases. The pleural effusion wasaspirated 4 times, and 3 of thespecimens were examined cytologi-cally. (1) (right base) N. 35, L. 29,Eos. 1, EC. 35. Frequent oat-cellspresent. (2) (right interlobar) N. 26,L. 62, EC. 12. Frequent oat-cellspresent. (3) (right base) Similar toprevious findings. The patient died amonth later at home. There was nonecropsy

N= neutrophil, L-- lymphocyte, M= macrophage, EC= endothelialcell, Eos= eosinophil, B= basophil, P= plasma cell, TC= tumour cell.

16 M 55

17 M 63

18 M 65

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