cells pleural fluidtrates in association with pleural effusion. the category "other...

Cells in Pleural FluidTheir Value in Differential DiagnosisRichard W. Light, MD; Yener S. Erozan, MD; Wilmot C. Ball, Jr., MD, Baltimore

Pleural fluids from 182 patients were

studied prospectively. Although red bloodcell (RBC) counts of greater than 10,000/cumm were common with all types of effu-sions, an RBC count greater than100,000/cu mm strongly suggested malig-nant neoplasm, pulmonary infarction, ortrauma. Of 31 exudative effusions with a

lymphocytic predominance, 30 were due ei-ther to tuberculosis or neoplasm. No tuber-culous effusions had more than 1% meso-thelial cells, while most other effusionscontained at least 5% mesothelial cells.Pleural fluid cytological studies showed ma-

lignant cells in 33 of 43 patients with effu-sions due to tumor. More than 50% of theeffusions with originally inconclusive pleuralfluid cytological findings were proved to bedue to neoplasm. When tumor is suspected,at least three separate pleural fluid speci-mens should be submitted for cytological ex-

amination.

Although pleural fluid red bloodcell (RBC) counts, white blood

cell (WBC) counts, and differentialWBC counts are performed routinelyin patients with pleural effusion, theusefulness of these measurements isnot clear. Some authors1·2 have re¬

ported that the presence of blood inthe pleural fluid is of no diagnosticutility, while others3 " have reportedthat a bloody effusion is stronglysuggestive of malignant neoplasm.Some authors have reported that theWBC count and differential WBCcount are useful diagnostically,5·6while others have concluded they are

of no use.2·3·7 Similarly, the yieldsfrom cytological studies of the fluidsecondary to malignant disease havebeen quite variable, ranging any¬where from 33%8 to 87%9 positivefindings. Most of these studies were

retrospective, and criteria for thevarious diagnoses were not stated.

The purpose of this study was toevaluate prospectively the utility ofpleural fluid cell counts and cytologi¬cal findings in the differential diag¬nosis of pleural effusions.

Received for publication Oct 2, 1972; acceptedOct 17.

From the departments of medicine and pathol-ogy, the Johns Hopkins University School ofMedicine and the Johns Hopkins Hospital, Balti-more.

Reprint requests to 601 N Broadway, Balti-more 21205 (Dr. Ball).

Materials and Methods

One hundred eighty-two pleural fluidscollected between April 1, 1970, and Oct 1,1971, from 182 different patients in themedical wards of the Johns Hopkins Hos¬pital and the Good Samaritan Hospitalwere studied prospectively. Precise criteriawere established prior to beginning thestudy, in order to place the patients intovarious diagnostic categories.

The diagnosis of malignant effusion re¬

quired that malignant tissue be demon¬strated by pleural biopsy, cytopathologicalfindings, or autopsy. When a pleural effu¬sion in a patient with proved malignantneoplasm was believed to be due to tumorbut could not be documented, it was desig¬nated a "possible" malignant effusion.

The diagnosis of congestive heart failureas a cause of the pleural effusion requiredthat all four of the following criteria besatisfied: (1) an enlarged heart; (2) an ele¬vated central venous pressure, or dis¬tended neck veins and pitting edema, or

ventricular cardiac gallop; (3) absence ofpulmonary infiltrates, purulent sputum,thrombophlebitis, and pleuritic chest pain;and (4) clearing of the effusion in responseto a therapeutic cardiac regimen or evi¬dence of uncomplicated congestive heartfailure on the basis of the autopsy report.

The diagnosis of tuberculous pleuritisrequired either demonstration of Mycobac-terium tuberculosis by culture of pleuralfluid or pleural tissue, or granulomas on

pleural biopsy (open or closed.).The diagnosis of pneumonia with effu¬

sion required an acute febrile illness withpurulent sputum and pulmonary infil-

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trates in association with pleural effusion.The category "other exudates" encom¬

passes those effusions that were clearlydue to pancreatitis, collagen vascular dis¬ease, pulmonary emboli, postmyocardialinfarction (Dressier) syndrome, and vari¬ous other rare but well-documented causesof exudative pleural effusions. The diag¬nosis of pulmonary infarction required ar¬

tériographie demonstration of pulmonaryemboli. The effusions classified as "othertransudates" are those clearly due to cir¬rhosis or nephrosis.

For cell counts, at least 5 ml of pleuralfluid was withdrawn into a heparinized sy¬ringe. Then one drop of undiluted pleuralfluid was placed in a counting chamber andcell counts were done by one of the au¬thors. The counts were performed rou¬

tinely as for cerebrospinal fluid. Withgrossly bloody pleural fluids, it was neces¬

sary to dilute the pleural fluid with Turksolution in order to effect hemolysis ofRBCs. It was also necessary to dilute thefluids with high WBC counts in order to ob¬tain accurate counts.

A Wright stain was made for each pleu¬ral fluid in the following manner. The cellswere concentrated by centrifugation of thepleural fluid, followed by resuspension ofthe sediment in about 1 ml of pleural fluidand by thorough mixing. Then one drop ofthe concentrated specimen was placed on a

cover slip, spread evenly (as done with fin¬ger smears of peripheral blood), andstained with Wright stain. It was foundempirically that fluids with high WBCcounts required several minutes of stain¬ing in order to stain the cells adequately.

For cytological examination, fluid wascollected in a bottle that contained 3 unitsof heparin per milliliter of anticipatedfluid. The bottle was gently agitated whilethe fluid was collected in order to mix theheparin and fluid. The material was imme¬diately sent to the cytopathology labora¬tory without adding any fixative. Unfixedmaterial is essential for good Millipore fil¬ter preparations. Exposure to any kind offixative before preparation results inmarkedly inferior specimens. Cell spreads,Millipore filters (47-mm disks with 5umpore size), and cell blocks were preparedfrom this fresh material. They were imme¬diately fixed in 95% ethyl alcohol, exceptfor one of the cell spreads, which was airdried and stained with Giemsa stain. Therest of the slides, including Millipore fil¬ters and one section from the cell blocks,

were stained with a modified Papanicolaoustain. Two additional sections from the cellblocks were stained with PAS and alcianblue. After thorough screening by a eyto-technologist, they were examined by a

cytopathologist who then rendered hisdiagnosis and classified each specimen as

diagnostic of cancer (positive), as requir¬ing further studies to rule out cancer (in¬conclusive), or as showing no evidence ofcancer (negative).

ResultsThe origins, or presumed origins,

for the 182 effusions are as follows:

Transudates (47)Congestive heart failure 39Cirrhosis 5Nephrosis 3

Exudates (102)Malignant neoplasm 43Pneumonia with effusion 26Tuberculosis 14Pancreatitis 5Pulmonary infarction 5Postmyocardial infarction 3

(Dressier) syndromeTrauma 2Systemic lupus erythematosus 1Rheumatoid pleuritis 1Actinomycosis 1Infectious hepatitis 1

Unknown or mixed (33)Probable malignant neoplasm 7Probable viral pleuritis 7Postoperative 5Congestive heart failure 4

plus purulent sputumProbable tuberculosis 3Probable pulmonary infarction 3Probable uremie pleuritis 1Unknown 3

Definite diagnoses were obtained ac¬

cording to the preset clinical criteriafor 149 of the 182 effusions, while nodefinite diagnosis was obtained fromthe remaining 33. The patients listedas having possible malignant neo¬

plasm had tumor demonstrated else¬where, but not in the pleural space.

The distribution of the pleural fluidRBC counts is shown in Fig 1. Thegroup of malignant effusions had thehighest percentage of pleural flu¬ids with RBC counts of more than10,000/cu mm. However, nearly 50%

of the effusions in each of the otherthree categories of exudates and 15%of the transudative effusions also hadpleural fluid RBC counts of higherthan 10,000/cu mm. Pleural fluid RBCcounts of greater than 100,000/cu mm

were most frequently associated withthe groups of malignant and otherexudative effusions. All the effusionsin the category of other exudateswith RBC counts this high were dueeither to pulmonary infarction3 or

trauma.2The distribution of the pleural fluid

WBC counts is shown in Fig 2. Morethan 80% of the transudative effu¬sions, but less than 20% of the exuda¬tive effusions, had pleural fluid WBCcounts of less than 1,000/cu mm. Theeffusions associated with pneumoniahad the highest pleural fluid WBCcounts on the average; 50% of the ef¬fusions in this category had counts ofmore than 10,000/cu mm. However,some of the effusions in each of theother three categories of exudatesalso had pleural fluid WBC counts ofmore than 10,000/cu mm. In the cate¬gory of other exudates, two of fiveeffusions secondary to pulmonary in¬farction, two of five effusions second¬ary to pancreatitis, one of three effu¬sions secondary to the postmyocardialinfarction syndrome, and the one ef¬fusion secondary to systemic lupus ery-thematosus had pleural fluid WBCcounts of more than 10,000/cu mm.No effusion other than those associ¬ated with pneumonia had pleuralfluid WBC counts of more than50,000/cu mm.

For the present study, the pleuralfluid WBCs were partitioned intothree classifications: (1) polymorpho-nuclear leukocytes, including eosino-phils; (2) small lymphocytes; and (3)mononuclear cells other than smalllymphocytes. The latter category in¬cluded mesothelial cells, macro¬

phages, plasma cells, large lympho¬cytes, and malignant cells.

The predominant cell type in eachof the effusions for which a definiteorigin was established is shown in


100-,

> 100,000

Transudative Tuberculous Other ExudativeMalignant Parapneumonic

Effusions

Fig 1.—Distribution of pleural fluid RBC counts.

Table 1.—Predominant Cell Type in Pleural Fluids of Various Origins*Number of Effusions With More Than 50%

Category Total No. PMN LYMPH MONO No PredominanceTransudative

effusions 47 16 22Malignant

neoplasm 43 18 16Pneumonia 26 21Tuberculosis 14 13PancreatitisPulmonary

infarctionPostmyocardial

infarction syndromeTraumaRheumatoid

pleuritisSystemic lupus

erythematosusActinomycosisInfectious

hepatitis* PMN indicates polymorphonuclear leukocytes; LYMPH, lymphocytes; MONO, mono-

nuclear leukocytes.___

100-,

> 10,000

2,500-10,000

Transudative Tuberculous Other ExudativeMalignant Parapneumonic

EffusionsFig 2.—Distribution of pleural fluid WBC counts in pleural effu¬

sions of different origins.

Table 1. Transudative effusions were

usually characterized by a majority oflymphocytes or other mononuclearcells, although 13% had mostly poly-morphonuclear leukocytes.

When the exudative effusions are

considered, all but one of the tuber¬culous fluids had more than 50% smalllymphocytes. This pattern of lympho-cytic predominance was not unique totuberculous exudates, as it was alsothe most common pattern for the ma¬

lignant fluids. However, only one ofthe 45 nonmalignant, nontuberculousexudates had predominantly smalllymphocytes. A pattern of predomi¬nantly polymorphonuclear leukocyteswas seen with most effusions second¬ary to pneumonia, pancreatitis, andpulmonary infarction, and, in some

effusions, secondary to tumor or col¬lagen vascular disease. A pattern ofpredominantly monocytic cells other


Fig 3.—Group of four typical mesothelial cells with two small lym¬phocytes. Note finely stippled chromatin and prominent nucleoli(Wright stain, original magnification 1,000).

than small lymphocytes was sugges¬tive of neoplasm, as 16 of 25 exuda¬tive effusions with this pattern were

secondary to tumor.Another impressive characteristic

of tuberculous pleural fluids was thesparsity of mesothelial cells. Theseare the large cells that line the pleu¬ral surfaces and are characterized on

Wright stain by basophilic cytoplasm,a large nucleus with finely stippledchromatin, and one to three brightblue nucleoli (Fig 3). All 14 tuber¬culous fluids showed fewer than 1% ofthese cells. In contrast, most nontu-berculous fluids had at least 5% meso¬thelial cells. A small number ofmacrophages are frequently presentin tuberculous fluids and should bedifferentiated from mesothelial cells.They arise from either mesothelialcells or circulating mononuclear cells.Their cytoplasm is grey, cloudy, and

Fig 4.—Group of six macrophages. Note numerous cytoplasmicvacuoles, lacy chromatin pattern, and bean-shaped nuclei with lackof nucleoli (Wright stain, original magnification 1,000).

full of vacuoles, and their nuclei arecharacterized by lacy rather thanstippled chromatin (Fig 4).

The pleural fluid differential WBCcount showed more than 10% eosino-phils in eight of the 182 pleural effu¬sions (Table 2). Pleural fluid eosino-philia was associated with pleuraleffusions of widely varying origins,but a few interesting observationswere made. Patients with pneu¬mococcal pneumonia and eosinophilicpleural effusions developed the pleu¬ral effusion between two and threeweeks after the pneumonia began.The initial pleural fluid smear fromthe patient with tuberculosis hadall little lymphocytes, but a smallpneumothorax was induced when thisspecimen was obtained; the followingday when fluid for our studies was ob¬tained, many eosinophils were pres¬ent. The diagnosis of actinomycosis

was made by demonstrating sulfurgranules in tissue obtained during an

open thoracotomy in a 35-year-oldman with a serous pleural effusionand a right hilar mass, both of whichresponded to 12 months of tetracy-cline therapy. The pleural fluid eo-

sinophilia persisted for four monthsin the patient with the pancreaticpseudocyst.

Pleural fluid from 120 patients was

examined cytologically. The cyto-pathological cancer categorization forthe first specimen submitted is shownin Table 3. Of the 67 patients whoseoriginal cytological results were neg¬ative, only two were subsequentlyfound to have malignant neoplasmin the pleural space-one was a smallcell undifferentiated bronchogeniccarcinoma and the other was amesothelioma. A subsequent pleuralfluid cytological finding was positive


Table 2.—Diagnoses in Eight Patients With Pleural Fluid Eosinophilia*Pleural Fluid

DiagnosisRBC/

cu mmWBC/cu mm EOSIN PMN MONO

Pneumococcal pneumonia 3,636 7,776 60 30 10Pneumococcal pneumonia 3,708 2,016 21 16 63Probable viral pleuritis 24,400 8,000 11 81Probable viral pleuritis 10,000 8,000 64 10 26Mesothelioma 1,512 1,050 15 85Pancreatic pseudocyst 11,360 4,650 15 25 60Actinomycosis 1,200 7,100 34 15 51Tuberculosis/pneumothorax 11,880 1,728 24 70

* EOSIN indicates eosinophils; PMN, polymorphonuclear leukocytes; MONO; mononuclearleukocytes.

Table 3.—First Cytopathology Cancer Categorization in 120 Pleural Fluids

DiagnosisCytopathologic Cancer Categorization

No. Negative Inconclusive PositiveMalignant neoplasm 43 14 27Possible

malignant neoplasmBenign exudates 27 25Transudates 24 20Unknown diagnosisTotal

19120

1567 26 27

Table 4.—Cytological Results for 43 Malignant Effusions

Diagnosis No.

Positive SamplesFirst Any None

Bronchogenic carcinomaAdenocarcinomaUndifferentiatedSquamous

Breast carcinomaAdenocarcinoma

uncertain originAdenocarcinoma

below diaphragmLeukemia-lymphomaMiscellaneous

Osteogenic sarcoma

PlasmacytomaMelanomaMesothelioma

Total 43 27 33 10

in the first patient; repeat pleuralfluid cytological studies were not per¬formed on the second. It should benoted that 14 of the 26 (54%) patientswhose first pleural fluid cytologicalfindings were inconclusive were sub-

sequently found to have a malignantorigin.

Table 4 summarizes the pleuralfluid cytological findings of the 43 pa¬tients with definite malignant effu¬sions. In 42 of the 43 patients, the tu-

mor was confirmed by means otherthan pleural fluid cytological studies;the only patient for whom no addi¬tional confirmation was obtained stillhas bilateral recurrent pleural effu¬sions nine months after the cytologi¬cal diagnosis of cancer was made. Thefirst sample examined showed cancerin 27 of the 43 (63%). In six othercases, subsequent pleural fluid speci¬mens showed cancer cytologically(four on the second specimen and twoon the third). Five of the six had beenclassified as inconclusive originally.

Of the 43 patients with proved ma¬

lignant neoplasm, ten never had pos¬itive pleural fluid cytological findings.Neoplasms other than carcinoma ac¬counted for six of these ten—twoosteogenic carcinomas, one melano¬ma, one mesothelioma, one plasma-cytoma, and one chronic lymphocyticleukemia—and all but the mesothe¬lioma were classified as inconclusive.Of the four patients with carcinomaand no positive pleural fluid cytologi¬cal results, three had only one speci¬men submitted for cytologie studyand the fourth had only two speci¬mens submitted. Pleural fluid cytolog¬ical results for all four of these pa¬tients were reported as inconclusive,strongly suggestive, but not diagnos¬tic of malignant neoplasm.

CommentThe importance of blood-tinged

pleural fluid has been debated. Tin-ney and Olsen4 reported that malig¬nant neoplasm was the origin for 95%of blood-tinged pleural fluids, whencongestive heart failure could beruled out. Poppius with Kokkola8 andWallaert3 reported that less than 10%of tuberculous fluids were blood-tinged. On the other hand, Zinnemanet al7 reported that more than 50% oftuberculous fluids were blood-tinged,and Leuallen with Carr1 and Paddock2concluded that the presence or ab¬sence of blood was of little value inindicating the origin of the effusion.The present series is in agreementwith the latter two studies. Since a


substantial proportion of the pleuralfluids in each of the diagnostic cate¬gories had RBC counts of greaterthan 10,000/cu mm, this finding hadno diagnostic importance. The lack ofspecificity of blood-tinged pleuralfluid is probably related to the factthat it takes a leak of but 2 ml of pe¬ripheral blood into 1,000 ml of pleuralfluid to impart a blood-tinged charac¬teristic.

Although blood-tinged pleural fluiditself had no diagnostic importance,pleural fluid RBC counts of more than100,000/cu mm were highly sugges¬tive of maligant neoplasms, pulmo¬nary infarction, or trauma. It shouldbe emphasized that the pleural fluidassociated with pulmonary infarctionis not invariably bloody; two of thefive effusions secondary to pulmonaryinfarction in the present series hadpleural fluid RBC counts of less than10,000/cu mm. Also, in Griner's10 au¬

topsy study, less than 50% of the effu¬sions associated with pulmonary em¬boli were hemorrhagic.

The present study, like previousones,127 indicates that the pleuralfluid WBC count is of very limited usein the differential diagnosis of pleuraleffusions. Although pleural fluid WBCcounts of less than 1,000/cu mm are

usually associated with transudateswhile those of more than 1,000/cu mmare usually associated with exudates,the pleural fluid WBC count is defi¬nitely inferior to the lactic dehy-drogenase and protein levels for theseparation of transudates from exu¬dates as reported previously." Thepleural fluid WBC count does not sep¬arate exudates arising from differentcauses. In addition to being foundwith effusions associated with pneu¬monia, pleural fluid WBC counts ofless than 10,000/cu mm are also fre¬quently found with pancreatitis, pul¬monary infarction, collagen vasculardiseases, and occasionally with malig¬nant neoplasm and tuberculosis.

Several authors1·2·7 have concludedthat the differential WBC count is notparticularly helpful in the differ-

ential diagnosis of a given pleuralfluid. Nevertheless, the present studyseems to support the findings of Yam5and Spriggs and Boddington6 whoconcluded that it is quite helpful.

The presence of predominantlypolymorphonuclear leukocytes inpleural fluid indicates that the fluid isthe result of acute pleural inflamma¬tion, hence raising the probability ofpneumonia with effusion, pulmonaryinfarction, pancreatitis, or otheracute inflammatory conditions of thepleura. Most of the effusions in thepresent series due to these diagnoses,but with pleural fluids not dominatedby polymorphonuclear leukocytes, hadbeen present for more than five dayswhen the fluid was analyzed. Three ofthe seven effusions presumably of vi¬ral origin were predominated by poly¬morphonuclear leukocytes at the timeof initial thoracentesis. One of these,when tapped 24 hours later, containedonly small lymphocytes and othermononuclear cells. Nevertheless, itshould be noted (Table 1) that a poly¬morphonuclear predominance does notrule out the possibility of trans¬udative or malignant effusions. Fur¬thermore, in previous studies,112 asmuch as 10% of tuberculous fluids,particularly those of recent acute on¬

set, had predominantly polymorpho¬nuclear leukocytes.

Among the groups of exudative ef¬fusions, only the tuberculous and ma¬

lignant effusions frequently had morethan 50% lymphocytes in the pleuralfluid. Of the group of 102 exudativeeffusions, 31 had predominantly smalllymphocytes, and 30 of these weredue either to tuberculosis or malig¬nant neoplasm. Herein lies the expla¬nation for the observation of Yam5that the yield of definite diagnosisfrom pleural biopsy was much higherwhen pleural fluid contained morethan 50% lymphocytes, since only tu¬berculosis or neoplasm can bediagnosed definitely with pleural bi¬opsy. However, since many malig¬nant effusions contained predomi¬nantly mononuclear cells and a few

contained mostly polymorphonuclearleukocytes, the absence of a lympho-cytic predominance should not deterone from doing a pleural biopsy whenmalignant neoplasm is suspected.

The presence or absence of meso¬thelial cells in pleural fluid was foundto be quite useful in the differentialdiagnosis of pleural effusion. All 14 ofthe pleural fluids secondary to tu¬berculosis contained fewer than 1%mesothelial cells. This is in agreementwith Spriggs and Boddington" whofound that only one of 65 tuberculousfluids had more than 0.1% mesothelialcells, and with Yam.5 It should be em¬

phasized that macrophages may bepresent in tuberculous fluids, andthey should be differentiated frommesothelial cells.

Although the presence of numerousmesothelial cells very nearly excludedthe diagnosis of tuberculosis, the ab¬sence of mesothelial cells is not diag¬nostic of tuberculous pleuritis. It sim¬ply reflects the extensive involvementof the pleural surfaces and is commonwith empyema and other conditionsin which the pleura becomes coatedwith fibrin. It is also common withmalignant effusions after sclerosingagents have been injected to effect a

pleurodesis.Our results, like those of previous

authors,61314 indicate that the pres¬ence of pleural fluid eosinophilia is ofvery little use in the differential diag¬nosis of pleural effusions. The presentseries supports the conclusion of Camp¬bell and Webb1' that pleural fluid eo¬

sinophilia militates greatly againsttuberculosis and malignant neoplasm,as only two of 57 patients with thesediagnoses had pleural fluid eosino¬philia and the one patient with tu¬berculosis had a small pneumothorax.A study6 has emphasized that pleuralfluid eosinophilia frequently occurs inassociation with a pneumothorax, andthis phenomenon was dramaticallyshown by our patient who had tu¬berculosis and all small lymphocytesinitially, but who had 30% pleuralfluid eosinophilia the following day,


at which time a small pneumothoraxwas present. To our knowledge, thepatient in our series with actinomy-cosis is the first reported example ofan eosinophilic pleural effusion sec¬

ondary to actinomycosis.The cytologie results in the present

study, ie, 77% of the proved malignantneoplasms had positive cytological re¬

sults, compare favorably with previousones. Wallaert,3 Spriggs and Bodding-ton,6 Lopez-Cardozo,15 Johnson,16 andPoppius and Kokkola8 reported malig¬nant pleural cells in 58%, 54%, 62%, 33%,and 33% of 39,474, 546, 345, and 27 pa¬tients with malignant neoplasm, re¬spectively. Grunze9 reported that 87%of 200 malignant effusions had posi¬tive pleural fluid cytological results,but it is not clear whether the 87% in¬cluded inconclusive as well as positivecytological findings. If, in addition tothe 43 pleural effusions in which ma¬

lignant cells were demonstrated inthe pleural space, the seven possiblemalignant effusions (malignant neo¬

plasm demonstrated elsewhere butnot in the pleural space) are also in¬cluded in the analysis, still 66% of thepleural fluids will be positive for ma¬

lignant cells, and this is better thanany of the aforementioned series.

We believe there are three possible

reasons for the excellent results inthis series. First, all .cytological exam¬inations were performed by a pathol¬ogist experienced in cytology. Berge andHellsten17 believe exudates shouldbe examined by both a cytologist anda pathologist or by a single examinerspecialized in both general pathologyand in exfoliative cytology. Second,all the specimens submitted for cyto¬logical examination were fresh, whichis very important for the Milliporepreparations. Third, multiple tech¬niques including cellular spreads, Mil¬lipore filters, and cell blocks withseveral stains were used for eachspecimen.

It should be noted that repeat cyto¬logical examinations of the pleuralfluid are useful. A second specimen ofpleural fluid was submitted for 11 ofthe patients with proved malignantneoplasm and a negative or inconclu¬sive first cytological finding, and four(36%) of these were positive for ma¬

lignant cells. A third specimen wasexamined from four of the patientswith proved malignant neoplasmand nonpositive cytological findingson the first two specimens, and two(50%) were positive for malignantcells. The two proved malignant neo¬

plasms with inconclusive cytological

findings after three pleural sampleswere a melanoma and a chronic lym-phocytic leukemia.

It thus appears that when at leastthree separate pleural fluid specimensare examined cytologically, oneshould be able to demonstrate malig¬nant cells in nearly 90% of the casesin which the malignant neoplasm in¬volves the pleura. However, since ma¬

lignant neoplasms can cause pleuraleffusions by several mechanismsother than direct pleural involvement(including postobstructive pneu¬monia, hypoproteinemia, lymphaticobstruction, and complete obstructionof a bronchus), a sizeable percentageof effusions in patients with malig¬nant neoplasms that are at least in¬directly due to the tumor will nothave positive cytological findings.Mechanisms other than pleural seed¬ing were thought to be operable inproducing pleural effusions in four ofour seven cases classified as possiblemalignant neoplasm.

This investigation was supported in part byNational Heart and Lung Institute traininggrant 1 12 HE05885.

The work of Dr. Light was supported by grant1 F03 HE51315-01 from the National Heart andLung Institute.

References

1. Leuallen EC, Carr DT: Pleural effusion. N EnglJ Med 252:79-83, 1955.

2. Paddock FK: The diagnostic significance ofserous fluids in disease. N Engl J Med 223:1010-1015,1940.

3. Wallaert C: Les \l=e'\panchementspleurauxd'\l=e'\tiologieimpr\l=e'\cise:Apport des m\l=e'\thodesr\l=e'\centesde diagnostic. Lille Med 11:1105-1110, 1966.

4. Tinney WS, Olsen AM: The significance of fluidin the pleural space. J Thorac Cardiovasc Surg14:248-252, 1945.

5. Yam LT: Diagnostic significance of lympho-cytes in pleural effusions. Ann Intern Med 66:972\x=req-\982, 1967.

6. Spriggs AI, Boddington MM: The Cytology ofEffusions. New York, Grune & Stratton, Inc., 1968,pp 1-39.

7. Zinneman HH, Johnson JJ, Lyon RH: Proteinsand mucoproteins in pleural effusions. Am Rev Tu-berc 76:247-255, 1957.

8. Poppius H, Kokkola K: Diagnosis and differ-ential diagnosis in tuberculous pleurisy. Scand JRespir Dis (suppl)63:105-110, 1968.

9. Grunze H: The comparative diagnostic accuracy,

efficiency, and specificity of cytologic technics usedin the diagnosis of malignant neoplasm in serous ef-fusions of the pleural and pericardial cavities. ActaCytol 8:150-163, 1964.

10. Griner PF: Bloody pleural fluid following pul-monary infarction. JAMA 202:947-949, 1967.

11. Light RW, et al: Pleural fluid lactic acid dehy-drogenase and protein content, abstracted. Ann In-tern Med 76:880, 1972.

12. Levine H, Szanto P, Cugell DW: Tuberculouspleurisy: An acute illness. Arch Intern Med 122:329\x=req-\332, 1968.

13. Campbell GD, Webb WR: Eosinophilic pleuraleffusion. Am Rev Respir Dis 90:194-201, 1964.

14. Bower G: Eosinophilic pleural effusion. AmRev Respir Dis 95:746-751, 1967.

15. Lopez-Cardozo P: A critical evaluation of 3,000cytologic analyses of pleural fluid, ascitic fluid andpericardial fluid. Acta Cytol 10:455-460, 1966.

16. Johnson WD: The cytological diagnosis of can-cer in serous effusions. Acta Cytol 10:161-172, 1966.

17. Berge T, Hellsten S: Cytological diagnosis ofcancer cells in pleural and ascitic fluid. Acta Cytol10:138-140, 1966.


cells pleural fluidtrates in association with pleural effusion. the category "other...

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