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Thorax (1967), 22, 260.

Bronchiolar carcinoma: a case report withpulmonary function studies

N. H. DYER1, D. T. D. HUGHES, AND J. M. A. THOMPSONFrom the London Hospital, Lonzdoni, E.I

A patient with bilateral multinodular bronchiolar carcinoma is described in whom carbonmonoxide transfer factor and arterial oxygen saturation were greatly impaired but lung volumesand ventilation were only minimally reduced. We record this because we have not found previousreports of detailed pulmonary function studies in this condition.

A 57-year-old man was admitted to hospital inAugust 1965 with a three-week history of breath-lessness and cough which was initially dry but oneweek later became productive of a moderatequantity of mucoid sputum. He also complainedof shivering, sweating, palpitations, lassitude, in-somnia, anorexia, and a weight loss of 8 lb. (3-6kg.). He denied any other symptoms, includingchest pain and haemoptysis. He had spent most ofhis working life in furniture factories but had notbeen exposed to any industrial risk and there wereno previous respiratory symptoms. He smoked 20cigarettes per day.On examination he was an ill, wasted man

weighing 115 lb. (52 kg.). He was afebrile onadmission but subsequently showed occasionalspikes of temperature to 990 F. (37.20 C.). Shottylymph nodes were palpable in the right anteriortriangle of the neck and in both inguinal regions.Clubbing of the nails was not present. There wasobvious central cyanosis and the respiratory ratevaried from 17 to 36 respirations per minute, withmuch activity of the accessory muscles of respira-tion. Chest movements were normal and equalbut the trachea was deviated to the right, and thepercussion note, vocal fremitus, and breathsounds were reduced at the right lung base. Fineand coarse crepitations were scattered throughoutthe lower parts of both lungs. The pulse rate was95 per minute, regular, but the volume wasdiminished; the blood pressure was 150/70 mm.Hg. There was no evidence of heart failure. Aforcible right ventricular heave was present.There was a systolic murmur at the tricuspid area.The liver was palpable three fingerbreadthsbelow the right costal margin. Bilateral inguinal

'Present address: St. Bartholomew's Hospital, London, E.C.1

herniae and a right-sided hydrocoele werepresent.The haemoglobin was 183 g./100 ml. (125%)

and the leucocyte count was 18,200 per c.mm..85% of which were neutrophils. Blood urea'electrolytes, liver function tests, and E.S.R.(Westergren) were normal. An E.C.G. revealedright atrial hypertrophy and right axis deviationwith low voltage in all limb leads. The chestradiograph showed numerous small opacitiesscattered throughout the middle and lower zonesof both lung fields, with an area of consolidationand partial collapse involving the right lower lobe(Fig. 1). Tomograms indicated an opacity in theregion of the right middle and lower lobe bronchiwhich had the appearance of an enlarged lymphnode. Sputum culture produced coliformorganisms on several occasions, and cytologicalexamination revealed cells suggestive of adeno-carcinoma, some of which contained largeintracytoplasmic vacuoles filled with mucin, inthree out of four specimens. Pulmonary functionstudies were performed by the methods in routineuse at the London Hospital (Hughes and Lee.1963) and the results are shown in the Table.These indicate a high minute volume, a lownormal PACO.,, slight uniform reduction of lungvolumes, a normal R.V./T.L.C. ratio, minimalairways obstruction with an F.E.V.1.0 which is64% of the vital capacity, and severe reductionin transfer factor and arterial oxygen saturation.He remained ill and breathless to an extent

which made the performance of lung functionstudies difficult. There was temporary improve-ment on high doses of prednisone (60 mg. perday) followed by deterioration possibly associatedwith reduction of the dosage. Intravenous mus-tine was of no benefit and he died 10 weeks afterthe onset of his symptoms.

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Bronchiolar carcinoma: a case report with pulmonary function studies

FIG. 1. Chest radiograph. Bilateral multinodular disease with diffuseshadowing on the right of the cardiac shadow.

TABLE

PULMONARY FUNCTION STUDIES

Ventilation

Respiratory rate.17/min.Tidal volume. 1,400 ml.Minute volume. 24 ./min.Vital capacity (Bernstein spiro-

meter) .. 3,250 ml.F.E.V. . (Bernstein spirometer) 2,050 ml.% F.E.V.1.o/V.C. .. .. 64°',

Blood Gases

PACO2 (rebreathing) .. .. 36 mm.HgArterial 02 saturation .. .. 635%

Lung Volumes(Godart Pulmotest)

Vital capacity (ml.)Inspiratory capacity (ml.)Expiratory reserve volume (ml.)Functional residual capacity (ml.)Residual volume (ml.)Total lung capacity (ml.)Y. R.V./T.L.C.

Transfer factor.

Total blood volume (Volemetron)

Observed Predicted Predicted

3,400 3,900 862,500 2,600 861,250 1,300 963,100 3,700 831,850 2,400 775,250 6,300 83

35

6 23 26

5-9 1. 336 1. 164

PATHOLOGY

Necropsy was performed 34 hours after death. Acareful search for a possible source of primarycarcinoma was made, but none was found. Notumour was present outside the chest. There werebilateral, pale yellow, pleural effusions of about500 ml. The heart was normal apart from peri-cardial adhesions and mild right ventricularhypertrophy (the wall measured 0-6 cm. in thick-ness). Both lungs were heavy, retained their shapewhen removed from the chest, and containednodules of grey-white tumour, particularly in theleft lower lobe. The right lower lobe was almostsolid, showing a diffuse 'pneumonic' spread (Fig.2) which formed a fern-leaf pattern on the pleuralsurface, resembling the spread of bronchopneu-monia (no exact site of origin could be identified).There was involvement of superficial lymphaticsby tumour which formed a fine beading mostnoticeable on the sharp edges of the lobe. Thebronchi were apparently thickened by 'peri-

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FIG. 2. Cut surface of the right lower lobe. Fixation byintrabronchial formalin inflation.

bronchial' spread of tumour. The hilar andsubcarinal lymph nodes contained metastases.

MICROSCOPY

Tumour cells were regularly arranged in a singlelayer around the alveolar walls (Fig. 3). Theywere mostly columnar with an oval basal nucleus,which contained a prominent nucleolus, but insome areas the cells were more rounded and occa-sionally the alveoli were lined by a thin layerof small cuboidal cells. Mitoses were absent.There was abundant mucin production, and anoccasional group of ciliated cells could be found.Papillary projections were frequent (Fig. 4), witha variable amount of exfoliation. In some areasof the right lower lobe exfoliation was profuseand alveoli were completely filled with mucin andtumour cells, forming a 'tumour pneumonia'. Inthe more densely involved areas there was a defi-nite stroma containing young collagen. Elsewherethe underlying lung was free from interstitialfibrosis. Tumour extended up to but not throughthe pleura. The subpleural, intrapulmonary, andbronchial submucosal lymphatics containedtumour. Many intrapulmonary lymphatics weredilated. Other vessels were free, and no oblitera-tion by external compression (Liebow, 1956) wasseen. In the other lobes tumour was more nodular,although sometimes confluent, but the same

'A,4

FIG. 3. Alveolar septa lined by tumour cells. H. and E., X480.

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FIG. 4. Arrangement cf tumour cells with papillary projection. Elastic Van Gieson, x 120.

cellular arrangement and so-called lepidic spread.,in which the cells used the alveoli as scaffoldingand stroma, was always present. A similar'alveolar arrangement' was seen in the lymphnode metastases.

DISCUSSION

Cases of bronchiolar carcinoma are now beingrecognized with increasing frequency, and manyreports have appeated in the literature, includingthe excellent reviews of Storey, Knudtson, andLawrence (1953), Liebow (1960), and Watson andFarpour (1966).There is a variable gross anatomical pattern, but

three main groups may be recognized on radio-graphy or at necropsy, i.e., an isolated nodule,multiple bilateral nodules, and diffuse or 'pneu-monic' involvement of a segment or lobe (Liebow,1960). It therefore follows that the results of lungfunction studies will vary with the different types,and the degree of functional impairment willreflect the extent of the lung tissue replaced bycarcinoma (Bates and Christie, 1964). Two casesare mentioned by these authors. In the first thecarcinoma involved most of one lobe but pulmo-nary function was little disturbed. The second hadbilateral involvement which was associated withreduction in lung volumes but preservation of

y

ventilatory function. Although bronchiolar carci-noma is listed among the causes of 'alveolar-capillary block' (Comroe, Forster, DuBois,Briscoe, and Carlsen, 1962) or widespreadinvolvement of tissues distal to the terminalbronchiole (Cotes, 1965), no further details aregiven.Our patient had developed bilateral multi-

nodular disease with more diffuse involvement ofthe right lower lobe. There was some clinical andpathological evidence of pulmonary hypertension.The disturbance of lung function included slightreduction of lung volumes, hyperventilation atrest which was suggested by a high minute volumeand low normal PACO2, severe arterial oxygendesaturation at rest with secondary polycythaemia,and marked reduction in transfer factor. The verylow transfer factor and desaturation at rest indi-cate that the functional disturbance must be morethan a simple diffusion barrier and suggestventilation-perfusion inequality (Campbell, 1965).Similarly, although carcinoma cells lining thealveoli and interstitial collagen deposition providea good histological model for the discreditedalveolar-capillary block syndrome, the anatomicalpicture with lymphatic permeation, 'tumourpneumonia', capillary bed involvement, etc.,equally well results in ventilation-perfusion distur-bance.

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We should like to thank Dr. K. M. A. Perry forpermission to publish details of this case and for hishelp and advice; Mr. R. Hammond and Mr. R.Ruddick for the photographs; and Mrs. M. Bumardfor technical and secretarial help.

REFERENCESBates, D. V., and Christie, R. V. (1964). Respiratory Function in

Disease, p. 41 1. W. B. Saunders, Philadelphia.Catmpbell, E. J. M. (1965). Respiratory failure. Brit. *ned. J., 1, 1451.Comroe, J. H., Forster, R. E., DuBois, A. B., Briscoe, W. A., and

Carlsen, E. (1962). The Lung, 2nd ed., p. 111. Year Book MedicalPublisbers, Chicago.

Cotes, J. E. (1965). Lung Function, p. 337. Blackwell ScientificPublications, Oxford.

Hughes, D. T. D., and Lee, F. I. (1963). Lung function in patientswith systemic sclerosis. Thorax, 18, 16.

Liebow, A. A. (1956). Pulmonar,y Carcinoma, ed. E. Mayer andH. C. Maier, p. 156. New York University Press.(1960). Bronchiolo-alveolar carcinoma. Adranc. inter,,. Mle(d..10, 329. Year Book Publishers, Chicago.

Storey, C. F., Knudtson, K. P., and Lawrence, B. J. (1953). Bron-chiolar ('alveolar cell') carcinoma of the lung. J. thorac. Surg., 26,331.

Watson, W. L., and Farpour, A. (1966). Terminal bronchiolar or'alveolar cell' cancer of the lung'. Two hundred and sixty-fivecases. Cancer, 19, 776.

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