Thorax (1957), 12, i8.

BRONCHIAL INVOLVEMENT IN PULMONARY SARCOIDOSISBY

VATCHE V. KALBIANFrom Milford Chest Hospital, Godalming, Surrey

(RECEIVED FOR PUBLICATION SEPTEMBER 7, 1956)

It is probable that the lung is one of the com-monest sites of involvement by sarcoidosis. Inspite of the rapidly growing literature on thesubject there is scanty mention of the diseaseaffecting bronchi. This can be attributed to thefact that routine bronchoscopic and bronchialbiopsy investigations have not been carried out inpulmonary sarcoidosis.

In the study described in this paper an attemptwas made to find out the frequency of bronchialdisease in pulmonary sarcoidosis and to assess thevalue of bronchoscopic biopsy as a diagnostic pro-cedure. The cases investigated complied with thedefinition of the U.S. National Research Councilas quoted by Ricker and Clark (1949). All hadhistological evidence of epithelioid cell tubercleswithout central caseation (non-caseating tubercles)and with or without Langhans type giant cells. Atthe same time no tubercle bacilli could be grownfrom cultures of the sputum or cultures of lymphnode tissue and no tubercle bacilli were seen onhistology.

MATERIALThe last 11 consecutive cases at this hospital

considered on clinical and radiological grounds tobe suffering from pulmonary sarcoidosis in aperiod of nearly a year were examined broncho-scopically under general anaesthesia; at the sametime a bronchial biopsy was taken. In addition ascalene or other lymph node was removed forbiopsy. The bronchial biopsy was taken eitherfrom a region where the mucous membrane lookedabnormal, or, if the mucous membrane wasnormal, from the bronchus supplying the mostdiseased area of lung. Biopsy material wasexamined for tubercle bacilli by Ziehl-Neelsen'smethod, and histologically after staining withhaematoxylin and eosin and by the silver method.

Table I gives the relevant particulars of thepatients. There were five women and six men withages varying from 22 years to 45 years. All hadradiological evidence of lesions in the lungs and a

few had varying degrees of mediastinal lymphnode involvement.The duration of the disease, as far as could be

deduced from the history, varied from six monthsto at least five years in one case (No. 7). All exceptCase 1 had symptoms. Case 1 had been found atmass radiography two years before admission tohospital to have massive enlargement of medi-astinal lymph nodes without other change. Gradu-ally these nodes became smaller, and, three monthsbefore admission to hospital, miliary mottling ofboth lung fields appeared.Case 6 presented with erythema nodosum, Case

3 with a pleural effusion, and Case 9 with haem-optysis. The remainder had cough and expectora-tion, with or without dyspnoea on exertion, as theirpresenting symptoms.

FINDINGS

BRONCHOSCOPY.-Four of the 11 cases studiedhad no specific bronchoscopic abnormality, exceptslight increase of mucous secretion in two and atendency to bleed easily from the mucous mem-brane in one. Two (Cases 4 and 6) showed distor-tion of the carina presumably due to enlargedmediastinal lymph nodes which were evidentradiographically. In four cases, including Case 6,which also showed distortion of the carina, themucosa was granular and rough-looking and bledeasily. The granularity was due to small bleb-like elevations 2 to 3 mm. in diameter. Finallytwo cases had a very thickened mucous membranewith narrowing of the bronchus and oedema. InCase 9, the mucosa looked acutely inflamed. Thechest radiograph of this case (Fig. 1) showed thedisease mainly in the middle and lower zones ofthe right lung. The bronchogram (Fig. 2) con-firmed the bronchoscopic finding of stenosis of thewhole right bronchial tree, the middle and lowerlobe bronchi being most severely involved. Theright scalene node removed for biopsy showednon-caseating tubercles (Fig. 3).

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BRONCHIAL INVOLVEMENT IN PULMONARY SARCOIDOSIS 19

PIG. 1 Fia. 2

;. s e.::: ...j*.'

ew~~~~~~~~~r.. St t44 _4*

it~~~ ~ ~ ~ ~ ~~' M4:.cYiCt#

FIG. .Chest radiographof Case 9.

FIG. 2.-Left oblique viewof right bronchogramin Case 9. * I

FiG. 3.-Scalene node (Case ., . '.49), showing non- Ncaseating tubercles in r .~lymphatic tissue 4 1'Haematoxylinandeosin, ' t ¾ tIKx 107. ~

FIG. 3

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VATCHE V. KALBIAN

TABLE ISUMMARY OF FINDINGS IN It CASES OF SARCOIDOSIS EXAMINED BRONCHOSCOPICALLY

Case Sex AgeI(yr.)I

EstimatedDuration

ofDisease

I M 27 2 years

2

34

5

F

M

M

F

6 1 F

7

8

9

10

11

F

F

33

3434

39

22

38

39

6 months

2 years6 months

2 years

9 months

5 years

6 months

M 42 year

M

M

34

45

6 months

2 years

Chest Radiograph

HilarLymph LungsNodes

+

Miliary shadows

Fine mottling

Very slight finemottling

Coarse mottlingand fibrosis

Fine mottling

Fine mottlingand I inear fib-rosis

Fine mottling

Fine mottling inR. lung, mostin lower 2 3with linearfibrosis

Fine mottling

=Not enlarged. --r

Lymph NodeBiopsy

Site

Scalene

Result

N.C.T.

,, Giantcells

A,,lar N.C.T.Axillary ,,

Scalene

[Liver]

Scalene

=Slight. + +

Normal

N.C.T.

Bronchoscopy

Excess mucus

Mucosa bled easily

Excess mucusCarina distorted

Structurally normalmucosa, granularand alittle red allove

Carina distorted, excessmucus, granular,rough mucosa

Excess mucus, mucosarough and a littleoedematous

Mucosa thickened, up-per and lower lobeorifices narrowed

Mucosa of whole R.bronchus inflamedand oedematous,with stenosis mainlyof middle and lowerlobe bronchi

Normal

Mucosa of right upperlobe bronchus slight-ly irregular and hy-peraemic

Bronchial Biopsy

Fibrous thickening ofsubmucosa withscanty lymphocyticinfiltration

Submucosal thicken-ing

No biopsyLanghans giant cells

with fibrosis ofsubmucosa

Normal

N.C.T.

Epithelioid cells andgiant cells

Giant cells of Lang-hans type

Submucosa thickenec

N.C.T.

-Moderate. + +--Gross. N.C.T.- Non-caseating tubercles.

The bronchoscopic findings could be sum-

marized in four groups: (1) No abnormalitydetectable (four cases) ; (2) external lymph nodepressure causing deformity (two cases) (3)granular and rough mucous membrane (fourcases); (4) oedematous, thickened and inflamedmucous membrane with possible stenosis ofbronchus (two cases). One case showed changesof both group (2) and group (3).BRONCHIAL Biopsy.-In 10 of the 11 cases,

specimens of bronchial mucosa were taken forbiopsy. In one, the mucous membrane was histo-logically normal. In three, there was fibrousthickening of the submucosa. In three, in addi-tion to thickening of the submucosa, there were

giant cells of the Langhans type. Finally, threecases showed definite tubercles without centralcaseation. Fig. 4 is the chest radiograph of Case6 and Fig. 5 shows the bronchial biopsy of thesame case with several non-caseating tubercles inthe submucosa.Summarizing in table form the biopsy findings:

(a) Normal mucous membrane case(b) Thickening of mucous membrane 3 cases

(c) Thickening of mucous membrane + giant cells .. 3 cases

(d) Non-caseating tubercles .. 3 cases

The non-caseating tubercles were found in thethree cases that showed roughness and granularityof the mucous membrane. On the other hand,two of the cases with bronchostenosis and oedema-

FIG. 4.-Chest radiograph of Case 6.

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PresentingSymptoms

None

Dyspnoea,lassitude

PleurisyDyspnoea

Lassitude,dyspnoea

Erythema nod-osum, nochest symp-toms

Cough,sputum

Cough, spu-tum, dyspnoea

Haemoptysis,wheezing,cough,sputum

Lassitude,cough, sputumDyspnoea

+

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BRONCHIAL INVOLVEMENT IN PULMONARY SARCOIDOSIS

tous and inflamed mucous mem-brane showed only fibrosis withgiant cells of the Langhans type.Could they have been a more ad-vanced stage in the natural historyof the sarcoid granuloma ?

If an attempt is made to corre-late the bronchoscopic with thebronchial biopsy findings it seemsthat with a normal bronchoscopicappearance no more than somethickening of the mucous mem-brane can be expected, while witha granular rough mucous mem- - .brane non-caseating tubercles maybe found, the granular surface ofthe mucous membrane being dueto collections of non-caseating , .tubercles in the submucosa.

SCALENE NODE Biopsy.-Of the11 cases, one (Case 6) had had aliver biopsy before admission ; thishad shown non-caseating tuberclesso no lymph node biopsy was per-formed. One case (Case 4) hadenlarged axillary lymph nodes,one of which was removed forbiopsy and showed non-caseatingtubercles.Of the remaining nine none had t

enlarged palpable lymph nodes, FIG. 5.-Bronchial tand in all the scalene node was re-moved. One of these was normal,one showed groups of giant cells of the Langhanstype, and the remaining seven (77%) had non-caseating tubercles.

REVIEW OF THE LITERATUREIt has only been possible to trace 11 individual

case reports of bronchial wall involvement bysarcoidosis confirmed by bronchoscopic biopsy inthe medical literature. Benedict and Castleman(1941) described the first case. It was a 20-year-old woman who had radiographic evidence oflarge mediastinal lymph nodes but no pulmonarylesions. Bronchoscopy showed numerous bleb-like nodules 2 to 3 mm. in diameter in the mainbronchi, whose lumina were narrowed. Bronchialbiopsy showed non-caseating epithelioid celltubercles with giant cells. Olsen (1946) reportedthe case of a 47-year-old man who had radio-graphic evidence of enlarged bilateral hilar lymphnodes with infiltration in the upper zone of theright lung. Bronchoscopy showed a faintlynodular appearance of the lateral wall of the right

.J ,-.

biopsy of Case 6, showing non-caseating tubercles in the submucosa.Haematoxylin and eosin, x 107.

main bronchus, and biopsy confirmed the presenceof epithelioid cell tuberculoid granulomata sur-rounded by lymphocytes. There was no caseation.Jacobs (1949) reported a case with generalizedsarcoidosis, the chest radiograph showing miliarynodules and enlarged hilar lymph nodes on bothsides. Bronchoscopy showed narrowing of the leftmain bronchus by external pressure and severalfaintly haemorrhagic flat areas 2 to 3 mm. in dia-meter in the right main bronchus. On histology,these areas showed non-caseating tubercles withmany giant cells in the submucosa. Harvier,Turiaf, Claisse, and Rose (1950) and Turiaf,Marland, Rose, and Sors (1952) reported five casesof pulmonary sarcoidosis with bronchial lesionsconfirmed by bronchoscopy and bronchial biopsy.They claim that in all their five cases the bronchialtree was the site of changes more or less apparent,but always sufficient to attract attention. Some-times they were generalized over the wholetracheo-bronchial tree and at times localized to abronchus or to a lobe. The findings at broncho-

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VATCHE V. KALB1AN

scopy varied from thickening of the mucousmembrane to inflammatory changes. They foundbronchial biopsy a very valuable investigation. Inall their cases they found the typical histology ofsarcoidosis whether the chest radiograph showedslight or severe lung involvement. The sarcoidtubercles were seen below the bronchial mucousmembrane and the epithelium was usually intact,although occasionally it was eroded.

Siltzbach and Som (1952) reported two morecases. One was a 40-year-old man who had evi-dence of hilar adenopathy and " shrinkage " andconsolidation of the right middle lobe on a chestradiograph, together with fine linear and nodulardensities scattered throughout both lung fields.Bronchoscopy showed the mucosa of the middlelobe bronchus to be granular and thickened andnarrowed. Biopsy showed non-caseating epithelioidcell tuberculoid granulomata consistent with sar-coidosis. The second case was of a 35-year-oldwoman who had a chest radiograph showingenlargement of lymph nodes in both hilar areaswith some linear densities in the medial and lowerpart of the right lung field. On bronchoscopythere was some narrowing of the right bronchusabove the level of the middle lobe bronchialorifice. The left main bronchus was also nar-rowed but to a lesser extent. The narrowing inboth instances was due to external pressure andthe mucous membrane was normal. In the middlelobe bronchus, however, the mucosa was thick-ened, leading to virtual occlusion of this bronchus.Biopsy showed many non-caseating epithelioidtuberculoid granulomata containing many giantcells of the Langhans type. Finally, Cowdell(1954), discussing the diagnosis of 90 cases ofsarcoidosis, mentioned that in one case the diag-nosis was confirmed by histological findings atbronchial biopsy.

DISCUSSIONCombining the experience of 11 cases with the

11 cases from the literature, it seems that thereare three possible abnormal bronchoscopic findingsin pulmonary sarcoidosis: (1) External pressure(from enlarged lymph nodes); (2) granular,nodular, rough-looking mucous membrane withsmall blebs 2 to 3 mm. in diameter; (3) thickened,oedematous mucous membrane with stenosis of thebronchus.Of the bronchoscopic changes described above,

Group 1 is not specific to sarcoidosis, as lymphnode enlargement may be due to many othercauses. Group 3 is not specific either, as it is theend-result of a fibrosing process with secondary

changes brought on by superimposed infection.Group 2 is very probably a typical change of pul-monary sarcoidosis with bronchial wall involve-ment. When the mucosa showed this granularappearance, both in the cases described in theliterature and in the cases in this series, non-caseating tubercles were found on histology ofbronchial biopsy.There is no doubt that bronchoscopy can show

abnormalities in pulmonary sarcoidosis. Is it anexamination worth doing ? Its diagnostic valuedepends mainly upon the incidence of bronchialinvolvement. The series reported here is too smallas statistical evidence, but considering that thecases have been unselected and of varying degreesof severity and duration, it is significant that sevenout of 11 showed bronchoscopic abnormality andthat nine out of 10 bronchial biopsies wereabnormal. Bronchial disease has not been a widelyrecognized feature of pulmonary sarcoidosis.Before a final opinion on its incidence is givenmore routine bronchoscopic and biopsy examina-tions must be done. There are certain difficultiesand objections to bronchial biopsy as a diagnosticaid. One is that biopsy material is usually small.The other is the difficulty of choosing a site forthe biopsy if the mucous membrane appears nor-mal. It is reasonable to take it from the bronchuswhich drains the area which, on the radiograph,shows the maximum disease.As to scalene node biopsy, it is sufficient to say

that seven out of nine cases gave histologicalevidence of sarcoidosis. In every one of the 11cases studied there was positive histological evi-dence of sarcoidosis in either the scalene nodeand in bronchial mucosa or in both these tissues.The final diagnosis of sarcoidosis should be

histological, with demonstration of the non-caseating tubercles. Biopsy examination of distantorgans has been recommended. In pulmonarysarcoidosis it seems that histological evidence ofthe disease is more likely to be found in the lungsand its draining lymph nodes than in distantorgans. It is true that sarcoidosis is often ageneralized disease, but it is not necessarily so. Inall of the 11 cases reported in this paper, histo-logical evidence was obtained from either a scalenenode or from bronchial mucosa, and in some fromboth. In no case had we to resort to biopsy ofother organs for diagnosis. I suggest that everycase of pulmonary sarcoidosis should be inves-tigated by bronchoscopy with bronchial biopsy,and by scalene node biopsy if there are no pal-pable lymph nodes. It is doubtful if after theseprocedures there will be many cases in which liver

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biopsy will be necessary to secure histologicalevidence. Turiaf and others (1952) wrote: " By itsimportance and its practical interest bronchoscopyshould occupy a privileged place amongst thehierarchy of investigations considered indispen-sable for establishing the diagnosis of (pulmonfary)sarcoidosis."

SUMMARYEleven consecutive cases of pulmonary sarcoid-

osis have been investigated by bronchoscopy,bronchial biopsy and scalene node biopsy. Thisinvestigation has suggested that the bronchi are

frequently involved, that pulmonary sarcoidosiscan usually be diagnosed by histology of bronchialbiopsy material, and that a combination of bron-chial biopsy and scalene node biopsy is the best

way to obtain histological evidence of pulmonarysarcoidosis.

I wish to express my thanks to Dr. F. E. Joules forhis encouragement and help, to Mr. M. MeredithBrown for bronchoscopies and biopsies, and to Dr.W. K. Taylor, group pathologist, for help in the histo-logical studies.

REFERENCESBenedict, E. B., and Castleman, B. (1941). New Engl. J. Med., 224,

186.Cowdell, R. H. (1954). Quart. J. Med., 23, 29.Harvier, P., Turiaf, J., Claisse, R., and Rose, J. (1950). Bull. Soc.

mid. Hdp., Paris, 66, 192.Jacobs, E. (1949). Acta clin. belg., 4, 301.Olsen, A. M. (1946). Ann. Otol. (St. Louis), 55, 629.Ricker, W., and Clark, M. (1949). Amer. J. clin. Path., 19, 725.Siltzbach, L. E., and Som, M. L. (1952). J. Mt Sinai Hosp., 19,473.Turiaf, J., Marland, P., Rose, Y., and Sors, C. (1952). Bull. Soc. mdd.

Hop., Paris, 68, 1098.

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