cavitary histoplasmosis complicated by fungus ball

Cavitary Histoplasmosis Complicated byFungus Ball*

JAN SCHWARZ, M .D ., GERALD L . BAUM, M.D . and MANUEL STRAUB, M.D .

Cincinnati, Ohio

5PERCILLOSIS of the lung has been known forA many years [24,34], especially in Francewhere numerous cases have been observed andreports published [7,26] . In this country,aspergillus infection of the lung has been foundin increasing frequency in autopsy material andoccasionally in surgical specimens [8,11,28,37] .Although "primary" aspergillosis has beendescribed [1,4,15,18,32,36], the rarity of this entityand its relation to other debilitating diseasesplaces it beyond the scope of this paper .

Solitary pulmonary nodules have been ob-served for many years. However, prior to thewidespread use of photofluorograms and massx-ray surveys these were seen relatively infre-quently. The presence of such lesions in autopsymaterial also was rare . In the period since WorldWar it there has been a tremendous increase inresection of such lesions because of suspectedlung cancer. A significant percentage of theseresected lesions turned out to be granulomatousrather than neoplastic . A large pathologicmaterial of granulomatous solitary pulmonarynodules therefore has accumulated .

When these lesions were first recognized theywere called tuberculoma because, despite diffi-culty in demonstration of etiologic agents,tuberculosis was considered the invariablecause of such lesions. With the advent of specialstains and particularly with greater understand-ing of the frequency of fungus infections, thetrue nature of these lesions has been elucidated .Although tuberculomas do of course occur,they are at present, in the respective endemicareas, less frequently seen than histoplasmo-mas, coccidioidomas and other non-tuberculousgranulomas .

With greater understanding of the varied

etiology of such lesions has come recognition of aparticularly interesting one . This is a circum-scribed lesion made up of a cavity (of variousetiology) filled by a mat of mycelium most fre-quently of species of aspergillus . These so-calledaspergillomas may temporarily be indistinguish-able from the other solitary pulmonary nodulesmentioned. However, certain x-ray signs, par-ticularly the appearance of a crescent-shapedshadow of air between the intracavitary inclu-sion and the wall of the cavity and the move-ments of the cavity contents on fluoroscopyhave made the preoperative diagnosis of suchlesions possible . The etiology of the cavitiescould not always be clearly established and theyare frequently referred to as bronchiectatic .

The purpose of the present paper is to reviewover fifty cases of so-called aspergilloma and todescribe four cases of cavitary histoplasmosisassociated and complicated by aspergillosiswithin the histoplasmic cavity . (Table I .)

MATERIAL AND METHODS

A total of fifty-eight cases, including the sevencases we have seen (the four cases reported in detailand three others of unknown cause noted in Table I),make up the review from which the following clinicalfindings were noted . Of the fifty-eight cases, thirty ofthe fungus balls were found in the upper lobe of theright lung, twenty-three in the upper lobe of the leftlung and only two in the middle lobe of the right lungand two in the lower lobes;t in both instances theselatter two were in the apical segments of the lowerlobes. Hemoptysis was a symptom in twenty-sixcases (45 per cent). The cause of the cavity wasknown or suspected to be bronchiectasis in twenty-onecases. Tuberculosis was suspected as the cause ineleven cases, malignancy in two cases and histo-

t In three instances the lobes were not specified andtwo patients had cavities in two lobes .

* From the Clinical Laboratories, Jewish Hospital; the Pulmonary Disease Section, Medical Service, VeteransAdministration Hospital ; Departments of Pathology, Medicine and Dermatology, University of Cincinnati, College ofMedicine, Cincinnati, Ohio. This study was aided in part by Grant E576 ofthe National Institute ofHealth. Manuscriptreceived February 13, 1961 .

692 AMERICAN JOURNAL OF MEDICINE

Fungus Ball-Schwarz et al .TABLE I

FIFTY-EIGHT CASES OF "FUNGUS BALL"

* R .U .L ., right upper lobe; L.U .L., left upper lobe ; R .M.L., right middle lobe ; R .L .L.,

lower lobe .}R,L,resectionotle

eryaelastfollnw-up ;L,livingatlastfollow.ap ;R,D,res noonflcsionbusdied ;Dn,L,eavitydraived ;pa-tievt living sod well at last follow-up .

$ Following report by Levin [24]. Patient seen and resected with pathologic examination at Jewish hospital, Cincinnati, Ohio .

VOL . 31, NOVEMBER 1961

693

Author

Schwarz, Baum

Bar low [2]

Brim,[.3] . .Corps, Cap . [5]

UeMinjer[6]

Enjzlbcrt ct al. [7]

Pinegold d al . [€]

Fingerland et al. [9] . . . .

Ageyr .),

NO '

endS"

Gase Race fLoearionofFunguaRall* Fungus

HowfdeoxifiedI

Aspergillus

HistologyAspergillus


HistologyUnknownAspergillus

Culture ofurology

g lib's

Histologyan, ymig/gates Cuban,

Aspergillus?

HistologyAsperglu? HistologyAspergillus



HistologyAspergdhis

Histology

A futoigus

CytologyA . fum'taatus Culture

A . fumigates Culture

Aspergillus



Histology

Aspergillus

HistologyAspergilus


Histology

Aspergillus


HistologyA . fumigates CultureAspergillus

Culture

(Aspergillus

HistologyNot identified

. . .Aspergillus or Histologycaodida

Aspergillus

Culture ofcavity

Aspergillus

Histology

A, fumigatus CultureA.fumigams CultureA. fumigatus Culture of

sputumAspergillus

HiseolaavAspergillus? HistologyNot named

. .Aspergillus

Culture andhistology

Candida (?)

HistologyUnidentified HistologyUnidentified HistologyAspergillus




Histology andf

culture'Aspergillus

Histology andculture

Not namedNot named

. .Aspergillus

CultureAspergillus

Culture andhistology

A

Us

Culturetus Culture a

bronchialaspirate

N egiiven

CultureNone, given

Histologyonly) c

A .fumigatus Culturefrecevh uevhuAspeorales

HistologyyAspergillus

o

A,fumigamsCulture ilt nchiectasis

Cause of Cavity

HisroplannosisHiatoPlasmosisHiatoplasmosisHiamplasmosisTuberculosis, bronehlectasis

UnknownS thb ro a

saesuis absmsstwith roncbiectayctuba

Cavity possibly tuberculosisCavity gosublytubesent 0eBroncBro as o aers 7

100 year,)er

vs

IN..-specific

pneumoniaNon-specificpneumonia with

IatccsIcallinfer possible a

w'afect5on (portop bscessly7iH udg koma wets

bscesstclg)ly7

Hadgkfn'adiseaxalteraltert herapyfac

Severe mumsrotizing sraphylocoreal(2) pneumonia

BronchiectasisPoatpveumonic abscessHealed tuberculosis ; bronchiecm-

sTuberculosisBroncMectanaBrvnrhiectasis

RmnchiecmsisBronchiectasisUnknown, granulomatousPossibly tubaudnsis

iBronnhiecmtic cystUnknownAbscess, etiology aaknuwn

Bronchiectasis (2)

Cravulomatous with coainophils,etiology unknown

ProvchiectasiaBro nchial c yst orbconchiectasisBronchiectasis

BrnnchiecmsisUnknown, granulomatousUnknown, bronchiectasis PBrunchiectasis7

UnknownUnknownUnknownBronchiectasisProbable tuberculosiaTuberculosisTuberculosis

Tuberculosis

UnknownLung cyst, possibly tuberculosisBronchiectasisUnknown

HismplasmosisBrooohieaaafa Q)Granulomatons (?)

SroochiectaeSmooth walied cysq etiology tin-known

Gowlomatons cyst, etiologyuv-know.Benchiro

Rmvchieaasis

Outcome}

DiedR,LDiedLR,L

R,L

R,LR,i.Rl.Die .DiedDied

DiedDied

R .D

RI,

Rl.RI .

RLRLRI .

R,DR,1 .R,LR,LR?,R,LR,f .

R .T .

Dr.,L

R,LR,LR,L

R,LDiedR,LR,L

DiedRI .R :LRf.R,I)R,DR,L

R,L

R,DDr .,LR,LUnknown

R,LL

R,LR,iL

R,L

R,LR,LR,L

1 45,W,M2 47,W,M3 49,W,M4 70,W,MI

25,F

1

521

5C

1 21M44,M

1

19 .WF2 74W,FI 1 74,W,M4 ?8, W,M

6 58,W,M53,WM

8 68,W,M

1 51 W,M2

31,W,F3 25,W,F

4 35,W,F5 47,W,F

R.U .L .LU.L.R.U .L . (hemoptysis)L .U L .L .U .I..

R.U .L. (hemoptysis)R.U .L . (hemoptysh)

R.U.L.R.U .L .R .U L. (hemoptysis)L .U .L . per

log"Both up IvesRight lung

Left fungRK.U.L . `multiple)

L .U .L . .

L.U .L .R .L .L . ayexR.U.L . (hemoptysis)

L.U .I_L.U .L .L.U .L . (massive hemop'rye )L.U .LR.U.L .R .U .L .R.U.L. (hemoptysis)L.U .L . (hemoptysis)R.U.L . (hemoptysis)R .U L .

Aicopoatedor segmentT.U.L.R.U.L .

R.U .L .R.M .L .Apical SegmentL.U.L . (hemoptysis)R.D.L. (hemoptysis)R.U .L. (hemoptysis)L .U.L . (hemoptysis)L .U.L . (hemoptysis)

R .U .L.R .U . L. (hemoptysis)R .U .L. (hemoptvss)R.U .L.IR.U .L.L.U.L.R.U.L ., R.M .L .(hemoptysis)L .U .L . (hemoptysis)

R.U .L . (hemoptysis)L.U .L . (hemoptysis)L.U.L . (hemoptysis)Cavities not localized

R.U .L . (hempR.U.L. (hemo

L.U .L .SuperiorsegmentR .L .L .

Superior segment L .U .L.

Foushee, Norris [70) . . . .Fridman et al . [77] . . . .Geratl et al. [72]Godfrry [73]Graves, Millroan [74/ . . .

Hausman [76]

Hamphill [77]

Hiddlestone tt al . [79] . . .

Hiuson et al . [20]

Hochberg et al . [27] .,, .Hughes et al .[22]

6

53,W,F

7 45,W,M8 55,W,F1

44,M1

55,N,F1

33,F2 52,M1

-,2,W.M

1

52,1

1

55,M

2 28,M3 30,M2 58,M

57,MSo,F48,W M56,N,}s4

Levi . [24] 1

82,M2 3P,M

3 25,M

Memaa,'Thomas[25] . . .Pecora, Toll [27]

Peale, Monad [25]

Pimental [291'

Prockvow Loewen [30] . .Sansei C37]

4 ; 60,M1 40,M1

42-10l2

161,1,1

3 39,M

33,F42,M3 .5,M

4

1

28,W,M1

57,M

et al. peon . . .We., Thompson [35] .~

1 J .W.F~ 42,2 42W,F

YesvegHurwitz(37]

Schwarz, Baunri

1

35,W,M

64,W M

6

36~17

o6,W,MIL.Li .L.(hmnuptyvs)

R.U .L . (hemoptyss)R.U .L .

694

Fro . 1 . Case 6 (Table I) . Large apical cavity with frag-ments of fungus ball (arrow) . Dilated bronchus leadinginto cavity.

plasmosis was known or suspected as the cause of thecavity in five cases . In forty-eight cases aspergilluswas the fungus producing the fungus ball ; twenty-seven of these were diagnosed by histology alone, whiletwenty-one were proved by culture . Only one case ofcandida and one case of mucorales were noted in thisseries . The age range in this group of cases was fromnineteen to eighty-two years, most of the cases (seven-teen) occurring in the fifty-one to sixty year agegroup . There were forty-two men, fifteen women, andone case in which the sex was not noted . In twenty-eight cases no mention was made of the race, but inthe thirty in which this was mentioned twenty-sevenwere white and three were Negro. In forty cases thelesion was resected and the patients were living whenlast heard from; three were drained rather thanresected but recovered from the surgery withoutcomplications. Thirteen of the fifty-eight patients weredead at the time reported . No attempt has been madeto correlate the extent of the disease in the lungs withmortality since a large number of these patients hadassociated pulmonary insufficiency or were incom-pletely described .

RESULTS

It is safe to say that in the majority of the casesreported the origin of the cavities was assumed tobe bronchiectatic and that the aspergillus foundthe environment of the bronchiectatic cavityfavorable to its rapid development . (Fig. 1 .)

The following case reports are unique in thatthe etiology of the cavity lesions was established

Fungus Ball-Schwarz et al.

TABLE II

CONFIRMATIVE RESULTS OF DIAGNOSTIC LABORATORYPROCEDURES IN FOUR CASES OP CAVITARY HISTOPLASMOSIS

COMPLICATED BY FUNGUS HALL

NOTE : * positive culture ; # microscopic demonstrationin tissue section ; - negative; YP yeast phase antigen .

with certainty as histoplasmic . The presence ofaspergillus in the lumen of the cavities causedspecial diagnostic problems . (Table n .)

CASE REPORTS

CASE 1. This forty-five year old white man wasfirst hospitalized in 1941 because of "tuberculosis."The basis for this diagnosis is unknown . From thattime until 1952 he was hospitalized repeatedly, thediagnosis of tuberculosis again being made withoutbacteriologic proof. In 1952 he was hospitalizedand his sputum was positive on one occasion for acid-fast bacilli . In August 1954, during hospitalization,multiple sputum examinations for acid-fast bacilliwere negative, but roentgenograms showed extensiveinflammatory changes bilaterally. At this time thepatient was overtly psychotic and from then until hisdeath spent most of his life in a state mental hospital .Physical examination revealed normal vital signs butmarked emaciation and evidence of emphysema .Roentgenograms showed bilateral infiltrate in theupper lobes with cavitation . In one of the cavities amass was seen with a crescent air meniscus above it,and the diagnosis of fungus ball was suspected . Dur-ing hospitalization in November and December 1957a sputum specimen was culturally positive for Histo-plasma capsulatum . The patient's course was one ofgradual deterioration and he died on December 16,1957, apparently of cachexia and malnutrition .At necropsy the left lung was covered by massive

adhesions, which in many parts measured up to 4 mm .The upper lobe showed two cavities which werelocated approximately 4 cm. below the anatomicapex. The lower cavity was larger than the superiorand its lower border approached the lower lobe . Thiscavity measured approximately 3 cm . in diameter andwas separated from the smaller superior cavity by aseptum. In the apex numerous bronchiectatic cavities

AMERICAN JOURNAL OF MEDICINE

Case

Histo-plasmaCapsu-

HighestComplement

Fixation Aspergillus Species

No . latum Titer Demonstrated

Demon-strated

forHsstoplasmin

in Cavity

t Not done #2 - 512 YP #,3 512 YP #4 2048 YP No anatomic material

available

Fungus Ball-Schwarz et al .of a few millimeters in diameter were found, all ofwhich had thin walls lined with a glistening surface . Inthe apex, heavy anthracotic pigmentation and fibrosiswere found . No distinct nodular lesions were palpatedin the upper or lower lobe . In the lower lobe therewere extensive bronchiectases and several calcitic foci .

The right lung was greatly enlarged and hadadhesions covering the major part of the upper lobe .In the upper third of this lobe a huge cavity wasfilled with a brownish mass, typical for aspergillus .This cavity communicated through a narrow tunnel,of about 2 mm . in length and diameter, with a secondcavity of approximately 3 cm . in diameter . The latteralso was filled with the brown crumbly material,typical of a "fungus ball ." The lining in both cavitieswas smooth and shiny . The wall of the major cavitywas only 1 to 2 min, thick in some parts and could beruptured easily . The main bronchus contained a mix-Lure of mucus and brownish material (aspergillus) .In the upper lobe, close to the lower border of thecavity, a focus 15 by 10 mm . was found which had apeculiar shiny appearance, and was suspected to be achondrorna .

Gross diagnosis: Bilateral cavitary histoplasmosis,with extensive pleural adhesions and thickening andfungus ball in the cavity in the upper lobe of the rightlung .

The main feature of the microscopic examinationwas progressive, chronic fibrosis of the lungs as a resultof scarring of inflammatory disease . Numerousbronchiectases and bronchiectatic cavities were found,some of which showed the presence of aspergillus ;others demonstrated caseation of the wall . H .capsulatum was present in the wall in addition to theaspergillus found in the lumen . This was an extremelyadvanced pulmonary lesion, as evidenced by scarringand bronchiectases .

Case 2. This forty-seven year old white man wasadmitted to the Dunham Hospital on August 9, 1959,with a history of cirrhosis, chronic cholecystitis andquestionable duodenal ulcer in 1955 . In addition,there was a history of unresolved pneumonia withpleural effusion in 1956 . At that time both PPD andhistoplasmin skin tests were positive. Four monthsprior to admission, symptoms of weight loss, produc-tive cough and hemoptysis developed, and theirprogression prompted his admission . Physical findingsof interest revealed dullness at the apices of the lungswith vales, and a 'palpable liver . Anemia was presentas were signs of moderate hepatic damage . Searchesfor acid-fast organisms in the sputum were repeatedlynegative. Chest roentgenograms revealed an infiltratein the upper lobe of the right lung . Following admis-sion the cough and fever continued . Serologic studiesfor histoplasmosis were positive in titers up to 1 to 512 .All cultures of sputum for H . capsulatum werenegative. Treatment with amphotericin B was begunon September 19, 1959, and discontinued on Februaryvor . . 31, NOVEMBER 1961

695

i Th3a ao:w

'',f4ifillf!{Hthl/llfllll

Fic . 2 . Case 2, surgical specimen . Chronic cavitaryhistuplasmosis with marked scarring in surrounding tis-sue and massive thickening of pleura . Brownish massesadherent to wall of cavity are visible .

12, 1960. No change was noted in the size of thecavity but laminograms revealed an intracavitaryinclusion . An upper lobectomy of the left lung wasperformed on April 29, 1960, which was followed by atailoring thoracoplasty on May 17, 1960 . The patientwas discharged on August 5, 1960, in good condition,clinically and radiologically . (Fig . 2, 3, 4 and 5 .)

The resected upper lobe of the left lung wasmarkedly shrunken, with pronounced thickening ofthe pleura, which in many parts measured up to 5 mm .in thickness and was extraordinarily firm due tofibrosis and hyalinization . In the apex there was acavity 3 by 3.5 cm ., the walls of which were coveredby brownish crumbly masses, typical of the presenceof aspergillus . The major part of this material hadbeen removed at operation for culture and photog-raphy. The pulmonary tissue adjacent to the cavitywas fibrotic, grayish in color except for a few areas inwhich bronchi could be recognized. The bronchi weremarkedly distended and the wall of the bronchi wasmassively thickened by inflammation . In some of thesebronchi, even far distal from the cavity, the brownishmasses of aspergillus were found, proliferating in thelumen of the bronchi .

Gross diagnosis : Severe chronic scarring of upperlobe of the left lung with bronchitis, bronchieceasesand cavity filled by aspergillus . Extensive pleuralthickening with hyalinization .

696

Fungus Ball-Schwarz et al .

FIG. 3 . Partial content of histoplasmic cavity in Case 2 .Several species of aspergillus were grown from thismaterial .

On microscopic examination this lung showed apicture analogous to Case I in all respects, withchronic fibrosis and distortion of pulmonary archi-tecture, bronchiectases, caseation of some of thebronchial lining and numerous aspergilli in thelumen of the enlarged cavity. The only difference was

FIG . 5 . Head of aspergillus in bronchial cast . Magnifica-tion X 800, hematoxylin and eosin stain .

Fin. 4 . Hyphac (of aspergillus) in sputum . Potassiumhydroxide preparation, magnification X 600 . Broadseptate hyphat can be identified only by culture ordemonstration of spores or other specific structures . SeeFigure 5 .

that despite the examination of numerous specimens,histoplasma could not be demonstrated unequivocallyin the tissue sections .

CASE 3 . This forty-nine year old white man wasknown to have had chronic obstructive pulmonaryemphysema, chronic bronchitis and bronchiectasesfor many years . He had been hospitalized at theVeterans Administration Hospital, Cincinnati, threetimes prior to his final admission on September 14,1959. All previous hospitalization had been forpulmonary insufficiency and occasional hemoptyses .Roentgenogrants taken throughout his course revealedbilateral pulmonary emphysema with inflammatorydisease of the upper lobes . Cavitation was suspectedfrom the earliest film, dated 1956. Bronchogramsrevealed bronchiectases of the upper lobe of the rightlung. (Fig . 6 .) Sputum studies for acid-fast bacilliwere negative on many occasions. During 1958 and1959 the diagnosis of histoplasmosis was suspectedbecause of serologic titers of complement fixing anti-bodies fur histoplasmosis up to 1 to 512 . Numeroussputum specimens were cultured for H . capsulatumbut all were negative . His final admission was becauseof an increase in the symptoms of pulmonary insuffi-ciency. His death occurred shortly after the injectionof medication on September 15, 1959 . At no time



during the patient's course was the presence of afungus ball suspected .

At necropsy the lungs weighed 1,500 gm . and werecovered by a greatly thickened pleura which adheredto the chest wall . In the right apex there was a fibrousarea, with a cavity 2 cm . in diameter. Throughoutboth lungs there were numerous small nodules 2 to 3mm. in diameter, some of which appeared to becalcified. Calcifications were found in the right hilarlymph nodes .

A large bronchus was traced in the upper lobe of theright lung . Brown, rather dry material, representingaspergillus, was present in the lumen of the cavity andbronchus .

Microscopic examination of the wall of the cavityshowed extensive ulceration of the epithelium withH. capsulatum demonstrable in the necrotic area . Inthe lumen, aspergillus could be recognized . Adjacentto the wall of the cavity there were several cascatedfoci . each of which contained H . capsulatum. Inother sections of the lung numerous caseous noduleswere found, 3 to 6 mm. in diameter . The smaller onesfrequcndy revealed a tendency to healing and werefibrocaseous . The larger ones showed mostly completedestruction of the elastic pattern and containednumerous organisms of H . capsulatum. In addition, acalcified primary focus was found with an osseous rimwhich contained numerous organisms of H . cap-sulatum. Several regional calcified lymph nodesshowed the stippled calcification of histoplasmosis .Numerous organisms were found in the calcifiedregional lymph nodes. Examination of the fungus ballrevealed several heads of aspergillus .

Case 3 is extremely interesting for several rea-sons. First, chronic cavitary histoplasmosis waspresent; complicated by the presence of a fungusball in the cavity. Secondly . there was activedisseminating histoplasmosis in the lungs, bron-chogenic in origin in all likelihood, originatingfrom aspiration of the cavitary contents . In thethird place there was a completely healed andvery old primary complex of histoplasmosis,implying that reinfection occurred sometimeduring the patient's course . Obviously, it isimpossible with the available information tostate whether this was endogenous or exogenousreinfection .

This man had lived on a farm all his life, andhe must have had considerable exposure tospores of H . capsulatum. We assume that theprimary complex was quite old since at leasttwo morphologic facts point in this direction .One is the complete calcification and boneformation, the other is that the organisms in theprimary focus and the regional lymph nodesstained with much less intensity than the organ-

VOL . 31, NOVEMBER 1961

697

FIG . 6 . Case 3 . A, chest roentgenogram showing bilateralnodular and linear densities in the upper lobes . B, bron-chograms showing definite bronchiectases in upper lobeof right lung.

isms seen in active lesions. This we find to occuronly when the organisms have been dead formany years .

Case 4 . This seventy year old white man wasadmitted to the Veterans Administration Hospital,Cincinnati, in the summer of 1958 for a cataractextraction_ At that time it was noted that he hadbilateral cavitary disease of the upper lobes . (Fig . 7 .)Studies for tuberculosis and all cultures were nega-tive; the tuberculin skin test was negative up to 250tuberculin units. Cataract extraction was accom-plished and the patient was discharged, to return inthe late fall of 1958 at which time the second cataractwas removed . No change was seen in the pulmonarylesions . Following cataract extraction a histoplasminskin test result was positive. Complement fixationstudies for histoplasmosis revealed high titers . Severalsputums were positive on culture for H . capsulatum .In early March 1959, treatment was begun with

698

Fm. 7 . Case 4 . A, chest roentgenogram, showing bilateraldisease in the upper lobes with cavity on the left . B,laminograph showing details of cavitary disease. Thesefilms were taken before fungus ball developed .

amphotericin B. This was continued until early June1959, to a total dose of 870 mg. No change in the chestroentgenograms occurred. The patient was dischargedand followed in the outpatient clinic . No change in theroentgenogram was noted from June to November1959, at which time some filling of the cavity of theupper lobe of the left lung was seen . (Fig. 8 .) Roent-genograms taken in February and May 1960 revealedfurther filling of the cavity . These spot films taken atfluoroscopy revealed the mass filling the cavity to befreely movable . (Fig. 9.) In May 1960, cultures ofsputum were positive for H . capsulatum . These hadbeen repeatedly negative for the preceding elevenmonths . The patient was therefore readmitted in earlyJune and amphotericin B therapy was again begun .The patient was given 2,500 mg . In September 1960,he was discharged with little change evident on thechest roentgenogram, but with symptomatic improve-ment. Since discharge the patient has been well, withnegative sputum cultures for H . capsulatum .


FIG . S . Case 4 . Chest roentgenogram after developmentof fungus ball in cavity of upper lobe of left lung .

FIG . 9 . Case 4. A, spot film of upper lobe of left lung isleft side down position . Note crescent air lying medialllB, patient in reverse position with left side elevated . Notthe lateral location of the air crescent in this view .

AMERICAN JOURNAL OF MEDICIN

Comments : A few generalizations can be madeconcerning the four cases described . All werechronically ill white men . All were forty-fiveyears of age or over . All had had chronic pul-monary inflammatory disease in the upper lobesfor several years . All but one (Case 3) showedevidence of symptoms of progressive wasting .Hemoptysis was a prominent symptom in two ofthe four cases . It is of particular significance thatthere was nothing in the history, physical orlaboratory data, except the cultures, to differ-entiate the chronic pulmonary inflammatorydisease due to histoplasmosis from similar casesdue to tuberculosis . It is of interest that theroentgenologic diagnosis of intracavitary fungusball was made or suspected in three of the fourcases .

In three of the cases there was adequateanatomic evidence for the association of cavitaryhistoplasmosis and intracavitary fungus ball . Inthe fourth case, although the clinical and roent-genological impression could not be corroboratedby the anatomic findings, there seems littledoubt that the free-lying, movable, intracavitaryinclusion was a fungus ball, most likely due toaspergillus infection . The histoplasmic nature ofthe cavity had been established by repeatedpositive cultures .

COMMENTS

The development of the fungus balls in thepresent cases was obviously secondary to severeunderlying disease. All the patients had bron-chiectases and hronchiectatic cavities, frequentlywith ulcerative endobronchitis and caseationnecrosis of the bronchial wall . The aspergilluswas always found merely lying upon the intactbronchial epithelium or upon the ulceratedwall without any penetration into the pul-monary tissue . One can come to the conclusionthat the presence of the fungus ball preventsclosure of the cavity and this may be a mostundesirable side effect . It can be postulatedthen, in our Case 3, that bronchogenic dis-semination almost certainly occurred from thecavity and it can be surmised that removal of thefungus ball by drainage or resection could haveresulted in collapse of the cavity and potentialhealing . That this occurred in only one of thecases does not diminish the importance of thisobservation .The role of aspergillus in the respiratory

tract is not clear . This fungus is common but notto the exclusion of many other saprophyticVOL . 31, NOVEMBER 1961

Fungus Ball-Schwarz et al . 699fungi. However, when the fungus producing theso-called fungus ball was at all identifiable,it almost always turned out to be a species ofaspergillus, together with debris, bacteria,exudate and sometimes other fungi . Frequentlythe morphologic identification is dubious be-cause the diameter of the hyphae found in themycelial conglomerate within the pulmonarycavity is markedly greater than the width seenin culture mounts . The hyphal elements oftenlook macerated, stain poorly, and the cytoplasmseems to have escaped- It is our impression thatspecies of aspergillus enter cavities and prolifer-ate very fast to a point where oxygen and nutri-tional requirements cannot be met, at least in thecenter of the proliferating fungal mass, where thefungus undergoes death and maceration .

Addition of gastric mucin to artificial mediaproduced a marked increase of the hyphal diam-eter of several species of aspergilli . This mayexplain why aspergilli growing in bronchialmucus appear as noted .

The fungus hall, once formed, must largelydepend in its development on the anatomic situa-tion of the bronchus leading to the cavity. Anopen bronchus obviously will provide oxygen .Several of our patients expectorated largeamounts of hyphae of aspergillus periodically,while at other times no fungus elements werepresent, which would indicate a valve mecha-nism or some other periodic bronchial occlusion .

It is unlikely that multiplication of theaspergillus organisms within the cavity wouldcontribute to expansion of the cavity . It seemscertain, however, that the fungus ball, onceestablished within the cavity, prevents shrinkageand healing . The valve mechanism or bronchialstricture, which one has to postulate for theformation of bronchiectatic cavities in locationswhere postural drainage could be anticipated,very likely produces accumulation of mucuswhich over months or years results in formationof cavities .

The overwhelming majority of fungus balls(including those in our patients) complicatinghronchiectatic and histoplasmic cavities arelocated in the apical regions of the upper lobes,where postural drainage should be at its best .This is in marked contrast to localization in thelower lobes of bronchiectases in general . Whenbronchiectases of the upper lobes do occur theunderlying process (tuberculosis or histoplasmo-sis) results in narrowing constriction and distor-tion of the bronchi, with poor bronchial drainage

700and perhaps poor aeration of the areas of lunginvolved, which may explain the apical locationof the fungus balls .

SUMMARY

A review of recorded and our own experiencewith intracavitary fungus balls reveals aspergil-lus to be the most commonly identified fungus .

Such fungus balls are characterized roent-genologically by a crescent-like shadow above amovable ball-like structure. The cavities invadedby aspergillus most commonly are of bron-chiectatic origin .

Four proved cases of cavitary histoplasmosiscomplicated by intracavitary development ofaspergillus are presented herein .

Acknowledgment : We would like to thank Dr .Herman Nimitz for supplying us with the detailsof Case 2 . Dr. Milton B . Spitz collected some ofthe clinical data .

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cavitary histoplasmosis complicated by fungus ball

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