BRONCHIAL ASPERGILLOSIS OCCURRING AS AN INTRACAVITARY
"FUNGUS BALL"
FRANK VELLLOS, M.D., ALVIN S. CRAWFORD, M.D., CHRISTOS D.
GATZIMOS, M.D., AND EDITH HAYNES, P H . D .
Department of Pathology, Indiana. University School, of Medicine, Indianapolis,
Indiana
Species of Aspergillus are frequently isolated from patients with diseases of
the lungs, and the fungi are generally regarded as contaminants. 1 During the
examination of surgically resected tissues, or at autopsy, masses of the fungus
are frequently found in lesions that are produced initially by other organisms.
In a few instances, species of Aspergillus may actually be pathogenic. 1, 10
There is one form of involvement of the lung by Aspergilli that results in characteristic clinical, radiologic, and pathologic findings. In this type of lesion there
is an entangled mass of hyphae in an epithelial-lined space that communicates
with a bronchus. The radiologic examination usually reveals a rounded density
that is capped by a crescent of air. The patients frequently complain only of
hemoptysis, or they may be asymptomatic. The first description of this type of
lesion was that by Dev6, in 1938, as noted in the excellent study of Monod.8 A
total of 21. similar instances were found in the literature, including IS that were
examined pathologically, and the organisms were cultured from the specimens
removed from 5 of the patients.
This paper deals with the description of another patient who had an intracavitary "fungus ball" in the lung. The condition was suspected when the specimen was examined grossly, and cultures were made at that time, inasmuch as
the authors had recently noted the description of this condition in Levin's
paper. 0
CLINICAL
SUMMARY
History. The patient was a 54-year-old white man (a machinist) who was admitted to the hospital at the Indiana University Medical Center on February 2,
1956, for the diagnosis and treatment of a mass that had been present for at
least 2 months in the upper lobe of the left lung.
The patient had a history of biliary colic, and a cholecystectomy was performed in December 1955 as a treatment for acute cholecystitis. During the postoperative period he developed pain in the chest; a roentgenogram of the chest
revealed atelectasis of the lower lobe of the right lung and, in addition, a mass
in the upper lobe of the left lung. The subsequent postoperative course was
uneventful and the patient was referred to this hospital for further observation
and treatment. He had experienced no symptoms that were referable to the
Received, August; 7, 1956; revision received, August 31; accepted for publication October 22.
Dr. Vcllios is Associate Professor of Pathology; Dr. Crawford is Assistant in Pathology;
Dr. Gatzimos is Resident Instructor in Pathology; and Dr. Haynes is Instructor in Clinical Pathology.
68
Jan.
1957
BRONCHIAL ASPERGILLOSIS
G9
TABLE 1
SUMMARY OP F I N D I N G S IN P U B L I S H E D D E S C R I P T I O N S OF P A T I E N T S WITH PULMONARY
INTRACAVITARY " F U N G U S B A L L S "
Reference
Dev68
Me tills 7
Hemphill 4
Gorstl and associates 2
Weens"
Yesncr and
Hurwitz 1 2
Monod and associates 8
Graves 3
Hinson and associates 6
Schinz and associates 8
Levin 0
Present case
Total
Number
of
Patients
Sex
Number of
Number
Patients
Positive
Examined
with Hemop- Cultures
FePathologically Male
tysis
male
1
1
1
1
1
1
1
1
2
1
1
1
1
5
4
3
1
3
1
3
1
3
1
1
1
1
1
1
Probably
1
1
4
1
3
1
3
1
22
19
15
4
Proved Cases
RUL* RLL* LUL* LLL*
1
1
1
0
1
0
0
0
0
?
1
0
1
1
3
3
2
2
1
2
0
1
1
1
2
1
?
2
0
0
1
3
13
6
10
1
1
1
1
1
1
1
7
1
* R.UL = upper lobe of the right lung; R L L = lower lobe of the right lung; LUL =
upper lobe of the left lung; LLL = lower lobe of the left lung.
respiratory system (except for an episode of pneumonia approximately 20 .years
prior to admission), and there had been no loss of weight. There was no family
history of pulmonary disease, and his wife and daughter are living and well.
Physical, examination. The patient's temperature was 97.8 F., pulse rate .100
per min., respiratory rate 18 per min., and blood pressure 130/90. He was welldeveloped, slightly obese, cooperative and in no apparent distress. The skin was
normal and no lymph nodes were palpable. There was no evidence of Horner's
syndrome and the neck was supple, with the trachea in the midline. Respiratory
excursions were symmetric and equal, but there was an area of dulness to percussion anteriorly in the upper part of the left side of the chest. The lungs were
clear to auscultation, with no changes present in the region of the dulness, and
the lieart seemed to be normal. The right paramedian abdominal scar was well
healed, and no masses were palpated in the abdomen. The prostate was slightly
enlarged, with a nodular area of firmness in the right lobe.
Laboratory findings. The level of hemoglobin was 15.8 Gm. per 100 nil., with
a red blood cell count of 4,820,000 and a white blood cell count of 8350 per cu.
mm.; the differential count indicated 66 per cent polymorphonuclear leukocytes,
4 per cent band forms, 29 per cent lymphocytes, and 1 per cent monocytes. The
results of urinalysis were within normal limits. The serum contained 3.7 IvingArmstrong units of acid phosphatase. Serologic tests for syphilis were negative.
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VELLIOS ET
AL.
Vol. 27
Posteroanterior and lateral roentgenograms of the chest revealed a somewhat
rounded density in the left apical region. The density extended several centimeters below the level of the clavicle (Fig. 1), and critical examination revealed
that the density was partially surrounded by a crescent-shaped zone of air. The
trachea was deviated slightly to the left.
Clinical course. A thoracotomy was performed on the left side, with the patient anesthetized endotracheally. There were numerous adhesions about the
upper lobe of the left lung; these were firmly attached and required dissection.
The mass was palpated in the posterior basilar segment of the upper lobe of the
left lung. There was no enlargement of lymph nodes. A segmental resection was
performed. Intercostal drainage was established and 500,000 units of penicillin
were placed in the pleural cavity prior to closure of the incision. The postoperative period was uneventful and the patient has remained well since the operation
(approximately 4 months). Subsequent skin tests with extracts of Aspergillus
himigatus and Aspergillus niger were negative.
Pathologic Studies
The specimen (I.TJ.M.C. No. 79582) consisted of a segment of lung that
measured 6.5 by 5 by 3.8 cm. (Fig. 2). The parietal pleura contained a small
amount of fat that was adherent to the surface of the specimen, and a fluctuant
mass was palpable. The interior of the specimen consisted chiefly of a cavity that
was almost 4 cm. in diameter. I t was filled with soft, friable, dark gray and yellow
material with a consistency similar to that of putty. The lining of the cavity was
smooth, glistening, and pink, and its wall varied from 5 to 8 mm. in thickness,
grossly resembling a dilated bronchus. Proximally, the cavity was continuous
with a bronchus, and, peripherally, a few small compartments communicated
with the cavity through small openings. The small spaces contained the same
type of material as that observed in the large cavity. The adjacent pulmonary
tissue was atelectatic.
Study of histologic sections revealed that the wall was lined by epithelium
that was chiefly of pseudostratifled, ciliated, columnar type (Fig. 3), with regions
of squamous metaplasia. Smooth muscle was observed in occasional segments of
the fibrous wall. In the wall of the large cavity and in the smaller tributaries,
there was fibrosis and a dense cellular infiltration that consisted chiefly of lymphocytes and plasma cells, with several polymorphonuclear leukocytes and
eosinophils. The intima of the blood vessels was prominent, and there was conspicuous subintimal fibrosis associated with greatly narrowed lumens. The plates
of cartilage in the wall were not arranged in any recognizable pattern and some
of them were partially calcified or ossified.
FIG. 1 (upper). Roentgenogram of the left side of the chest. There is a rounded density in the apical region. The arrow indicates a portion of the inferior margin of the
density, within which there is a thin, crescent-shaped zone of radioluoency.
FIG. 2 (lower). Photograph of the resected portion of lung. The tissue on the left represents approximately half of the wall of the cavity, which is lined with a glistening membrane. The tissue on the right represents the other half of the cavity, with the "fungus ball"
in place.
Jan. 1957
BHONCHIAL ASPEKGILLOSIS
71
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V E L L I O S ET
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The material in the lumen of the main cavity and its branches consisted of a
closely packed mycelial mass of filaments with thin septums and wide hyphae
(Fig. 4). There was a slight amount of amorphous eosinophilic material intermingled with the fungus colony. In some regions, especially at the periphery,
there was an infiltration of leukocytes, consisting chiefly of polymorphonuclear
leukocytes, lymphocytes, and plasma cells. The staining varied in intensity, the
mycelium in the central region staining palely. No fructification forms were
found.
Microbiologic studies. No acid-fast bacilli were observed in smears and cultures
of the material. Portions of the intracystic material were removed aseptically
from the central and the most peripheral regions and planted on Sabouraud's
dextrose agar that also contained penicillin and streptomycin. The cultures were
incubated at room temperature. White, cottony, surface filamentous growth was
first noted on the third day. At 7 days the colonies had increased in size rapidly
and they were dark green. After 2 weeks, the surfaces of the larger colonies (up to
1.5 cm. in diameter) were radially wrinkled from the center, superficially resembling a cart wheel. The petri dish was examined microscopically (with the
low-power objective), and the growth consisted of septate filamentous colonies
with many spore-heads to which long chains of spores were attached. A wetmount preparation revealed conidiophores with swollen ends. The upper twothirds of the vesicle-like swellings contained a single row of sterigmata that were
approximately equal in size (Fig. 5). Only an occasional sterigma had a few
conidia (spores), but many conidia were floating in the preparation. A suspension
of this culture in physiologic solution of sodium chloride was injected into the
ear vein of a rabbit, and lesions developed in several sites. Fungous organisms
were identified histologically, and Aspergillus sp. was recovered in cultures.
DISCUSSION
The pathogenesis of pulmonary intracavitary "fungus ball" is not completely
known. One theory is that a small nidus of hyphae or mycelium is deposited in
a normal bronchus; the fungus may then grow and, by virtue of its expansion,
cause gradual dilatation of the bronchus.8 This theory is not entirely satisfactory
when one considers the relatively soft texture of the "fungus ball" and the looseness with which it frequently lies in the cavity. I t seems more likely that the
"fungus ball" develops within a previously dilated bronchus or bronchial cyst.
I t should be emphasized that this lesion differs from a mycelial mass of Aspergillus growing in an abscess cavity. The epithelial linings of the spaces in this
FIG. 3 (upper). Photomicrograph of a portion of the wall of the resected cavity and adjacent pulmonary tissue. The lining consisted of respiratory and transitional epithelium.
There was conspicuous subintimal fibrosis in the blood vessel illustrated in the leftside of
the field. No fungi were observed in the tissue adjacent to the cavity. Hematoxylin and
eosin. X 175.
FIG. 4 (lower left). Photomicrograph of a histologic section of the resected portion of
lung, illustrating the contents of the cavity. Note the matted hyphae of the fungus. Hematoxylin and eosin. X 175.
FIG. 5 (lower right). Photomicrograph of a wet-mount preparation from a colony on
Sabouraud's dextrose agar. The ends of the conidiophores were enlarged into vesicles,
with sterigmata that bore relatively long chains of conidia (spores), most of which were
detached during preparation of the wet-mount. No stain. Approximately X 1000.
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V E L L I O S ET
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Vol. 27
man's lung were intact. No fungi were found in the patient's tissues, and fungous
structures were not observed in tissues of other patients described in the literature. Fructification forms also have not been observed in the fungous growths
within the cavities.
The present case is the sixth instance in which growth was obtained by culturing the material from the cavity, although cultures were made in several of the
cases described in published papers. Microscopic examination of the mycelium
usually reveals variations in the intensity of staining of the fungous elements in
different regions, probably because some of the organisms are not viable. I t is
suggested that cultures be prepared with inoculums from several depths of the
mass, in order to increase the probability that viable organisms will be included
in the inoculum. In the 6 instances in which organisms grew, species of Aspergillus
were isolated. In the remaining cases the organisms resembled Aspergillus,
although some were regarded as Candida. 6
SUMMARY
1. This paper deals with the description of a 54-year-old white man who had a
"fungus ball" in an ectatic bronchus. The lesion was clinically asymptomatic,
but a rounded density with a radiolucent cap was noted in a roentgenogram of
the chest that was made after the patient had undergone cholecystectomy for
cholecystitis. The mass was removed in a segmental resection of the posterior
basilar portion of the upper lobe of the left lung.
2. Grossly, the mass was gray and putty-like. I t lay within a cavity, 4 cm. in
diameter, lined by a smooth membrane; the cavity connected directly with a
bronchus, and it was lined with respiratory type of epithelium. The wall of the
cavity was fibrous and contained plates of cartilage, as well as smooth muscle
and large blood vessels with conspicuous subintimal fibrosis. The vascular changes
are of some clinical significance, inasmuch as hemoptysis was the presenting
symptom in 13 of the 18 patients previously described.
3. Aspergillus sp. was isolated in cultures of the putty-like material from this
patient's bronchiectatic cavity, as well as in the 5 previously published instances
in which fungi were identified in cultures.
SUMMARIO I N
INTEKLINGUA
1. Le articulo describe le caso de un homine blanc de 54 annos de etate qui
habeva un "ballo de fungo" in un broncho ectatic. Le lesion esseva clinicamente
asymptomatic, sed un ronde densitate con un cappello de radiolucentia esseva
notate in un roentgenogramma thoracic obtenite post que le patiente habeva
essite subjicite a cholecystectomia pro cholecystitis. Le massa esseva abferite in
un resection segmental del portion postero-basilar del lobo superior del pulmon
sinistre.
2. Macroscopicamente le massa esseva gris e del consistentia de mastico. Illo
se trovava intra un cavitate que habeva un diametro de 4 cm e esseva revestite
de un membrana lisie. Le cavitate esseva connectite directemente con un broncho.
Su revestimento interior esseva epithelio de typo respiratori. Le pariete del
cavitate esseva fibrose e contineva plattas de cartilagine e musculo lisie e grande
Jan. 1957
BRONCHIAL
ASPERGILLOSIS
75
vasos sanguinee con conspicue fibrosis subintimal. Le alterationes vascular
possede un certe signification clinic in tanto que 13 del .18 previemente describite
patientes se presentava al consultation medical a causa del sj'mptoma de hemoptysis.
3. Aspergillus sp. esseva isolate in culturas del massa de "mastico" ab le
cavitate bronchiectatic de iste patiente. Le mesmo valeva pro le 5 previemente
publicate casos in que fungos esseva identificate in culturas laboratorial.
ADDENDUM
After the manuscript was submitted for publication, we noted another report
of an unusual case of primary pulmonary aspergillosis (Hughes, F . A., Gourley,
R. D., and Burwell, J. R.: Primary pulmonary aspergillosis: report of an unusual
case successfully treated by lobectomy. Ann. Surg., 144: 138-144, 1956). The
patient was a 56-year-old Negro plasterer who complained of hemoptysis,
dyspnea, and chronic productive cough. A characteristic solitary density with a
crescent-shaped area of radiolucency was observed in the roentgenograms. The
cultures of bronchial washings yielded growth of Aspergillus sp. The upper lobe
of the left lung was resected, and it contained a bronchiectatic cavity (4 cm. in
diameter) that was filled with gray-black granular material. Histologic examination revealed that the granular material was composed of a tangled mass of
branched, septate hyphae; numerous spore-heads were also observed. A culture
of material from the resected specimen yielded growth of Aspergillus fumigatus.
Acknowledgments.
T h e p a t i e n t was first observed b y D r . John H . Alward, Kokomo,
Indiana, and the resection of the segment of lung was performed by D r . James S. B a t t e r s b y ,
D e p a r t m e n t of Surgery, Indiana University School of Medicine. We a r e indebted to these
physicians for their cooperation and help in the s t u d y of this p a t i e n t . We also appreciate
the assistance of D r . John A. Campbell, D e p a r t m e n t of Radiology a t t h e School of Medicine, for his review and interpretation of t h e x-ray film.
The photographs and photomicrographs were prepared by Messrs. James F . Glore and
Paris Johnson, D e p a r t m e n t of Illustration, I n d i a n a University Medical Center.
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