Pseudotumour with Bacillus sphaericus · Pseudotumour ofthe lung causedby infection with Bacillus sphaericus of a viscous matrix by the organism, which accounted for much of the tumour

J. clin. Path., 1976, 29, 806-811

Pseudotumour of the lung caused by infection withBacillus sphaericusP. ISAACSON, P. H. JACOBS, A. M. R. MACKENZIE, AND A. W. MATHEWS

From the Departments ofPathology and Microbiology, Southampton General Hospitaland the Wessex Cardiac and Thoracic Centre, Southampton

SYNOPSIS A patient is described who suffered from severe chronic asthma complicated by repeatedchest infections. She developed a large gelatinous pseudotumour of the lung which was found tobe caused by Bacillus sphaericus.

Human infections with organisms of the Bacillusgenus other than anthrax are uncommon although,especially under conditions of decreased resistance,the pathogenicity of these organisms is well recog-nized (Farrar, 1963; Pearson, 1970; Ihde andArmstrong, 1973). The most commonly reportedpathogen of this genus has been Bacillus subtilis butother members of the genus have been incriminatedfrom time to time.The following case report is the fourth in which

Bacillus sphaericus has been documented as apathogen, and it is unique in that the organismproduced a massive pseudotumour of the lung.

Case reportThe patient, who was born in 1939, developed severebronchial asthma at the age of 2 years after an attackof whooping cough. During childhood she alsosuffered from eczema, hay fever, and angioneuroticoedema. She was first seen in Southampton in 1963when, at 24 years of age, she demonstrated a per-sistent grade II dyspnoea with central cyanosis andevidence of pulmonary hypertension with rightventricular hypertrophy. Chest x-rays showed wide-spread fine mottling throughout the lungs, andpulmonary function tests showed severe fixed air-ways obstruction. Skin tests were positive to a widevariety of antigens including Aspergillus fumigatus,but aspergillus precipitins were negative. TheMantoux test was negative. Treatment was startedwith prednisone, 5 mg three times per day, andprophylactic isoniazid. Steroid therapy in one formor another was continued throughout the course ofthe illness. Over the next few years there was nosignificant change in the chest x-ray but there wassome improvement of clinical status and pulmonary

Received for publication 10 February 1976

function. In 1965 she was able to visit a relative inCalifornia, but she continued to suffer from attacksof severe wheezing dyspnoea associated with purulentsputum. These episodes of infection became morefrequent and severe. Klebsiella pneumoniae wasisolated from the sputum and the patient was givenfrequent courses of ampicillin, gentamicin, andcotrimoxazole. In 1971 the chest x-ray showed anincrease in the diffuse lung shadowing, and there wasa persistent leucocytosis of over 20 x 109/l.

In November 1973, after her return from a secondvisit to California, she deteriorated considerably, andthe chest x-ray showed a large area of consolidationin the anterior segment of the left upper lobe, whichgradually increased in size over the next year (fig 1).Bronchoscopy on two occasions showed the leftupper lobe segmental bronchi to be occluded by thickmucus which could not be aspirated easily. Culturefrom bronchoscopy grew coliforms and Pseudomonaspyocyanea. Serum immunoglobulins were measuredat this time and were normal. Skin tests and serologyfor coccidioidomycoses and histoplasmosis werenegative.

In October 1974 she was admitted in terminalrespiratory failure, and a soft fluctuant swelling wasnoted in the second left intercostal space anteriorlywith a similar swelling over the sternum. She diedshortly after admission, aged 35 years.

NECROPSYThe body was that of an emaciated young woman. A6 cm soft subcutaneous mass was present in the leftsecond intercostal space anteriorly, and a similar3 cm mass bulged parasternally in the third inter-costal space on the left. On reflecting the sternum itwas apparent that these subcutaneous masses wereextensions of a large, soft, mucoid tumour that

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Pseudotumour of the lung caused by infection with Bacillus sphaericus

Fig 1 Chest x-ray taken in November 1973 showing anarea of consolidation in the left upper lobe. t 2 3 4 5

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cmreplaced the medial half of the upper lobe of the leftlung (fig 2). The tumour infiltrated the intercostalmuscles and the mediastinum, where it closely sur-rounded the large vessels. The remainder of the leftlung, and the right lung, showed marked fibrosis andbasal bronchiectasis with scattered locules of pus andclear fluid. Fragments of the tumour were taken forbacteriological examination, as were swabs from thepurulent foci.

Other significant macroscopic findings wereobliterative fibrous pericarditis, right ventricularhypertrophy (the right ventricle weighing 76 g witha total heart weight of 290 g), and atrophy of theadrenal glands, which together weighed 5 g.

Microscopic examination of multiple sections ofthe mass in the left chest showed it to consist ofmasses of eosinophilic organisms. These wereelongated, frequently curled, and coiled, and rangedin length from 3 75 ,u to 12-5 It and in width from1-25 ,u to 2-5 ,t. They were separated by fine fibrousbands and mixed with an infiltrate of neutrophilpolymorphs (figs 3 and 4). A broad, fibrous bandseparated this process from the lung parenchyma butclumps of similar organisms were seen in bronchi ofthe left upper lobe. Gram stain showed that theorganisms consisted of a Gram-negative sheathenclosing long bacilliform rods which were bothGram-positive and Gram-negative (fig 5). ThisGram-negative material around the organismsstained faintly positive with periodic acid-Schiff but

Fig 2 Sagittal section of left lung showing replacementofmost of the left upper lobe by gelatinous tumourwhich encircles the great vessels.

mucicarmine, Ziehl Nielsen, and Grocott stains wereall negative.

BACTER IOLOGYA direct smear of the 'tumour' revealed a Gramvariable bacillus similar to that seen in histologicalsections. No capsule was demonstrable but theorganisms were surrounded by a viscous matrix.Fungal and mycobacterial cultures were negative.

No growth was obtained on horse blood agar afterovernight incubation, but after four days' aerobicincubation at 37°C slight growth was obtained inglucose heart infusion broth. Gram stain revealed apleomorphic Gram variable bacillus, 0 5 ,u to over50 ,u in length (fig 6). Morphology was essentiallysimilar to that seen in the tissue sections. Someunusual features included swelling and bulging of thecell wall with pseudobranching and serpiginousforms. 'Horseshoe' and 'boomerang' shapes werefrequently seen in cultures incubated at 37°C butinfrequently at 30°C. Colonies were best establishedon horse blood agar and on heated chocolate agarand were an opaque, smooth, greyish-yellow with an

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808 P. Isaacson, P. H. Jacobs, A. M. R. Mackenzie, and A. W. Mathews

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Fig 5 Gram stain ofhistological section oftumour. Gram variablepleomorphic bacilli areenclosed in a Gram-negative sheath.(x 750)

Fig 6 Gram stain oforganism grown at37°C showing Gramvariability with markedpleomorphism.(x 975)

entire edge and a papillate centre having an averagediameter of 1 mm.At 30°C growth was more easily established in

both broth and plate cultures. Soft, emulsifiablecolonies were up to 2 mm in diameter, flat andirregular, and exhibited a chrome yellow pigment

with faint haemolysis. In contrast to organismsgrown at 37°C (fig 6), incubation at the lowertemperature produced a straight, more uniform rod(fig 7).

Motility, which lessened with increasing incuba-tion temperature, was of a rapid gyrating type. After

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P. Isaacson, P. H. Jacobs, A. M. R. Mackenzie, and A. W. Mathews

Fig 7 Gram staini oforganiism grown at30°C showing straightuniform Gram variablerods. ( x 975)

one week spores were produced, most of which werespherical, subterminal or terminal with bulging ofthe sporangia. No anaerobic growth was obtainedat 37°C or at 30°C.

Biochemical characteristics are summarized in thetable. The organism was accordingly identified asBacillus sphaericus, and this identity was confirmedby Dr. L. R. Hill, Curator of the National Collectionof Type Cultures, and Professor J. R. Norris, of theMeat Research Institute, Bristol.

Oxidase Glucose - GlycerolCatalase Lactose - GluconateVP Sucrose - GlycogenNitrate Mannitol - Casein hydrolysis -

Indole Maltose - Starch hydrolysis -Urea Salicin - Lecithin hydrolysis -Citrate DextrinONPG - Fructose -H'S - Tylose -

Table Biochemical characteristics

Discussion

Before the appearance of the pseudotumour thepatient had developed persistent infection with avariety of pathogenic organisms. There is a wellrecognized group of patients with chronic asthma inwhom persistent infection is a feature, and this isknown to affect the prognosis unfavourably (Ogilvie,1962). Although there was no evidence of immuno-globulin deficiency or fibrocystic disease in thispatient it is possible that a defect of cellular immunity

could have been responsible for repeated infections.No studies of lymphocyte function were, however,performed.Although the initial response to steroids was good,

there can be little doubt that the long period of treat-ment predisposed to the development of an op-portunistic infection. Previous reports of infectionswith members of the bacillus genus have emphasizedpredisposing factors leading to diminished hostresistance which have included diabetes mellitus,chronic alcoholism, and malignancy (Farrar, 1963;Ihde and Armstrong, 1973). A significant number ofinfections have, however, occurred in previouslyhealthy individuals (Pearson, 1970; Ihde and Arm-strong, 1973). Of the three previously reported in-fections with B. sphaericus (Lacorte, 1932; Farrar,1963; Allen and Wilkinson, 1969), two had anassociated debilitating condition (chronic alcoholismand nephrotic syndrome) (Lacorte, 1932; Farrar,1963).This case serves once again to illustrate that, while

it is traditional to regard aerobic spore-formingbacilli, when isolated, as contaminants, they maycause serious infections. With regard to B. sphaericus,in particular, the ease of growth at 30°C as comparedto 37°C has not been commented on previously. It isof interest, too, that in vitro morphology at 37°C soclosely resembled that seen in tissue sections.The formation of a large pseudotumour in a

patient has not to our knowledge previously beendescribed in association with bacillus infections or,indeed, with any bacterial infection. The production

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of a viscous matrix by the organism, whichaccounted for much of the tumour bulk, has beennoted in laboratory cultures of the bacillus group(Gibson, 1944) but not in human infections, althoughIhde and Armstrong (1973) describe a gelatinousexudate from a necrotic axillary tumour infectedwith B. subtilis; the tumour, however, is not furthercharacterized. Pulmonary cryptococcosis may resultin the formation of well circumscribed fibroustumours containing gelatinous foci (toruloma)(Spencer, 1968), and with the history of this patient'svisit to California, it was this diagnosis that wassuspected and led to bacteriological examination ofwhat, at first sight, appeared to be an unusual mucus-producing adenocarcinoma of the lung.

We are grateful to Dr. L. R. Hill, of the NationalCollection of Type Cultures, to Professor J. R.Norris, Meat Research Institute, Langford, Bristol,for confirming the identity of the organism as B.

sphaericus, and to Dr. W. Macleod, of the WesternHospital, Southampton, whose patient this was.

References

Allen, B. T. and Wilkinson, H. A. III (1969). A case ofmeningitis and generalized Schwartzman reaction caused

by Bacillus sphaericus. Johns Hopk. med. J., 125, 8-13.Farrar, W. E. Jr. (1963). Serous infections due to 'non-

pathogenic' organisms of the genus Bacillus. Amer. J.Med., 34, 134-141.

Gibson, T. (1944). A study of Bacillus subtilis and relatedorganisms. J. Dairy Res., 13, 248-260.

Ihde, D. C. and Armstrong, D. (1973). Clinical spectrum ofinfection due to Bacillus species. Amer. J. Med., 55,839-845.

Lacorte, J. G. (1932). Bacillus serositis; new species (isolatedfrom a human case of a primary inflammation of the serousmembranes). Mem. Inst. Osw. Cruz, 26, 8-13.

Ogilvie, A. G. (1962). Asthma: a study in prognosis of 1000patients. Thorax, 17, 183-189.

Pearson, H. E. (1970). Human infections caused by organismsof the Bacillus species. Amer. J. clin. Path., 53, 506-515.

Spencer, H. (1968). Pathology of the Lung, 2nd edition, pp.300-301. Pergamon, Oxford.

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Pseudotumour with Bacillus sphaericus · Pseudotumour ofthe lung causedby infection with Bacillus sphaericus of a viscous matrix by the organism, which accounted for much of the tumour