J Clin Pathol 1981 ;34:267-270

An unexpected fungal infection in a patient withleukaemiaBERYL JAMESON, RL CARTER, JG WATSON, AND RJ HAY*

From the Royal Marsden Hospital, Sutton, Surrey, and *The London School of Hygiene and TropicalMedicine, UK

SUMMARY A 58-year-old man, who was entering remission from acute monocytic leukaemia, diedunexpectedly after five days of fever. Cultures of necropsy material grew the yeast Trichosporonbeigelii, and subsequent histological examination showed a widely disseminated infection. Thisfungus usually causes a localised lesion of the hair shaft (piedra). Deep-seated infections due toTrichosporon spp. have been recorded infrequently and disseminated infections on only five previousoccasions. None of these has been from the United Kingdom. This case report describes some ofthe difficulties of diagnosis.

A 58-year-old chartered engineer was well until hepresented with a two-month history of indigestionand a loss of 5 kg in weight. He had had seven days'cough with clear sputum, night sweats, and leftpleuritic chest pain.

Examination showed a small faucial ulcer, a one-fingerbreadth palpable liver, and a small fundalhaemorrhage. A blood count revealed haemoglobin8-1 g/dl, white cells 10 x 109/l, and platelets68 x 109/l. The bone marrow contained 60%monocytoid blasts, and a diagnosis of acute mono-cytic leukaemia (M5) was made.He was treated with seven days' 6-thioguanine,

five days' cytosine arabinoside, two days' Rubida-zone, and seven days' prednisolone. During thistime he was nursed in protective isolation and givenoral co-trimoxazole, nystatin, and amphotericin B asantimicrobial prophylaxis. Fourteen days later thebone marrow contained 6Y% blasts, and the chemo-therapy course was repeated.Two days after this ended he complained of

generalised aches, optic myalgia, and faintness. Feverof 39-20C was treated empirically with gentamicinand ticarcillin. During the next four days he re-mained pyrexial, developed right-sided pleurisy anda pericardial rub, and became jaundiced. Bacterial,fungal, and viral cultures were uninformative. Chestx-rays were normal.Next morning he was in mild cardiac failure, and

the liver was palpable at three finger-breadths. Onthat day he died.

POSTMORTEM EXAMINATIONA necropsy was performed 48 hours after death.Both lungs appeared congested and haemorrhagicwith small scattered zones of consolidation; thepleural sacs were dry. The heart showed a fewepicardial haemorrhages, and the myocardium waspale. There was no evidence of pericarditis.The stomach contained several shallow erosions.

The liver was pale and soft and contained firm,white foci, up to 0 5 cm in diameter, scatteredthroughout its substance. Similar nodules werefound in the spleen, which was slightly enlarged.Both kidneys had focal haemorrhage in the renalpelves. Spinal and femoral bone marrow were pale.

HistologyHistological examination showed that the whitefocal lesions in the spleen and liver were mycoticabscesses. Similar microscopic lesions were found insmaller numbers in both lungs, the myocardium,and both kidneys. The abscesses consisted of densemasses of 'hyphae' and yeasts surrounded bynecrotic tissue debris (Fig. 1). The 'hyphae' werecharacteristically broad, measuring 8-10 ,u in diam-eter, and in some regions showed a banded appear-ance due to the presence of arthrospores (Fig. 2).Demonstration of fungal elements by periodic-acid-Schiff (PAS) and Grocott's methenamine silverstains proved to be difficult, and prolonged stainingwas necessary. Inflammatory cells were absent, and

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Jameson, Carter, Watson, and Hay

9"'° "

Fig. 1 Mycoticabscesses in spleenstained byperiodic-acid-Schif:x 220.

Fig. 2 Characteristic arthrosporesindicated by arrow. x 840.

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An unexpectedfungal infection in a patient with leukaemia

the abscesses were not encapsulated. No evidence of The organism was demonstrated in liver tissue byresidual leukaemia was found. indirect immunofluorescence.'

Necropsy microbiologyAfter overnight incubation on blood agar at 37°C,cultures of lung and pericardium grew rough,yellow-grey colonies resembling those of Bacillusspp. On Sabouraud's medium, at room temperatureand at 37°C, equally rapid growth resulted in dis-crete, heaped-up, cream-coloured colonies. Gram-stained films showed both pear-shaped yeasts anddistinctive chains of arthrospores (Fig. 3). Theorganism was later identified as Trichosporonbeigelii. Geotrichum spp. were excluded by thepresence of blastospores, and the isolate was dis-tinguished from T. capitatum by the production ofurease and the pattern of carbohydrate assimilation.The fungus was grown after three weeks' incuba-

tion from a blood culture taken on the day beforedeath.

SerologyThe patient's stored antemortem serum was ex-amined for fungal antibodies. There was no evidence,using either immunofluorescence (IF) or counter-immunoelectrophoresis, of antibodies to candida orAspergillus species. With IF, however, using T.beigelii blastospores air-dried on to glass slides, thepatient's serum showed an antibody titre of 1:8.Control sera were all negative, and the reactioncould be blocked by absorption with T. beigelii cells.

Discussion

Disseminated infections with T: beigelii and theclosely related T. capitatum are rare. Five have beenreported: three due to T. beigelii (cutaneum),2 3 oneto T. capitatum,4 and one to Trichosporon sp.5 Allwere in severely immunosuppressed hosts.

Focal, deep-seated infections are infrequent.Pulmonary infections have been recorded:6 7 twopatients with endophthalmitis have been described8and one instance each of endocarditis,9 brainabscess,10 and peritonitis during dialysis."

T. beigelii is associated with a superficial infectionof hair (white piedra), while T. capitatum is notusually recognised as a pathogen. Both are widelydistributed in the soil and other parts of the en-vironment12 as well as being recognised as con-stituents of the normal human microbial flora.13They have been isolated from sputum, and it issuggested that inhalation is the route of entry toinfected patients.The unusually rapid (overnight) growth of this

fungus on culture media should make recognitioneasy, and its presence in a diagnostic specimen oughtto alert the clinician to the possibility of its being apathogen in an immune-suppressed patient. Intissue section, it should be noted that staining of thefungus is difficult. In the case described here it was

Fig. 3 Grain-stained filmof overnight cultureshowing pear-shapedformsand arthrospores. x 1200.

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270 Jamesoni, Carter, Watson, an1d HaY

necessary to extend exposure to periodic acid in thePAS stain from the normal time of 8 to 30 minutes;and in the Grocott methenamine silver method,instead of the normal 45-60 minutes, up to 2 hourswas required.So far, disseminated infections have been recog-

nised only at necropsy, but increasing awareness oftrichosporon as a lethal pathogen should lead to amore vigorous search, for example in the paranasalsinuses, as suggested by Winston et al.4

Amphotericin B, possibly in combination witlh5-fluorocytosine, might be successful treatment,4 9

but in our patient it seems unlikely that treatmentwould have been successful because the short dura-tion and non-specific nature of the symptoms wouldnot have indicated the use of empirical antifungaltherapy.

We thank the Mycology Laboratory of the Bromp-ton Hospital for primary identification of the fungus,and the Mycological Reference Laboratory, TheLondon School of Hygiene and Tropical Medicine,for serology and immunofluorescence. We are grate-ful to Dr RL Powles for permission to publish thiscase report.

References

Kaplan W, Kratt DE. Demonstration of pathogenic fungiin formalin-fixed tissues by immuniofluorescence. Anii JClin Pathol 1969;52:420-37.

2 Rivera R, Cangir A. Trichosporoni sepsis and leukaemia.Cancer 1975;36:1106-10.

Evans HL, Kletzel M, Lawsoni RD, Franikel LS, HopferRL. Systemic mycosis due to Trichosporon cutaneomn.Cancer 1980;45:367-71.

Winston DJ, Balsley GE, Rhodes J, Linne SR. Dissemi-nated Trichosporon capitatumn infection in an immuno-suppressed host. Arc/h Intern Med 1977;137:1 192-5.

Kirmani N, Tuazon CU, Geelhoed GW. DisseminatedTrichiosporon infection. Occurrence in an immunosup-pressed patient with chronic active hepatitis. Arch/Intern Med 1980;140:277-8.

6 Gemeinhardt H. Lungenpathogenitat von1 Trichosporoncapitatumn beim Menschen. Zentralbl Bakteriol (Orig A)1965;196:121-33.

7 Fonseca OD. Deep skin and pulmonary mycosis in Brazil.In: Tlherapy of Fungal Diseases. London: Churchill.1956.

8 Sheikh HA, Mahgoub S, Badi K. Postoperative endo-phthalmitis due to Trichosporon cuttaneitani. Br J Ophthal-mtiol 1974;58:591-4.

Marier R, Zakhireh B, Downs J, Wynne B, HammonidGL, Andriole VT. Trichosporon c<taneiunm endocarditis.ScandJ Infect Dis 1978;10:255-6.

10 Watsoni KC, Kallichurum S. Brain abscess due to Trichio-sporon cutanewn. J Med Microbiol 1970;3:191-3.

Khauna R, Oreopoulos DG, Vas S, McNeely D, McCreadyW. Treating fungal infections (letter). Br Med J 1980;2:1147.

12 Lodder J. The Yeasts. 2nd edn. Amsterdam: North Hol-land Publishing Co, 1971.

Ahearn DG. Medically important yeasts. Annii Rev.Microbiol 1978 ;32:59-68.

Requests for reprints to: Dr Beryl Jameson, The RoyalMarsden Hospital, Downs Road, Sutton, Surrey SM25PT.

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