Large Pulmonary Cryptococcomaand Cryptococcal Meningitis inan Immunocompetent Patient:A Case ReportRanbeer Singh, M.D., Deepti Joshi, M.D., Anupama Gupta, M.D., and Nitin Gangane, M.D., D.N.B.*

Pulmonary cryptococcoma is a life threatening mycosis and isan unusual disease for immunocompetent individuals. Herein wereport a case of large pulmonary cryptococcoma associated withcryptococcal meningitis, presenting radiologically as a lungmass in right upper lobe, in a previously healthy, HIV negative,immunocompetent young individual. Since cryptococcosis contin-ues to be an important infection in HIV negative patients and isassociated with substantial overall and cause-specific mortality,the need for consideration of this entity in the differential diag-nosis of a lung mass is emphasized. Diagn. Cytopathol.2010;38:929–931. ' 2010 Wiley-Liss, Inc.

Key Words: cryptococcoma; HIV

C. neoformans is a ubiquitous pathogenic encapsulated

yeast that causes human diseases ranging from asymptom-

atic pulmonary colonization to fatal meningitis and over-

whelming cryptococcimia.1,2 Pulmonary cryptococcoma is

a life threatening mycosis and is an unusual disease for

immunocompetent individuals. Chest radiograph shows

varying pictures and the commonest appearance is a

round shadow usually in the lower lobe without any

enlarged hilar shadow, less common radiological findings

are diffuse miliary shadows, or areas of consolidation.3,4

Disease may occur in healthy hosts, but the majority of

the patients are apparently immunocompromised, having

significant underlying predisposing factors such as

advance HIV disease, hematological malignancies, sar-

coidosis, solid organ transplantation, tuberculosis, and

corticosteroid treatment.5–8 Particularly HIV infection has

emerged as the leading cause of immunodeficiency predis-

posing to cryptococcal infection. However, 10–40% HIV

negative patients with cryptococcosis have no apparent

immune deficiency, although selective defects in lympho-

cytes responsiveness to C. neoformans or other subtle

abnormalities may explain disease occurrence in other-

wise normal hosts.9–14 Common presentation of crypto-

coccosis are related to pulmonary, central nervous system

(CNS) and skin involvement. We present a case of pul-

monary cryptococcoma with cryptococcal meningitis in

an immunocompetent young individual.

Case Summary

A 32-year-old male patient was admitted to the hospital

with the complaints of fever, dyspnea, chest pain, and

cough for a duration of 3 months. Fever was moderate

grade, intermittent without any localizing features. There

was also history of anorexia and significant weight loss

over past 3 months. There was no history of hemoptysis,

hemetemesis, melena, abnormal behavior or movements,

dysuria, oligouria or hematuria, blood transfusion, multi-

ple injections in past, drug abuse or contact with commer-

cial sex worker. There was no history to suggest diabetes

mellitus or tuberculosis. However, he subsequently devel-

oped neck rigidity during hospital stay.

On examination, the patient was a thin built male with

mild pallor, and crepitations on right side of chest. There

was no organomegaly and the rest of the general as well

as systemic examination was unremarkable. Hematologi-

cal investigations, renal function tests, urine examination

and liver function tests were within normal limits. Serol-

ogy for HBsAg, anti-HCV and anti HIV-1 and HIV-2 was

negative. Chest X-ray showed a well circumscribed

shadow (mass lesion) in the upper lobe of right lung

(Fig. 1). USG thorax showed evidence of solid hypoechoic

area in the right upper lobe of lung with minimal air

Department of Pathology, Mahatma Gandhi Institute of Medical Scien-ces, Sevagram, Wardha, Maharashtra, India

*Correspondence to: Nitin Gangane, M.D., D.N.B., Professor andHead, Department of Pathology, Mahatma Gandhi Institute of MedicalSciences, Sevagram, Wardha, Maharashtra, India.E-mail: nitingangane@rediffmail.com

Received 25 September 2009; Accepted 23 December 2009DOI 10.1002/dc.21345Published online 18 March 2010 in Wiley Online Library

(wileyonlinelibrary.com).

' 2010 WILEY-LISS, INC. Diagnostic Cytopathology, Vol 38, No 12 929

specks within, along with evidence of thickening of adja-

cent pleura and overlying intercostals region, suggesting ?

Consolidation, ? mass lesion likely to be malignant. C T

thorax showed evidence of well defined, lobulated, heterog-

enous enhancing hyperdense mass lesion approximately of

size 7.13 3 8.38 cm in the posterior segment of right

upper lung zone with nonenhancing necrotic area within.

There was also volume loss of right lung due to partial col-

lapse. An opinion of malignant lung mass with partial col-

lapse and pneumothorax was given. C T head revealed no

obvious abnormality in the brain parenchyma. Ultrasound

guided Fine Needle Aspiration (FNA) of the lung mass

was performed and the aspirates showed sheets of reactive

bronchial cells, inflammatory cells and aggregates of cryp-

tococcal organisms with mucinous capsule and large

amount of mucoid matrix in the background (Fig. 2). Cere-

brospinal fluid (CSF) examination revealed glucose 27 mg

dl�1, protein 100 mg dl�1 and cytology showed presence

of cryptococcal organisms with an associated mixed

inflammatory infiltrate (Fig. 3). In India Ink preparation of

cerebrospinal fluid, cryptococci appeared as thick walled

spherules varying in size from 10 to 20 l in diameter.

Discussion

Cryptococcal lesions may be entirely localized, mostly

affecting lungs and also the skin and mucosae. If local-

ized lesions appear to be tumor like, they are called as

cryptococcomas. Any localized lesion is a potential focus

of dissemination which is extremely dangerous, even if

symptoms of spread may not be evident for several years.

Localized pulmonary cryptococcoma consists of circum-

scribed subpleural, pulmonary, or mediastinal tumor like

lesions composed of well defined gelatinous masses. The

size may be upto 10 cm and the lesions are sometimes

multiple. In some cases the infection is silent, leaving no

trace of the disease and heals spontaneously.1,2

The majority of cryptococcal infections terminate in

cryptococcal meningoencephalitis which may linger for

years without causing more symptoms other than a head-

ache. Any seemingly localized cryptococcal focus other

than in the skin or in the lung usually indicates that dis-

semination has already taken place even if there are no

general symptoms to indicate this clinically. The tissue

reaction to C. neoformans is often extremely poor. Pus

formation is usually absent. Foci often have a gelatinous

Fig. 1. Chest radiograph showing solitary, well circumscribed mass inupper lobe of right lung.

Fig. 2. Aspirate showing sheet of reactive bronchial cells and cryptococ-cal organisms. (Giemsa, 3100). [Color figure can be viewed in theonline issue, which is available at wileyonlinelibrary.com.]

Fig. 3. CSF cytology showing cryptococci and their characteristic cap-sule. (Papanaicolaou, 3400). [Color figure can be viewed in the onlineissue, which is available at wileyonlinelibrary.com.]

SINGH ET AL.

930 Diagnostic Cytopathology, Vol 38, No 12

Diagnostic Cytopathology DOI 10.1002/dc

appearance due to abundant production of capsular sub-

stance. Localized cryptococcal granulomas are not infre-

quently mistaken for myxomas, chondromas, and other

tumors.3,4

C. neoformans occurs in two variant forms: Cryptococ-cus neoformans var neoformans and Cryptococcus neofor-mans var gattii. Distribution of Cryptococcus neoformansvar neoformans is worldwide and responsible for most

infections in humans. Cryptococcus neoformans var gatti

shows restricted geographical distribution to tropical and

subtropical Asia and Australia but is responsible for caus-

ing infections in immunocompetent hosts. The diagnosis

can be made by demonstration of these organisms on per-

cutaneous ENA or on pulmonary or CSF cytology. These

organisms have a mucicarmine/PAS positive capsule

which can also be highlighted by use of India ink stain.

Distinction between C. neoformans and C. gattii cannot

be made by morphology or by immunohistochemistry, but

depends on serotyping.15

The unique manifestation of the present case is that the

lesion was seen in an immunocompetent patient and no evi-

dence for the presence of any debilitating disease was found.

The well circumscribed shadow gave the appearance of a

mass lesion in right upper lobe of lung and the lesion was con-

fused both radiologically and clinically as carcinoma lung. By

the use of a simple, inexpensive and minimally invasive tech-

nique like FNA, we were able to demonstrate clusters of yeast

like encapsulated organisms, showing abundant amount of

capsular matrix. Presence of similar organisms on CSF cytol-

ogy which showed characteristic capsular halo on India ink

stain enabled us to confirm our diagnosis.

Conclusion

Our case presents unique challenge for diagnosis as the

significant weight loss and fever associated with a large

lung mass on radiology were highly suspicious for a ma-

lignant lung mass. Cytology remains a reliable mode of

diagnosis for cryptococcosis. Present case indicates that

cryptococcal disease in HIV negative hosts may also be

widespread; hence this possibility should be kept in mind

while encountering such cases.

References1. Levitz SM. The ecology of Cryptococcus neoformans and the epide-

miology of cryptococcosis. Rev Infect Dis 1991;13:1163–1169.

2. Duperval R, Hermans PE, Brewer NS, Roberts GD. Cryptococcosis,with emphesis on the significance of isolation of Cryptococcus neo-formans from the respiratory tract. Chest 1977;72:13–19.

3. Chang ET, Wang AH, Lin CB, Lee JJ, Liu SH. Pulmonary crypto-coccosis mimicking solitary lung cancer in an immunocompetentpatient. Thorax 2008;63:478.

4. Huang CJ, Yang MC, Ueng SH. Large cryptococcoma mimickinglung cancer in an HIV-negative, type 2 diabetic patient. J ThoracImaging 2005;20:115–117.

5. Perfect JR, Durack DT, Gallis HA. Cryptococcimia. Medicine (Bal-timore) 1983;62:98–109.

6. Kwon Chung KJ, Bennett JE, editors. Cryptococcosis: Medicalmycology. Philadelphia: Lea & Febiger; 1992. p 397–446.

7. Dismukes WE. Cryptococcal meningitis in patients with AIDS.J Infect Dis 1988;157:624–628.

8. Diamond RD, Bennett JE. Prognostic factors in cryptococcal menin-gitis. Ann Intern Med 1974;80:176–181.

9. Bennet JE, Dismukes WE, Duma RV, et al. A comparision ofamphotericin B alone and combined with flucytosine in the treat-ment of cryptococcal meningitis. N Engl J Med 1979;301:126–131.

10. Dismukes WE, Cloud G, Gallis HA, et al. Treatment of cryptococ-cal meningitis with combination amphotericin B and flucytosine forfour as compared to six weeks. N Engl J Med 1987;317:334–341.

11. Diamond RD, Bennett JE. Disseminated cryptococcosis in man:Decreased lymphocyte transformation in response to Cryptococcusneoformans. J Infect Dis 1973;127:694–697.

12. Graybill JR, Alford RH. Cell mediated immunity in cryptococcosis.Immunology 1974;14:12–21.

13. Schimpff SC, Bennett JE. Abnormalities in cell mediated immunityin patients with Cryptococcus neoformans infection. J Allergy ClinImmunol 1975;35:430–441.

14. Sorensen RN, Boehm KD, Kaplan D, Berger M. Cryptococcal oste-omyelitis and cellular immunodeficiency associated with interlukin-2 deficiency. J Pediatr 1992;121:873–879.

15. Agarwal V, Sachdev A, Agarwal G, Mohan H, Anjali. Disseminatedcryptococcosis mimicking lymphoreticular malignancy in a HIVnegative patient. A case study. JK Sci 2004;6:93–95.

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