2017, Volume 33, Number 1, Page(s) 077-080
Disseminated Cryptococcosis in an Immunocompetent Child
Bhawna Bhutoria JAİN, Debdas BOSE, Rajat MONDAL, Sarbani CHATTOPADHYAY
Department of Pathology, Medical College, Kolkata, WEST BENGAL, INDIA
Keywords: Cryptococcus, Disseminated, Skin diseases
A case of disseminated cryptococcus infection in an immunocompetent
host is described. The present case attests to the importance
of using a cautious approach for the diagnosis of granulomatous
lymphadenitis. The patient was initially misdiagnosed and treated as
disseminated tuberculosis. Later the patient developed visual loss and
skin lesions. Periodic Acid Schiff stained sections of lymph node biopsy
and cerebrospinal fluid culture established the diagnosis.
Cryptococcus neoformans is capsulated yeast commonly
found in soil contaminated by bird faeces throughout the
. Infection is principally caused by two species in
the Cryptococcus genus, namely Cryptococcus neoformans
var. neoformans and Cryptococcus neoformans var. gattii.
Cryptococcus neoformans is found worldwide, commonly
in pigeon excreta in soil, and it causes disease in immunecompromised
hosts. Cryptococcus neoformans var. gattii.
has recently been recognised as a distinct emerging
pathogen causing disease in humans and animals. It is
found predominantly in tropical and subtropical regions
and causes disease in immunocompetent individuals2
. In addition to HIV infection, immunosuppressive
medications, solid-organ transplantation, chronic organ
failure, hematologic malignancy, chronic lung disease, and
rheumatologic disorders can also predispose individuals to
Reported cases of cryptococcal infections in an immunocompetent
host have primarily included pulmonary manifestations
and cutaneous lesions4. In this case report, we
describe a case of disseminated cryptococcosis in an immune
competent child that was initially misdiagnosed as
tuberculosis and later on led to characteristic skin lesions.
A 7-year-old boy suffered from intermittent high
grade fever, severe headache followed by vomiting and
irritability for six months. Physical examination revealed
splenomegaly with right sided cervical lymphadenopathy.
Bilateral chest crepitations were noted on auscultation.
Hematological investigations done revealed total white
blood cell count-23200, eosinophilic leucocyte percentage
54%, haemoglobin-7.4g/dl, and erythrocyte sedimentation
rate: 58 mm/hour. Chest x-ray showed bilateral diffuse
infiltrates. Sputum for acid fast bacilli (AFB) was negative.
Blood malaria parasite was negative, Bactec blood culture
showed no growth. Urine culture did not show any growth
after 48 hours. Stool examination revealed red blood cells
and test for occult blood was positive.
The patient was nonreactive for HIV1 and HIV 2 antibodies.
Widal test and serum anti-nuclear antigen was negative.
Liver function tests were within normal limits. C-reactive
protein was 215.6mg/L.
Ultrasonography of the abdomen showed enlarged liver
with heterogeneous parenchyma and retroperitoneal lymph
nodes. Bone marrow aspiration was reported as myeloid
hyperplasia with increase in eosinophilic leucocyte count.
Cerebro-spinal fluid (CSF) analysis failed to demonstrate any organism. CSF adenosine deaminase (ADA) level was
within reference range. The blood culture and Widal test
were also negative. Lymph node FNA C revealed granulomas.
The patient was put on anti-tubercular drugs (AT D).
However, the fever persisted. Then the patient suddenly developed
bilateral loss of vision. Ophthalmoscope examination
showed bilateral choroiditis, tuberculomas and papillitis.
Magnetic resonance imaging (MRI) brain showed mild
prominent cortical sulci with dilation of lateral ventricles
suggestive of meningitis sequel. Biopsy of cervical lymph
node demonstrated non-caseating epithelioid cell granulomas.
The patient was advised to continue ATD.
Afterwards the patient developed umbilicated papules over
face and trunk (Figure 1A). Serum IgE level was 1175 IU/
ml (reference normal< 90IU/ml). As the fever persisted, the
lymph node biopsy was sent to us for review. On careful
examination of the granulomatous lesion, small fungal
yeasts were demonstrated inside the macrophages and confirmed by PAS stain (Figure 2A-C). Skin biopsy done
later (Figure 1B-D) also revealed ill-formed granulomas
and yeast cells within macrophages. CSF fluid and blood
sent for fungal culture (Figure 2D) to the School of Tropical
medicine, which identified the organism as Cryptococcus
neoformans. The patient was treated with Amphotericin-B
followed by Fluconazole and is in remission at present.
Click Here to Zoom
|Figure 1: A) Skin papules with central umbilication. Microphotograph of skin lesion. B) (H&E; x40), C) (H&E; x400), D) (H&E; x1000).
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|Figure 2: Microphotograph of PAS stained sections of lymph node. A) Non-caseating granulomas in low power view (PAS , x40). B) A
giant cell in high power view showing intracellular cryptococcus surrounded by clear halo (PAS , x400). C) Oil immersion view showing
yeast cells with narrow based budding (PAS , x1000). D) Culture showing cream-coloured smooth, mucoid colonies (SDA).
The purpose of presenting this case is to highlight the
importance of careful evaluation of granulomatous
lymphadenitis particularly in tuberculous endemic regions.
We also discuss how presenting features of such uncommon
infections mimic tuberculosis.
Cryptococcus is a soil saprophyte and is abundant in the
faeces of pigeons and other birds. It is basidiomycetous
yeast that exists in the environment in the sexual form
and produces hyphae with terminal basidiospores (chains of unbudded yeast). When the 3 micron basidiospores
break off they become aerosolized and may be inhaled
into the alveoli. An infection is asymptomatic in most
persons, but the organism may enter the circulation
and survive in vivo in a haploid, asexual state, leading to
disseminated disease in persons with severe cell-mediated
immunodeficiency. In humans, cryptococci may survive
because of a polysaccharide capsule that allows them to
evade phagocytosis. In addition, a phenol oxidase enzyme
uses catecholamine as substrate to produce melanin, which
accumulates in the cell wall, and synthesis of catecholamine
for neurotransmitters may predispose to involvement
of the central nervous stem5. However, disseminated
cryptococcal infection is uncommon and almost always
occurs in HIV-infected patients4.
Disseminated cryptococcosis is defined by1 a positive
culture from at least two different sites or2 a positive blood culture6. In the present case organisms were
cultured from blood and CSF.
Clinical presentation of disseminated cryptococcosis is
variable and depends on the organ systems involved7.
Central nervous system involvement is the most common
manifestation of disseminated disease6. Common presenting
symptoms include headache, fever, and malaise.
Classic meningitis signs, such as nuchal rigidity, are absent
in 75% of cases8. Our case also presented with fever,
headache and vomiting. Neck rigidity was absent.
In tuberculous endemic regions, cryptococcosis may be
misdiagnosed as tuberculous infection9. Visual changes
have been reported, such as the field defects, as well as new
onset seizure activity10. Secondary involvement of skin
is apparent in about 10% to 20% of immune-compromised
patients with cryptococcosis11. The skin lesions typically appear as pedunculated, dome-shaped papules with an
umbilicated centre12. Similar findings were noted in our
Philip K. et al. have described similar case as ours with
generalised lymphadenopathy, hepatosplenomegaly, skin
lesions and miliary mottling of chest radiograph13.
Cryptococcosis among immunocompetent patients tended
to be associated with lower rates of fungaemia, when
compared to non-HIV-infected patients with predisposing
Microscopically, C. neoformans organisms are pale narrowbased
budding yeasts that average 2 to 7 microns in size
with a prominent surrounding capsule. The yeast cells
appear pale blue and ovoid while the capsule is round
and clear with routine hematoxylin-eosin stained tissue
sections or on Papanicolaou stained cytological material.
With the capsule, the organisms are 5 to 20 microns. The
accompanying scanty inflammation contains a few small,
scattered lymphocytes or macrophages with phagocytized
organisms14. The cellular pleomorphism of cryptococci,
larger cell size, and lack of pseudohyphae help to distinguish
it from Candida. The football-shaped C. neoformans yeasts
are much larger than the small round cells of H. capsulatum
To conclude one should apply a cautious approach towards
the diagnosis and treatment of granulomatous lymphadenitis
and should not be biased towards TB. Caseation should be
looked for and if absent, other causes of granulomas to be
considered. Absence of immunosuppression should not
be a reason to exclude cryptococcosis from the differential
1) Gaskill T, Payne D, Brigman B. Cryptococcal abscess imitating a
soft-tissue sarcoma in an immunocompetent host: A case report.
J Bone Joint Surg Am. 2010;92:1890-3.
2) Mitha M, Naicker P, Mahida P. Disseminated Cryptococcosis in
an HIV-negative patient in South Africa: The elusive differential
diagnosis. J Infect Dev Ctries. 2010;4:526-9.
3) Pappas PG, Perfect JR, Cloud GA, Larsen RA, Pankey GA,
Lancaster DJ, Henderson H, Kauffman CA, Haas DW, Saccente
M, Hamill RJ, Melissa MS, Warren RM, Dismukes WE.
Cryptococcosis in human immunodeficiency virus-negative
patients in the era of effective azole therapy. Clin Infect Dis.
4) Suchitha S, Sheeladevi CS, Sunila R, and Manjunath GV.
Disseminated Cryptococcosis in an immunocompetent patient:
A case report. Case Rep Pathol. 2012;2012:652351.
5) Warkentien T, Crum-Cianflone NF. An update on Cryptococcus
among HIV-infected patients. Int J ST D AIDS. 2010;21:679-84.
6) Chuang YM, Ho YC, Chang HT, Yu CJ, Yang PC, Hsueh PR.
Disseminated cryptococcosis in HIV-uninfected patients. Eur J
Clin Microbiol Infect Dis. 2008;27:307-10.
7) Kokturk N, Ekim N, Kervan F, Arman D, Memis L, Caglar K,
Kalkanci A, Demircan S, Kurul C, Akyurek N. Disseminated
cryptococcosis in a human immunodeficiency virus-negative
patient: A case report. Mycoses. 2005;48:270-4.
8) Lui G, Lee N, Ip M, Choi KW, Tso YK, Lam E, Chau S, Lai R,
Cockram CS. Cryptococcosis in apparently immunocompetent
patients. QJM. 2006;99:143-51.
9) Patro S N, Kesavadas C, Thomas B, Kapilamoorthy T R, Gupta AK.
Uncommon presentation of intracranial cryptococcal infection
mimicking tuberculous infection in two immunocompetent
patients. Singapore Med J. 2009;50:e133-7.
10) Mwanza JC, Nyamabo LK, Tylleskar T, Plant GT. Neuroophthalmological
disorders in HIV infected subjects with
neurological manifestations. Br J Ophthalmol. 2004;88:1455-9.
11) Tilak R, Prakash P, Nigam C, Tilak V, Gambhir IS, A K Gulati
AK. Cryptococcal meningitis with an antecedent cutaneous
cryptococcal lesion. Dermatology Online Journal. 2009;15:12.
12) Probst C, Pongratz G, Capellino S, Szeimies RM, Schölmerich J,
Fleck M, Salzberger B, Ehrenstein B. Cryptococcosis mimicking
cutaneous cellulitis in a patient suffering from rheumatoid
arthritis. BMC Infect Dis. 2010;10:239.
13) Philip KJ, Kaur R, Sangeetha M, Masih K, Singh N, Mani A.
Disseminated cryptococcosis presenting with generalized
lymphadenopathy. J Cytol. 2012;29:200–2.
14) Edward C. Klatt. Pathology of AIDS. available on http://library.
med.utah.edu/WebPath/AIDS2013.PDF. Accessed on 30/09/2013
15) Shibuya K, Coulson WF, Wollman JS, Wakayama M, Ando
T, Oharaseki T, Takahashi K, Naoe S. Histopathology of
cryptococcosis and other fungal infection in patients with
acquired immunodeficiency syndrome. Int J Infect Dis. 2001;5: