Medical Mycology Case Reports 1 (2012) 8587

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Medical Mycology Case Reports

journal homepage: www.elsevier.com/locate/mmcr

Oral histoplasmosis masquerading as oral cancer in HIV-infected patient:

A case report
Shaulla Mohammed a, Mahua Sinha a,n, Purushottam Chavan b, CS Premalata c, MR Shivaprakash d,
Arunaloke Chakrabarti d, Rudrapatna S Jayshree a
a
Department of Microbiology, Kidwai Memorial Institute of Oncology, Bangalore 560029, India
b
Department of Head and Neck Surgery, Kidwai Memorial Institute of Oncology, Bangalore 560029, India
c
Department of Pathology, Kidwai Memorial Institute of Oncology, Dr MH Marigowda Road, Bangalore 560029, India
d
Department of Medical Microbiology, Postgraduate Institute of Medical Education & Research, Sector 12, Chandigarh 160012, India

a r t i c l e i n f o abstract

Article history: Histoplasmosis is an endemic mycoses caused by Histoplasma capsulatum with endemicity around
Received 24 August 2012 midwestern United States and central America. The endemicity of histoplasmosis in India is not clearly
Received in revised form known. Histoplasmosis, especially oral histoplasmosis, is now increasingly being reported from India.
4 September 2012
We report here a culture-conrmed and sequence conrmed, oral histoplasmosis in a HIV seropositive
Accepted 6 September 2012
individual who was referred to our regional cancer centre with a suspicion of oral cancer.
& 2012 International Society for Human and Animal Mycology. Published by Elsevier B.V.
Keywords: Open access under CC BY-NC-ND license.
Histoplasma capsulatum
HIV
Oral cancer
Oral histoplasmosis

1. Introduction 2. Case

Histoplasmosis is an endemic fungal infection caused by
inhalation of microconidia of Histoplasma capsulatum, a dimorphic
fungus. Yeast forms of this fungus replicate within the reticulo-
endothelial system and disseminate in the absence of a good
immune status [1]. Histoplasmosis presents clinically as
acute or chronic pulmonary infection; disseminated histoplasmo-
sis; and mediastinal brosis [1]. The endemicity of histoplasmosis
in India is not clearly known with pockets of distribution in
Eastern India and Vellore [27]. With the emergence of
Acquired Immunodeciency Syndrome (AIDS) in India, the num-
ber of cases of acute progressive disseminated histoplasmosis has
steadily increased [24]. A considerable number of cases present
as chronic disseminated disease with oropharyngeal ulcers [2,6,7].
The awareness of such manifestation is important, as the diagnosis
can be facilitated by taking biopsies from the accessible lesions.
We report here, a case of histoplasmosis presenting as a solitary
oral lesion, in a human immunodeciency virus (HIV) infected
individual.
n
Corresponding author.
E-mail address: mahuasinha@gmail.com (M. Sinha).
A 35 years old male farmer, from Chikamagalur, Karnataka,
was referred to our tertiary care cancer hospital with a solitary
oral lesion, with a suspicion of oral malignancy. He was known to
be HIV seropositive, receiving anti-retroviral therapy from the
local health centre for the past 3 years, and had a CD4 T cell
count of 67/ml at the time of presentation to our hospital. He
presented with fever and cough of four months duration, and was
on anti-tubercular therapy for the past one month after sputum
revealed acid fast bacilli. The patient presented on day 0 in the
out-patient services with two months history of gradually enlar-
ging, solitary ulcer on the right lateral margin of the base of his
tongue. The ulcer was 2 cm in diameter, non-tender, indurated
and with rolled up margins. No signicant ndings could be
elicited on physical examination, other than cervical lymphade-
nopathy. He had no history of diabetes, hypertension or asthma,
or any signicant travel history. He was a chronic smoker and had
history of alcohol intake for twenty years.
Chest radiograph done on day 2 revealed a non-homogenous
opacity in right mid zone consistent with consolidation. Routine
hemogram showed leucopenia with subnormal differential counts
(leucocytes 2800/ml; lymphocytes 500/ml, granulocytes 1900/ml). The
biochemical parameters were within normal limits. Punch biopsy
from the oral lesion was performed on day 2. Histopathological

2211-7539 & 2012 International Society for Human and Animal Mycology. Published by Elsevier B.V. Open access under CC BY-NC-ND license.
http://dx.doi.org/10.1016/j.mmcr.2012.09.002
86 S. Mohammed et al. / Medical Mycology Case Reports 1 (2012) 8587
examination showed chronic inammatory cells and numerous oval,
24 mm, intracellular, narrow-based budding yeast like cells,
with a halo around them (Fig. 1). On culture of the same sample
on Sabourauds Dextrose Agar (SDA) slants with antibiotics (Chlor-
amphenicol50 mg/ml and Gentamicin5 mg/ml) at 25 1C, white
mycelial growth was observed after nine days of incubation. Micro-
scopic examination of the isolate revealed thin hyaline hyphae with
two types of conidia: thick walled round macroconidia of size
714 mm with prominent tuberculate projections and thin smooth
walled, oval microconidia of size 25 mm (Fig. 2). After repeated
subculture of the growth on brain heart infusion agar (BHIA) at 37 1C
yeast colony developed, conrming thermal dimorphism of the
fungus. The isolate was provisionally identied as Histoplasma
capsulatum on the basis of characteristic tuberculate macroconidia
seen in the mould phase, subsequent conversion to the yeast phase
and morphology of yeast in the tissue. Blood culture did not yield
any fungus. As oral cancer was excluded, the patient desired to
return to his hometown for further treatment of histoplasmosis.
Fig. 1. Periodic acid Schiff (PAS) stain of punch biopsy from tongue lesion showing
numerous intracellular, oval, narrow-based budding yeast like cells with a halo
around them (white arrows) (40X magnication).
Fig. 2. Lacto phenol cotton blue (LPCB) mount of histoplasma colonies grown in
culture showing numerous hyaline hyphae with few tuberculate macroconidia
(arrows) and many smooth walled oval microconidia. (40X magnication).
On day 23, oral uconazole (800 mg daily for 2 weeks) was initiated
along with anti-retroviral therapy and reported excellent response
within day 35. The lesion had resolved completely and did not
relapse for day 600 (20 months) after his rst evaluation.
The identity of the isolate was conrmed by DNA sequence of the
28 s (partial) ribosomal region of rDNA at the National Culture
Collection of Pathogenic Fungi (NCCPF), Postgraduate Institute of
Medical Education and Research (PGIMER), Chandigarh, India.
Amplication of the target was done using primer pairs NL1
50 GCATATCAATAAGCGGAGGAAAAG-30 & NL4 50 GTCCGTGTTTC-
AAGACGG-30 . Nucleotide sequencing of the same region was per-
formed with Big Dye Terminator Cycle Sequencing kit, Version 3.1
(Applied Biosystems, CA, USA) for both strands. All the sequencing
reactions were puried and analysed on ABI 3130 Genetic Analyser
(Applied Biosystems). Sequence of both the strands was used to
create the consensus sequence by using BioNumerics software
version 6.5 (Applied Maths, Ghent, Belgium). The sequence obtained
was compared with that in the GenBank DNA and CBS databases.
The sequence of the isolate gave 100% identity with Ajellomyces
capsulatus (IFM 49721, IFM 50248, IFM 50249 and IFM 50250), the
teleomorphic state of Histoplasma capsulatum. Sequence data was
submitted to the GenBank (Accession no. JX310660). The strain is
stored at NCCPF, Chandigarh, as NCCPF 230014.
3. Discussion
Histoplasma capsulatum is known to have restricted geogra-
phical niches in different parts of the world. The endemic area is
well-delineated in USA but not well dened in the rest of the
world [1]. In Asia too, the disease has been reported from many
countries, but the endemic areas are not clearly demarcated [3].
The disease was considered rare in India, but over the years, the
incidence is on the rise. Although there have been histoplasmosis
case series in HIV negative individuals [5], histoplasmosis in India
is attributed primarily to an increase in prevalence of HIV infected
patients [24,6]. The present case was also an HIV seropositive
patient and had very low CD4 counts at presentation.
Histoplasmosis may present clinically as pulmonary infection;
mediastinal brosis or granulomas; and in patients with impaired
cell mediated immunity, as disseminated histoplasmosis (DH) [6].
DH is one of the AIDS-dening diseases and isolated mucocu-
taneous (including oral) lesions in these patients are considered
to be a manifestation of disseminated disease [1,3]. With the
advent of effective antiretroviral therapy, DH is seen much less
frequently in AIDS patients in the United States but remains a
signicant opportunistic infection in Central America [1]. Studies
from endemic areas have shown that 3.6% to 6.6% of HIV-infected
patients present with DH while one of them showed that 66% of
these DH patients presented with orofacial lesions. [8,9] DH
should be considered while diagnosing patients with prolonged
fever, weight loss, oropharyngeal ulcers, hepatosplenomegaly,
lymphadenopathy and adrenal enlargement [6]. Oral histo-
plasmosis in AIDS patients can be the primary or the only
manifestation of this disease and may occasionally even herald
HIV seropositive status [1012].
In India, oropharyngeal histoplasmosis, with or without hepa-
tosplenomegaly, is recognised as a common manifestation of
chronic DH. This has been highlighted by Padhye et al. (19 of
25 cases), Subramanian et al. (7 of 19 cases) and Goswami et al.
(2 of 5 cases) in their series [2,6,7] and many more case reports in
the recent years [1217]. Lack of awareness of histoplasmosis
commonly manifesting as oral ulcers in India may result in
misdiagnosis. In the present case, the patient was referred to us
with a suspicion of oral malignancy and histoplasmosis was not
suspected though the patient was HIV seropositive.
 S. Mohammed et al. / Medical Mycology Case Reports 1 (2012) 8587
In the present case, histoplasma was successfully cultured
from the oral biopsy tissue. However, in most of the other reports
from India, diagnosis of oral histoplasmosis is based on histo-
pathology alone and only few are culture-proven [2,7,17]. Besides
oropharyngeal involvement, H. capsulatum has also been reported
to affect adrenal gland resulting in adrenal insufciency in several
Indian studies [6,7]. In this patient, bone marrow and adrenal
biopsy could not be performed and hence presence of the fungi at
these sites could not be ascertained. However, blood culture was
negative in the patient.
Although, in many patients with DH, spontaneous remission is
known to occur, antifungal therapy initiation is mandatory with
amphotericin B and itraconazole being the preferred antifungals
and uconazole, a second line antifungal [1]. In the present case,
treatment with uconazole at the appropriate dose, proved
effective; the lesion healed completely within a few weeks of
starting treatment and has not relapsed in over a year and a half.
In India, where oral cancer is widely prevalent, oral histoplas-
mosis masquerading as carcinoma is not unknown [15,18]. If the
clinicians are aware of oral histoplasmosis in India, especially in
AIDS patients, it can be diagnosed promptly by taking a biopsy
from accessible oropharyngeal sites. Furthermore, in patients in
whom oral histoplasmosis is diagnosed, HIV status if not known,
needs to be assessed. The present case thus highlights the fact
that oropharyngeal manifestations of DH are indeed very com-
mon in India, especially in HIV seropositive patients, and the need
for early diagnosis to aid prompt targeted therapy.
Conict of interest
There are none.
Acknowledgements
None.
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