Medical Mycology Case Reports 1 (2012) 85–87

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Oral histoplasmosis masquerading as oral cancer in HIV-infected patient: A case report Shafiulla 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 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 b

a r t i c l e i n f o


Article history: Received 24 August 2012 Received in revised form 4 September 2012 Accepted 6 September 2012

Histoplasmosis is an endemic mycoses caused by Histoplasma capsulatum with endemicity around midwestern United States and central America. The endemicity of histoplasmosis in India is not clearly known. Histoplasmosis, especially oral histoplasmosis, is now increasingly being reported from India. We report here a culture-confirmed and sequence confirmed, oral histoplasmosis in a HIV seropositive 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. All rights reserved.

Keywords: 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 reticuloendothelial system and disseminate in the absence of a good immune status [1]. Histoplasmosis presents clinically as acute or chronic pulmonary infection; disseminated histoplasmosis; and mediastinal fibrosis [1]. The endemicity of histoplasmosis in India is not clearly known with pockets of distribution in Eastern India and Vellore [2–7]. With the emergence of Acquired Immunodeficiency Syndrome (AIDS) in India, the number of cases of acute progressive disseminated histoplasmosis has steadily increased [2–4]. 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 immunodeficiency virus (HIV) infected individual.

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 CD4þ 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 enlarging, 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 significant findings could be elicited on physical examination, other than cervical lymphadenopathy. He had no history of diabetes, hypertension or asthma, or any significant 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


Corresponding author. E-mail address: [email protected] (M. Sinha).

2211-7539/$ - see front matter & 2012 International Society for Human and Animal Mycology. Published by Elsevier B.V. All rights reserved.


S. Mohammed et al. / Medical Mycology Case Reports 1 (2012) 85–87

examination showed chronic inflammatory cells and numerous oval, 2–4 mm, intracellular, narrow-based budding yeast like cells, with a halo around them (Fig. 1). On culture of the same sample on Sabouraud’s Dextrose Agar (SDA) slants with antibiotics (Chloramphenicol—50 mg/ml and Gentamicin—5 mg/ml) at 25 1C, white mycelial growth was observed after nine days of incubation. Microscopic examination of the isolate revealed thin hyaline hyphae with two types of conidia: thick walled round macroconidia of size 7–14 mm with prominent tuberculate projections and thin smooth walled, oval microconidia of size 2–5 mm (Fig. 2). After repeated subculture of the growth on brain heart infusion agar (BHIA) at 37 1C yeast colony developed, confirming thermal dimorphism of the fungus. The isolate was provisionally identified 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.

On day 23, oral fluconazole (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 first evaluation. The identity of the isolate was confirmed 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. Amplification of the target was done using primer pairs NL1 50 –GCATATCAATAAGCGGAGGAAAAG-30 & NL4 50 –GTCCGTGTTTCAAGACGG-30 . Nucleotide sequencing of the same region was performed with Big Dye Terminator Cycle Sequencing kit, Version 3.1 (Applied Biosystems, CA, USA) for both strands. All the sequencing reactions were purified 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

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 magnification).

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 magnification).

Histoplasma capsulatum is known to have restricted geographical niches in different parts of the world. The endemic area is well-delineated in USA but not well defined 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 [2–4,6]. 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 fibrosis or granulomas; and in patients with impaired cell mediated immunity, as disseminated histoplasmosis (DH) [6]. DH is one of the ‘‘AIDS-defining’’ diseases and isolated mucocutaneous (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 significant 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 histoplasmosis in AIDS patients can be the primary or the only manifestation of this disease and may occasionally even herald HIV seropositive status [10–12]. In India, oropharyngeal histoplasmosis, with or without hepatosplenomegaly, 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 [12–17]. 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) 85–87

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 histopathology 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 insufficiency 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 fluconazole, a second line antifungal [1]. In the present case, treatment with fluconazole 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 histoplasmosis 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 common in India, especially in HIV seropositive patients, and the need for early diagnosis to aid prompt targeted therapy.

Conflict of interest There are none.

Acknowledgements None.


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Oral histoplasmosis masquerading as oral cancer in HIV-infected patient: A case report.

Histoplasmosis is an endemic mycoses caused by Histoplasma capsulatum with endemicity around midwestern United States and central America. The endemic...
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