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| Erythematous ulcero-proliferative exophytic lesion in an oral squamous cell carcinoma patient- An unusual case of Trichosporonosis |
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Umamaheswari Kesavachandran1, C Arun Kumar2
1 Department of Biotechnology, University of Madras, Chennai, Tamil Nadu, India
2 Department of Dental Surgery, Arignar Anna Memorial Cancer Hospital and Research Institute, Kancheepuram, Tamil Nadu, India
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| Date of Submission | 30-May-2021 |
| Date of Decision | 20-Dec-2021 |
| Date of Acceptance | 21-Dec-2021 |
| Date of Web Publication | 11-May-2023 |
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 Abstract | | |
The emergence of non-Candida yeast infections in humans has been increasingly recognized over the last decades. Trichosporon is the third most isolated non-candidal yeast in patients with an impaired immune system. We report a rare case of Trichosporon asahii causing erythematous oral lesion in a patient with squamous cell carcinoma. Our case highlights the occurrence of unusual yeast pathogens in patients with cancer with typical clinical presentations and warrants suspicion of fungal etiology to prevent misdiagnosis of trichosporonosis.
Keywords: Antifungal therapy, ITS domain, squamous cell carcinoma, trichosporonosis
How to cite this URL:
Kesavachandran U, Kumar C A. Erythematous ulcero-proliferative exophytic lesion in an oral squamous cell carcinoma patient- An unusual case of Trichosporonosis. Indian J Pathol Microbiol [Epub ahead of print] [cited 2023 Jun 1]. Available from: https://www.ijpmonline.org/preprintarticle.asp?id=376682 |
| Introduction | |  |
There has been a perceptible emergence of non-Candida yeast from various cancer centers around the world.[1] Oral squamous cell carcinoma (OSCC) is the most common oral malignancy, representing up to 80–90% of all malignant neoplasms affecting various regions of the oral cavity, the pharynx, and salivary glands.[2] OSCC is a disease of the adults and elderly and the major etiological and predisposing factors for OSCC include smoking and drinking habits, ultraviolet radiation, other factors such as human papillomavirus (HPV) and Candida infections, nutritional deficiencies, and genetic predisposition.[3] Trichosporon is being increasingly reported in malignancies as the second most frequent yeast species other than candidiasis. The most evident emerging yeast pathogens are Trichosporon, Malassezia, Rhodotorula, and Hansenula which primarily infect immunocompromised patients, newborns, and the elderly[4] The Trichosporon species are extremely rare, basidiomycetous, opportunistic yeast-like anamorphic fungi that are widely distributed in nature and occasionally colonize the human gastrointestinal and respiratory tracts, oral cavity, and skin and includes seven species reported to cause human infections: T. asahii, T. asteroides, T. cutaneum, T. inkin, T. jirovecii, T. mucoides, and T. ovoides. T. asahii is most commonly associated with disseminated trichosporonosis, while the other species are involved in superficial skin lesions particularly in patients with underlying hematological malignancies, AIDS, burns, solid tumors, and critically ill patients exposed to multiple invasive medical procedures.[5] Trichosporonosis has been recognized with increased frequency during the past 10–15 years and may resemble disseminated candidiasis in clinical presentation.[6] Trichosporonosis resembles other invasive fungal infections such as invasive candidiasis, aspergillosis, and cryptococcosis and can also coexist with other fungal, bacterial, or viral infections. Therefore, the differentiation between these organisms mainly relies on laboratory testing instead of a clinical scenario. T. asahii has primarily been isolated from blood, lung tissues, and urine of patients with deep-seated infections. The clinical features of T. asahii include septic shock, pneumonia, renal failure, cutaneous lesions, and eventually endocarditis, meningitis, esophagitis brain abscess, and uterine infections.[7] The species identification is critical as trichosporonosis may appear like disseminated candidiasis in its clinical and histopathologic appearance and the type of individuals infected. Here, we report a rare case of erythematous oral trichosporonosis caused by T. asahii in an elderly patient with squamous cell carcinoma. To the best of our knowledge, this is the first case in the literature of infection by Trichosporon asahii involving oral mucosa.
| Case Description | | |
A 60-year-old healthy female attending the department of Oral Oncology at Arignar Anna Memorial Cancer Hospital, Kancheepuram, complained of severe pain and swelling in the left lower jaw with trismus for the past 1 month. The intra-oral examination revealed an ulcero-proliferative exophytic lesion in the left alveolar ridge with mandibular erosion. The lesion was red, ulcerated with central necrosis and irregular borders, and suggestive of OSCC (stage cT4aN0M0). No bleeding was reported and her past medical history was not significant. The patient had betel quid chewing habit for over 15 years with poor oral hygiene. The physical examination revealed that the patient was febrile with normal pulse and heart rate and no abnormalities in the chest X-ray and routine hematological/serological investigations. The patient had a normal differential count of neutrophil (8.1 × 109), lymphocyte (1.2 × 109), and monocyte (0.7 × 109). The serum chemistry profile showed normal blood glucose (101 mg/dL) and creatine level (0.8 mg/dL) with lower urea level (3.6 mg/dL). The patient was non-diabetic and seronegative for HIV and hepatitis infections. The tissue specimens obtained from the mandibular lesion in the alveolar ridges were subjected to direct microscopic, histopathological, and microbiological studies. The biopsy revealed nests and lobules of squamous cells exhibiting significant nuclear pleomorphism with prominent individual cell keratinization and numerous keratin pearls, diagnostic of well-differentiated squamous cell carcinoma. The tumor infiltrated the adjacent connective tissue and mandibular bony trabeculae. The direct microscopic examination of the tissue specimens using 10% KOH revealed the presence of yeast cells with pseudo-hyphae and a few arthroconidia. The tissue specimen obtained was inoculated on bacterial and fungal mediums. White cream-colored raised yeast colonies with radial furrows and irregular folds were observed on the fungal isolation medium after 48 h of incubation whereas the bacterial culture was negative. The yeast colonies appeared turquoise in color on CHROM agar Candida medium with gram-positive cells with few hyphae and arthroconidia. A slide microculture on cornmeal agar demonstrated the presence of non-branching true and pseudohyphae with abundant rectangular barrel-shaped arthroconidia and scanning electron microscopic images were recorded using FESEM (Hitachi S-3000 N, Japan) [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d, [Figure 1]e, [Figure 1]f, [Figure 1]g. The yeast was resistant to 0.01% cycloheximide and sensitive to 0.1% cycloheximide. It showed gamma hemolysis on blood agar, positive for urea hydrolysis, and sugar assimilation (glucose, galactose, sucrose, maltose and lactose, and l-arabinose) but failed to utilize melibiose and raffinose. The yeast was identified as Trichosporon asahii based on the phenotypic and biochemical characteristics and confirmed by molecular sequencing of the internal transcribed spacer (ITS) region using ITS1 (5′-TCCGTAGGTGAACCTGCGG-3') and ITS4 (3′-TCCTCCGCTTATTGATATGC-5′) primers. The ITS sequence (521 bp) was analyzed by BLAST and matched 100% with the Trichosporon asahii isolate CDCF 2026 ITS1 partial sequence of 5.8 S rRNA gene and the sequence of ITS domain of T. asahii (accession number MK141006) was deposited in GenBank. The susceptibility of T. asahii to various triazoles (fluconazole, voriconazole, posaconazole, itraconazole) and polyene (amphotericin B) antifungals was tested and the minimum inhibitory concentration (MIC) was determined by the microbroth dilution method as per the CLSI guidelines. | Figure 1: (a) Cream-colored colonies on SDA. (b) Bluish-green colonies on CHROMagar. (c) KOH mount of the mandibular lesion. (d) Gram-positive yeast cells. (e) Slide microculture on cornmeal agar. (f and g) Scanning electron micrograph showing pseudohyphae and rectangular barrel-shaped arthroconidia
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The isolate was found to be susceptible to all the tested antifungal drugs and the MICs were calculated to be 0.25, 1.0, 2.0, 2.0, and 4.0 μg/mL to voriconazole, fluconazole, itraconazole, posaconazole, and amphotericin B, respectively. The patient was administered oral fluconazole therapy of 200 mg twice/day and underwent radiotherapy for the treatment of squamous cell carcinoma. The patient responded well to the fluconazole therapy and palliative treatment with remission of lesions. Further evaluation was, however, not possible as the patient left the hospital against medical advice and could not be followed up.
| Discussion | | |
The incidence of non-Candida yeast infections is increasing in light of the advance of life expectancy, immunosuppressive therapy, higher survival of patients with cancer, and chronic diseases.[8] Trichosporon spp. is emerging as an important agent of invasive mycoses in patients with malignant hematological diseases. This genus has been reported to be the second most common agent of disseminated yeast infections besides Candida spp., leading to 50–80% of mortality despite antifungal therapy.[9] In humans, Trichosporon colonize and proliferate in the GI and respiratory tracts, skin, vagina, and oral cavity[4] and cause deep-seated, mucosa-associated and superficial infections, fungemia, and catheter-related infections, pneumonia, prosthetic valve and joint infections, brain abscess, ventriculo-meningeal and disseminated infections.[1],[10] Invasive trichosporonosis was reported in patients with hematological malignancies and immunosuppression and superficial infections in immunocompetent hosts.[6],[8] No cases of trichosporonosis involving the buccal mucosa, alveolus, and mandible of the oral cavity have been documented in the literature to date. Cutaneous lesions are common in patients with Trichosporon infection and may serve as the immediate clinical clue for the diagnosis of trichosporonosis. Trichosporon differ from the Candida species in several respects: they do not produce a germ tube, produce arthroconidia while both species can form hyaline septate hyphae as well as pseudohyphae. The morphological and biochemical tests do not allow the complete identification of Trichosporon isolates at the species level and molecular methods, including sequencing of the IGS region, are necessary for the accurate identification of the Trichosporon strains. In the present study, we report the rare case of oral trichosporonosis involving alveolar mucosa and mandible as evidence of mucosa-associated infection in a patient with squamous cell carcinoma. The use of prosthetics and poor oral health has been frequently claimed to be the predisposing factors of yeast infections. The patient had a habit of betel quid chewing for 15 years with poor oral hygiene and this could be a possible predisposing factor of this yeast infection.
T. asahii was identified as the etiological agent based on the phenotypic characteristics and the species was confirmed by ITS sequencing. The dissemination of Trichosporon could not be ascertained as blood cultures were not performed and the isolate was susceptible to all tested antifungals. The efficacy of fluconazole for initial therapy and voriconazole for treating patients with trichosporonosis, including cases of acute leukemia and myelodysplastic syndrome with disseminated infection, have been reported.[11] In the present study, we noted that the patient responded well with oral fluconazole therapy. Our case highlights the occurrence of unusual yeast pathogens in patients with cancer and emphasizes the need to suspect fungal etiology to prevent misdiagnosis of trichosporonosis. An accurate species-level identification and susceptibility testing are of paramount importance in the effective treatment of trichosporonosis.
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Conflicts of interest
There are no conflicts of interest.
| References | | |
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Correspondence Address:
Umamaheswari Kesavachandran,
Department of Biotechnology, University of Madras, Chennai, Tamil Nadu - 600025
India
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/ijpm.ijpm_536_21
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