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ORIGINAL ARTICLE
Year : 2021  |  Volume : 48  |  Issue : 3  |  Page : 171-178

Clinicopathological analysis of fungal lesions with unique presentations in immunocompetent adults – A case series from a tertiary care hospital in North Karnataka


Department of Pathology, Mahadevappa Rampure Medical College, Kalaburagi, Karnataka, India

Date of Submission20-Dec-2020
Date of Acceptance02-Jul-2021
Date of Web Publication28-Dec-2021

Correspondence Address:
Dr. Debarghya Sutradhar
Room No. 4, Gulbarga Apartments, Sai Nagar Colony, Old RTO Cross, Sedam Road, Kalaburagi, Karnataka - 585 105
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jss.jss_122_20

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  Abstract 


Introduction: Fungal infections are mostly an opportunistic infection in immunocompromised patients and posttraumatic in immunocompetent adults. However, there has been a recent increasing trend of cases among immunocompetent adults with no history of trauma. Very few case series describing the clinicopathological picture of prevalent fungi are available from the various regions of India. Aims and Objectives: The present study aims to analyze clinicopathological features of various cases of fungal etiology with unique or rare presentations. Materials and Methods: This study included a clinicopathological analysis of surgical specimens received for histopathological examination at our hospital with special emphasis on cases with rare or unique presentations during the 1-year period from June 2019 to June 2020. Results: A total of 11 cases of fungal lesions with rare or unique clinicopathological presentations were selected for analysis. Majority of the patients were male, and most of them were from a rural background. There were four cases of aspergillosis, two cases of fungal keratitis, one case of renal aspergillosis, and one case of a subcutaneous swelling with discharging sinus. There were three cases of chromoblastomycosis, which presented as subcutaneous swellings with no lesion of overlying skin. There was an incidental finding of Candida sp. in two esophageal endoscopic biopsies, which primarily revealed esophageal adenocarcinoma. There was one case each of eumycetoma and mucormycosis. However, the mucormycosis case occurred in the setting of fungal abscess with osteomyelitis of the left mandible. Conclusion: Fungal lesions have revealed an increasing trend of infections in immunocompetent individuals in recent years, with various unique clinicopathological presentations. Therefore, there is a need for increased vigilance and analysis of such cases.

Keywords: Aspergillosis, candidiasis, chromoblastomycosis, eumycetoma, mucormycosis, fungal, rare, unique


How to cite this article:
Masgal M, Patil AG, Sutradhar D, Mahanta AA. Clinicopathological analysis of fungal lesions with unique presentations in immunocompetent adults – A case series from a tertiary care hospital in North Karnataka. J Sci Soc 2021;48:171-8

How to cite this URL:
Masgal M, Patil AG, Sutradhar D, Mahanta AA. Clinicopathological analysis of fungal lesions with unique presentations in immunocompetent adults – A case series from a tertiary care hospital in North Karnataka. J Sci Soc [serial online] 2021 [cited 2022 Jan 18];48:171-8. Available from: https://www.jscisociety.com/text.asp?2021/48/3/171/333839




  Introduction Top


Fungal infections are mostly an opportunistic entity exhibited in immunocompromised patients. In immunocompetent patients, they mostly occur posttraumatic implantation. However, through the ages, there have been many case series in the literature that have studied increasing cases among immunocompetent adults.

Due to tropical climate, South Asia has a high incidence of fungal infections; those commonly involved in humans are opportunistic yeasts such as Candida albicans or filamentous fungi such as Aspergillus. Fungi such as Fusarium, Trichosporon, and Malassezia species are now emerging as leading causes.[1],[2]

There is a paucity of data from India on fungal infections with variable results. These studies are mostly from Delhi along with few sporadic reports from Chandigarh, Kolkata, Pune, and Dehradun.[2] There is a need for surveillance studies on fungal infections from different healthcare institutions nationwide to provide data on this subject.

Very few case series describing the clinicopathological picture of prevalent fungi are available from the various regions of India. In the present study, clinicopathological features of various cases of fungal etiology, in a tertiary care hospital catering to the northeastern region of Karnataka, were examined.


  Materials and Methods Top


This study included a retrospective analysis of clinicopathological features of surgical specimens received for histopathological examination (HPE) at our hospital, during 1-year period from June 2019 to June 2020.

From the patient records, history of presenting illness, demographic data, occupation, and history of trauma were collected. Detailed clinical examination findings were noted to study the clinical presentation.

The surgical specimens received were grossly examined, and sections were submitted for routine histopathological processing. The slides were stained with hematoxylin and eosin and examined. Further special stains such as periodic acid–Schiff (PAS) and Grocott-Gomori's methenamine silver (GMS) stain were done. Microbiological cultures were used for few cases for confirmation.


  Results Top


A total of 11 cases of fungal infections were studied during the 1-year duration. There were 8 males and 3 females; the age ranged from 6 to 70 years. Majority of the cases were from rural background [Table 1].
Table 1: The demographic data, clinical presentation, and provisional diagnosis of all the cases

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The demographic data, clinical presentation, and provisional diagnosis are tabulated in [Table 1].

Out of the 11 cases, only three of them recalled a history of trauma, apart from the fact that a 6-year-old child could very well have had a history of trauma outside of his parents' knowledge.

The gross and histopathological findings of all the cases are tabulated in [Table 2].
Table 2: The gross and histopathological findings of all the cases

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Microscopically, all of the cases revealed one or more characteristic signs of fungal infections, which included acute and/or chronic inflammatory infiltrate with/without giant cell granulomas, necrotic and/or granulation tissue, and fungal colonies and hyphae typical to the species [Table 2].

All 3 subcutaneous cystic swelling cases had no lesion of the overlying skin & microscopically revealed neutrophilic abscesses, giant-cell granulomas & demonstrable characteristic brown thick walled sclerotic bodies or “Copper-Penny” bodies either within or outside the giant cells [Table 2] & [Figure 1] B & [Figure 1]C. “Copper-Penny” bodies, also known as sclerotic or muriform cells, or Medlar bodies are thick-walled cells (5-12 microns) with multiple internal transverse septa or chambers that resemble copper pennies. When present in skin or subcutaneous tissue, the cells are indicative of chromoblastomycosis.[3] Also, fungal hyphae were demonstrated in Periodic Acid Schiff & Grocott-Gomori's Methenamine Silver-stained slides [Table 2] & [Figure 1]D.
Figure 1: (a) Gross presentation of the right wrist subcutaneous cystic mass obtained from one of the patients. It was a globular grey-brown cystic mass measuring 4cm×3cm×2cm; cut section of which revealed approximately 80 ml of creamy white fluid. Histopathological examination revealed foreign body giant cell granuloma(b, HandE stain, ×10). Pigmented fungal sclerotic bodies or “Copper-Penny” bodies were seen both within giant cells(c, arrows, HandE stain, ×40) and scattered singly(c, inset, arrows, H and E stain, ×40). Branching, septate hyphal forms were identified in Grocott-Gomori's methenamine silver-stained slides(d, GMS stain, ×10). All this led to the diagnosis of chromoblastomycosis

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The creamy-white cyst fluid [Figure 1]A was subjected to micro-biological culture in Sabouraud-Dextrose-Agar medium with Actidione and other antibiotics. The medium showed slow-growing, greenish-brown to black mycelial colonies in two cases. The third case showed slow-growing greenish-brown dome-shaped colonies. The colony morphology & further microscopy confirmed F. Pedrosoi in two cases and P. Verrucosa in the third case. Therefore, these factors led to the diagnosis of Chromoblastomycosis.

The two ophthalmologic cases revealed filamentous, septate, dichotomous (into two nearly equal branches, or 45 degrees) branching fungal hyphae with vascular invasion upon microscopic examination; suggestive of infection by Aspergillus sp. The case of left forearm swellings with discharging sinus revealed numerous conidiophores with vesicles completely capped by one layer of phialides; radiating upto the conidial heads (fruiting bodies) at the extremity producing pigmented spores; along with filamentous, septate, dichotomous branching fungal hyphae [Table 2], [Figure 2], A &[Figure 2]B. The post-mortem HPE of the kidney in an Autopsy case of death during sleep revealed similar hyphal structures in the renal tubules; along with mixed inflammatory infiltrates in the rest of the parenchyma [Table 2], [Figure 3]D, [Figure 3]E. Sections stained with Per-Iodic Acid Schiff & Grocott-Gomori's Methenamine Silver revealed magenta/pink colored & black colored branching, septate fungal hyphae, respectively [Table 2], [Figure 2]C & [Figure 3]F. Microbiological culture showed typical fast-growing yellow-brown to brown-black colonies with radiating chains of conidia leading to the diagnosis of Aspergillus Fumigatus & Aspergillus Niger [Table 2].
Figure 2: Filamentous, septate, dichotomous branching fungal hyphae of Aspergillus (a, H and E, ×40) and conidiophores with radiating conidial heads producing pigmented spores (b, H and E, ×40). (c) Magenta-colored hyphae of Aspergillus under periodic acid–Schiff stain (c, PAS, ×40). (d) Broad branching at 90° angles, nonseptate hyphae of mucormycosis (H and E, ×40)

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Figure 3: (a) Esophageal lining epithelium replaced by tumor cells in the top right corner of the photomicrograph and fungal mycelial growth in the bottom left corner(HandE, ×10); (b) The magnified image of the same field from the bottom left corner of the previous image; showing numerous budding yeast forms with psuedohyphae and few areas of septate hyphae of Candidia sp. (HandE, ×40). (c) Fungal colony consisting of interlacing hyphae embedded in brown matrix; confirming eumycetoma(HandE, ×40). (d) Renal parenchyma with renal tubules and glomeruli(HandE, ×10). (e) The magnified image of the same field from the bottom left corner of the previous image showing renal tubules filled with filamentous, septate, acute angle branching fungal hyphae(HandE, ×40). (f) Grocott-Gomori's methenamine silver-stained slide showing black-colored branching, septate fungal hyphae(×40)

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  Discussion Top


Fungal lesions have always been a significant cause of morbidity and mortality, but a changing trend has been observed in the prevalent fungal species detected in cultures from sites of fungal infections in humans. Candida, Aspergillus, and mucormycosis are the most commonly detected fungi in the Indian landscape. However, the predominantly detected species of each of these fungi in India are different from those seen in the global trends.[4]

In India, non-albicans Candida are more prevalent than C. albicans; with Candida tropicalis being the most commonly cultured fungi in recent years.[2] In the present study, we encountered two cases of esophageal candidiasis with hallmark microscopic pictures of numerous budding yeast forms with pseudohyphae and few areas of septate hyphae. Naito et al. and Underwood et al. had reported the prevalence of esophageal candidiasis to be 0.71% and 1.17%, respectively.[5]

The present study also came across four cases of aspergillosis, two of which were fungal keratitis cases; one case of renal aspergillosis in a postmortem specimen; other one presented as fungal abscess. Fungal etiology of keratitis/corneal ulcer is considered to be one of the leading causes of ocular morbidity, particularly in developing countries, including India. More importantly, Fusarium and Aspergillus are reported commonly. The incidence of fungal keratitis reported is highly variable across the Indian states: Southern and Western India with 36.7% and 36.3%, Northern 7.3%, Northeastern 25.6%, and Eastern India 26.4%.[6] Genitourinary infections are a part of disseminated infections in immunocompromised patients. Isolated renal aspergillosis in immunocompetent adults is rare. In 2001, Gupta et al. studied patients with antemortem and postmortem diagnosis of renal aspergillosis in a case series and found the mortality rate to be 81%. Renal failure was seen in 55% of patients with renal aspergillosis.[7] Microscopic and microbiological assays revealed typical features of A. fumigatus.

The third most common invasive fungal infection with high morbidity and mortality is mucormycosis. It is an emerging clinical entity that has been recorded increasingly from north Indian patients. Rhizopus arrhizus is the predominant causative agent worldwide, whereas Apophysomyces variabilis is the second most common agent in India.[8] However, osteomyelitis involving the facial bones is rare, and involvement of the maxilla is less common than that of the mandible due to high vascularity. Furthermore, osteomyelitis occurring due to fungal infection is rare and occurs in an indolent manner. Urs et al., in their study from 2011 to 2013, found only five cases of fungal osteomyelitis. Niranjan et al., in their study from 2005 to 2015, found that 52% of all the osteomyelitis cases were fungal osteomyelitis and that it was frequently found in individuals above 40 years of age and was more common in males. This is consistent with the case encountered in the present study and microscopic picture showed typical numerous broad, branching, nonseptate hyphae at 90° angles along with necrotic bone fragments, leading to diagnosis of mucormycosis.[9]

Mycetomas are chronic subcutaneous infections which can be due to fungi or actinomycetes, known as eumycetomas or actinomycetomas, respectively. India and Sudan have a higher prevalence of the infection. Black grain eumycetomas include Exophiala jeanselmei, Madurella mycetomatis, Trematosphaeria grisea, and Curvularia geniculata. White grain eumycetoma includes Aspergillus nidulans, Scedosporium apiospermum complex, Acremonium falciforme, and Fusarium species. The present study includes one case of eumycetoma with typical microscopic picture showing chronic inflammatory infiltrate along with fungal colonies consisting of large black grains with interlacing hyphae embedded in interstitial brown matrix leading to the diagnosis of M. mycetomatis.[10]

CBM is a chronic cutaneous/subcutaneous fungal infection following the traumatic implantation of certain pigmented or dematiaceous fungi through the skin. The disease is mainly reported from humid tropical and subtropical regions of Asia and Africa.[1] In India, it is commonly seen in humid subtropical regions such as the base and foothills of the Himalayas and tropical regions such as South India.[2] The fungi causing CBM are found in soil, plant debris, and wood. Therefore, farmers working in the fields are at a higher risk, making it an occupation-related disease.[1],[11]

The usual clinical presentation is an initial cutaneous lesion in the form of a localized papule, nodule, plaque, or verrucous growth at the site of inoculation, followed by subcutaneous tissue involvement. The most common causative agents are F. pedrosoi, P. verrucosa, Fonsecaea compacta, and Cladosporium carrionii.[1],[11]

Due to tropical climate, South Asia has a high incidence of fungal infections; those commonly involved in humans are opportunistic yeasts such as Candida albicans or filamentous fungi such as Aspergillus. Fungi such as Fusarium, Trichosporon, and Malassezia species are now emerging as leading causes.[2]

CBM was originally reported from Brazil. In India, Thomas et al. first reported two cases of CBM from Assam (1957). Since then, there have been several case reports from sub-Himalayan belt, western and eastern coasts.[1],[11] CBM is a chronic localized infection of the skin and subcutaneous tissue caused by a group of dematiaceous or black Fungi.

The causative agent lives in soil, wood, and plant debris. The events proceed as:

  1. Traumatic implantation from an environmental source leading to initial cutaneous lesion at the inoculation site
  2. Progressive involvement of cutaneous and subcutaneous tissue and a granulomatous reaction with neutrophilic abscesses
  3. A nonprotective Th2 immune response
  4. The presence of sclerotic cells in the affected tissue.[12]


The infection usually occurs in the age group of 20–40 years with a male preponderance. Rural males from an agricultural background are commonly affected as are vegetable vendors, gardeners, etc., In a review from India by Sharma et al. in 1999, 34 cases were studied.[13] An increase in the number of cases in the last 5 years has been noticed, where 68 cases were published between 1957 and 2011 and 101 cases between 2012 and May 2016.[1] Aggarwal et al. in 2017 showed the highest number of cases had been reported from Kerala, followed by Karnataka, Assam, Himachal Pradesh, and Maharashtra.[1]

Dematiaceous fungi include three different types of infection, i.e. phaeohyphomycosis, CBM, and mycetoma.[14] CBM presenting as subcutaneous cystic swelling, as seen in the present study, needs to be differentiated from pheomycosis which usually presents as subcutaneous cystic swelling. Muriform cells (aka Medlar bodies or sclerotic bodies or “Copper-Penny” bodies) are absent in pheohyphomycosis.[14]

The diagnosis of CBM should be confirmed by:

  1. Direct microscopy in 20% KOH of lesion scrapings, where dark-brown, thick-walled form of the fungus (Copper-Penny bodies) is seen
  2. HPE showing granulomatous reaction and sclerotic bodies
  3. Culture of scraping or biopsy specimen.[11]


In the present study, microscopically, all the cases were proven with the characteristic features of CBM with the presence of sclerotic bodies and branching, septate hyphae using special stains PAS and GMS. Microbiological culture confirmed F. pedrosoi and P. verrucosa.

Gitanjali et al.(March 2017) and Chandran et al.(2012) studied 11 and 35 cases, respectively. The disease was predominantly seen in middle-aged male farmers from a rural background. The lower extremity was more commonly affected. Verrucous and nodular lesions were the most common clinical presentation. Sclerotic bodies were demonstrated in histopathological sections.[11],[15]

The present study correlated with their findings, but the differentiating feature was varied clinical presentation of subcutaneous cystic swelling in all the patients and without any overlying cutaneous lesion in two of the cases.

The existing literature consists of few reports of unusual geographic and/or clinicopathologic presentations of CBM. Mittal et al., in 2014, reported a case from Udaipur, Rajasthan, which is a non-endemic area.[16] Shresta et al. reported of a case presenting as an isolated nasal mass as did Sharma et al., about a case presenting on the face, both of which are unusual sites of presentation.[17],[18]


  Conclusion Top


Fungal lesions have revealed an increasing trend of infections in immunocompetent individuals in recent years, with various unique clinicopathological presentations. Candida, Aspergillus, and mucormycosis are the most commonly detected fungi in the Indian landscape.

The present study came across cases of aspergillosis, candidiasis, mucormycoses, CBM, and eumycetoma. However, most of these cases had unique presentations. The mucormycosis case occurred as fungal osteomyelitis and the candidiasis case was an incidental finding in a case of esophageal adenocarcinoma. There was also a case of renal aspergillosis which is rare in immunocompetent hosts; further, three cases of CBM with unique presentation of subcutaneous cystic swellings with no lesion of overlying skin.

Review of existing literature confirmed the rarity of these unique presentations and a paucity of case series and studies on fungal lesions in the existing literature, therefore necessitating further insight into this entity and further vigilance while making a diagnosis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Singh T, Kashyap AK, Ahluwalia G, Chinna D, Sidhu SS. Epidemiology of fungal infections in critical care setting of a tertiary care teaching hospital in North India: A prospective surveillance study. J Clin Sci Res 2014;3:14-25.  Back to cited text no. 2
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Chakrabarti A, Chatterjee SS, Shivaprakash MR. Overview of opportunistic fungal infections in India. J Med Mycol 2008;49;165-72.  Back to cited text no. 4
    
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Lakshmy JA, Katragadda R, Balaji J. Speciation and antifungal susceptibility of esophageal candidiasis in cancer patients in a tertiary care hospital in South India. J Med Allied Sci 2016;6:29-34.  Back to cited text no. 5
    
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Manikandan, Palanisamy et al. Fungal Keratitis: Epidemiology, Rapid Detection, and Antifungal Susceptibilities of Fusarium and Aspergillus Isolates from Corneal Scrapings. BioMed research international vol. 2019 6395840. 2019. doi:10.1155/2019/6395840.  Back to cited text no. 6
    
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Prakash H, Ghosh AK, Rudramurthy SM, Singh P, Xess I, Savio J, et al. A prospective multicenter study on mucormycosis in India: Epidemiology, diagnosis, and treatment. Med Mycol 2019;57:395-402.  Back to cited text no. 8
    
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Arani R. Mucormycotic Osteomyelitis Involving the Maxilla: A Rare Case Report and Review of the Literature, Case reports in infectious diseases vol. 2019 8459296. 22 Jan. 2019, doi:10.1155/2019/8459296.  Back to cited text no. 9
    
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Dubey N, Capoor MR, Hasan AS, Gupta A, Ramesh V, Sharma S, et al. Epidemiological profile and spectrum of neglected tropical disease eumycetoma from Delhi, North India. Epidemiol Infect 2019;147:e294.  Back to cited text no. 10
    
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Sarangi G, Dash M, Paty BP, Mohapatra D, Majhi S, Chayani N. A study on chromoblastomycosis in a tertiary care hospital of Eastern Odisha. J Med Soc 2017;31:201-4.  Back to cited text no. 11
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Queiroz-Telles F, de Hoog S, Santos DW, Salgado CG, Vicente VA, Bonifaz A, et al. Chromoblastomycosis. Clin Microbiol Rev 2017;30:233-76.  Back to cited text no. 12
    
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Sharma NL, Sharma RC, Grover PS, Gupta ML, Sharma AK, Mahajan VK. Chromoblastomycosis in India. Int J Dermatol 1999;38:846-51.  Back to cited text no. 13
    
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Ponnuswamy K, Muthureddy Y, Sigamani K. Two cases of multiple subcutaneous cystic phaeohyphomycosis in immunocompromised patients with a rare causative organism. Indian J Dermatol 2014;59:421.  Back to cited text no. 14
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Mittal A, Agarwal N, Gupta LK, Khare AK. Chromoblastomycosis from a non-endemic area and response to itraconazole. Indian J Dermatol 2014;59:606-8.  Back to cited text no. 16
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Shresta D, Kumar R, Durgapal P, Singh CA. Isolated nasal chromoblastomycosis. Indian J Pathol Microbiol 2014;57:519-21.  Back to cited text no. 17
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Sharma M, Misra RN, Gandham NR, Jadhav SV, Gupta N. Chromoblastomycosis of the face: A rare case report from the district of Western Maharashtra, India. J Clin Diagnostic Res 2012;6:899-901.  Back to cited text no. 18
    


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