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| ORIGINAL ARTICLE |
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| Year : 2021 | Volume
: 16
| Issue : 2 | Page : 261-265 |
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Clinicopathological features of extranasal rhinosporidiosis: Pitfalls and differential diagnosis
Varun Kumar Singh1, Riti Bhattacharya2, Padmapriya Jaiprakash2, Archana Shivamurthy3
1 Department of Pathology, Melaka Manipal Medical College, Manipal Campus, Manipal Academy of Higher Education, Manipal, Karnataka, India
2 Department of Pathology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
3 Department of Pathology, Apollo NGS Hospital, Mysore, Karnataka, India
| Date of Submission | 04-Jan-2020 |
| Date of Decision | 08-Oct-2020 |
| Date of Acceptance | 18-Dec-2020 |
| Date of Web Publication | 18-Oct-2021 |
Correspondence Address:
Dr. Riti Bhattacharya
Department of Pathology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal - 576 104, Karnataka
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jdmimsu.jdmimsu_1_20
Aim: The present series aims to highlight the sites,clinical presentation, histopathological features, anddiagnostic dilemmas of extra-nasal rhinosporidiosis. Materials and methods: A review of pertinent demographic and laboratory data for patients diagnosed with extra-nasal rhinosporidiosis, over a period of 7 years (2012- 2019) was done. Results: Amongst the 8 cases of extra-nasal rhinosporidiosis, the sites of involvement were medialcanthus (2/8), trachea (2/8), skin and bone (1/8), hard palate (1/8), and concurrent multiple sites (2/8). Clinical differential diagnoses included fungal osteomyelitis, laryngeal papilloma, conjunctival tumor, disseminated rhinosporidiosis, and carcinoma palate.The presence of sporangia, endospores,chronic inflammation, histiocytes was the most consistent histopathological features. Sevencases were managed with a laser-guided excision, and one underwent wide local excision with cauterization. Recurrence was seen in 5/8 cases (62.5%). Conclusion: The diagnosis of extra-nasal rhinosporidiosisis often missed due to an unusual site of presentation, or mistaken for a tumor. A proper history and histopathological examination must be carried out in patients with bleeding polyps, especially in an endemic region. The rate of local recurrence is high, which may be reduced by the use of lasers during surgery.
Keywords: Chronic granulomatous disease, dapsone, endospores, polyp, rhinosporidiosis
How to cite this article:
Singh VK, Bhattacharya R, Jaiprakash P, Shivamurthy A. Clinicopathological features of extranasal rhinosporidiosis: Pitfalls and differential diagnosis. J Datta Meghe Inst Med Sci Univ 2021;16:261-5 |
| Introduction | |  |
Rhinosporidiosis is a chronic granulomatous disease of infective etiology caused by Rhinosporidium seeberi of the mesomycetozoa group. R. seeberi is opined to be not a classic fungus; however, a human pathogen from Dermocystidium, the rossette agent, and Psorospermium clade.[1],[2],[3] Although the disease is prevalent globally, >90% of cases occur in Southeast Asia, particularly India and Sri Lanka, making it endemic to this region.[4],[5] The natural habitat of rhinosporidiosis is reservoirs of water such as lakes, ponds, and wells, and sometimes, soil contaminated by water. Infection occurs through traumatized epithelium or by close contact with water, soil, or soiled clothing.[1],[5],[6] The most common site of involvement is the nose and nasopharynx (70%), followed by the conjunctiva. Other rarer sites involved are the larynx, maxillary antrum, skin and subcutaneous tissue, lacrimal sac, external female genitalia, urinary tract, bone, and rectum.[1],[4],[5],[7],[8] Hematogenous spread to distant sites is documented in literature, however, lymphatic spread has been suggested, but not successfully demonstrated in studies.[1] Nasal rhinosporidiosis is usually discernible by the presence of a polypoidal mass, mostly red and granular owing to increased vascularity and yellowish pinhead type spots on the surface due to the mature sporangia, thus imparting a strawberry-like appearance. Extranasal rhinosporidiosis, however, presents as a subcutaneous soft, friable bleeding mass and is often mistaken for soft-tissue tumors, benign cystic lesions, or papillomas. In the ocular region, it usually presents with watering, itching, conjunctivitis, and photophobia. Laryngeal rhinosporidiosis also mimics a laryngeal tumor and is challenging to manage due to its propensity to bleed. Rhinosporidiosis presenting as an oropharyngeal mass can be misdiagnosed as juvenile nasal angiofibroma or an antrochoanal polyp.[1],[5] Disseminated rhinosporidiosis, occurring primarily in immunocompromised individuals, carries a risk of high mortality. Due to the unusual site and nature of presentation, they usually escape clinical suspicion.[5],[9] Diagnosis is confirmed by the demonstration of organism in the tissue section directly or by tissue reaction, which can also be seen on cytological smears of superficial lesions.[1],[7] The management strategy employed includes medical with dapsone and multidrug regimens and surgical with total excision of polyp by electrocautery. It is, however, associated with high rates of local and distant recurrence.[1],[5],[10],[11]
The present study aims to highlight the sites, clinical presentations, histopathological features, and diagnostic difficulties of extranasal rhinosporidiosis.
| Materials and Methods | | |
This was a single-center, retrospective, observational study conducted in the Department of Pathology, Kasturba Medical College, Manipal, between June 2012 and June 2019. Patients presenting to the hospital with rhinosporidiosis occurring at extranasal sites between June 2012 and June 2019 were identified. Following ethical clearance from the institutional ethics committee, their relevant demographic, clinical details, and management were extracted from the medical record department. Hematoxylin and eosin, special stains such as periodic acid–Schiff (PAS), and Gomori methenamine silver (GMS)-stained slides were studied for histopathological diagnostic features. The data were recorded and entered into Microsoft Excel sheets and analyzed with descriptive statistics.
| Results | | |
Twenty-five cases of rhinosporidiosis were identified. Eight cases with a primary presentation at an extranasal site were included in the study, which constitutes 32% of all rhinosporidiosis cases. The age in the included cases ranged from 11 to 73 years, with a mean of 48.5 years. All patients were male. Out of the eight, two patients presented with disseminated disease, two presented with conjunctival involvement, two with tracheobronchial disease, and one each with hard palate and skin and bone involvement [Figure 1]. The spectrum of clinical features shown by the patients included hoarseness of voice (4/8), medial canthus mass (2/8), nasal obstruction or mass (2/8), breathing difficulty (2/8), and skin nodules/ulcer and dysphagia in one patient each. [Table 1] summarizes the varied clinical diagnosis in the cases along with their clinicopathological features. The specimens received were in multiple tissue bits, and histopathological examination of slides in all the cases showed features of chronic inflammation, sporangia, and various developmental stages of trophocytes, endospores, and released electron-dense bodies [Figure 2]; one case showed acute inflammatory response along with necrosis and endospores [Figure 3]. Granulomatous inflammation in the form of ill-formed granulomas and histiocytes was seen in six cases [Figure 4]. PAS and GMS stains helped in the identification of spores by highlighting the cell walls [Figure 5]. Three cases showed infiltration of tissues by eosinophils. [Table 2] summarizes the histopathological features of all the cases. Out of eight, seven cases were treated with laser-guided excision, and one underwent wide local excision with cauterization of the base. Two cases of disseminated disease and one case of bone involvement received dapsone pre- and postsurgery. Nearly 62.5% (5/8) of the cases presented with a local recurrence in the next 3 years. | Figure 1: Cutaneous rhinosporidiosis. Skin-covered tissue mass with cut section showing yellow fatty to fibrous areas, resembling soft-tissue sarcoma
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 | Figure 2: Laryngeal rhinosporidiosis showing sporangia and its developmental stages in an inflammatory background (H and E, ×400)
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 | Figure 3: Ruptures sporangia with numerous endospores along with acute inflammatory infiltrate (H and E, ×200)
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 | Figure 4: Granulomatous reaction with foreign body giant cells and histiocytes in response to a ruptured sporangium (H and E, ×200)
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 | Figure 5: (a) Trophocytes and immature sporangia along with histiocytic infiltrate (H and E, ×200). The cell walls of the sporangia and the endospores attain positively with periodic acid–Schiff (b, ×200), Mucicarmine (c, ×100), and GMS (d, ×100)
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| Discussion | | |
R. seeberi was first described as a sporozoon by Malbran and a protozoan by Seeber.[3] It is now considered a member of the Mesomycetozoaclade, which includes fish and amphibian pathogens in the former DRIP clade (Dermocystidium, the rosette agent, ichthyophonus, and psorospermum clade).[1],[3] Rhinosporidiosis has been reported from around seventy countries, but its prevalence is limited to sporadic case reports; however, it is endemic to Southeast Asia, particularly India and Sri Lanka, and also been reported in a variety of farm, domestic, and wild animals.[1] The highest prevalence has been reported in the age group of 21–40 years with a male preponderance (M: F – 4:1).[4] The present study has cases from the Southwest coastal population of India. All the patients in the present study were male and between the ages of 11 and 73 years. The mean age of the presentation in the current series was 48.5 years.
The most common site has been observed to be the nasal cavity, accounting for 85% of the total cases.[1],[4],[5] Following the nasal cavity, the second most common site of involvement of rhinosporidiosis is the ocular region, accounting for 11.2% of cases worldwide, and included involvement of conjunctiva, lacrimal sac, lids, and sclera.[5],[12],[13] Two cases included in the present study presented with a medial canthus mass and were suspected to be conjunctival tumors, which is a common clinical diagnosis made in cases of ocular rhinosporidiosis. Complete surgical laser-guided excision was performed, which is the treatment of choice in these cases; none of these cases showed a recurrence in the follow-up period of 3 subsequent years.
Rhinosporidiosis involving the oropharyngeal cavity usually occurs following a nasal infection, isolates oropharyngeal involvement is rare. It often presents as an irregular fleshy mass causing dysphagia, and foreign body sensation. This raises clinical suspicion of an inverted papilloma or an antrochoanal polyp.[4],[5],[14] Tracheal and laryngeal involvement occurs by seeding of the tract by sloughed off spores by trauma or surgery, usually presenting with hoarseness of voice, which leads to the suspicion of malignancy.[4],[5],[15] In the present study, one case of hard palate, irregular mass presenting with dysphagia and two cases with tracheal involvement, presenting with hoarseness of voice, clinically suspected to be papillomas, were seen. A local recurrence was seen in two cases involving the palate and trachea.
Involvement of soft tissue and bone in rhinosporidiosis is a rare phenomenon. Records of osseous involvement are limited to a few case reports in English literature. The common bones involved are the talus, tibia, femoral condyle, clavicle, and calcaneum. The typical presentation is that of an ulcer with draining pus and friable growth.[4],[5],[16] Primary subcutaneous involvement is a rare occurrence; commonly, subcutaneous involvement occurs in an immunocompromised patient as a part of disseminated disease. Subcutaneous involvement has also been reported in immunocompetent patients, and in such cases, there is a high clinical suspicion of a soft-tissue tumor.[5],[17],[18],[19] The present study reports one case of an immunocompetent male with simultaneous involvement of subcutaneous tissue and bone involvement, which was evaluated on the lines of a fungal infection. The patient presented with multiple subcutaneous nodules on the anterior abdominal wall, right thigh, and a pus-draining ulcer in the right foot. Fine-needle aspiration revealed only acute inflammatory cells, and fungal cultures were negative. A diagnosis of rhinosporidiosis was established on histopathological examination of the wide local excision of the thigh nodule and pus from the foot ulcer. The patient was managed with excision, cryotherapy, and dapsone.
Disseminated rhinosporidiosis refers to the clinical condition with simultaneous involvement of multiple sites. A history of sinonasal rhinosporidiosis is usually present in such patients. Immunosuppression is the initiating factor in dissemination and can show extensive involvement of the nasal cavities, nasopharynx, oropharynx, trachea, bones, and subcutaneous tissue. Such cases are associated with significant morbidity and show multiple recurrences.[1],[4],[5],[9] The present series describes two such cases with extensive nasal cavity, nasopharynx, and tracheal involvement. Both the patients were managed by a laser-guided excision with electrocoagulation of the base, however showed multiple recurrences involving the nasal cavity as well as trachea in the next 3 years. None of the cases in the present series was immunocompromised.
Histopathological tissue examination is the mainstay for diagnosis. The demonstration of sporangia, endospores, and maturing trophocytes on tissue sections is confirmatory. The sporangia appear aschitinous, thick-walled, spherical structures containing endospores along with chronic inflammatory infiltrate composed of lymphocytes, plasma cells, and macrophages in a fibromyxomatous background. A granulomatous tissue reaction is seen frequently accompanying the sporangia. In case of rupture of sporangia, endospores are released into the tissue and elicit an acute inflammatory response.[1],[4] The histopathological differential diagnosis of rhinosporidiosis induces conditions and organisms, which present as large spherules in the tissues. It is essential to distinguish the endospores of R. seeberi from those of other fungal lesions such as Coccidioides immitis and Chrysoporium parvum var cresens, and spherulocystic disease (Myospherulosis). The endospores of C. imitis are smaller in size (1–2 μm, in contrast to 3–5 μm in R. seeberi) along with the presence of arthoconidia and hyphae. The spores of Cryptosporidium parvum var cresens are larger (20–70 μm) and elicit a fibrotic granulomatous host response, in contrast to the chronic inflammatory tissue response seen in rhinosporidiosis. Both C. inimitis and C. parvum var cresens do not stain with mucicarmine in contrast to endospore walls of R. seeberi, which is carminophilic. The ruptured sporangia with endospores in the tissue mimic a picture of C. parvum infection, which has similar staining characteristics with PAS and GMS. In such a scenario, a fungal culture can help to rule out cryptosporidiosis.[1],[4],[20] Myospherulosis is not an organism but described as red blood cells altered by lipids, which take a spherical nomenclature, however do not stain in GMS.[20] Other pitfalls in the histopathological diagnosis of extranasal rhinosporidiosis include scant endospores with dense inflammatory cell infiltrate in the tissues, nonrepresentative biopsy sites, empty endospore walls which simulate a nonrhinosporidial etiology, and thin-walled sporangia, all of which could lead to a false-negative diagnosis.[1],[20],[21]
Cytodiagnosis of rhinosporidiosis, especially in extranasal superficial sites, has taken the forefront of evaluation in recent times. An aspirate with numerous endospores and sporangia can provide very sensitive and specific diagnostic clues. Pitfalls in such cases include a nonrepresentative sampling, the absence of sporangia, and goblet cells mimicking residual sporangial material. Keeping these pitfalls in mind while reporting cytology smears is warranted.[1],[7],[8]
The treatment for rhinosporidiosis is usually case based and has both medical and surgical approaches. The major drugs used in medical management include dapsone, amphotericin B, ketoconazole, trimethoprim-sulfadiazine, and sodium stibogluconate. The primary action of these drugs is endospore static rather than endospore cidal and can be used pre- or postoperatively to control the infection or in cases of disseminated rhinosporidiosis. More recently, cycloserine has been added to the multidrug regimen.[10],[11] Surgical management is the treatment of choice in majority of cases. Laser-guided excision of the pedunculated polyp by electrocautery is the most common modality. Sessile and broad-based polyps are difficult to remove entirely and are associated with more recurrences.[1],[4],[5] In the present series, laser-guided excision with electrocautery was the treatment of choice. Surgery and dapsone are common modality of treatment in cases of disseminated rhinosporidiosis. Dapsone has been shown to reduce the rate of recurrence by arresting the maturation of the sporangia and promote fibrosis in the stroma.[10]
| Conclusion | | |
In cases of extranasal rhinosporidiosis, the diagnosis is often delayed due to atypical presentations. Cases with soft tissue or skin involvement can be misdiagnosed as tumors. The natural course of rhinosporidiosis is marred by recurrences and widespread dissemination. Thus, in cases presenting with friable polypoidal/granular masses, which bleed on touch, it is imperative to take a detailed personal and occupational history. In patients who have been exposed to stagnant water or bathing in muddy water, rhinosporidiosis should be considered as a differential, and histopathological examination should be performed without delay for appropriate treatment.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]
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