https://orcid.org/0000-0003-4373-9641
A 75-year-old woman with a past medical history of diabetes mellitus presented with a recurrent right nostril growth (Figure 1). It first appeared more than 4 decades ago. In the 1990s, she had 2 surgeries to remove the nasal mass. The growth recurred during the past year and began to protrude from the nares, causing complete right nasal obstruction and contact bleeding. There were no constitutional symptoms. As a second-generation Singaporean of ethnic Indian descent, she had spent her youth in a rural village in premodernized Singapore. Interestingly, she swam in stagnant ponds where water buffalos frequented. Two childhood friends who swam with her in the stagnant ponds later developed similar nasal masses. There was no further exposure after childhood. A contrast-enhanced computed tomography scan of the sinuses demonstrated a lobulated 6.4cm mass within the right nasal cavity. It extended along the floor of the nasal cavity, from the nasal vestibule anteriorly to the hard palate posteriorly. On magnetic resonance imaging, there was no sign of invasion into the surrounding soft tissue and no cervical lymphadenopathy. The patient underwent endoscopic resection of the right nasal mass. The mass was friable, had a strawberry-like appearance (Figure 2), and a stalk arising from the nasal septum. The base of the stalk was cauterized. Incidentally, the right inferior turbinate was noted to be absent, likely resected in a previous surgery. Tissue was obtained for cultures and histological evaluation (Figure 3). Acid-fast bacilli and fungal cultures were negative. Additional histology slides are provided in the Supplementary Figures.
Clinical photograph demonstrating a fleshy erythematous growth protruding from the right nares.
Gross specimen of the excised right nasal mass.
Histology of nasal polyp. Magnification × 20.
What is your diagnosis?
Diagnosis: Rhinosporidiosis. The histological findings confirmed the clinical suspicion of rhinosporidiosis. Histology of the nasal mass displayed numerous sporangia (100–300 µm in size) that contained sporangiospores, highlighted by Gomori methenamine silver stains (Figure 3). Ruptured sporangia had dispersed sporangiospores (Figure 4, brown arrow) within the lamina propria, leading to a florid granulomatous and neutrophilic reaction. The walls of the sporangia and endospores were also highlighted by periodic acid-Schiff and mucicarmine stains (Supplementary Figures). The tissue specimen was sent for polymerase chain reaction analysis and returned 100% positive for Rhinosporidium seeberi.
Gross specimen of the excised right nasal mass. The polypoidal mass is vascular and friable, with a reddish, granular appearance that is speckled with whitish dots, imparting an appearance similar to a strawberry.
Rhinosporidiosis is a chronic granulomatous mucocutaneous disease of the nose [1] that is endemic in hot tropical climates such as in India and Sri Lanka [1]. Symptoms include nasal obstruction, epistaxis, and nasal discharge [1].
The offending organism is R. seeberi, an enigmatic microorganism not amenable to microbiological culture. After extensive debate on its taxonomical classification, it has been recently reclassified as a Mesomycetozoea [2]. It is the first known human pathogen from this clade of aquatic eukaryotic parasites [2] that is hypothesized to originate from a branch proximal to the point of divergence between animals and fungi within the evolutionary tree [1]. Rhinosporidium seeberi exists in the trophic stage (juvenile sporangium) prior to developing into a mature sporangium that produces endospores that again develop into sporangia [3]. Morphologically, the nasal masses resemble a strawberry because the erythematous mass is studded by submucosal, round and white, thick-walled sporangia (Figure 5) [1, 4].
Ruptured sporangium releasing endospores (brown arrow). The walls of the sporangia and endospores are highlighted by Gomori methenamine silver stains. Magnification × 20.
Prior direct contact with contaminated water is universal to all rhinosporidiosis infections [5]. The organism penetrates through minor epithelial breaches in moist mucosal sites such as the nasal cavity [1]. Risk factors include pond bathing, wet agriculture, and cattle farming [4]. Stagnant water bodies may be contaminated by spore-containing feces of animals such as cattle [1, 4], which are also known to be affected by this disease [1]. Rarely, hematogenous spread facilitates disseminated disease to the skin [6], bones, and viscera [1]. Direct transmissions from human to human [1] or animal to human have yet to be reported. The incubation period of R. seeberi is unknown, but most authors agree that there is a long incubation period from initial exposure (eg, childhood) before disease manifestation (eg, adulthood) [7]. Similarly, our patient had rhinosporidiosis manifest decades after first exposure.
A notable histological mimic is coccidioidomycosis (Valley fever), a fungal infection that causes pneumonia or pulmonary granulomas [8]. Though the spherules resemble those of rhinosporidiosis on histology (both demonstrate ruptured sporangia releasing endospores), the sporangia of Coccidioides immitis are smaller in diameter (10–100 µm) [8] compared with those of R. seeberi (100–400 µm) [1] and do not stain for mucin.
The failure to grow R. seeberi in vitro has impeded the study of its drug susceptibility [4]. The thick sporangial walls are impenetrable to most antimicrobial agents. Host immune response is futile as the organism is larger than phagocytic cells and outnumber the surrounding vascular components [4]. The gold standard treatment for rhinosporidiosis is complete excision biopsy with cauterization of the polyp base to destroy any residual spores [1, 4]; however, surgical treatment alone is often futile. The infection is notorious for recurrence [4]. Dissemination to adjacent sites can occur when intraoperative trauma to the polyp releases spores [4]. Our patient had recurrent rhinosporidiosis. The resected right inferior turbinate was probably a prior site of polyp growth. Considering its proximity to the site of recurrence at the nasal septum, it is plausible that the adjacent epithelium was autoinoculated by sporangia that were inadvertently released during polyp removal [4].
Dapsone, an oxidizing agent, has demonstrated efficacy in preventing post-operative recurrence [1] and treating disseminated disease [6] when taken for a minimum of 6 months [1]. Dapsone arrests the maturation of sporangia and promotes fibrosis in the stroma, preventing disease proliferation [9]. It is limited by the side effect of hemolytic anemia, particularly in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Where dapsone use was contraindicated, a multidrug therapy regimen combination of cycloserine, ketoconazole, and amphotericin B has reportedly been given with improvement, although evidence remains limited [10]. Our patient was prescribed a course of oral dapsone at 100 mg daily. Although she was not G6PD-deficient, follow-up laboratory tests revealed anemia with the presence of bite cells, reticulocytosis, and low haptoglobin, suggesting dapsone-related hemolytic anemia. Consequently, dapsone was discontinued after 1 month. At follow-up 15 months post-surgery, she remained disease-free with no recurrence seen on interval nasoendoscopy.
Rhinosporidiosis is preceded by a history of environmental exposure and has a characteristic appearance. Clinical recognition is crucial as random biopsies could inadvertently lead to iatrogenic dissemination of spores and eventual disease recurrence [4]. Dapsone has demonstrated utility in preventing disease recurrence.
Supplementary Data
Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.
Notes
Author Contributions. Design of the manuscript: R. T., A. C. T. Drafting and editing of the manuscript: R. T. Reviewing and editing of the manuscript: D. D. R., M. M. B., A. C. T. Research supervision and overview: A. C. T., J. K. S.
References
Author notes
Potential conflicts of interest. The author: No reported conflicts of interest. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.
