Nasal Rhinosporidiosis: Clinical Presentation, Clinical Findings, and Outcome in Dogs
The purpose of this study was to describe the clinical presentation, imaging findings, and outcome in 10 dogs diagnosed with Rhinosporidium seeberi infections. Histopathology and cytology records were searched at a veterinary teaching hospital and a veterinary diagnostic laboratory to identify dogs with rhinosporidiosis. Medical records were reviewed for clinical, imaging, endoscopic, and surgical findings. Outcome was determined via evaluation of records and, where possible, telephone conversation with the primary care veterinarian and/or owner. Young to middle-aged large-breed dogs with an approximately equal sex distribution were represented. Unilateral signs predominated. Diagnosis was confirmed by histopathology in 9 cases, and cytology was diagnostic in only 1 of 3 cases. Histopathology was superior to cytology. Masses were soft tissue and contrast enhancing with no evidence of bony lysis on computed tomography (2 dogs). Direct or rhinoscopic (2 dogs) visualization revealed white to yellow pinpoint foci. Surgical resection (4 dogs) can result in long-term disease-free periods (up to 2659 days), although repeat surgery can be required. Dapsone was well tolerated in 1 dog, and relapse was not noted despite incomplete surgical resection (follow-up 749 days). Visualization of pale foci on a rostral intranasal mass in an endemic region should prompt consideration of rhinosporidiosis.
Introduction
Rhinosporidium seeberi is an infectious agent that is part of the Mesomycetozoea class of organisms, which causes slow-growing nasal masses in dogs.1 It is the causative agent of rhinosporidiosis, which has been reported in humans and in sporadic reports in veterinary species.2 In dogs, rhinosporidiosis typically affects young to middle-aged large-breed dogs; however, small-breed dogs have also been reported.1,3 The route of transmission is not fully understood, although mucosal contact with infected water or airborne transmission of spores is suspected.1 Once sporangia enter the tissues, mucous membrane secretions stimulate endospore release, and the endospores induce an inflammatory reaction typically resulting in a slow-growing rostral nasal mass, which can on occasion be externally visualized.1,4,5 Diagnosis is typically based on cytology or histopathology of affected lesions.1,5,6 Surgical excision of lesions via the nares or by rhinotomy is commonly performed, and the recurrence rate is suspected to be low.2,5–13 However, in cases in which surgery is declined or the disease relapses, topical (povidone-iodine) and systemic (ketoconazole, dapsone) therapies have been attempted.1,3,9
The aim of this study was to describe clinical, imaging, endoscopic, and surgical findings in the largest cohort of newly reported cases of rhinosporidiosis in dogs. A further aim was to report outcomes associated with different treatment methodologies.
Materials and Methods
Case Selection
Electronic records were searched to identify all dogs with a histo-pathological or cytological diagnosis of rhinosporidiosis in the databases of the Mississippi State University College of Veterinary Medicine Animal Health Center and the database of the Mississippi State University Veterinary Research and Diagnostic Laboratory between January 1, 2007, and December 31, 2019. These databases contain cases from external submissions from primary practice and internal cases from the veterinary teaching hospital. The inclusion criterion was that R seeberi organisms were documented on the cytology and/or histopathology reports to confirm the diagnosis. All cytology and histopathology samples were reviewed by diplomates of the American College of Veterinary Pathologists. Fine-needle aspirate and biopsy samples were assigned a diagnosis of rhinosporidiosis based on previously described clinical features.6,10 No exclusion criteria were applied.
Medical Record Review
The medical records pertaining to the cases identified above were subsequently reviewed by one of two authors (H.C. and N.M. for the following information: signalment, weight, environment, clinical signs, physical examination findings, diagnostic imaging findings, treatment, and follow-up information. The cytology and biopsy reports were also evaluated. If data were unavailable in the medical record, attempts were made to contact the primary care veterinarian and/or owner for further case details. A follow-up survey was not used as part of this study.
Results
Animals
Ten client-owned animals, four females (three spayed, one intact), four males (three neutered, one intact), and two of unknown sex, were included in the study. The median age at the time of diagnosis was 4.5 yr (range 1.5–10 yr). The median recorded weight was 39.5 kg (range 6.7–51.0 kg), although weight could not be identified in the medical records of three dogs. Three mixed-breed dogs were included. A variety of other breeds, including Labrador retriever (n = 2), Doberman pinscher (n = 1), German shepherd dog (n = 1), and rottweiler (n=1), were also reported. The breed of two further dogs was unknown. Four patients had environment type documented in the medical record, two of whom were predominantly outdoor (one with known access to water bodies) and two of whom had indoor and outdoor access. Three patients were evaluated at a veterinary teaching hospital, and seven cases were solely evaluated by primary care veterinarians. Nine cases resided in Mississippi at the time of cytology or biopsy submission, and one case resided in Tennessee. No travel history was reported in the medical records. The following counties were represented: Hinds, Mississippi (n = 2), Rankin, Mississippi (n = 2), Coahoma, Mississippi (n = 1), Chester, Tennessee (n = 1), Kemper, Mississippi (n = 1), Leflore, Mississippi (n = 1), Newton, Mississippi (n = 1), and Tallahatchie, Mississippi (n = 1).
History, Clinical Signs, and Physical Examination Findings
All dogs presented with unilateral signs of nasal disease when anatomical location was specifically noted in the medical record (4/4). Clinical signs included epistaxis (n = 4), serous nasal discharge (n = 1), and a visible mass protruding from the nares (n = 2). Additional clinical signs included sneezing (n = 2), epiphora (n = 1), and dyspnea (n = 1). The nature of the breathing pattern was not further characterized. Presenting clinical signs were unavailable for review in three cases. Clinical signs were documented for a median of 26 days before initial presentation (range 14 days to 7 mo). When recorded in the medical record, nasal airflow was decreased to absent unilaterally (n = 2/2); both of these patients presented for sneezing and nasal discharge. One patient had a focal area of alopecia with erythema and eschar/crusting measuring ˜1 cm diameter above the affected nares. A second patient had areas of alopecia circumferentially around both eyes and extending down the nasal planum. Two patients had a visible soft-tissue mass protruding from the nares reported in the medical record, and one of the masses was noted to have multifocal white regions on its surface. There was no recorded evidence of facial deformation in any of the available medical records (n = 9).
Bloodwork and Diagnostic Imaging
No clinically significant abnormalities were detected on routine complete blood count (CBC; three dogs) and serum chemistry (four dogs) evaluation. Clotting times were within normal limits in the two cases evaluated. Radiographs of the head were performed in two patients, which revealed no areas of bone lysis (n = 2), and one patient had suspected soft-tissue opaque material within the nares and frontal sinus as recorded in the medical record; radiographs were evaluated by the primary care veterinarian and were unavailable for review. Two dogs had unremarkable thoracic radiographs, confirmed by a radiologist, before head computed tomography (CT) scan. Pre- and postcontrasta CT images were evaluated by a radiologist. A soft-tissue–attenuating, contrast-enhancing nodule measuring 0.6 × 0.4 × 2 cm was noted in one dog, located within the rostral aspect of the right nasal cavity, confluent with and medial to the right alar fold and lateral to the cartilaginous nasal septum. A fracture of tooth 101 was also noted and was considered an incidental finding. In the second dog, a soft-tissue–attenuating mass measuring 0.7 × 0.7 × 2.0 cm was present within the rostral aspect of the right nares (Figure 1). There was no evidence of bony lysis on either of the head CT scans. One further dog had a head CT performed after biopsy of a mass with the primary care veterinarian, and the CT revealed no residual abnormalities. Two dogs underwent anterior and posterior rhinoscopy at the veterinary teaching hospital. Anterior rhinoscopy was performed using a 2.7 mm rigid telescope with operative sheath, and posterior rhinoscopy was performed using a 5.2 × 85 mm flexible bronchoscope. In the first dog, anterior rhinoscopy revealed an erythematous soft-tissue multi-lobulated mass within the rostral aspect of the right nasal passage. The surface of the mass was noted to have multifocal white foci present, and the mass was noted to occupy the entire nasal passage (Figure 2A). The remainder of the nasal mucosa had a diffuse mild cobblestoned appearance, suspected to be due to inflammation. The left nares and posterior rhinoscopy were unremarkable. Biopsies were collected and were consistent with a diagnosis of rhinosporidiosis (discussed below). In the second dog, an oral examination was performed before rhinoscopy and revealed no abnormalities. Anterior rhinoscopy revealed a mass lesion on a broad base within the rostral right nasal cavity with irregular white to yellow multi-focal pinpoint lesions present on its surface. The mass extended 2–3 cm into the nasal cavity (Figure 2B). In the left nares, small accumulations of purulent material were present in addition to an irregular dark lesion present within the mucosa. Biopsies from the right nasal cavity were consistent with rhinosporidiosis. Biopsies from the left nasal cavity revealed pyogranulomatous rhinitis with an intralesional arthropod (flea) and intra-arthropod fungal hyphae. The origin of the fungal elements was unclear, but they appeared to be growing from within the body of the flea outwards. The hyphae were thick and bulbous and measured 10–15 μm with parallel walls, irregular septa, and nondichotomous right-angle branching. Additional testing was not performed because the organism appeared to be associated only with the flea, and morphology was not consistent with aspergillosis or pythiosis or other known causes of nasal disease in dogs, as determined by a board-certified veterinary pathologist.
Citation: Journal of the American Animal Hospital Association 57, 3; 10.5326/JAAHA-MS-7121
Citation: Journal of the American Animal Hospital Association 57, 3; 10.5326/JAAHA-MS-7121
Cytology and Histopathology
Histopathology was used to definitively diagnose 9 of the 10 cases. In each of these cases, findings were pathognomic for R seeberi (Figures 3, 4). Nasal turbinates were markedly expanded by intense mixed inflammation composed of predominantly neutrophils and macrophages with fewer lymphocytes and plasma cells. Scattered throughout each lesion were large numbers of endosporulating sporangia ranging from 10 to 500 μm wide in various stages of maturation. Juvenile sporangia were characterized by a unilamellar eosinophilic wall with a central nucleus and prominent nucleolus surrounded by abundant basophilic granular material. Intermediate sporangia were characterized by a bilamellar amphophilic wall that contained a myriad of immature basophilic endospores. Mature sporangia had a basophilic bilamellar wall and were filled with both immature basophilic spores located at the periphery, and central eosinophilic mature endospores. Occasionally, endospores were seen spilling out of ruptured mature sporangia (Figure 4).
Citation: Journal of the American Animal Hospital Association 57, 3; 10.5326/JAAHA-MS-7121
Citation: Journal of the American Animal Hospital Association 57, 3; 10.5326/JAAHA-MS-7121
In three of the reviewed cases, cytology was performed but was diagnostic in only one case. Findings in this case included large numbers of degenerate and nondegenerate neutrophils admixed with abundant mucus, squamous epithelial cells, and clusters of ˜7 μm wide basophilic structures with a thin bilamellar cell wall filled with eosinophilic globules, consistent with free endospores (Figure 5). Findings were nonspecific in the remaining two cases and consisted mainly of dysplastic or hyperplastic epithelial cells, without inflammation or organisms present. In these two cases, histopathology was used for definitive diagnosis.
Citation: Journal of the American Animal Hospital Association 57, 3; 10.5326/JAAHA-MS-7121
Treatments and Follow-Up Data
Four dogs had attempted surgical removal of each mass following biopsy. Surgery was performed by the primary care veterinarian in three cases and performed by a board-certified veterinary surgeon in one case. Follow-up data were available for three of these patients (two treated by the primary care veterinarian and one treated by the board-certified surgeon). One dog had surgical removal of a right-sided mass by the board-certified surgeon via rhinotomy. A 2–3 cm elliptical incision was made on the dorsolateral aspect of the nose, rostral to the incisive bone. The subcutaneous tissue was then dissected with Metzenbaum scissors, and the dorsal nasal cartilage was removed using a scalpel blade. The tissue was directly visualized, removed, and submitted for margin evaluation via histopathology. Histopathology revealed that inflammation and R seeberi organisms extended to surgical margins on one of two sectioned pieces of tissue submitted for evaluation. This dog was subsequently prescribed dapsoneb (0.7 mg/kg per os q 8 hr) for a minimum of 113 days, although the exact timing of discontinuation could not be definitively determined. Repeat bloodwork (CBC and serum chemistry) was performed 16, 36, 50 (chemistry only), 78, and 106 days after prescribing dapsone, and no clinically significant abnormalities were noted. The dog returned to the referral institution 749 days for follow-up reassessment. At that time the dog was noted to have no clinical or physical examination findings consistent with nasal disease. The owners did report an episode of right-sided facial swelling that occurred ˜2 mo before recheck examination, which was diagnosed as a suspected tooth root abscess by the primary care veterinarian. The swelling resolved with ˜1 mo of antimicrobial therapy. Repeat imaging was not performed at the time of reassessment. Another dog presented to the primary care veterinarian 916 days after surgical removal of the mass for a dental examination. During the dental anesthetic episode, recurrence of proliferative tissue was reported to be present within the nose, and it was removed via traction applied to forceps. Cytological or histo-pathological confirmation was not pursued. No clinical signs of nasal disease were reported at this time. A further dental procedure was performed 2508 days after surgery, and there was no evidence of a nasal mass. At the time of last follow-up (2659 days after surgery), the dog was displaying no signs of nasal disease. One dog had removal of a right-sided nasal mass via cautery, and the mass recurred 6 mo later. At the time of initial surgery, there was concern that the whole mass had not been removed because of the size of the dog (6.7 kg shih tzu–Pomeranian) and limited access via the nares. At the time of the second surgery, a mass was noted to be present caudodorsally within the right nares, coming from a similar location as the previous excised mass. No further follow-up was available for this patient. The median time to recurrence in patients who underwent surgery after diagnosis was 749 days (range ˜180–916 days).
Five other patients did not undergo additional surgery following biopsy; however, it is unclear whether the initial biopsy was incisional or excisional in nature, which may have affected the need for additional surgery. Specific follow-up information was available for three of these dogs. One dog was initially scheduled for referral but had resolution of clinical signs following biopsy, and no further treatment was pursued. The dog was reported to be doing well with no signs of nasal disease at the time of last follow-up (187 days after biopsy). One further dog was referred to the veterinary teaching hospital 7 days after diagnosis for further evaluation. The dog had resolution of nasal signs following biopsy with the primary care veterinarian, and a head CT revealed no detectable abnormalities. No further treatments or diagnostics were recommended. The dog had regular recheck examinations with the primary care veterinarian and displayed no signs of nasal disease and was doing clinically well at the time of last follow-up, 2274 days after diagnosis. One dog who did not undergo biopsy or surgery (diagnosed via the presence of organisms on cytology) was prescribed ketoconazolec at 150 mg per os q 12 hr (weight unavailable). The dog was reportedly doing well at time of last recheck, 88 days after diagnosis, and medications were refilled. No additional follow-up data were available for this dog. Followup information was unavailable for the other two cases who did not undergo additional surgery.
It is unclear whether the 10th case underwent treatment, because only the biopsy and patient age were available for review. The primary care veterinarian was contacted for this case; however, additional information was unavailable.
Discussion
Rhinosporidiosis is an uncommon cause of nasal masses in dogs. Sporadic case reports have been reported in the United States, in addition to Canada, Argentina, Brazil, Colombia, Uruguay, Italy, and the United Kingdom.2,5–19 The largest case series to date documented rhinosporidiosis in 6 dogs and predominantly focused on histo-pathological features of R seeberi infections.10 The aim of this current case series was to expand upon previously documented literature and document clinical features, diagnostic findings, endoscopic findings. and outcome following both surgical and medical treatments in a cohort of 10 dogs.
Rhinosporidiosis is reported to affect young to middle-aged large-breed dogs with a male predominance.1,2 In this case series, the median age of dogs affected was 4.5 yr, consistent with prior reports. The majority of patients in this study were large-breed dogs, although a shih tzu–Pomeranian weighing 6.7 kg was also affected. In this case series, 4/8 animals of known sex were female, in contrast to some prior studies, suggesting that a male predominance is not always seen. All dogs in whom environmental factors were reported in the medical record had outdoor access. One had known access to bodies of water. Exposure to water is a suspected predisposing factor, because R seeberi is associated with aquatic environments.5 The 10 dogs in this retrospective study originated from seven counties in Mississippi and one nearby county in Tennessee. This suggests a wide distribution of R seeberi in the Mississippi region.
Dogs in this study typically presented with unilateral signs of nasal disease, with epistaxis seen in four patients and serous nasal discharge seen in one patient. Two of the 10 dogs in this study had an externally visible mass noted within the medical record. In the other cases, although the masses may have been externally visible, it was not specifically noted within the medical record whether the masses were visible or obtained via blind nasal biopsies. Interestingly, two patients who presented to the veterinary teaching hospital had decreased air flow through one nostril but did not have a visible mass present. Both of these cases had the mass detected on CT and rhinoscopy. It is likely that only cases that could not be identified and diagnosed at primary care level were subsequently referred for evaluation at the veterinary teaching hospital. Two of the medical records documented alopecia around the nose and eyes, and this is suspected to be due to self-induced trauma associated with scratching at the nose. No skin scrapes or cytology were available to confirm this assumption.
Radiographs of the head were performed in two cases and revealed suspected soft-tissue opaque material within the nares and frontal sinus of one dog. No abnormalities were reported on the radiographs of the second dog, although they were not available for review. Radiography has been reported to be insensitive in the detection of nasal rhinosporidiosis.1,12 Both dogs in this study who had a head CT performed as part of an initial diagnostic approach had evidence of a soft-tissue–attenuating contrast-enhancing mass in the rostral aspect of the nasal cavity without evidence of bony lysis (Figure 1). Although nasal/head CT is considered superior to radiographs for detection of many infectious and noninfectious diseases of the nasal cavity, insufficient direct comparisons were available in this case series to evaluate this hypothesis specifically for rhinosporidiosis.20–23 One further case had a head CT performed to assist in the evaluation of completeness of prior resection (via biopsy) of a Rhinosporidium mass. Anterior and posterior rhinoscopy was performed in two dogs. In both of these dogs, anterior rhinoscopy provided clear visualization of a mass, and multifocal pinpoint white to yellow foci were present on the surface of each mass (Figure 2). These foci are suspected to represent Rseeberi sporangia.5 These gross features may increase the clinical suspicion for rhinosporidiosis and may prompt a clinician to attempt excisional biopsy rather than obtain an incisional sample for diagnosis, which would then necessitate a second anesthetic episode for removal.
Dogs in this study were treated at both a primary practice level and a referral institution. Of the four dogs who underwent surgery after diagnosis, the median time to recurrence of the mass was 749 days (range ˜180–916 days). Data were unavailable for one of the four dogs who was lost to follow-up. The patient with the shortest time period to recurrence of the nasal mass (˜6 mo) had suspected residual mass left at the time of original surgery due to limited surgical access to the mass via the nares. This patient may have benefited from surgical removal via rhinotomy. Additional studies are required to determine the effect of surgical approach on recurrence of rhinosporidium in dogs. The dog who had incomplete margins via rhinotomy received dapsone. Dapsone is a sulfa medication that has been used in both humans and dogs with Rhinosporidium infections.24,25 It is unclear whether this medication helped to prevent recurrence of clinical rhinosporidiosis during the follow-up period or whether other factors such as variability in patient response or surgical technique were responsible. In a prior case report documenting the use of dapsone for 6 days in a dog with a chronic skin disease, the dog subsequently developed severe thrombocytopenia, which was attributed to an adverse effect from dapsone.25 The dog who received dapsone in this study had no evidence of thrombocytopenia as demonstrated by four repeat CBCs. Repeat surgery for recurrent masses appears to be useful in this study, with one dog with multiple surgeries having a complete follow-up time of 2659 days after initial surgery (1743 days after the second surgery). This patient had surgery performed in primary practice, thus demonstrating that prolonged survival times can be achieved in primary care practice with rhinosporidiosis in dogs. One of the two dogs with known or suspected incomplete margins had a relapse of disease. Of the five dogs who did not have surgery following biopsy, only three had follow-up data available. Two dogs had complete resolution of signs following biopsy (follow-up period: 187–2274 days), and another dog was prescribed ketoconazole and was doing well at the time of last follow-up (88 days). Ketoconazole is an oral azole antifungal medication that has been prescribed previously with palliative intent in a case of rhinosporidiosis in a dog.3 Similar to this case, the dog had apparent clinical response, although the follow-up was limited.
Given that povidone-iodine is thought to be effective against R seeberi based on in vitro integrity and viability dye studies, it has been suggested that it could be applied topically after removal in an attempt to reduce recurrence.1,26 Topical povidone-iodine has, however, been associated with impaired wound healing.27 Sustained release dressings of povidone-iodine have been suggested to maintain antimicrobial activity without impairing wound healing.28,29 Topical povidone-iodine dressings have been investigated in canine nasal disease and have been shown to be effective with minimal adverse effects in dogs with mycotic rhinitis.30 However, concerns do exist with regard to the invasive nature of such dressings.30 Povidone-iodine was not applied to any of the cases in this study, and a randomized controlled study would be required before determining whether such treatments should be routinely performed following resection of masses with clinical features consistent with rhinosporidiosis. Definitive diagnosis does, however, require cytology or histopathology. Cytology and biopsy features were as previously reported and include pyogranulomatous rhinitis with typically large numbers of sporangia (consistent with R seeberi) in various life stages (Figures 3–5).
One significant limitation of our study was the limited data and follow-up available for some cases, as is often seen with a retrospective study design. Additional studies with more comprehensive follow-up will be needed to determine the efficacy of various surgical approaches for removal of nasal masses associated with rhinosporidiosis in dogs. A further limitation is the limited number of dogs (two) who underwent CT and rhinoscopy, which may mean that the findings described here may not represent the full range of abnormalities that could be seen in clinical patients. We therefore recommend further studies in this area. Surgical intervention was only performed after biopsy in four dogs, and this may limit the significance of the findings of this study; nonetheless this study significantly expands upon previous literature given the rare nature of this infection in dogs.
Conclusion
In conclusion, nasal rhinosporidiosis should be suspected in endemic regions in young to middle-aged male and female dogs with unilateral nasal disease or a visible mass present within the nasal cavity. Nasal CT may be characterized by soft-tissue contrast-enhancing masses just inside the rostral nares in the absence of bony lysis. Further study is required to determine the full range of potential CT abnormalities in clinical patients. White to yellow multifocal pinpoint foci present on the surface of a nasal mass may suggest the presence of rhinosporidiosis. Long-term survival is possible in both the primary care and referral environments, although repeat surgery may be required. Future studies are required to determine the efficacy of a full range of medical treatments including dapsone, azole antifungals, and topical povidone-iodine therapy in canine rhinosporidiosis. Furthermore, only one of three cytology samples were diagnostic for rhinosporidiosis, and histopathology should be considered superior to cytology for this disease.
Soft-tissue postcontrast cross-sectional computed tomography image of the nasal cavity of a dog with rhinosporidiosis. A soft tissue contrast-enhancing mass is present within the rostral right nasal cavity (outlined). The masss measures 0.7 × 0.7 × 2.0 cm. No lysis of bony structures is present.
(A and B) Anterior rhinoscopic images of the white-yellow multifocal variably sized foci present on the surface of proliferative masses that were subsequently identified as rhinosopridiosis via biopsy. These foci are commonly reported on the surface of Rhinosporidium seeberi lesions and are suspected to represent sporangia.
Hematoxylin and eosin–stained section from a submitted nasal biopsy. The lamina propria is expanded by large numbers of macrophages, lymphocytes, and plasma cells, but in other sections neutrophils predominate. Scattered throughout the inflammatory population are Rhinosporidium sporangia in various life stages. Seen here are the smaller juvenile sporangia with an eosinophilic unilamellar cell wall, granular amphophilic cytoplasm, and a prominent nucleus (black arrows) as well as a single large intermediate sporangium with an amphophilic bilamellar cell wall and cyptoplasm filled with abundant punctate basophilic endospores (red arrow).
Hematoxylin and eosin–stained section from a submitted nasal biopsy. Seen here is a ruptured mature sporangium spilling out mature endospores. Large numbers of degenerate neutrophils are found marginating the ruptured endospore.
Diff-Quick stain of a diagnostic nasal smear, original magnification ×1000. Clusters of deeply basophilic endospores are seen interspersed among degenerate neutrophils. A 10 μm marker is shown in the bottom right-hand corner of the image.
Contributor Notes
From the Department of Clinical Sciences (H.C., A.J.M.) and Department of Pathobiology and Population Medicine (N.M., B.B.), Mississippi State University College of Veterinary Medicine, Mississippi State, Mississippi.
H. Cridge’s present affiliation is the Department of Small Animal Clinical Sciences, Michigan State University College of Veterinary Medicine, East Lansing, Michigan.
