Introduction
A 9-year-old spayed female Maine Coon cat was presented at the University of Veterinary Medicine Vienna with the history of nonpruritic bilateral ear disease and unilateral Horner syndrome. Additionally, the patient had recurrent coughing episodes for several months and was diagnosed with a mixed (mycoplasmic and bacterial) neutrophilic bronchopneumonia and a follicular nasopharyngitis. Successful treatment with marbofloxacin (2 mg/kg, PO, q 24 h) and prednisolone (1 mg/kg, PO, q 24 h) was accomplished several weeks before the current presentation.
Right-sided Horner syndrome and an approximately 20° right head tilt were present on initial physical examination. Otoscopy with a hand-held otoscope revealed a small pink nodule in the right and several nodules in the left proximal horizontal external ear canal (EEC) without any discharge and the cytology of both EECs was unremarkable.
Further, a combination of CT (SOMATOM Emotion 16-slice configuration; Siemens Healthcare), MRI (Magnetom Espree 1.5 T; Siemens Healthcare) and video-otoscopy (VO) of both ears was performed under general anesthesia. According to the CT examination, both middle ear cavities (MECs) were filled with a soft tissue opacity material. Furthermore, mild thickening of the right tympanic bulla (TB) wall was present. Both TBs were bulging outwards into the EEC, while the EEC appeared normal bilaterally (Figure 1). A soft tissue opacity was also identified in the caudal portion of the nasal cavity, the left nasopharyngeal meatus and the right frontal sinus. Contrast MRI study proved bilateral “bulla lining,” suggestive of the middle ear mucosal inflammation. Additionally, the medial compartment of the right TB showed a softer tissue-like signal while the signal of the lateral division indicated fluid accumulation. The mucosa had an irregular to small nodular appearance with some contrast enhancement close to the TM (tympanic membrane). The lymph nodes of the head and neck region were mildly enlarged, but symmetric. In conclusion, otitis media (OM) with suspicious small polyps or nodules of other origin (like neoplasia) as well as rhinitis and sinusitis were described in diagnostic imaging.
A—Transverse CT image (in bony window) of the head at the level of the middle ear of the cat. Both bullae show a soft tissue density indicative for fluid accumulation or a mass. Both tympanic membranes are bulging into the external ear canal (EEC). The right (left of the image) bony wall of the bulla is mildly thickened. B—Corresponding transverse MRI image (T1 weighted, with contrast media). Note the different signals within the medial and lateral compartment of the right tympanic bulla. The moderately hypointense signal is more indicative for fluid in the T1-weighted sequence (asterisk). In T2-weighted (not shown) sequences, the lateral compartment had a hyperintense signal. However, hyperintense bulla lining is visible bilaterally while it seems to be more irregular or nodular on the right side (arrows).
Citation: Journal of the American Veterinary Medical Association 260, 10; 10.2460/javma.21.03.0149
VO of both EECs using a rigid endoscope (Veterinary Otoscope Set 67260 OSA; Karl Storz GmbH & Co KG) revealed 2 multilobular nodules (approx 6 mm in diameter) in the proximal part of the right horizontal EEC (Figure 2) located in the usual position of a TM, and on the septum of the TB. Several smaller nodules (2 to 4 mm in diameter) were detected in the left EEC/TB interface. Both TMs were ruptured.
Two multilobular nodules, one located in the right proximal horizontal EEC (black arrow) and the second in the ECC/MEC interface and right MEC, respectively, (white arrow).
Citation: Journal of the American Veterinary Medical Association 260, 10; 10.2460/javma.21.03.0149
A fine-needle aspiration from the nodules was performed using a flexible 0.7-mm myringotomy needle (67071 XS; Karl Storz Endoscopy Inc; outer tube, 1.7 mm). One drop was placed on the microscopy slide, air-dried, and stained with a Romanowsky type stain. Cytologic examination revealed protein rich material with erythrocytes, degenerated neutrophils and few ciliated epithelial cells.
All nodules from the left TB/EEC interface were removed endoscopically using biopsy forceps (67161 Z, flexible, oval, double action jaws, 5F, 34 cm; Karl Storz Endoscopy Inc) and submitted for the histopathological analysis. Muco-hemorrhagic fluid was collected from both MECs using sterile polyvinyl chloride feeding tube of 1 mm in diameter with its end cut to 25 cm in length. Samples for cytology and microbial cultures were collected from both MECs; cultures did not reveal any microbial growth.
After the complete video-otoscopic removal of all nodules from different anatomic parts of both ear canals, both MECs were flushed with warm (37 °C) saline (0.9% NaCl) solution using sterile polyvinyl chloride feeding tubes. Later, 2 mL of a mixture of enrofloxacin, dexamethasone, and Tris-EDTA buffer solution (1 part [10 mg] of injectable enrofloxacin 2.5%, 1 part [0.8 mg] of injectable dexamethasone Na-P 2 mg/mL; and 3 parts of ear cleanser with Tris-EDTA) was applied into each EEC and MEC, since filled MECs and bulla lining seen on MRI were suggestive for the middle ear inflammation or infection.
Next, sampled nodules were fixed in neutral-buffered 10% formalin, embedded in paraffin wax and stained with H&E. Throughout all sections loosely arranged fibrovascular tissue with numerous empty clefts, characteristic for cholesterol crystals (Figure 3) was observed. Cholesterol crystals, which were commonly surrounded by microhemorrhage and macrophages, comprising multinucleated giant cells with abundant, amphophilic, pale, finely granulated cytoplasm. Additionally, numerous neutrophil granulocytes and fewer plasma cells were interspersed and, interjacent, focal infiltrations with lymphocytes were evident. The surface epithelium was partially covered by exudate and regionally displayed a marked hyperplasia with orthokeratotic hyperkeratosis and mild focal hydropic degeneration. Neovascularization within the inflamed area and focal mineralizations were present in 1 biopsy too.
Histologic image of videoendoscopically removed biopsy material. H&E staining. A—Abundant cholesterol clefts throughout the tissue sample; bar = 400 µm. B—Cholesterol clefts surrounded by numerous macrophages and neutrophil granulocytes. Note multinucleated giant cells (arrow); bar = 40 µm.
Citation: Journal of the American Veterinary Medical Association 260, 10; 10.2460/javma.21.03.0149
Local treatment was administered daily into both EECs until the negative microbial culture as well as the negative cytology from the EECs 1-week post VO. Prednisolone (1.5 mg/kg, PO, q 24 h) was administered until the results of microbiology and histopathology 7 days later. At this point, clinical signs were resolved, otoscopy and cytology of both EECs were unremarkable, and the treatment was discontinued.
At the recheck examination 6 months later, the physical and otoscopic examinations were unremarkable; both TMs were regrown. At this point a CT/MRI recheck was declined by the owner, as the patient did not show any clinical signs of otic or sinonasal disease.
Discussion
The term cholesterol granuloma (CG) or xanthogranuloma histologically describes a granulomatous lesion containing cholesterol clefts, hemosiderin, or other endogenous byproducts, which cannot be absorbed by giant cells. Cholesterol granulomas have been reported in various tissues eg the petrous apex, orbita, brain, maxillary sinus, lungs and breasts in humans.1–3 Also, they have been described in the middle ear, maxilla, brain, temporal limbus area, and anterior chamber in dogs4–8 and in the brain and uterus in cats.9–11 A case of a unilateral CG localized close to the TM of a cat with OM, diagnosed and treated through ventral bulla osteotomy, has been reported with mild symptoms remaining during the rechecks.12
Here we describe an unusual case of a bilateral aural CGs in a cat, discovered via VO, performed after the middle ear contents were detected via CT and MRI.
To the best of our knowledge, this is the first case report of feline bilateral CGs, located in the EEC/MEC interface, successfully treated by minimally invasive videoendoscopic removal of the nodules, followed by short term ear drops and systemically administered oral glucocorticoids. Systemic prednisolone can be used to reduce the severe inflammation of the middle ear mucosa.13–15 Nowadays, topical treatment of OM is considered essential for the successful treatment of OM in dogs and cats.15 Here, injectable enrofloxacin was added to the topical solution14,15 until negative microbial culture results from the MECs were obtained. Concerns may arise for the development of antimicrobial resistance by using antimicrobials before the results of the susceptibility testing. Though, since topical antibiotics can achieve multiple times the blood minimal inhibitory concentration, they are utilized empirically in topical treatment.15 For practical purposes, topical treatment can be applied into the MEC when the patient is anesthetized for the VO. Enrofloxacin, as like as other fluoroquinolones, has been proven to be safe to use in the middle ear with less ototoxic potential.16
Cholesterol clefts were described in a severe exudative and/or hemorrhagic middle ear inflammation in a cat postmortem17 as well as in people18 and presumably may initiate a foreign body reaction, resulting in a granuloma formation.
According to the literature, CG is a foreign body granuloma, representing an inflammatory reaction of mucosal epithelium,19 and several hypotheses about the pathogenesis were proposed.8,20 Factors like local bleeding, interference with clearance or drainage of the cavity, as well as obstruction of ventilation are suspected causes in humans.21
Cats with sinonasal disease have a higher prevalence of MEC effusion, possibly due to the potential of eustachian tube (ET) obstruction by inflammatory tissue or neoplasia,22,23 while both unilateral and bilateral OM/otitis interna can result from soft palate abnormalities.24
Cholesterol granulomas have been experimentally induced in the MEC of cats through ET obstruction leading to middle ear effusion because of inflammation of the MEC mucosa25,26 and in the middle ears of guinea pigs following the injection of sterile cholesterol suspensions.20
In our case, we hypothesize that chronic respiratory disease (eg, follicular nasopharyngitis) could have led to the mechanical obstruction/inflammation of the ET with subsequent reduced ventilation and formation of CGs.
Ventilatory obstruction is assumed to play a role in the CG formation.19,27 Mucosal inflammation or edema may initially obstruct the pneumatic pathways to the ciliated epithelial cells. Trapped gas resorption could then result in negative pressure within the epithelial cells leading to mucosal hemorrhage. Evidence supporting this theory has been published after experimental obstruction of the pharyngeal orifice of the ET in squirrel monkeys leading to development and expansion of CG in the mastoid region.22 Also, trauma, infection or a sterile inflammation can lead to local hemorrhage.28,29 Lack of ventilation and drainage could lead to stasis of blood and possibly other tissue elements and therefore to deposition of cholesterol and other byproducts originating from erythrocytic membranes, not capable to be phagocytosed by giant cells. Cholesterol and the other irritants stimulate a foreign body reaction and the formation of the granuloma.
Treatment of CGs of the petrous apex in humans consisted of either endoscopic or surgical removal of the granulomas.1 In one cat and one dog, the lesions were removed surgically after bulla osteotomy,8,12 while in another cat the diagnosis was confirmed post mortem.9 To our knowledge, this is the first case of feline bilateral CGs diagnosed with a combination of CT, MRI, VO, and histopathology and removed minimal invasively via VO, which led to remission of all symptoms and no relapse for 6 months of medium-term follow-up. Unfortunately, because of the necessity of anesthesia, the patient was not rechecked with a use of CT or MRI at this time point and therefore the effect of the treatment on the nasal cavity, the left nasopharyngeal meatus and the right frontal sinus cannot be evaluated.
Acknowledgments
No third-party funding or support was received in connection with this study or the writing or publication of the manuscript. The authors declare that there were no conflicts of interest.
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