JPC SYSTEMIC PATHOLOGY

SPECIAL SENSES SYSTEM

April 2024

S-M02

 

SLIDE A: Signalment (JPC #2168075): Fuzzy rat (WF/PmWp-“fz”): An inbred strain of hypotrichotic rat derived from a Wistar Furth colony

 

HISTORY: The fuzzy rat was sacrificed as part of a quality assurance program.

 

HISTOPATHOLOGIC DESCRIPTION: Transverse section of head, middle ear: Unilaterally, the tympanic cavity is filled with high numbers of degenerate neutrophils, macrophages, and fewer lymphocytes and plasma cells admixed with moderate amounts of fibrin and proteinaceous fluid. The tympanic membrane is thickened up to six times by a similar population of inflammatory cells, fibrin, edema, and congested vessels (myringitis). The mucoperiosteum is similarly thickened up to six times normal, contains many small caliber blood vessels and fibroblasts (granulation tissue) and occasionally forms small polypoid projections into the tympanic cavity. The auditory ossicles and osseous walls of the middle ear, including the tympanic bulla and extending into petrous temporal bone, have multifocal irregularly scalloped edges, with osteoclasts in Howship’s lacunae and resorption lines (bone lysis). Inflammatory cells surround and infiltrate the perimysium and superficial aspects of the stapedius muscle; rarely, associated myocytes are multifocally shrunken with hypereosinophilic cytoplasm and pyknotic nuclei (necrosis). Changes within the contralateral middle ear are limited to a mild, focally extensive mucoperiosteal inflammatory cellular infiltrate.

 

MORPHOLOGIC DIAGNOSIS: Middle ear: Otitis media, unilateral, suppurative and histiocytic, chronic-active, diffuse, moderate, with myringitis, granulation tissue, bone lysis, and stapedius muscle myositis, fuzzy rat (WF/PmWp-“fz”), rodent.

 

CONDITION: Otitis media

 

SLIDE B: SIGNALMENT (JPC# 4021103): 7-year-old female spayed, Jack Russell terrier mix (Canis familiaris), canine.  

 

HISTORY: Animal presented for bilateral otitis. The left ear resolved and the right ear was refractory to treatment resulting in the rupture of the tympanic membrane. A total ear canal ablation (TECA) was performed. 

 

HISTOPATHOLOGIC DESCRIPTION: Ear canal: Circumferentially, markedly elevating the hyperplastic superficial aural epithelium and severely expanding the subepithelial connective tissue are many ectatic and frequently hyperplastic coiled tubular apocrine ceruminous glands. Multifocal to coalescing, apocrine glands are markedly dilated, lined by either a single layer of cuboidal epithelium, multiple layers of compacted epithelium or rarely undergo squamous metaplasia. Affected glands frequently are surrounded by moderate numbers of macrophages which often contain a golden brown granular to globular pigment (cerumen or hemosiderin), lymphocytes, plasma cells and fewer neutrophils, as well as concentric rings of dense fibroblasts and collagen (fibroplasia). Multifocally, apocrine glands are filled with either an eosinophilic, acellular material (serum), a basophilic flocculent material or are filled with eosinophilic cellular and karyorrhectic debris (necrosis) admixed with degenerate and non-degenerate neutrophils and swollen macrophages. Multifocally, sebaceous glands are similarly hyperplastic, disorganized and irregular, while the subepithelial connective tissue is markedly expanded by previously described fibroplasia admixed with high numbers of small caliber blood vessels. The overlying epidermis is hyperkeratotic and acanthotic occasionally forming short rete ridges. Multifocally, keratinocytes within the stratum spinosum contain intracellular edema and there are prominent cellular bridge (spongiosis). Multifocally throughout the section there are ectatic lymphatics (edema). 

 

MORPHOLOGIC DIAGNOSIS: Ear canal: Otitis externa, histiocytic and lymphoplasmacytic, diffuse, moderate with neutrophilic and histiocytic adenitis, fibroplasia, glandular ectasia and hyperplasia, and epithelial hyperkeratosis and hyperplasia, Jack Russel terrier, canine. 

 

CONDITION: Otitis externa

 

GENERAL DISCUSSION: 

• Ear anatomy:

• External ear: Pinna and external auditory meatus 
• Middle ear: Tympanic membrane, tympanic cavity (within temporal bone, includes tympanic bulla), bony ossicles (stapes, malleus, and incus), and the auditory/Eustachian tube (connects ear with the nasopharynx & equalizes pressure on both sides of the tympanic membrane)
  • Direct apposition of epithelia and submucosa with periosteal connective tissues (i.e. in tympanic bulla) is unique to the ear, sometimes known as auricular mucoperiosteum
  • Tympanic membrane has unique ability to heal quickly while remaining thin via epithelial migration (membrane rupture is closed by migrating epithelial cells; then granulation tissue closes the underlying mesenchymal portion of tissue)
  • Mucociliary apparatus is important defense mechanism in auditory tube and parts of tympanic cavity
  • Cuboidal epithelial cells lining auditory tube produce surfactant (90% lipid, 10% surfactant proteins SP-A); auditory surfactant contain collectins (opsonize microorganisms and antigens), reduces local surface tension helping to keep the auditory tube open 
  • Auditory tube-associated lymphoid tissue (ATALT): “Tubal tonsil”
• Inner ear: Semicircular canals, vestibule, and cochlea, each composed of a membranous labyrinth (containing endolymph) within a bony labyrinth (containing perilymph)

• Otitis media: Inflammation of the tympanic cavity; typically bacterial; ruminants and swine most severely affected, also common in laboratory animals; less common in cats & dogs
  • Acute otitis media: Tympanic cavities and bullae are filled with suppurative exudate; mucoperiosteum is edematous; mucosal epithelium may be eroded/ulcerated; auditory ossicles may undergo bony erosion
  • Chronic otitis media: Edematous mucoperiosteum begins to form polypoid projections and folds resulting in formation of pseudoglands; discrete lymphoid nodules may form; bone remodeling may occur (numerous/prominent reversal lines); aggregates of acicular clefts (cholesterol derived from membranes of RBCs or inflammatory cells); cholesterol granulomas may occur; myringitis (tympanic membrane inflammation)
• Otitis externa
  • Most common in dogs and cats; dogs are most severely affected (15-20.4% of dogs; 4% of cats); complex and multifactorial
  • Primary causes (factors that initiate inflammation of the external ear canal): Allergic, immune-mediated, endocrine, epithelialization, glandular, parasitic, and viral
  • Secondary causes: Bacterial or mycotic infections; alteration of the microenvironment (medication or excessive ear cleaning)
  • Predisposing factors (factors promote an environment suitable for survival or the perpetuating factors): External ear conformation, local aural environment, concurrent systemic disease, negative effects of local treatment
  • Perpetuating factors (factors that sustain the established disease): Acquired changes à narrowing of the ear canal, impaired or altered epithelial migration, inflamed glandular adnexa, or concurrent middle ear disease

 

PATHOGENESIS:

• Otitis media: Usually either an ascending infection via the eustachian tubes or following perforation of tympanum 
  • In dogs, otitis media is often a sequela of chronic otitis externa, often associated with tympanic membrane rupture; less important in cats where ascending infection from the pharynx thru the auditory tube is more common
    • Bacterial causes: E. coli, Enterobacter spp., Enterococcus spp., Streptococcus spp., B-hemolytic Streptococcus spp., Staphylococcus spp., Proteus spp., and Clostridium spp.
    • Ceruminous gland hyperplasia and ectasia may precede clinical signs of otitis externa in American Cocker Spaniels and a genetic etiological component is likely (Kaimio, J Comp Pathol, 2021)
  • There is circumstantial evidence in all species of hematogenous localization in middle and inner ear
  • Otitis interna almost always results from spread of infection from the middle ear
  • Otitis externa predisposes to otitis media; may be related to perforation of the tympanic bullae 
• Vestibular disease may be caused by concurrent otitis interna & media 
• Horner’s syndrome: Rare; otitis media occasionally causes demyelination, axonal injury, & partial paralysis of post ganglionic sympathetic fibers that run through the middle ear to innervate the eye
• Pourfour du Petit syndrome: Rarely injury to postganglionic sympathetic fibers results in hyperexcitability (opposite of Horner’s); spontaneous resolution; typically cats with ear exam/flush under anesthesia
• Para-aural abscesses: Abscess lyse bullae walls and may form a draining tract that exits the ventrolateral neck in animals with septate bullae (cattle, pigs, goats, camelids)
• Otitis externa: Narrowing of the EAM and irreversible osseous and fibrous metaplasia à ear canal becomes increasingly stenotic à medical management fails à may require TECA
  1. TECA tissue should be submitted for histopathology to assess for predisposing factors 

 

TYPICAL CLINICAL FINDINGS: 

• Otitis media: Usually none, possibly head tilt and circling, nasal discharge
• Horner’s syndrome: Miosis, endophthalmos, ptosis, narrowed palpebral aperture, protrusion of third eyelid, vasodilation in skin of face (warm)
• Pourfour du Petit syndrome (opposite of Horner’s): Mydriasis, exophthalmos, widened palpebral aperture, cool skin all over face
• Otitis interna: Vestibular dysfunction

 

TYPICAL GROSS FINDINGS:

• Bullae filled with fibrinopurulent to caseous exudate; underlying mucosa ulcerated or thickened/fibrotic (if chronic); +/- bony remodeling or lysis; in severe cases, tympanic membrane/bony ossicles may be missing
• Tympanic bullae containing any fluid should be suspect for otitis media 
• Secretion from the external auditory canal is serous, hemorrhagic or suppurative 
• Otitis externa: Discharge from the ear (otorrhea), hemorrhage from the ear (otorrhagia, pain during ear palpation (otodynia or otalgia); auricles are red, warm, and edematous; 

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Myringitis: Tympanic membrane is thickened by inflammatory cells (neutrophils, macrophages +/- bacteria) or fibrosis/granulation tissue (more chronic); may be perforated in severe cases; purulent to granulomatous exudates in tympanic cavity
  • Tympanic cavity goblet cell hyperplasia/metaplasia (mucus very viscoelastic> decreased mucociliary clearance); areas of tympanic cavity lined by pseudostratified columnar epithelium may form small cystic cavities 
  • Ciliary atrophy of auditory tube (due to pressure) 
• In chronic or severe infections, the tympanic bulla and petrous portion of the temporal bone may exhibit periosteal proliferation, osteosclerosis, bone resorption and new bone formation 
  1. Chronic otitis media
     • Bullae: Filled with fibrinopurulent to caseous exudate with mucoperiosteal epithelial ulceration, congestion, and edema 
     • Remodeling of bony components; with chronicity mucoperiosteum is thickened by fibrosis and granulation tissue à progresses to destruction of the tympanic membranes and auditory ossicles 
     • May be inspissation of exudates, lysis of ossicles/tympanum, and spread to inner ear and brainstem
     • Dogs and cats may mineralize necrotic material in tympanic bullae leading to formation of otoliths which may be referred to as mucoperiosteal exostoses – in African lions found to be composed of osteonal bone and not calcified necrotic tissue; (Note the term “otolith” also refers to structures within the utriculus and sacculus of the vestibular system of the inner ear)
     • May be associated with inflammatory polyps in dogs or cats
• Otitis externa: 
  • Epidermal, sebaceous, ceruminous, or follicular hyperplasia
  • Dermis: Edema, fibrosis; lymphoplasmacytic, mastocytic, or neutrophilic inflammation; diffuse or nodular
    • Chronic infections: Dense fibrosis; surrounding soft tissue osseous metaplasia with cords of bone that appose pre-existing auricular cartilage; osseous metaplasia may also arise from the auricular cartilage; external auditory meatus may develop proliferative exostoses 
  • Ceruminous glands: Hyperplastic, luminal and periglandular inflammation; increased number of glands

 

ADDITIONAL DIAGNOSTICS: 

• Cytology: Primary goal is to identify overgrowth or infection that may contribute to otitis externa; findings include
  1. Cerumen: Combination of keratin, squamous epithelium, and oily secretions from sebaceous and ceruminous glands
  2. Keratinocytes
  3. Bacteria: Normal ears contain a small number of bacteria; abnormal numbers are generally 25/40x hpf or greater (dogs) and a median of 0.3 cocci per 40x hpf in cats or average of four or fewer cocci (cats); culture and sensitivity required to inform antibiotic selection
  4. Fungi: Malassezia pachydermatitis is the most common yeast associated with otitis externa in dogs and cats; can be seen in the normal ear; finding of yeast should be paired with clinical signs before treating; others include Candida, Microsporum, Penicillium, and Aspergillus 
  5. Mites: Otodectes cynotis; Otobius megnini; Demodex canis 
  6. Inflammatory cells: Normal ears do not contain inflammatory cells and not all forms of otitis contain inflammatory cells; neutrophils and macrophages may be present and bacterial phagocytosis indicates infection rather than overgrowth 

 

DIFFERENTIAL DIAGNOSIS:

• Parasitic otitis externa, with mites penetrating the tympanic membrane
• Neoplasms in the external auditory canal may cause secondary otitis media

 

COMPARATIVE PATHOLOGY:

• Mice: Associated with Mycoplasma pulmonis and Pasteurella pneumotropica
  • Single report of Burkholderia gladioli-associated otitis externa, media, & interna with vestibular disease in immunodeficient mice
  • NOD scid gamma knock out, female mice: otitis media is a cause of death in aging female NSG mice; common causative organisms include: M. pulmonis, P. aeruginosa, Klebsiella oxytoca, Streptococcus sp., reovirus and sendai virus
• Guinea pigs: Associated with S. pneumoniae, S. zooepidemicus, Bordetella sp., and Pseudomonas sp
• Rat: Otitis media most frequently associated with Mycoplasma pulmonis infections; other bacteria isolated include: Streptococcus pneumoniae, Pasteurella pneumotropica, Staphylococcus spp., Corynebacterium kutscheri, and Klebsiella spp.
• Rabbits: Associated with Pasteurella multocida (snuffles)
• Dogs and cats: 
  • Otitis externa is more common than otitis media; associated with ear mites (Notoedres cati, Otodectes cynotis) in cats; more complex pathogenesis in dogs (breeds with pendulous/hairy ear canals predisposed; atopy); Staphylococcus, Pseudomonas sp., Proteus sp. and lipophilic Malassezia spp. commonly isolated
  • Feline proliferative & necrotizing otitis externa: Unknown cause, 2mo- 5yrs old; spontaneous resolution; resembles canine erythema multiforme
    • Gross: Well-demarcated, coalescing, erythematous plaques involving the concave aspect of the pinnae and external ear canals
    • Histo: Epidermal hyperplasia, hyperkeratosis, apoptotic keratinocytes (often with lymphocytic satellitosis), and lymphocytic exocytosis; lesions prominent in the infundibula of hair follicles
  • Less common routes of infection include extension via the temporohyoid joint or migration along vascular or neural pathways (v extension of otitis externa or ascending)
  • Cavalier King Charles spaniels: Primary secretory otitis media (PSOM)- a mucus plug fills the middle ear causing tympanum to bulge outward> head/neck pain or neurological signs and hearing impairment may occur; this is now thought to more likely be otitis media with effusion (OME) a condition found in humans
• Avians: Mild to severe inflammation of the external and middle ear due to bacteria such as E. coli, Pseudomonas aeruginosa, Staphylococcus aureus, Pasteurella multocida (fowl cholera), Proteus mirabilis, Mycoplasma gallisepticum and Enterococcus sp., has been observed  
  1. Among viruses, fowl pox is one of the most common causes of otitis externa
  2. Yeast infections (Candida, Microsporum) have been reported
  3. Mites including Megninia ginglymara and Knemidocoptes sp can cause otitis externa and media in chickens and psittacines respectively
  4. Foreign material (plants/dust) is one of the most common causes of otitis in various species of birds
• Pet birds: Otitis externa is uncommon in birds; hemorrhage, necrosis and exudate are seen; diagnosis depends on identification of the organism on culture or histologic examination
  1. Otitis media may be associated with Chlamydia spp. In psittacines (Walsh, Vet Pathol, 2023)
  2. Otitis media is rarely reported; possible secondary to oral/pharyngeal disease with extension via the pharyngotympanic tube 
• Horses: Guttural pouch disease; guttural pouch empyema (often Streptococcus spp); chronic exudate may become inspissated and form chondroids
• Swine: Result of nasopharyngeal ascent of bacteria through the auditory tubes; Pasteurella multocida, Trueperella pyogenes, and Mycoplasma hyorhinis are likely; piglet dysfunction of the auditory tube is an initial contributing factor; dysfunction due to acute inflammation, goblet cell hyperplasia of mucoperiosteum, and acute inflammatory exudate of the tympanic cavity 
  1. Older pigs: more severe and suppurative; auditory tube lesions more severe; neutrophilic infiltration, fibrosis, and goblet cell hyperplasia leading to ulceration
  2. Colonization of the tympanic cavity > lysis of bone > otitis interna and inflammation of the cochlea and vestibule with extension into the leptomeninges and neuropil
• Ruminants: Histophilus somni, P. multocida, T. pyogenes, Mycoplasma bovis, and Streptococus spp. Are associated with otitis media; mites and nematodes may contribute to severity; nasopharyngeal ascent of bacteria through auditory tubes
  1. Routes of infection: congenital infection; ingestion of colostrum, ingestion of contaminated milk, exposure to infected vaginal secretions; or ingestion or inhalation of respiratory secretions > nasopharyngeal colonization 
  2. M. bovis can infect and colonize the tonsils and enter the eustachian tubes, causing otitis media > chronic infection > meningitis (Suwanruengsri, J Comp Pathol, 2021)
  3. Goat kids: Aspiration of meconium from the oropharynx was transferred through the auditory tube to the middle ear; case report (Newman, J Vet Diagn Invest, 2019)
  4. Cattle: Mycoplasma bovis is associated with endocarditis, pneumonia, mastitis, arthritis, and otitis media (Kanda, J Comp Path, 2019)
• Bighorn sheep: Concomitant otitis media may be seen in association with epizootic bronchopneumonia of bighorn sheep (multifactorial) 
• Goats: Otitis media has been reported from meconium aspiration into the Eustachian tube (Newman, J Vet Diag Invest, 2019)
• Cetaceans: Severe mycotic otitis media due to Aspergillus terreus has been reported in a juvenile stranded harbor porpoise; otitis media can also be caused by Nasitrema globicephalae 
  1. Harbor porpoises: Tympanoperiotic complex; nematode Stenurus minor is the major pathogen found in the middle ear of juvenile and adult animals; hyperplastic lymphoid tissue at entrance to middle ear cavity seen on histo; damage to hearing structures may explain starvation due to impaired ability to catch prey or cause straining or entanglement in nets (Wohlsein, J Comp Pathol, 2019)
• Reptiles: Abscesses in the middle ear have been associated with Pasteurella spp.
• Common thresher sharks (Alopias vulpinus): common thresher shark strandings may be associated with Carnobacterium maltaromaticum; endolymphatic ducts act as portals of entry to the brain; histology revealed severe meningoencephalitis and inflammation of the inner ear and subcutaneous tissues surrounding the endolymphatic ducts (Steele, Vet Pathol, 2022)
• Amphibians: Otitis media may result from bacteriemia 
• Red kangaroo (Macropus rufus): Chronic otitis caused by Bacteroides pyogenes à intracranial inflammatory polyp; tympanic cavity effaced by neutrophils and macrophages, surrounded by lymphoplasmacytic inflammation and edematous fibrovascular tissue; lymphoplasmacytic leptomeningitis (Riker, J Vet Diagn Invest, 2023) 

 

REFERENCES:

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