JPC SYSTEMIC PATHOLOGY
SPECIAL SENSES SYSTEM
April 2018
S-M02

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:  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.  The mucoperiosteum is similarly thickened up to six times normal, and occasionally forms small 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, adjacent inflammatory cells and resorption lines (osteomyelitis and remodeling).  Inflammatory cells surround and infiltrate the perimysium and superficial aspects of thestapedius muscle; rarely, associated myocytes multifocally shrunken, have hypereosinophilic cytoplasm and pyknotic nuclei (necrosis).  Changes within the contralateral middle ear are limited to a mild, focally extensive submucosal inflammatory cellular infiltrate.

MORPHOLOGIC DIAGNOSIS:  Middle ear:  Otitis media, unilateral, suppurative and histiocytic, chronic-active, diffuse, moderate, with osteomyelitis, bony remodeling, and myositis, fuzzy rat (WF/PmWp-“fz”), rodent.

CONDITION:  Otitis media

GENERAL DISCUSSION:

• External ear: Pinna and external auditory meatus
• Middle ear: Tympanic membrane, tympanic cavity, bony ossicles (stapes, malleus and incus), and the auditory or 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 (with perilymph)
• Otitis media: Inflammation of the tympanic cavity within the temporal bone; 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: the 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 (membrane cholesterol derived from RBCs or inflammatory cells); cholesterol granulomas may occur; myringitis (tympanic membrane inflammation)

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
• 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
• 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)

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
• Secretion from the external auditory canal is serous, hemorrhagic or suppurative

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
• Chronic otitis media
  • Tthere may be inspissations 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

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 & internal 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: pulmonis, P. aeruginosa, Klebsiella oxytoca, Streptococcus sp, reovirus and sendai virus
• Guinea pigs: Associated with pneumonia, 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 , Corynebacterium kutscheri, and Klebsiella spp
• Rabbits: Associated with Pasteurella multocida (snuffles)
• Dogs and cats:
  • Otitis externa is more common; 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 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 tem-porohyoid 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
  • Horses: Guttural pouch disease; guttural pouch empyema (often Streptococcus spp); chronic exudate may become inspissated and form chondroids
  • Reptiles: Abscesses in the middle ear have been associated with Pasteurella
  • Saker Falcon: Cryptosporidium baileyi (one case report)

REFERENCES:

1. Barthold SW, Griffy SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: John Wiley & sons; 2016: 60-65, 134-136, 143-145, 231, 283-285.
2. Bougioulkis PA, Weissenbock H, Wells A et al. Otitis media associated with cryptosporidium baileyi in a Saker Falcon (Falco cherrug). 2013. J Comp Pathol. 148; 419-423.
3. Njaa BL. The ear. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017: 1237-1241;1251-1252.
4. Novales M, Ginel PJ, Diz A et al. Mucoperiosteal exostoses in the tympanic bulla of African lions (panther leo).  2015. Vet Pathol. 52(2): 377-383.
5. Santagostino SF, Arbona RJR, Nshat MA et al. Pathology of aging in NOD scid gamma female mice.  2017. Vet Pathol. 54(5): 855-869.
6. Sula MM, Njaa BL, Payton ME. Histologic characterization of the cat middle ear: in sickness and in health. 2014. Vet Pathol. 51(5):951-967.
7. Wilcock BP, Njaa BL. Special senses In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals.  Vol 1. 6th ed. St. Louis, MO: Elsevier Limited; 2016: 496-498

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