JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

January 2023

N-M15

 

Signalment (JPC #1777435): Bear  

 

HISTORY: This bear had a one-year history of seizures uncontrollable with antiepileptics.   

 

HISTOPATHOLOGIC DESCRIPTION: Cerebrum: Subjacent to the ependyma; expanding, compressing, and replacing portions of the periventricular gray and white matter; and extending to cut borders is a well demarcated mass composed of coalescing granulomas up to 2 mm in diameter. Granulomas are characterized by a center of numerous acicular clefts (cholesterol clefts) admixed with small amounts of amphophilic crystalline debris, surrounded by many multinucleate giant cells (Langhans, foreign body, and touton type) and few gitter cells, hemosiderin-laden macrophages, lymphocytes, plasma cells, neutrophils, fibrin, hemorrhage, and a small amount of fibrous connective tissue (fibrosis). The adjacent neuropil is multifocally vacuolated (spongiosis) and there is mild microgliosis. 

 

MORPHOLOGIC DIAGNOSIS: Cerebrum: Cholesterol granulomas, multifocal to coalescing, bear, ursid. 

 

SYNONYMS: Cholesteatoma, cholesteatosis of the choroid plexuses

 

GENERAL DISCUSSION:  

• Choroid plexus cholesterol granulomas are common, often incidental findings in mature and aged horses, with an incidence of 15-20% and are rare in other species
• Usually benign with minimal destruction of adjacent tissue

 

PATHOGENESIS:  

 

TYPICAL CLINICAL FINDINGS:  

• Commonly this condition is asymptomatic
• Large masses that compress and destroy cerebral tissue can present with seizures, aggression, dullness, ataxia, and circling

 

TYPICAL GROSS FINDINGS:  

• Affected plexus is swollen and occasionally the whole plexus is occupied by the cholesterol granuloma, which is a firm, crumbly, and gray to tan nodule that has a gleaming, pearly appearance on cut surface; crystals can be expressed from the cut surface  
• More frequently found in the choroid plexus of the fourth ventricle than the lateral ventricle (JKP)
• Masses present in lateral ventricle are more clinically important, as they may grow to be massive and compress adjacent tissue; they may also obstruct the interventricular foramen, leading to acquired hydrocephalus à dilation and pressure atrophy of the walls of the ventricles 
  1. Source of cholesterol is likely membranes from necrotic erythrocyte due to intermittent hemorrhage 
• Massive cholesterol granulomas of the lateral ventricles are more often associated with young horses
• Mineralization possible

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

 

DIFFERENTIAL DIAGNOSIS:  

For gross findings:

• Choroid plexus papilloma or carcinoma (N-N06): These are rare, highly vascular, papillary growths of the choroid; neoplastic cells maintain choroidal appearance; resultant hydrocephalus is common
• Meningioma (N-N07): Common in dog/cat, rare in cattle; multiple morphologic variants, e.g.:
  • Meningotheliomatous meningioma – neoplastic cells in sheets or pseudoalveoli on a vascular, collagenous stroma
  • Psammomatous meningioma– neoplastic cells in whorls with central lamellar hyaline tissue and calcium/iron salts
  • Angioblastic meningioma– neoplastic spindle cells surrounding endothelial cells in vessels lining vascular clefts 

 

COMPARATIVE PATHOLOGY:  

• Report of a dog with an intradural cholesterol granuloma that was associated with degenerative neuropathy in the cauda equina   
• Aural cholesteatoma (Tympanokeratoma): cysts containing keratinized epithelium in external auditory canal; associated with chronic otitis externa or otitis media; reported in the dog, cat, gerbil (over 50% affected by 2 years of age)
• Chronic otitis media with cholesterol clefts (Cholesterol Granulaoma): the mucoperiosteum in chronic otitis media becomes expanded by granulomatous inflammation, granulation tissue formation, fibroplasia, invaginated glands, and frequently contain cholesterol; common in dogs, cats, pigs, and cattle
  1. Sources of cholesterol are likely cell membranes from necrotic cells, previous hemorrhage, and surfactant 
• Xanthomatosis: Green (Chinese) water dragons and geckos; cholesterol granulomas in the brain à displacement of the adjacent brain and involvement of the spinal cord; may be caused by nutritional factors

References:  

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents & Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016:207.
2. Cantile C, Youssef S. Nervous system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier; 2016:304.
3. Miller AD, Porter BF. Nervous system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:966.
4. Njaa BL. The Ear. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1375.
5. Origgi FC.  Lacertilia.  In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London: Elsevier/Academic Press; 2018:879-880.
6. Tanaka Y, Watanabe K, Miller AD, Matsumoto K, Kobayashi Y. Cholesterol granuloma associated with degenerative neuropathy in the cauda equina of a dog.  J Vet Diagn Invest. 2022;34:1011-1014.

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