JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

February 2023

N-N06

 

Signalment (JPC #1849481): 5-year-old female Afghan hound

 

HISTORY: This dog was stuporous, depressed, and unable to walk for 5 days prior to death. Dysphagia was noted for 4 days before death. At necropsy, a spherical mass approximately 1 cm in diameter occupied the third ventricle, displacing adjacent brain tissue. The lateral ventricles were expanded.

 

HISTOPATHOLOGIC DESCRIPTION: Diencephalon, thalamus and third ventricle: Arising from the choroid plexus, filling the third ventricle, and compressing and minimally invading into the adjacent neuropil is a 7mm diameter, unencapsulated, moderately cellular, expansile neoplasm composed of columnar epithelial cells 1-3 cell layers thick, forming numerous arborizing papillary projections supported by moderately dense fibrovascular stalks.  Neoplastic cells have indistinct borders and a moderate amount of granular eosinophilic cytoplasm. Nuclei are variably basally to apically oriented and round to oval with finely stippled chromatin and 1 variably distinct magenta nucleolus.   Mitoses average 1 per 2.37mm². There is mild anisokaryosis and anisocytosis. Multifocally the stroma is mildly expanded by clear space (edema), hemorrhage, and fibrin, with rare lymphocytes, plasma cells, and hemosiderin-laden macrophages. Between neoplastic papillary projections, there are many irregularly round to ovoid, lamellated, pale basophilic concretions up to 100 µm in diameter (psammoma bodies). The adjacent neuropil is mildly vacuolated and edematous (spongiosis) with mild gliosis, occasional reactive astrocytes, numerous small caliber blood vessels lined by hypertrophic (reactive) endothelium, and perivascular hemorrhage.

 

MORPHOLOGIC DIAGNOSIS: Diencephalon, third ventricle: Choroid plexus papilloma, Afghan hound, canine.

 

GENERAL DISCUSSION:  

• Choroid plexus epithelial cells are specialized ependymal cells that secrete cerebrospinal fluid (CSF) 
• Choroid plexus tumors (CPTs) are derived from the neuroepithelium of the choroid plexus
• Uncommon in dogs (10% of primary CNS tumors), rare in horses and cattle, and very rare in other species

• Golden retrievers may be overrepresented
• Usually seen in middle-aged to older dogs 

• Usually in the fourth ventricle but can be in third and lateral ventricles

• Obstructive hydrocephalus is a common complication

• The World Health Organization (WHO) classifies human choroid plexus tumors (CPTs) into 3 different grades (a similar scheme has been suggested in dogs) (Higgins, Tumors 2017):

• Choroid plexus papilloma (CPP, grade I)
• Atypical choroid plexus papilloma (atypical CPP, grade II, least common)
• Choroid plexus carcinoma (CPC, grade III, most common)

 

PATHOGENESIS:

• Mitotic index, cell density, and multilayering of papillae are the main significant histologic markers of malignancy for grading CPTs in dogs
• Intraventricular spread within ventricular system and subarachnoid space may not be indicators of malignancy

 

TYPICAL CLINICAL FINDINGS:

• CNS signs - spastic tetraparesis, positional nystagmus, head tilt, vomiting, seizures 
• CSF may be bloody or contain increased protein, neoplastic cells are not  usually evident

• CPC usually has a higher CSF protein concentration than CPP

 

TYPICAL GROSS FINDINGS:

• Well-defined, grayish white to red, granular or papillary masses that grow into the ventricle and compress adjacent nervous tissue
• Hydrocephalus (due to CSF obstruction)

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Choroid plexus papilloma (grade I; CPP): Regularly arborizing exophytic connective tissue lined by a single layer of uniform cuboidal to columnar epithelium;  mitoses are rare (<1 per 10 HPF); mild anisokaryosis may be evident
• Atypical choroid plexus papilloma (grade II; atypical CPP): Intermediate grade between CPP and CPC; not universally recognized in dogs; atypical CPP may exhibit increased cellular density, nuclear pleomorphism, higher mitotic activity (≥2 per 10 HPF), and areas of solid growth
• Choroid plexus carcinoma (grade III; CPC): Piling up of epithelium, invasion of adjacent neuropil, desmoplasia, and/or anaplastic features (nuclear atypia, loss of papillary pattern with transition to cellular sheets, increased mitotic rate (>5 per 10 HPF), necrosis)
• While not part of WHO scoring, using glomeruloid microvascular proliferation (GMVP), desmoplasia, and increased vascular density (IVD) may also help delineate the grade of CPT (Muscatello, Vet Pathol. 2018)
• All CPT grades may metastasize throughout the ventricular system or subarachnoid space with implantation in the ependymal or meninges respectively; even histologically benign CPP can behave as aggressive carcinomas with widespread metastasis
• There is frequent mineralization and formation of psammoma bodies

 

ULTRASTRUCTURAL FINDINGS:

• Juxtaluminal tight junctions, microvilli, and apical ciliary basal bodies (but cilia are rare)  
• Lateral cell surfaces lack interdigitations
• Cells rest on a continuous basal lamina

 

ADDITIONAL DIAGNOSTIC TESTS:

Immunohistochemistry:

• Positive immunohistochemical markers:

• Vimentin (strongly immunolabels the connective tissue core around blood vessels, but not the neoplastic epithelial cells)
• Cytokeratin (often)
• Laminin (basement membrane underlying neoplastic epithelial cells)
• E-cadherin (as opposed to ependymoma which is E-cadherin negative)

• E-cadherin expression is not significantly different for different grades

• Kir7.1 can distinguish CPT from other primary brain tumors and cerebral metastatic carcinoma

• Variable immunohistochemical markers:

• GFAP variable 

• Negative immunohistochemical markers:

• S-100 protein negative

Cytology:

• Polygonal cells arranged in rafts, columns, or papillary projections around capillary structures
• Papillomas and carcinomas may only be differentiated via histopathological examination as they have very similar cytological appearance

 

DIFFERENTIAL DIAGNOSIS:

• Ependymoma (N-N03): May occur within ventricles; neoplastic cells form true rosettes on a scant fibrillar stroma; typically lack papillary projections; E-cadherin negative
• Metastatic adenocarcinoma/carcinoma:  Adenocarcinoma/carcinoma metastasis to the brain is uncommon in animals   
• Choroid plexus cholesteatomas in horses (N-M15); most often in 4th ventricle, macrophages with cholesterol clefts

 

COMPARATIVE PATHOLOGY:

 

References:

1. Cantile C, Youssef S. Nervous system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:401. 
2. De Lorenzi D, Mandara MT. The Central Nervous System. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2023:552-554. 
3. Higgins RJ, Bollen AW, Dickinson PJ, Sisó-Llonch S. Tumors of the nervous system. In: Meuten DJ, ed. Tumors in Domestic Animals. 5th ed. Ames, IA: Wiley Blackwell; 2017:853-855.
4. Levine GJ, Cook JR. Cerebrospinal Fluid and Central Nervous System Cytology. In: Valenciano AC, Cowell RL, eds. Cowell and Tyler’s Diagnostic Cytology and Hematology of the Dog and Cat. 5^th ed. St. Louis, MO: Elsevier; 2020:224. 
5. Miller AD, Porter BF. Nervous system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:957-958.
6. Muscatello LV, Avallone G, Serra F, et al. Glomeruloid microvascular proliferation, desmoplasia, and high proliferative index as potential indicators of high grade canine choroid plexus tumors. Vet Pathol. 2018; 55(3): 391-401.
7. Schmidt RE, Reavill DR, Phalen DN. Pathology of Pet and Aviary Birds. 2^nd ed. Ames, IA: John Wiley & Sons; 2015: 232. 

 

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