AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

February 2017

N-N02

 

Signalment (JPC # 1525763):  Adult dog; age, breed, and gender unspecified

 

HISTORY:  This dog developed progressive deterioration of the CNS with sudden aggressive behavior.

 

HISTOPATHOLOGIC DESCRIPTION:  Cerebellum and brainstem:  Infiltrating the fourth ventricle and adjacent white matter of the brainstem and compressing the adjacent cerebellum, is an unencapsulated, poorly demarcated, densely cellular neoplasm composed of polygonal cells arranged solidly cellular areas supported by a scant fibrovascular stroma.  Neoplastic cells have variably distinct cell borders, a scant to moderate amount of eosinophilic, finely-granular to clear cytoplasm, and a prominent perinuclear clear zone (perinuclear halo).  Neoplastic cells have one round, hyperchromatic central to paracentral nucleus.  There is mild anisocytosis and anisokaryosis.  The mitotic rate is less than 1 per 10 HPF.  Neoplastic cells are admixed with hemorrhage, edema, fibrin, karyorrhectic and cellular debris.  Multifocally at the periphery of the neoplasm, within the brainstem, there is prominent capillary proliferation with occasional formation of glomerular-like tufts. 

 

MORPHOLOGIC DIAGNOSIS:  Cerebellum and brainstem:  Oligodendroglioma, breed unspecified, canine.

 

GENERAL DISCUSSION: 

·         Derived from oligodendrocytes; these cells are located in both the white and gray matter

·         Purpose of oligodendroglial cells is to myelinate axons and regulate the perineuronal microenvironment

·         Occur most commonly in dogs (accounts for 5-12% of all primary nervous system tumors)

·         Brachycephalic breed predilection (Boston terriers, boxers, and bulldogs)

·         Occur predominantly in adults; 5-11 years of age

·         No clear indices of malignancy; all should be regarded as malignant

·         Increase in VEGF expression correlates strongly with a high grade tumor

 

TYPICAL CLINICAL FINDINGS:

·         Dogs with oligodendrogliomas are three to four times more likely to have seizures than dogs with other types of primary intracranial neoplasms

·         Aggressive behavior, blindness, propulsive gait

 

TYPICAL GROSS FINDINGS: 

·         Variably-sized, spherical, well-demarcated neoplasm

·         Pink to gray, soft, gelatinous

·         Most commonly arises in the frontal, olfactory, temporal or piriform lobes

·         All areas of the cerebrum and brainstem, especially in close proximity to the lateral ventricles

o   Neoplasm can extend to meningeal and ventricular surfaces

·         Occasional multifocal hemorrhage; central area may be cystic in larger tumors

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

·         Nuclei are remarkably uniform, small, round, hyperchromatic, and centrally to paracentrally located

·         Cells have pale or non-staining cytoplasm (perinuclear halo) which imparts a classic fried-egg or honeycomb appearance

·         Capillary proliferation that resembles a chicken-wire pattern or glomeruloid vascular tufts at the neoplasm margins

·         Densely cellular with little to no stroma, patternless sheets, infrequent mitotic figures, mucinous cystic degeneration, mineralization (+/-), cells often arranged in rows and semi-circles at the periphery of the neoplasm

·         Gray matter infiltration with perivascular cuffing and perineuronal neoplastic cell satellitosis

·         Anaplastic (malignant) oligodendrogliomas:  Large areas of hemorrhage and necrosis, prominent glomeruloid vascular tufts (vasoproliferation), high mitotic rate, nuclear pleomorphism and CSF dissemination of neoplastic cells

   

ULTRASTRUCTURAL FINDINGS:

·         No distinctive features

·         Round nucleus, prominent nucleolus, small amount of round and smooth endoplasmic reticulum, abundant free ribosomes, few small mitochondria, vesicles, microtubules, and many short desmosome-like junctions

 

ADDITIONAL DIAGNOSTIC TESTS: 

·         MRI, plain radiographs

·         CNPase and Olig1/Olig2 positive

·         GFAP negative (intermingling astrocytes would be positive)

 

DIFFERENTIAL DIAGNOSIS: 

·         Gross

·         Cryptococcosis:  Gelatinous appearance (especially in cats)

·         Other brain tumors:  Primary or metastatic

·         Microscopic

·         Mixed gliomas:  Oligoastrocytoma (must contain 25% or more astrocytes); GFAP positive

·         Glioblastomas:  Differential diagnosis for anaplastic (malignant) oligodendroglioma; blastic astrocytes and oligodendrocytes are GFAP positive; glomeruloid vascular proliferation

·         Protoplasmic astrocytoma with cystic degeneration:  Small, stellate neoplastic cells separated by clear space

·         Extraventricular neurocytoma:  Scant eosinophilic cytoplasm with perinuclear halos (similar to the appearance of an oligodendroglioma), fine fibrillary neuropil-like areas resembling the “rosettes” of pineocytomas, ependymoma-like perivascular pseudorosettes

 

COMPARATIVE PATHOLOGY:

·         Rare in cats, cattle, white-tailed deer and horses

·         Uncommon in laboratory animals

 

References:

1.     Burger PC, Scheithauer BW. Tumors of neuroglia and choroid plexus epithelium. In: Burger PC, Scheithauer, eds. Tumors of the Central Nervous System. Fasicle 10. 3rd series. Washington, DC: Armed Forces Institute of Pathology; 1994:107-120.

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; 2016:400.

3.     Higgins RJ, Bollen AW, Dickinson PJ, Siso-Llonch S. Tumors of the nervous system. In: Meuten DJ, ed. Tumors in Domestic Animals. 5th ed. Ames, IA: Iowa State Press; 2017:844-848.

4.     Huisinga M, Henrich M, Frese K, et al. Extraventricular neurocytoma of the spinal cord in a dog. Vet Pathol. 2008;45(1):63-66.

5.     Ide T, Uchida K, Kikuta F, et al. Immunohistochemical characterization of canine neuroepithelial tumors. Vet Pathol. 2010;47(4):741-750.

6.     Koestner A, Bilzer T, Fatzer R, et al. Histological Classification of Tumors of the Nervous System of Domestic Animals. Vol 5. 2nd series. Washington, DC: Armed Forces Institute of Pathology; 1999.

7.     Mamom T, Meyer-Lindenberg A, Hewicker-Trautwein M, et al. Oligodendroglioma in the cervical spinal cord of a dog. Vet Pathol. 2004;41(5):524-526.

8.     Miller AD, Zachary JF. Nervous system. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier Mosby; 2017:872.

9.     Nagatani, M, Yamakawa S, Saito T, et al. GFAP-positive neoplastic astrocytes in spontaneous oligodendrogliomas and mixed gliomas of rats. Toxicol Pathol. 2013;41(4):653-661.

10.  Rissi DR, Levine JM, Eden KB, Watson VE, Griffin JF, Edwards JF, Porter BF.  Cerebral oligodendroglioma mimicking intraventricular neoplasia in three dogs.  J Vet Diagn Invest.  2015;27(3): 396-400.

11.  Sloma EA, Creneti CT, Erb HN, Miller AD.  Characterization of inflammatory changes associated with canine oligodendroglioma.  J Comp Path.  2015; 153 (2-3): 92-100.

12.  Snyder JM, Shofer FS, Van Winkle TJ, et al. Canine intracranial primary neoplasia: 173 cases (1986-2003). J Vet Intern Med. 2006;20(3):669-675.

13.  Summers BA, Cummings JC, de Lahunta A. Tumors of the central nervous system. In: Summers BA, Cummings JC, de Lahunta A, et al., eds. Veterinary Neuropathology. St. Louis, MO: Mosby; 1995:370-373.

 

 


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