JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

February 2017

N-N05

 

Signalment (JPC #2017772):  A 4-month-old female brown Swiss calf

 

HISTORY: This calf presented with a progressive neurologic problem of one month's duration. The lesion was tentatively localized to cerebellum and brainstem.  Grossly, a necrotic, hemorrhagic mass extended from cerebellar folia rostrally, caudally, and into the ventricular system.

 

HISTOPATHOLOGIC DESCRIPTION:  Cerebrum: Infiltrating and expanding the meninges and adjacent neuropil is an unencapsulated, poorly circumscribed, densely cellular neoplasm, with blastemal cells arranged in vague nests and packets supported by a scant fibrovascular stroma. Multifocally neoplastic cells form small radial arrangements clear central spaces of drop out (Flexner-Wintersteiner rosettes) or palisade around vessels (pseudo-rosettes). Neoplastic cells are polygonal to spindle, with indistinct cell borders and a scant amount of eosinophilic fibrillar cytoplasm. Nuclei are irregularly round to fusiform (“cartoon carrot-shaped”) with coarsely stippled chromatin and 1-2 distinct nucleoli.  The mitotic count averages 0-1 per 10-400x fields. There are multifocal areas of necrosis characterized by loss of neuropil with replacement by cellular and karyorrhectic debris, fibrin, hemorrhage and edema. Multifocally within and rimming the areas of necrosis, are moderate numbers of lymphocytes, plasma cells and fewer neutrophils, and macrophages. Multifocally within the meninges and adjacent neuropil, there is expansion of Virchow-Robin space with previously described inflammatory cells (perivascular cuffing). Adjacent to the neoplasm within the neuropil, there is a mild gliosis and focally extensive area of necrosis in the adjacent white matter.   

 

MORPHOLOGIC DIAGNOSIS:  Cerebrum: Primitive neuroectodermal tumor (PNET), brown-Swiss, bovine.

 

SYNONYMS: Medulloblastoma

 

GENERAL DISCUSSION:

·         Small, round cell tumors of neural crest origin; typically one type of neuroectodermal cell line dominates:

·         Neuronal (predominate)

·         Ependymal

·         Glial

·         Rare neoplasm, predominantly occurs in younger animals

·         Considered biologically aggressive

·         Originally characterized primarily in the central nervosus system; can be peripherally located (pPNET) which is closely related to Ewing sarcomas in humans

 

PATHOGENESIS:

·         The molecular basis of the tumorigenesis is unknown

 

TYPICAL CLINICAL FINDINGS:

·         Ataxia, head tilt, decreased proprioception, circling, and apathy

 

TYPICAL GROSS FINDINGS:

·         Solitary, well circumscribed, unilateral, soft, gray to pink cerebellar mass

·         Possible compression of the fourth ventricle with subsequent hydrocephalus

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

·         Poorly differentiated embryonal cells

·         Small round to polygonal to elongate cells

·         Scant cytoplasm with hyperchromatic dense sheets and bundles

·         Nucleus: “Cartoon carrot shaped” with sparse stroma, frequent mitoses

·         Rosette formations:

·         Neoplastic cells palisade around neuropil (Homer-Wright)

·         Neoplastic cells palisade around clear areas of drop out (Flexner-Wintersteiner)

·         Neoplastic cells palisade around vessels (pseudo-rosettes)

·         Subpial extension along the tumor margin; expansion of the perivascular space

·         Frequently invade leptomeninges and incite a fibrous reaction

·         Highly malignant with dissemination via CSF pathways

 

ULTRASTRUCTURE:

·         Microtubules, scant intermediate filaments,

·         Electron dense vesicles (neurosecretory granules)

 

ADDITIONAL DIAGNOSTIC TESTS:

·         Variable immunoreactivity for one or more of the following neural and glial markers:

·         Neuronspecific enolase (NSE)

·         Neurofilament (NF)

·         Glial fibrillary acidic protein (GFAP)

·         Synaptophysin

·         S100 protein

·         Negative: Cytokeratin [AE1/AE2], CK18

·   Cytology:

·            Small to medium-sized discrete round cells;

·            High N:C ratio, round nucleus

·            Vague rosettes and pseudorosette

 

DIFFERENTIAL DIAGNOSIS:

·         Ocular manifestations:

·         Medulloepitheliomas arise from the optic cup;rare in humans but not uncommon in animals, especially horses

·         Medulloepitheliomas originate from the embryonic neuroectoderm

·         May exhibit features of the retina, ciliary epithelium, vitreous, or neuroglia

·         Commonly a loose network of small basophilic neuroblasts that may form cords reminiscent of ciliary processes, or form primitive rosette-like structures

·         Teratoid medulloepitheliomas can contain cartilage, skeletal muscle, nervous  

·         Metastases are very rare, despite the malignant classification

·         Neuroblastoma: Nests of small round primitive neuronal cells separated by neuropil; often require  immunohistochemical staining to differentiate

·         Ependymoblastoma: Embryonal tumor with ependymal differentiation

 

COMPARATIVE PATHOLOGY:

·         Dogs and cats: Primarily associated with the central nervous system; sporadic case reports of diffuse visceral dissemination

·         Horses: Rarely described in horse; most commonly associated with the occular form; case report of  diffuse abdominal organ dissemination

·         Dolphin (Stenella coeruleoalba): One case report, with neoplastic cells arranged in ependymal rosettes;  primary brain tumors are rare in cetaceans

·         Dromedary camel (Camelus dromedarius): Case report of pPNET, exhibiting neuroblastic, glial and ependymomatous differentiation

 

References:

1.     Baily JL, et al. Primitive neuroectodermal tumour in a striped dolphin (Stenella coeruleoalba) with features of ependymoma and neural tube differentiation (medulloepithelioma). J Comp Path. 2013; 149(4): 514-519.

2.     Brewer DM, et al. Spinal cord nephroblastoma in dogs: 11 cases (1985–2007).  J Am Vet Med Assoc. 2011; 238(5): 618-624.

3.     Cantile C, et al.  Nervous system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016: 403.

4.     Choi US, et al. Cytologic and immunohistochemical characterization of a primitive neuroectodermal tumor in the brain of a dog. Vet Clin Pathol. 2012; 41(1): 153-157.

5.     Facemire PR, et al. Peripheral primitive neuroectodermal tumor in a two-year-old paint horse. J Vet Diagn Invest. 2012; 24(4): 794-796.

6.     Headley SA, et al. Central primitive neuroectodermal tumour with ependymal differentiation in a dog. J Comp Path. 2009; 140(1): 80-83.

7.     Higgins RJ, et al. Tumors of the nervous system. In: Meuten DJ, ed. Tumors in Domestic Animals. 5th ed. Ames, IA: Wiley Blackwell; 2017: 852, 860.

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

9.     Junginger J, et al. Peripheral primitive neuroectodermal tumour in a dog. J Comp Path. 2013; 149(4): 424-428.

10.  Miller AD, et al. Nervous system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Mosby Elsevier; 2016: 870.

11.  Patton KM, et al. Pathology in practice. J Am Vet Med Assoc. 2014; 244(3): 287-289.

12.  Regan DP, et al. Primary primitive neuroectodermal tumors of the retina and ciliary body in dogs. Vet Ophthalmol. 2013; 16(Suppl. 1): 87-93.

13.  Weiss R, et al. Peripheral primitive neuroectodermal tumour in a lumbar vertebra and the liver of a Dromedary camel (Camelus dromedarius). J Comp Path. 2009; 141(2-3): 182-186.

 


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