JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

February 2023

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, well circumscribed, densely cellular neoplasm composed of blastemal cells arranged in indistinct nests and packets and multifocally forming small, radial arrangements around clear central spaces of drop out (Flexner-Wintersteiner rosettes), around neuropil (Homer Wright rosettes), or around vessels (pseudo-rosettes) supported by a scant fibrovascular stroma. 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 variably distinct nucleoli. The mitotic count averages 0-1 per 2.37mm². There are multifocal areas of liquefactive necrosis characterized by loss of architecture 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 adjacent neuropil, there is expansion of Virchow-Robin space as well as the leptomeninges with previously described inflammatory cells (perivascular cuffing). Adjacent to the neoplasm there is a mild gliosis diffusely within the neuroparenchyma and focally extensive area of necrosis in the adjacent white matter. Rarely, medium caliber arteries contain foci of mineralization within the tunica media.   

 

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

 

SYNONYMS: Medulloblastoma

 

GENERAL DISCUSSION:

• Tumors of small, round cells 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 nervous system; can be peripherally located (pPNET) which is closely related to Ewing sarcomas in humans

PATHOGENESIS:

 

TYPICAL CLINICAL FINDINGS:

 

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 is “cartoon carrot shaped” 
• Frequent mitoses 

• Sparse stroma
• 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 immunohistochemical markers:

• Neuronspecific enolase (NSE)
• Neurofilament (NF)
• Glial fibrillary acidic protein (GFAP)
• Synaptophysin 
• S100 protein

• Negative immunohistochemical markers: Cytokeratin [AE1/AE2], CK18

 

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 and recapitulate attempts at neural tube differentiation 
• 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 tissue 
• 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 (negative for glial markers such as GFAP)
• Ependymoblastoma: Embryonal tumor with ependymal differentiation

 

COMPARATIVE PATHOLOGY:

• Dogs and cats: Primarily associated with the central nervous system; uveal tumors in dogs; sporadic case reports of diffuse visceral dissemination 
• Horses: Rarely described in horse; most commonly associated with the ocular form; case report of  diffuse abdominal organ dissemination 
• Reported rarely in Dolphins and Coho Salmon
• Dromedary camel (Camelus dromedarius): Case report of pPNET exhibiting neuroblastic, glial, and ependymomatous differentiation

 

References:

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