JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

February 2023

N-N10

 

Signalment (JPC #2131282): 112-week-old male Fischer 344 rat

 

HISTORY: None.

 

HISTOPATHOLOGIC DESCRIPTION: Metencephalon (Cerebellum and pons):  Expanding the meninges and compressing and laterally deviating the cerebellum and pons is an unencapsulated, well circumscribed, moderately cellular neoplasm composed of two cell morphologies in streams on a fine fibrovascular to myxomatous stroma. The majority of neoplastic cells are large polygonal cells with indistinct cell borders, abundant cytoplasm with numerous fine eosinophilic granules, and a round vesiculate nucleus with one distinct magenta nucleolus. Admixed with the first population are fewer neoplastic cells that are smaller and spindle with indistinct cell borders, a scant to moderate amount of pale eosinophilic cytoplasm, and an oval nucleus with dense chromatin and an indistinct nucleolus. In both populations, anisocytosis and anisokaryosis are moderate and there is 1 mitotic figure per 2.37mm². There are few macrophages with abundant brown granular cytoplasmic contents (hemosiderin), primarily at the periphery of the neoplasm. Within the adjacent compressed neuropil there is mild spongiosis with scattered hemorrhage, marked focal loss of purkinje cells within the cerebellar folia, and concomitant focal thinning of the granular cell layer (pressure necrosis). The 4^th ventricle is expanded up to 2.5mm (hydrocephalus).

 

MORPHOLOGIC DIAGNOSIS: Cerebellum and pons: Granular cell tumor, Fischer 344 rat, rodent.

 

SYNONYMS: Granular cell meningioma; Granular cell myoblastoma 

 

GENERAL DISCUSSION:  

• Granular cell tumors (GCT) are rare in animals; most commonly occur in the dog (tongue and meninges), horse (lung), and rat (meninges and trachea); also reported in cats, birds, ferrets, rabbits, and a reptile  
• In the rat, GCTs are the most common primary CNS tumor; most common in Sprague-Dawley, Fischer F344, Han-Wistar, and Wistar rat strains
• Cell of origin probably neuroectodermal; rats GCTs are presumably neural crest-derived; most GCTs in other species are thought to be Schwann cell derived
• Most are benign and rarely metastasize; may be locally invasive 

 

TYPICAL GROSS FINDINGS:  

• May occur in single or multiple nodules; small, white to tan, lobular, well circumscribed, poorly encapsulated, expansile neoplasm of meninges covering the superficial cerebellum, cerebrum, in the longitudinal cerebral fissure, or beneath the brain stem 
• Tumor size averages < 3 mm in diameter in the rat; can be up to 10 mm
• Frequently compresses adjacent tissue; non invasive 

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• Streams of large, round, densely packed polygonal cells with abundant cytoplasm containing abundant small fine acidophilic granules 
• +/-  second morphology of fewer, smaller cells, with less cytoplasm and hyperchromatic nuclei
• +/- perivascular cuffing with lymphocytes 

 

ULTRASTRUCTURAL FINDINGS:  

 

ADDITIONAL DIAGNOSTIC TESTS:  

Special stains:   

• PAS positive cytoplasmic granules that are diastase resistant, and alcian blue positive
• Differing reports for granules staining with Luxol fast blue  

Immunohistochemistry: (Conflicting reports regarding IHC) 

• Most often immunoreactive for S-100, LC3, vimentin, and p62 (Finnegan, J Comp Pathol. 2020)
• Positive for ubiquitin in dogs 
• Granular cell tumors positive for S-100, myelin basic protein, NSE 

Cytology: 

 

DIFFERENTIAL DIAGNOSIS:  

For gross findings in the rat:

• Pituitary adenoma: Common in Sprague-Dawley and Wistar rats; usually pars distalis origin and prolactin producing
• Pineocytoma: Very rare in rats, at surface of brain compressing adjacent mesencephalon

 

For histologic findings in the rat:

• Meningothelial meningioma with a granular cell component 
• Meningeal sarcoma: Subclassified into fibrosarcomas or spindle cell sarcomas based on degree of cellular differentiation; these frequently invade the surrounding brain parenchyma unlike GCTs
• Gemistocytic astrocytoma (N-N01): Neoplastic astrocytes have abundant eosinophilic cytoplasm and no PAS positive granules; these are invasive tumors and are GFAP and S-100 positive (although rat astrocytomas are typically GFAP-negative)

 

For histologic findings in other species: (Ultrastructural and immunohistochemical properties are sufficient for differentiating granular cell tumors from oncocytomas and rhabdomyomas /sarcomas)

• Oncocytoma: EM reveals numerous usually enlarged mitochondria; not immunoreactive to muscle immunohistochemical markers
• Rhabdomyoma (P-N01) /sarcomas: EM reveals numerous mitochondria and Z lines; immunoreactive for myoglobin and desmin

 

COMPARATIVE PATHOLOGY:  

• Dog: Usually benign; red, raised, <2cm, occurs most often in the eyelid, oral cavity and larynx, especially the base of the tongue. Granules are ultrastructurally phagolysosomes. 
  • Granular cell meningiomas are reported; occur over cerebral convexity, neurohypophysis, spinal nerve roots
• Horse: Most common primary lung tumor in the horse; benign and usually incidental finding, occurs only in the lung; arise from peribronchial Schwann cells, may bulge into bronchial lumen. Proliferative optic neuropathy may be a type of granular cell tumor 
• Cat: Reported in the tongue, vulva, and palate
• Mouse: Infrequent; found in the meninges, uterus, and subcutaneous tissue
• Rabbit: Recent study found that the majority of rabbit testicular tumors are GCTs (Reineking, J Comp Pathol. 2019)
• Humans: Occurs in oral cavity, pituitary gland, lung, skin of the penis and scrotum; most GCTs are derived from specialized pituicytes in the neurohypophysis or infundibulum
• Reptile: Recent case report of meningeal GCT in a Green tree python (Finnegan J Comp Pathol. 2020) 
• Psittacine: Amazon parrots, rare tumor of the tongue, dermis, head, abdomen. 

 

REFERENCES:  

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2. Bolfa P, DellaGrotte L, Weronko T, Armien AG. Cutaneous epithelioid hemangiosarcoma with granular cell differentiation in a dog: a case report and review of the literature. J Vet Diagn Invest. 2018 Nov;30(6):951-954. 
3. Boes KM. Respiratory System. In: Raskin RE, Meyer DJ, Boes KM, eds. Canine and Feline Cytology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2023:203. 
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