JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

February 2023

N-N09

 

Signalment (JPC #1948327): Adult Holstein cow

 

HISTORY: This cow was treated for toxic mastitis and recumbency. There was no improvement over a 5 day period. Cervical nerves were firm and 4 to 5 cm in diameter. The brachial plexus was thickened. The cervicothoracic ganglia were 6.0 x 6.0 x 8.0 cm, firm, and white. Intercostal nerves were thickened with multiple 2 to 3 cm nodules. The vagus nerve was 4 cm in diameter and epicardial nerves were prominent. The celiac ganglion was 15 cm in diameter.

 

HISTOPATHOLOGIC DESCRIPTION: Brachial plexus (per contributor): Multifocally and variably affecting approximately 50% of the brachial plexus nerves, expanding to effacing the perineurium, and peripheralizing or surrounding and separating extant nerve fibers are neoplasms that are up to 1.5cm in diameter, well-circumscribed, and densely cellular, composed of spindle cells variably arranged in storiform patterns, variably dense, short, interlacing streams and bundles, and occasionally whorling around blood vessels, supported by a fine fibrovascular stroma. Neoplastic cells have indistinct borders, a small amount of microvacuolated, eosinophilic, fibrillar cytoplasm, and an oval to elongate, vesiculate nucleus with 1 to 2 variably distinct nucleoli. There are less than 1 mitotic figures per 2.37mm² and there is scattered single-cell necrosis. Multifocally, there are low numbers of lymphocytes, neutrophils, and macrophages scattered throughout the neoplasm and concentrated around blood vessels where they are admixed with fibrin and small amounts of necrotic debris.

 

MORPHOLOGIC DIAGNOSIS: Brachial plexus (per contributor): Peripheral nerve sheath tumor, Holstein, bovine.

 

SYNONYMS: Bovine neurofibromatosis; neurofibroma or neurofibrosarcoma; Schwannoma or malignant Schwannoma; neurilemmoma

 

GENERAL DISCUSSION:  

• Three distinct types of peripheral nerve sheath tumors are generally recognized (some institutions lump them all under “soft tissue sarcoma”, see I-N13):

• Schwannoma – most common in the dog, rare in cat, horse, and cow; associated with the nerve roots in the brachial plexus
• Perineurioma – extremely rare; only reported in the dog
• Neurofibroma – rare, except for a benign neurofibromatosis syndrome in adult cattle; affects the eighth cranial nerve, brachial plexus, and intercostal nerves

• No reliable immunohistochemical markers for these neoplasms
• Benign and malignant forms exist

 

PATHOGENESIS:

 

TYPICAL CLINICAL FINDINGS:

 

TYPICAL GROSS FINDINGS:

• Schwannoma

• Nodular or varicose thickening of nerve trunks or roots
• May be soft or firm; color can be gray or white
• When on nerve roots, may extend through vertebral foramen out into the exterior

• Neurofibroma

• When occurring in the syndrome seen in cattle (benign neurofibromatosis syndrome), often found in:

• Eighth cranial nerve, brachial plexus, intercostal nerves, autonomic nerves of liver, heart, mediastinum, thorax, and rarely nerves in the skin

• Perineurioma

• No specific gross findings.

 

TYPICAL GROSS FINDINGS:

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Schwanomma

• Antoni A pattern – monomorphic sheets and interlacing fascicles of spindloid Schwann cells with poorly defined eosinophilic cytoplasm and collagenous stroma; frequently nuclei line up, forming Verocay bodies
• Antoni B pattern – spindloid Schwann cells with indistinct cytoplasm on a looser, myxomatous matrix

• Neurofibroma

• Numerous small nerve fibers (not seen in Schwannoma)
• Spindle cells with poorly defined eosinophilic cytoplasm and wavering to buckled nuclei
• Mast cells may be present
• Collagenous to myxoid matrix

• Perineurioma

• Concentric whorls of perineural cells that surround a central axon that stains for neurofilament stains, while neoplastic cells stain for laminin

 

ULTRASTRUCTURAL FINDINGS:

 

ADDITIONAL DIAGNOSTIC TESTS:

 

DIFFERENTIAL DIAGNOSIS:

• Fibroma/fibrosarcoma:  Lack palisades and whorls, have more pronounced collagenous stroma
• Leiomyoma/leiomyosarcoma:  Lack palisades and whorls, elongate nuclei with blunt ("cigar-shaped") ends; immunoreactive for muscle markers (i.e. desmin, muscle specific actin)

 

COMPARATIVE PATHOLOGY:

• Pig

• Pigmented neurofibroma reported in pig (Becker, J Comp Pathol. 2019)
• Malignant nerve sheath tumor reported in a pig (Stilwell, J Vet Diagn Invest. 2018)

• Cat:  PNSTs most frequently occur on the head, neck, and distal limbs; can involve skin, subcutis, skeletal muscle, and/or mucous membranes; 

• Malignant PNST is rare in cats, but a case report of one with rhabdomyosarcoma differentiation, i.e. “tritan tumor” (Stoll, J Comp Pathol. 2018)

• Dog:

• Case report of a malignant PNST in the urinary bladder (Lee, J Comp Pathol. 2020)
• Case report of a dog with dermal neurofibromas and spinal cord rhabdomyosarcoma (Hoon-Hanks, J Comp Pathol. 2018)

• Bat:

• Case report of a malignant PNST in a Seba’s short-tailed bat (Carollia perspicillata)

• Dolphin:

• Case report of an abdominal PNST with rhabdomyoblastic differentiation in a rough-toothed dolphin (Steno bredanensis), (Alves-Motta, J Comp Pathol. 2020)

• Dromedary camel
• Bearded dragon

 

REFERENCES:

1. Alves-Motta MR, Luz-Carvalho V, Nunes-Pinheiro DCS, Groch KR, Gonçalves-Pereira L, Sánchez-Sarmiento AM, Sacristán C, Catão-Dias JL, Díaz-Delgado J. Facial Squamous Cell Carcinoma and Abdominal Peripheral Nerve Sheath Tumour with Rhabdomyoblastic Differentiation in a Rough-toothed Dolphin (Steno bredanensis). J Comp Pathol. 2020 Apr;176:122-127.
2. Becker K, Kegler K, von Altrock, A, Kuchelmeister K, Baumgartner W, Wohlsein P. Cutaneous pigmented neurofibroma in a pig – morphology and immunohistochemical profile. J Comp Pathol. 2019;168:25-29. 
3. 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; 2015:404-406.
4. Franzen J, Soto S, Fasel NJ, Rüegg-van den Broek P, Veiga IB. Malignant Peripheral Nerve Sheath Tumour in a Seba's Short-Tailed Bat (Carollia perspicillata). J Comp Pathol. 2021 Apr;184:72-76.
5. Frasca SJ, Wolf JC, Kinsel MJ, Camus AC, Lombardini ED. Osteichthyes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:945-962, 967. 
6. Hoon-Hanks LL, Frank CB, Edmondson EF. Primary meningeal rhabdomyosarcoma of the spinal cord of a young dog with neuromelanocytosis and multiple cutaneous neurofibromas. J Comp Pathol. 2018;165:57-61. 
7. Lanigan LG, Russell DS, Woolard KD, Pardo ID, Godfrey V, Jortner BS, Butt MT, Bolon B. Comparative Pathology of the Peripheral Nervous System. Vet Pathol. 2021 Jan;58(1):10-33.
8. Lee SW, Baek SM, Lee AR, Kim TU, Kim D, Kwon YS, Yun S, Park SJ, Hong IH, Jeong KS, Park JK. Malignant Peripheral Nerve Sheath Tumour in the Urinary Bladder of a Dog. J Comp Pathol. 2020 Feb;175:64-68.
9. Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier; 2015:723-724.
10. Miller AD, Zachary JF.   Nervous system. In: Zachary JF, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022: 988-989.
11. Raskin RE, Conrado FO. Integumentary 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; 2023:87-90. 
12. Robinson WF, Robinson NA. Cardiovascular system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, PA: Elsevier; 2015:53.
13. Stilwell JM, Rissi DR. Pathology and immunohistochemistry of a malignant nerve sheath tumor in a pig: case report and brief review of literature. J Vet Diagn Invest. 2018;31(1):122-127.
14. Stoll AL, Suarez-Bonnet A, Summers BA, Priestnall SL. Malignant cutaneous peripheral nerve sheath tumor with rhabdomysarcomatous differentiation (Triton tumor) in a domestic cat.  Comp Pathol. 2018;165:1-5.

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