JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

February 2026

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 and effacing the perineurium, and peripheralizing or surrounding and separating remaining 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 is 1 mitotic figure per 2.37 sq mm and there is scattered single-cell necrosis. Multifocally, there are few 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:

• Unknown

TYPICAL CLINICAL FINDINGS:

• Often an incidental gross finding at slaughter (bovine neurofibromatosis)

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:

A diagnosis of suspect PNST can be made in the presence of neoplasms associated with a peripheral nerve root, showing cytologic features of moderate to high cellularity

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:

• Schwann cells: continuous basal lamina with type IV collagen, 10 nm diameter intermediate filaments, pinocytotic vesicles, and extracellular long-spaced collagen ("Luse" bodies)

ADDITIONAL DIAGNOSTIC TESTS:

• No reliable immunohistochemical markers for these neoplasms; variably positive for S-100, laminin, and GFAP, depending on tumor type and differentiation

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:

• Cat: PNSTs most frequently occur on the head (periocular), neck, and distal limbs; can involve skin, subcutis, skeletal muscle, and/or mucous membranes;
• Bat:
  • Case report of a malignant PNST in a Seba’s short-tailed bat (Carollia perspicillata)
• NHPs: tumors of the peripheral nervous system are uncommon; have been induced in rhesus macaques following inoculation of the carcinogen methylnitrosourea
  • Schwannoma has been reported in one collared brown lemur
• Birds: included benign and malignant varieties of schwannoma, neurofibroma, perineurioma, and neurilemmoma
  • Grossly: single to multiple firm, white nodules
  • Histo: storiform pattern typically, whorls, and bundles
  • Malignancy is considered if there is poor differentiation, necrosis and a high mitotic count
  • IHC and Em required for definitive diagnosis
  • Can occur anywhere in the PNS (plexi, nerves, spinal roots, within viscera and skeletal muscle)
  • Perineurioma in a chicken; neurofibroma in a macaw
• Dromedary camel
• Bearded dragon

REFERENCES:

1. 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.
2. Fisher DJ. Cutaneous and Subcutaneous Lesions. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:96, 144, 158.
3. 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;184:72-76.
4. 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.
5. 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;58(1):10-33.
6. 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.
7. Miller AD, Zachary JF. Nervous system. In: Zachary JF, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:988-989.
8. Miller AD. Neoplasia and Proliferative Disorders of Nonhuman Primates. In: Abee CR, Mansfield K, Tardif S, Morris T, ed. Nonhuman Primates in Biomedical Research. Volume 2: Diseases. 2nd ed. Oxford, UK: Elsevier Inc; 2012:345.
9. 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.
10. 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.
11. Struthers JD, Schmidt RE. Nervous system. In: Schmidt R, Struthers JD, Phalen DN, eds. Pathology of Pet and Aviary Birds. 3rd ed. Hoboken, NJ: John Wiley & Sons, Inc.; 2024:400.
12. Tse JL, Rebollada-Merino A, Pumarola M, Ortiz AL, Toni C. Multiple spinal nerve sheath tumors in a dog resembling schwannomatosis in humans. J Vet Diagn Invest. 2025;37(4):657-661.

Click the slide to view.

---