JPC SYSTEMIC PATHOLOGY

MUSCULOSKELETAL OF SYSTEM

April 2025

M-N01

 

Signalment (JPC #2548693): 5-year-old male ferret (Mustela putorius furo)

 

HISTORY: The ferret presented with a nodule at the tip of the tail.

 

HISTOPATHOLOGIC DESCRIPTION: Haired skin and subcutis, tail: Expanding the subcutis, elevating the overlying dermis and epidermis, and compressing adnexa is an unencapsulated, well-circumscribed, multilobulated, moderately cellular neoplasm composed of plump polygonal to spindloid cells arranged in lobules separated by a fine fibrovascular to mucinous stroma. Neoplastic cells have distinct cell borders, abundant cytoplasm that contains one or more discrete, clear, variably sized vacuoles that often peripheralize the nucleus, and nuclei are irregularly oval with coarsely clumped chromatin and indistinct nucleoli (physaliferous cells). At the periphery of the neoplastic lobules, neoplastic cells are stellate to spindle with scant eosinophilic fibrillar cytoplasm and round to oval nuclei with coarsely or finely stippled chromatin and 1-2 variably distinct nuclei. The mitotic count is less than 1 per 2.37mm². There is mild anisocytosis and anisokaryosis. Multifocally, neoplastic cells are embedded within a basophilic mucinous matrix and there are scattered islands of cartilage and woven and lamellar trabecular bone lined by osteoblasts and few osteoclasts in Howship’s lacunae. Within the central marrow space, there are loosely arranged spindle cells and scant hematopoietic elements. In the adjacent dermis, there are few small aggregates of lymphocytes and plasma cells and few mildly ectatic apocrine glands. There is diffuse mild orthokeratotic hyperkeratosis in the epidermis. 

 

MORPHOLOGIC DIAGNOSIS: Tail, haired skin and subcutis with bone: Chordoma, ferret (Mustela putorius furo), mustelid.

 

GENERAL DISCUSSION:

• Chordomas are slow growing, locally aggressive neoplasms composed of bone, cartilage, and physaliferous cells that can occur anywhere along the axial skeleton 
• Most common musculoskeletal tumor of ferrets and the 5th most common tumor of mink and European ferrets; uncommon in other animals and humans
• Presumed to arise from intraosseous remnants of fetal notochord: 
• Notochord arises from embryonic mesoderm, a pluripotent mesenchyme ventral to the neural tube
• Induces formation of the head and CNS; acts as an organizing center for vertebral body development
• Induces and develops the sclerotome that provides for the axial skeleton
• The only derivative persisting in adult animals is the nucleus pulposus of the intervertebral disc

 

TYPICAL CLINICAL FINDINGS:

• Large mass at tip of tail is often the only clinical sign; benign due to rare metastasis and slow growth rate 
• Problems ambulating or abnormal behavior due to pain if tumor invades surrounding tissue or bone

 

TYPICAL GROSS FINDINGS:

• Multilobulated, soft, friable, myxoid, gelatinous, gray, expansile mass with gritty areas of bone and scattered hemorrhage
• Often disrupts the vertebral body or disc space
• In ferrets, most commonly occurs on the tip of the tail, in other species, most chordomas occur in the sacrococcygeal region; may also occur in sphenooccipital and paraspinal regions 

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Neoplastic lobules well defined by bands of connective tissue
• Composed of variably combination of three components often arranged concentrically: 
• Physaliferous cells (principle cell type/ notochordal cells): Closely packed large polygonal cells with distinct borders and multiple large, clear, intracytoplasmic vacuoles arranged in unencapsulated lobules on a thin fibrovascular stroma; round to oval nuclei with stippled to clumped chromatin, indistinct nucleoli, and rare mitotic figures; smaller stellate cells, often with PAS-positive granules at periphery, may be germinative cells, and rarely have few mitoses
• Bone that is trabecular and often contains marrow and cartilage
• Mucin containing hyaluronidase-resistant sulfated mucopolysaccharides is found within the cytoplasm of larger neoplastic cells or may surround neoplastic cells extracellularly
•  

ADDITIONAL DIAGNOSTIC TESTS:

• Immunohistochemistry:
• Cytokeratin and vimentin positive
• Often S-100 and/or neuron specific enolase (NSE) positive
• Histochemical stains:
• Mucinous matrix is alcian blue and mucicarmine positive, hyaluronidase resistant
• Periphery smaller spindle cells are PAS positive

 

DIFFERENTIAL DIAGNOSIS:

• Histologic differential diagnosis:
• Myxoid chondrosarcoma: Histologically similar but rare in the axial skeleton, lack physaliferous cells, and are not immunoreactive for cytokeratin
• Liposarcomas: Not lobulated, not immunoreactive for epithelial (keratin) markers
• Chondroma: Does not have physaliferous cells and neoplastic cells are widely spread by chondroid matrix
• Chondrosarcoma: Does not have physaliferous cells, more cellular, pleomorphic, and has mitoses
• Myxoma or myxosarcoma: Does not contain chondroid matrix
• Other reported neoplasms of the tail tip in domestic ferrets:
• Sebaceous gland adenoma/adenocarcinomas
• Apocrine adenomas/adenocarcinomas

 

COMPARATIVE PATHOLOGY:

    

REFERENCES:

1. Cantile C, Youssel S. Nervous system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016: 265, 270, 396, 404.
2. Craig LE, Dittmer KE, Thompson KG. Bones and Joints. In: Maxie MG, ed. Jubb, Kennedy & Palmer's Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:57, 128. 
3. Fox JG, Muthupalani A, Kiupel M, Williams B. Neoplastic Diseases. In: Fox JG, Marini RP, ed. Biology and Diseases of the Ferret. 3^rd ed. Ames, IA : Wiley Blackwell; 2014: 612-614
4. Kittmer K, Bell C, Foster RA, Schulman FY, Avallone G, Roccabianca P, Murphy BG, Scruggs JL, Thompson D, Kiupel M. Notochordal tumors. In: Kieupel M, ed. Surgical Pathology of Tumors of Domestic Animals Volume 4: Tumors of Bone, Cartilage, and other Hard Tissues. Gurnee, IL: Davis-Thompson Foundation; 2020;147-152.
5. Miller AD, Porter, BF. Nervous System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:892.e3.
6. Williams BH, Burek-Huntington KA, Miller M. Mustelids. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:293-294. 

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