JPC SYSTEMIC PATHOLOGY
MUSCULOSKELETAL SYSTEM
MARCH 2022
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 and abundant cytoplasm filled by 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 rare 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 and frequently recur after excision
• 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 and extends from the midbrain to the tail of the developing embryo, ventral to the neural tube
  • Induces formation of the head and CNS and acts as an organizing center for vertebral body development
  • Developing vertebral column surrounds and almost completely obliterates the notochord; the only derivative persisting in adult animals is the nucleus pulposus of the intervertebral disc

 

TYPICAL CLINICAL FINDINGS:

• Problems ambulating or abnormal behavior
• Typically they are benign due to rare metastases (although has been reported to lungs), slow growth rate, and ease of excision especially those on the distal tail tip

 

TYPICAL GROSS FINDINGS:

• Multilobulated, soft, myxoid, gelatinous, gray mass
• In ferrets, most occur on the tip of the tail (beyond the last vertebral segment of the tail, not attached to preexisting bone); cervical vertebral column is the second most common location in ferrets
• In other species, most chordomas occur in the sacrococcygeal region (may also occur in sphenooccipital region or other locations)

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Composed of three components often arranged concentrically:
  • Physaliferous cells (principle cell type): Closely packed 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, but also have few mitoses
  • Bone that often contains marrow and cartilage:
    • These may represent true or induced metaplastic change in the connective tissue surrounding the neoplasm, or notocordal-induced differentiation within the neoplasm
  • Large lakes of extracellular mucin containing hyaluronidase-resistant sulfated mucopolysaccharides may surround neoplastic cells

 

ADDITIONAL DIAGNOSTIC TESTS:

• Immunohistochemistry:
  • Cytokeratin and vimentin positive
  • Often S-100 and/or neuron specific enolase (NSE) positive
  • Documented to be brachyury positive in some species (transcriptional regulator of notochord formation, used in human medicine)
• Histochemical stains:
  • Mucinous matrix is alcian blue and mucicarmine positive (alcianophilic and carminophilic) and hyaluronidase resistant
  • 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
• Other reported neoplasms of the tail tip in domestic ferrets:
  • Sebaceous gland carcinomas
  • Sweat gland carcinomas
  • Papillary cystadenomas
• Other tissues with dual expression of cytokeratin and vimentin:
• Mesothelium
  • Endothelium
  • Granulosa and rete ovarii cells
  • Sertoli cells
  • Endometrial epithelium
  • Choroid plexus
  • Meninges
  • Umbilical cord
  • Synovium

 

COMPARATIVE PATHOLOGY:

• Chordomas are rare tumors in the rat, cat, dog, and mink; metastasis, commonly to the skin, is documented in the human, ferret, and rat
• Rats: Chordomas in the F344 rat are often malignant
• Dogs: besides cervical and sacrococcygeal vertebrae, also reported in the brain, spinal cord, and skin
• Zebrafish: Primary intestinal chordoma in aged zebrafish is more common than chordoma of the axial skeleton (Cooper, Vet Pathol. 2015)
• Perdido key beach mouse: Chordomas occur in throughout the vertebral column (thoracic most common) with metastasis to the lung in 34% of the animals (Taylor, Vet Pathol. 2016)
• Degu: Case report in one degu with mass on coccygeal vertebra (Sautier, J Vet Diagn Invest. 2019)
• Naked mole rat: Case report of a sacral chordoma (Cole, J Vet Diagn Invest. 2020)
• Humans: three histological classifications: classical, dedifferentiated, and chondroid
  • Chondroid variant carries significantly better prognosis in humans
  • Most chordomas in ferrets, mink, and dog resemble the human chondroid type
  • Most chordomas in rats and cat are consistent with the human classical type

 

REFERENCES:

1. Camus MS, Rech RR, Choy FS, Fiorello CV, Howerth EW. Pathology in practice: Chordoma on the tip of the tail of a ferret. J Am Vet Med Assoc. 2009;235:949-951.
2. 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; 2016:404.
3. Carminato A, Marchioro W, Melchiotti E, Vascellari M, Mutinelli F. A case of coccygeal chondroid chordoma in a cat: Morphological and immunohistochemical features. J Vet Diagn Invest. 2008;20:679-681.
4. Cole JE, Steeil JC, Sarro SJ, Kerns KL, Cartoceti A. Chordoma of the sacrum of an adult naked mole-rat. J Vet Diagn Invest. 2020;32(1):132-135.
5. Cooper TK, Murray KN, Spagnoli S, Spitsbergen JM. Primary intestinal and vertebral chordomas in laboratory zebrafish.  Vet Pathol.  2015;52(5):388-392.
6. Fechner RE, Mills SE. Chordoma. In: Tumors of the Bones and Joints; Atlas of Tumor Pathology. 3rd series. Fascicle 8. Washington DC: Armed Forces Institute of Pathology; 1992:239-244.
7. Frohlich JR, Donovan TA. Cervical chordoma in a domestic ferret with pulmonary metastasis. J Vet Diagn Invest. 2015;27(5)656-659.
8. Gruber A, Kneissl S, Vidoni B, Url A. Cervical spinal chordoma with chondromatous component in a dog. Vet Pathol. 2008;45:650-653.
9. Hampel R, Taylor-Brown F, Priestnall SL. Cervical Vertebral Body Chordoma in a Cat. J Comp Pathol. 2016;154(4):319-322.
10. Koestner A, Bilzer T, Fatzer R, Schulman FY, Summers BA, Van Winkle TJ. Chordoma. In: Histological Classification of Tumors of the Nervous System of Domestic Animals. Vol V. 2nd series. Washington D.C: Armed Forces Institute of Pathology; 1999:36.
11. Munday JS, Brown CA, Richey LJ. Suspected metastatic coccygeal chordoma in a ferret (Mustela putorius furo). J Vet Diagn Invest. 2004;16:454-458.
12. Munday JS, Brown CA, Weiss R. Coccygeal chordoma in a dog. J Vet Diagn Invest. 2003; 15:285-8.
13. Sautier L, Guillier D, Coste M, et al. Coccygeal Chordoma in a degu: Case Report and Review of the Literature. J Vet Diag Invest. 2019;31(1):142-145.
14. Taylor KR, Garner MM, Russell K, et. al. Chordomas at high prevalence in the captive population of the endangered perdido key beach mouse.  Vet Pathol. 2016;53(1):163-169.

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