JPC SYSTEMIC PATHOLOGY
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 neoplasm, composed of spindle 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, varisized vacuoles that often displace the nucleus (physaliferous cells). Nuclei are irregularly oval with coarsely clumped chromatin and indistinct nucleoli. At the periphery of the 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. Mitotic figures average less than 1 per 10 HPF. 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 is loosely arranged spindle cells and few 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.
- 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 5th most common tumor of mink and European ferrets; uncommon in other animals and humans
- Presumed to arises 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:
- Mass at the distal tail tip (most common), cervical neck
- Problems ambulating or abnormal behavior
- Typically they are benign due to rare metastases (has been reported to lungs), slow growth rate and ease of excision especially those located 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 and 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:
- 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)
- Mucinous matrix is alcian blue and mucicarmine positive and hyaluronidase resistant
- Spindle cells are PAS positive
- Myxoid chondrosarcoma: Histologically similar but are rare in axial skeleton, lack physaliferous cells, and do not stain with cytokeratin
- Liposarcomas: Not lobulated and negative 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:
- Granulosa and rete ovary cells
- Sertoli cells
- Endometrial epithelium
- Choroid plexus
- Umbilical cord
- Chordomas are rare tumors in the rat, cat, dog, and mink
- Chordomas in the F344 rat are often malignant
- Humans – three histological classifications: classical, dedifferentiated, and chondroid
- Chondroid variant carries significantly better prognosis in humans
- Most in ferrets, mink, and dog resemble the human chondroid type
- Most in rats and cat are consistent with the human classical type
- Dogs: besides cervical and sacrococcygeal vertebrae, also reported in the brain, spinal cord, and skin
- Metastasis, commonly to the skin, is documented in the human, ferret and rat
- Primary intestinal chordoma in aged zebrafish is more common than chordoma of the axial skeleton
- Chordomas occur in perdido key beach mouse throughout the vertebral column (thoracic most common) with metastasis to the lung occurring in 34% of the mice
- Chordoma reported in Degu (Octodon degus) with mass on coccygeal vertebra
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- 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.
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