4-year-old male castrated sable
ferret (Mustela putorius furo).The ferret presented with a oneweek
history of ataxia. The owner noted a
mass on the left neck. The ferret was eating
but otherwise lethargic. Owners elected
euthanasia due to worsening of clinical signs
and the inoperable nature of the mass.
Within the subcutis and
skeletal muscle of the neck just caudal to the
skull, there is a large, firm, multinodular,
smooth, white to tan, 5 x 3.5 x 1.5 cm mass
extending to the left lateral and ventral
aspect of the neck. The mass is adhered to
the first cervical vertebra, extending
caudally to the mid-cervical region and
ventrally to the level of the trachea, but is
not adhered to the trachea or esophagus. The
central region of the mass is attenuated.
After removal of the skull, evaluation of C1
reveals that the mass infiltrates into and
effaces the left cranial articular fovea
(articular facet of the atlas). After
decalcification, further sectioning of the
mass reveals that it extends into the
vertebral canal and compresses the cervical
spinal cord. In the caudal aspect of the left cranial lung
lobe, a 0.5 cm diameter firm, smooth, white
nodule is observed. The spleen is diffusely
congested and enlarged, and contained a 2 x
2 x 1.2 cm soft, smooth, red nodule. Two
renal cortical cysts are observed in the right
kidney, measuring approximately 0.4 cm
transverse section through the
cervical vertebra, cervical spinal cord and
surrounding skeletal muscle is examined.
Infiltrating into the epaxial musculature,
cervical vertebral pedicle, articular processes
and extending into the vertebral canal
with compression of the adjacent cervical
spinal cord is a multilobular, infiltrative,
poorly demarcated neoplasm. Neoplastic
lobules are separated by eosinophilic fibrovascular
connective tissue. Lobules are
comprised of large polygonal cells with
distinct cell borders and abundant, amphophilic
to clear, vacuolated cytoplasm
(physaliferous cells) surrounded by variable
amounts of amphophilic, mucinous stroma.
Nuclei are round to oval and often peripheralized,
with finely stippled chromatin
and multiple nucleoli. There are zero mitotic
figures in 10 high power (400x) fields.
Multifocally in the center and at the
periphery of lobules, scattered aggregates of
cartilage and woven bone are interspersed
within the physaliferous cells. Bony trabeculae
contain osteocytes and are lined by
osteoblasts. Chondrocytes lie within a
lightly eosinophilic to amphophilic matrix or
are occasionally entrapped within bone.
Rare binucleate cells are found. Small
aggregates of lymphocytes, plasma cells and
macrophages are present at the periphery of the mass.
Vertebral bone has scalloped borders, with osteoclasts in Howships lacunae. Fragmented woven bone (reactive bone) is interspersed with numerous plump osteoblasts and fibroblasts. Neoplastic compression of the cervical spinal cord results in shifting of the ventral medial fissure away from the mass. The white matter of the spinal cord exhibits mild, multifocal vacuolation in the dorsal, lateral and ventral funiculi, within which are few Gitter cells containing myelin degradation products. Scattered, multifocal swollen axons (spherocytes) are present in the ventral and lateral funiculi. Variation in neuronal cytoplasmic staining is present with no loss of Nissl substance (decalcification artifact, presumptive). Surrounding epaxial skeletal muscles, and more prominently, muscle adjacent to the dorsal spinous process undergoes degeneration and regeneration, manifesting as myocyte size variation, sarcoplasmic hypereosinophila and vacuolation, loss of striation, satellitosis, central nuclei, and nuclear rowing.
1. Cervical spine: Chordoma, with local infiltration of skeletal muscle, vertebral bone
and vertebral canal.
2. Cervical spinal cord: Focal compression with midline shift, mild, moderate Wallerian degeneration and spheroid formation.
3. Cervical skeletal muscles: Multifocal myodegeneration and regeneration.
4. Lung (caudal aspect left cranial lung lobe, not submitted): Multifocal chordoma metastasis.
the 5th most common tumor in domestic
ferrets, and the most common musculoskeletal
tumor.1,11 Chordomas are slow
growing, locally aggressive neoplasms derived
from remnant fetal notochord 1,4,6-12,14
believed to originate from the primitive
mesoderm.1,2 The notochord persists between
the vertebrae and expands to form the
nucleus pulposus of intervertebral disks in
some animals (visible in the section).1,5,8,9
Cell rests of residual notochord remain
outside of the intervertebral disks in an
estimated 2% of humans, and chordomas are
thought to arise from these cell rests.1,4,8,9
Histologically, ferret chordomas are characterized
by lobules of physaliferous cells
surrounding cartilage with a central core of
bone and cartilage. 1,4,6-12,14 Notochordinduced
differentiation of bone and cartilage
within the neoplasm is one hypothesis for
the bone and cartilage formation within
Chordomas can occur anywhere along the axial skeleton. In the ferret, common sites include the tail tip (most common site), cervical vertebral column (second most common site), thoracic vertebral column, and the coccygeal region.1,4,6-12,14 The sacrococcygeal and spheno-occipital regions are the most common sites of chordoma occurrence in humans, with the remainder found in the vertebral axis.4,14 Up to 30% of human chordomas are reported to metastasize, typically during the phase of recurrent disease, with common sites of metastasis reported to be bone, lung, lymph node, skin and liver.1,4,14 Rare cases of local and distant skin metastases have been reported in the ferret.1,4,14 Vascular invasion was equivocal in the submitted section, however, was observed rarely in other sections of the mass and pulmonary metastases were present. One study evaluated cell proliferation indices in 5 ferret chordomas, and found that they were not predictive of metastatic potential.8
In humans, there are 3 recognized subtypes of chordoma: classic chordoma, chondroid chordoma, and chordoma with malignant spindle cell component (dedifferentiated). It has been suggested that ferret chordomas may act as an animal model for the chondroid subtype of human chordoma.4,14 Differentiation between classic and chondroid subtypes in humans is significant, as chondroid chordomas are associated with a survival rate 3 times greater than that of classic chordomas.1,8 Although the chondroid component was not prominent in the submitted section, it was more frequently observed in other sections of the mass.
Immunohistochemical analysis of chordomas in the ferret typically show dual expression of cytokeratin and vimentin, with variable expression of S-100 protein and neuron specific enolase (NSE).1,4,6-12,14 In one study of chordomas in 20 ferrets, 75% were positive for S-100 and 85% were positive for NSE.4 The S-100 positivity is thought to be due to glycosaminoglycan content within the stroma, and NSE is expressed in cells with high metabolic activity.1,4
Cervical vertebra (axis):
This case nicely
characterizes an example of a common
neoplasm in the axial skeleton of a ferret.
The contributor provides an excellent histologic
description, including the ancillary
findings of degeneration of the spinal cord,
peripheral nerves, and adjacent skeletal
muscle as a result of compression from this
Aside from humans and ferrets, chordomas have been rarely reported in the axial skeleton of Fischer 344 rats11, mice13, dogs6,9, and cats2. In addition, 24 cases of spontaneous primary intestinal chordomas as well as nine spontaneous vertebral chordomas, were recently reported in the aged laboratory zebrafish3. In dogs, chordomas have been reported in the brain, spinal cord, and skin6. Of the three reported cases of feline chordoma, one was initially diagnosed as chronic granulomatous inflammation due to the interpretation of the characteristic physaliferous cells as atypical, foamy macrophages; it was subsequently dis-covered to be an example of a classic chordoma-like subtype, which then metastasized to multiple lymph nodes2.
In all species, chordomas tend to be slow growing and locally invasive.1-14 Typically, distant metastasis is associated with the classic chordoma and dedifferentiated spindle cell subtypes in humans, rather than the chondroid type which forms islands of cartilage and bone most commonly in the ferret and mink.1,4,8,10,14 In a large study of Fischer 344 rats there was an exceptionally high 75% incidence of pulmonary metastasis in animals diagnosed with chordomas.11 The histomorphology of chordomas in the Fischer rat is similar to the classic type in humans, which may explain the more aggressive biologic behavior in these rodents as compared to other animals.11 Prior to this case, visceral metastasis had not yet been reported in the ferret. However, the contributor recently published this case report, to include pulmonary metastasis via hematogenous spread; this is the first known case of visceral metastasis in the ferret5. The authors hypothesized that the metastatic potential in ferrets may increase over time, highlighting the importance of prompt surgical excision. Most cases of ferret chordomas occur at the tail tip making complete surgical excision relatively simple.1,4,5,14 Chordomas in other locations, such as this case, are substantially more difficult to excise.5
Chordomas in ferrets may histologically resemble chondrosarcomas due to the cartilaginous component. Conference participants briefly discussed immunohistochemistry as a method by which to differentiate chordoma from chondrosarcoma. As mentioned by the contributor, chordomas consistently demonstrate dual immunopositivity for vimentin and cytokeratin, while chon-drosarcomas are immunonegative for cytokeratin. Chordomas are also typically positive for S-100 and neuron-specific enolase (NSE); the S-100 and NSE positivity does not suggest neural crest origin, however.10,12 Other neoplasms of interest that typically express both vimentin and cytokeratin include: mesothelioma, synovial sarcoma, meningioma, renal cell carcinoma, adrenal carcinoma, and endometrial sarcoma.12
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