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Conference1 24 August 2016 1 Joint Pathology Center Veterinary Pathology Services WEDNESDAY SLIDE CONFERENCE 2016-2017 Conference1 24 August 2016 CASE I: 48422 (JPC 4006379). Signalment: 4-year-old male castrated sable ferret (Mustela putorius furo). History: The ferret presented with a one- week 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. Cervical vertebrae, ferret. A large mass is present over Gross Pathology: Within the subcutis and the cranial cervical vertebrae. (Photo courtesy of: Animal skeletal muscle of the neck just caudal to the Medical Center, 510 East 62nd St. New York, NY 10065 skull, there is a large, firm, multinodular, http://www.amcny.org/) 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 In the caudal aspect of the left cranial lung the first cervical vertebra, extending lobe, a 0.5 cm diameter firm, smooth, white caudally to the mid-cervical region and nodule is observed. The spleen is diffusely ventrally to the level of the trachea, but is congested and enlarged, and contained a 2 x not adhered to the trachea or esophagus. The 2 x 1.2 cm soft, smooth, red nodule. Two central region of the mass is attenuated. renal cortical cysts are observed in the right After removal of the skull, evaluation of C1 kidney, measuring approximately 0.4 cm reveals that the mass infiltrates into and each. effaces the left cranial articular fovea (articular facet of the atlas). After Laboratory results: N/A decalcification, further sectioning of the mass reveals that it extends into the Histopathologic Description: A de- vertebral canal and compresses the cervical calcified transverse section through the spinal cord. cervical vertebra, cervical spinal cord and 2 surrounding skeletal muscle is examined. Infiltrating into the epaxial musculature, cervical vertebral pedicle, articular pro- cesses 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 fibro- vascular connective tissue. Lobules are comprised of large polygonal cells with distinct cell borders and abundant, am- phophilic to clear, vacuolated cytoplasm Cervical vertebra (presumptive axis), ferret. The cervical (physaliferous cells) surrounded by variable vertebra is partially effaced by the chordoma, which amounts of amphophilic, mucinous stroma. compresses the spinal cord. (HE, 5X) Nuclei are round to oval and often per- ipheralized, with finely stippled chromatin the mass. and multiple nucleoli. There are zero mitotic figures in 10 high power (400x) fields. Vertebral bone has scalloped borders, with Multifocally in the center and at the osteoclasts in Howship’s lacunae. Frag- periphery of lobules, scattered aggregates of mented woven bone (reactive bone) is cartilage and woven bone are interspersed interspersed with numerous plump ost- within the physaliferous cells. Bony tra- eoblasts and fibroblasts. Neoplastic com- beculae contain osteocytes and are lined by pression of the cervical spinal cord results in osteoblasts. Chondrocytes lie within a shifting of the ventral medial fissure away lightly eosinophilic to amphophilic matrix or from the mass. The white matter of the are occasionally entrapped within bone. spinal cord exhibits mild, multifocal vac- Rare binucleate cells are found. Small uolation in the dorsal, lateral and ventral aggregates of lymphocytes, plasma cells and funiculi, within which are few Gitter cells macrophages are present at the periphery of containing myelin degradation products. Scattered, multifocal swollen axons (sph- erocytes) 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 un- dergoes degeneration and regeneration, manifesting as myocyte size variation, sar- coplasmic hypereosinophila and vac- Cervical vertebra, ferret. This fixed specimen (likely uolation, loss of striation, satellitosis, central proximal C-3 with dorsal spinous process at 10 o’clock) is nuclei, and nuclear rowing. unilaterally effaced by a multilobular mass which also compresses the spinal cord. (Photo courtesy of: Animal Medical Center, 510 East 62nd St. New York, NY 10065 Contributor’s Morphologic Diagnoses: 1. http://www.amcny.org/) Cervical spine: Chordoma, with local 3 infiltration of skeletal muscle, vertebral bone Cell rests of residual notochord remain and vertebral canal. outside of the intervertebral disks in an 2. Cervical spinal cord: Focal compression estimated 2% of humans, and chordomas are with midline shift, mild, moderate Wallerian thought to arise from these cell rests.1,4,8,9 degeneration and spheroid formation. Histologically, ferret chordomas are cha- 3. Cervical skeletal muscles: Multifocal racterized by lobules of physaliferous cells myodegeneration and regeneration. surrounding cartilage with a central core of 4. Lung (caudal aspect left cranial lung lobe, bone and cartilage. 1,4,6-12,14 Notochord- not submitted): Multifocal chordoma induced differentiation of bone and cartilage metastasis. within the neoplasm is one hypothesis for the bone and cartilage formation within Contributor’s Comment: Chordomas are these neoplasms.4 the 5th most common tumor in domestic ferrets, and the most common mus- Chordomas can occur anywhere along the culoskeletal tumor.1,11 Chordomas are slow axial skeleton. In the ferret, common sites growing, locally aggressive neoplasms der- include the tail tip (most common site), ived from remnant fetal notochord 1,4,6-12,14 cervical vertebral column (second most believed to originate from the primitive common site), thoracic vertebral column, mesoderm.1,2 The notochord persists be- and the coccygeal region.1,4,6-12,14 The sacro- tween the vertebrae and expands to form the coccygeal and spheno-occipital regions are nucleus pulposus of intervertebral disks in the most common sites of chordoma some animals (visible in the section).1,5,8,9 occurrence in humans, with the remainder Cervical vertebra (presumptive axis), ferret. The neoplasm is composed of polygonal cells with large clear vacuoles which often peripheralize the nucleus (physaliferous cells) separated by moderate amounts of blue mucinous matrix (arrow). (HE, 400X) 4 found in the vertebral axis.4,14 Up to 30% of Immunohistochemical analysis of cho- human chordomas are reported to met- rdomas in the ferret typically show dual astasize, typically during the phase of expression of cytokeratin and vimentin, with recurrent disease, with common sites of variable expression of S-100 protein and metastasis reported to be bone, lung, lymph neuron specific enolase (NSE).1,4,6-12,14 In node, skin and liver.1,4,14 Rare cases of local one study of chordomas in 20 ferrets, 75% and distant skin metastases have been were positive for S-100 and 85% were reported in the ferret.1,4,14 Vascular invasion positive for NSE.4 The S-100 positivity is was equivocal in the submitted section, thought to be due to glycosaminoglycan however, was observed rarely in other content within the stroma, and NSE is sections of the mass and pulmonary met- expressed in cells with high metabolic astases were present. One study evaluated activity.1,4 cell proliferation indices in 5 ferret chordomas, and found that they were not JPC Diagnosis: Cervical vertebra (axis): predictive of metastatic potential.8 Chordoma. In humans, there are 3 recognized subtypes Conference Comment: This case nicely of chordoma: classic chordoma, chondroid characterizes an example of a common chordoma, and chordoma with malignant neoplasm in the axial skeleton of a ferret. spindle cell component (dedifferentiated). It The contributor provides an excellent his- has been suggested that ferret chordomas tologic description, including the ancillary may act as an animal model for the findings of degeneration of the spinal cord, chondroid subtype of human chordoma.4,14 peripheral nerves, and adjacent skeletal Differentiation between classic and cho- muscle as a result of compression from this ndroid subtypes in humans is significant, as infiltrative neoplasm. chondroid chordomas are associated with a survival rate 3 times greater than that of Aside from humans and ferrets, chordomas classic chordomas.1,8 Although the cho- have been rarely reported in the axial ndroid component was not prominent in the skeleton of Fischer 344 rats11, mice13, submitted section, it was more frequently dogs6,9, and cats2. In addition, 24 cases of observed in other sections of the mass. spontaneous primary intestinal chordomas as well as nine spontaneous vertebral chor- domas, 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 mac- rophages; it was subsequently dis-covered to be an example of a classic chordoma-like subtype, which then metastasized to multiple Cervical vertebra (presumptive axis), ferret. Multifocally, 2 several lobules of the neoplasm contain foci of lymph nodes .
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