Progressive inappetence, weight loss, and coughing in a 14-year-old male neutered Plott Hound

Claire N. Quinn Wheat Ridge Animal Hospital, Veritas Veterinary Partners, Wheat Ridge, CO

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Andrea Musarra Wheat Ridge Animal Hospital, Veritas Veterinary Partners, Wheat Ridge, CO

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Deanna D. Dailey Zoetis Reference Laboratories, Wheat Ridge, CO

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Lisa J. Schlein Zoetis Reference Laboratories, Wheat Ridge, CO

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History

A 14-year-old castrated male Plott Hound was presented to the emergency department of a private practice specialty facility for evaluation of a 3-week history of progressive inappetence, weight loss, and coughing or gagging. The owners reported that a left cervical (neck) mass had been present for 2 years but had recently grown rapidly.

Clinical and Clinicopathologic Findings

Physical examination revealed a 13 X 15 X 3-cm firm, nonmovable (fixed) mass in the left ventrolateral cervical region and severe dental disease but was otherwise unremarkable. Three-view thoracic radiography revealed severe right-lateral deviation of the cervical trachea and a large left cervical mass. Cervical ultrasonography revealed a cavitated, mineralized, and highly vascular mass in the left cervical region extending to the thoracic inlet, with no discernible normal thyroid tissue visible and moderate medial retropharyngeal lymphadenopathy. Fine-needle aspiration of the cervical mass was obtained, and squash preparations were made immediately.

Formulate differential diagnoses, then continue reading.

Cytologic and Histopathologic Findings

Cytology revealed a low- to moderate-cellularity sample of excellent diagnostic quality (Figure 1). Atypical, round to spindle-shaped cells were present on most slides and were arranged individually and in epithelioid aggregates. These cells had discrete cytoplasmic borders; variable cell morphology (round, stellate, or spindle-shaped); large, round to irregularly shaped nuclei; coarsely stippled to lacey chromatin; prominent, variably sized nucleoli; and lightly vacuolated, moderately basophilic cytoplasm, occasionally with small, wispy cytoplasmic extensions. Some cells exhibited erythrophagia or siderophagia (phagocytosed, dark-green pigment, consistent with hemosiderin and chronic erythrocyte degradation). Anisokaryosis and anisocytosis were moderate. One submitted slide was noted to be cytologically distinct. The background of this slide focally contained pale, eosinophilic, proteinaceous material with cell-free lipid, bare nuclei, and platelet clumps. On this slide, there was a distinct population of epithelioid cells with neuroendocrine morphology. These cells had variably distinct cell borders, coarsely stippled chromatin, inconspicuous nucleoli, and light blue-gray to amphophilic cytoplasm. Many of these cells were ruptured, leaving free nuclei in “spilled” cytoplasm, and some pseudoacinar structures were noted. Anisocytosis and anisokaryosis of these cells were mild. Rare, multinucleated giant cells were also observed in this sample. General differential diagnoses for large, multinucleated cells include osteoclasts, a multinucleated member of a neoplastic cell population, or a multinucleated giant cell macrophage. In this case, osteoclasts were cytologically favored, as cells contained finely granular, amphophilic cytoplasm, as well as very uniform, round nuclei without evidence of other potential inflammatory cells or phagocytosed material in these cells (Figure 2).

Figure 1
Figure 1

Photomicrographs of ultrasound-guided fine-needle aspirate samples obtained from a firm mass (approx 13 X 15 X 3 cm) in the neck of a 14-year-old castrated Plott Hound evaluated for a 3-week history of progressive inappetence, weight loss, and coughing or gagging. A, B, and C—Examples of atypical, round to spindle-shaped cells appearing in epithelioid aggregates. There is evidence of erythrophagia in the atypical cell population (arrow). D—A large, multinucleated cell. E—A separate population of neuroendocrine-like, epithelioid cells with minimal cytologic atypia. Modified Wright-Giemsa stain; bar = 10 µm (500X; A, B, and E) or 20 µm (1,000X; C and D).

Citation: Journal of the American Veterinary Medical Association 261, 10; 10.2460/javma.23.02.0113

Figure 2
Figure 2

Neoplastic cells are associated with production of osteoid. H&E stain; bar = 100 µm (200X).

Citation: Journal of the American Veterinary Medical Association 261, 10; 10.2460/javma.23.02.0113

It was thought that the osteoclasts may have been present secondary to osseous metaplasia, association of the tumor with underlying bone, or osteosarcoma. Neuroendocrine-appearing cells in the sample were compatible with thyroid tissue origin in this location, thought to represent either aspiration of normal, incidentally aspirated thyroid tissue or a well-differentiated thyroid neoplasm (either unrelated to the atypical cell population or representing a more well-differentiated area of an anaplastic thyroid carcinoma). The atypical spindle cell population was interpreted as a malignant neoplasm, likely a sarcoma with an epithelioid arrangement of cells (such as hemangiosarcoma or osteosarcoma). The atypical cells had moderate to strong cytoplasmic reactivity for ALP (Figure 3), most suggestive of osteosarcoma in this case.

Figure 3
Figure 3

Photomicrograph of a cytologic sample from the mass described in Figure 1 showing epithelioid cells with strong cytoplasmic ALP immunoreactivity. Nitroblue tetrazolium chloride and 5-bromo-4-chloro-3-indolyl phosphate toluidine salt-phosphatase substrate; bar = 10 µm.

Citation: Journal of the American Veterinary Medical Association 261, 10; 10.2460/javma.23.02.0113

Immediately postmortem, 3 punch biopsy samples were obtained percutaneously of the cervical mass and submitted in neutral-buffered 10% formalin fixation. Histopathology revealed spindle to oval cells with moderate, eosinophilic cytoplasm. Cell borders were variably distinct. One or multiple prominent nucleoli were present within the irregularly marginated nuclei. These cells were arranged in dense sheets. Anisokaryosis and anisocytosis were moderate. Thirteen mitotic figures were noted in 2.37 mm2 (approx 13 mitotic figures in 10 hpf [400X]). Variably mineralized osteoid was associated with cells in varying amounts. No normal thyroid tissue was noted in examined sections.

Diagnosis

The cytologic diagnosis in this case was malignant neoplasia, likely an epithelioid osteosarcoma, with evidence of neuroendocrine tissue, likely thyroid in origin. The morphologic diagnosis was extraskeletal osteosarcoma.

Case Outcome

Owners elected palliative care, and the patient was prescribed carprofen (Carprovet; 1.76 mg/kg, twice daily), maropitant citrate (Cerenia; 1.88 mg/kg, once daily as needed), and capromorelin (Entyce; 2.82 mg/kg, twice daily as needed). The dog re-presented to the same emergency department 27 days after initial presentation for euthanasia due to declining quality of life.

Comments

Extraskeletal osteosarcoma (EOS) is an uncommon tumor of mesenchymal origin in companion canines. EOS is classified as an osteoid-producing neoplasm without primary periosteal or bone involvement.1 Prognosis is traditionally considered poor, though prolonged survival following surgical resection has been documented.1,2 They have been reported in a variety of viscera and soft tissues and can be divided into soft tissue osteosarcoma and mammary gland osteosarcoma, as biologic behavior varies in mammary locations.1 EOSs are malignant and have a high rate of distant metastasis.2 It has been proposed that chronic inflammation is associated with development of these neoplasms, though this has not been proven. No known source of local chronic inflammation was recorded in the described case.

The majority of EOS cases reported have been of osteoblastic origin.3 Previously established criteria for diagnosis of EOS include morphologically sarcomatous tissue, malignant production of osteoid, lack of osseous-tissue origin, and indices of malignancy such as an increased mitotic count.3,4 The case described above satisfied the documented criteria for diagnosis of EOS. Given other cytologic features of this sample, positive ALP staining was supportive of osteosarcoma in this case. In 1 study5, ALP staining of cytology slides was 100% sensitive and 89% specific for osteosarcoma. Some other tumor types that have reported ALP positivity include multilobular tumor of bone, amelanotic melanoma, and chondrosarcoma.5

This case described an uncommon canine neoplasm and highlighted the value of histopathology in instances for which there are multiple possible interpretations of cytopathology data. A differential diagnosis of EOS should be considered for malignant tumors in nonosseous tissues with sarcoma morphology, evidence of mineralization on imaging, or cytologic evidence of osteoid production or evidence of bony remodeling. ALP immunocytochemical staining can provide diagnostic support when osteosarcoma is a cytologic differential diagnosis.

Acknowledgments

No third-party funding or support was received in connection with this case. The authors declare that there were no conflicts of interest.

References

  • 1.

    Langenbach A, Anderson MA, Dambach DM, Sorenmo KU, Shofer FD. Extraskeletal osteosarcomas in dogs: a retrospective study of 169 cases (1986-1996). J Am Anim Hosp Assoc. 1998;34(2):113120. doi:10.5326/15473317-34-2-113

    • Search Google Scholar
    • Export Citation
  • 2.

    Duffy D, Selmic LE, Kendall AR, Powers BE. Outcome following treatment of soft tissue and visceral extraskeletal osteosarcoma in 33 dogs: 2008-2013. Vet Comp Oncol. 2017;15(1):4654. doi:10.1111/vco.12141

    • Search Google Scholar
    • Export Citation
  • 3.

    Patnaik AK. Canine extraskeletal osteosarcoma and chondrosarcoma: a clinicopathologic study of 14 cases. Vet Pathol. 1990;27(1):4655. doi:10.1177/030098589002700107

    • Search Google Scholar
    • Export Citation
  • 4.

    Kuntz CA, Dernell WS, Powers BE, Withrow S. Extraskeletal osteosarcomas in dogs: 14 cases. J Am Anim Hosp Assoc. 1998;34(1):2630. doi:10.5326/15473317-34-1-26

    • Search Google Scholar
    • Export Citation
  • 5.

    Barger A, Graca R, Bailey K, et al. Use of alkaline phosphatase staining to differentiate canine osteosarcoma from other vimentin-positive tumors. Vet Pathol. 2005;42(2):161165. doi:10.1354/vp.42-2-161

    • Search Google Scholar
    • Export Citation
  • Figure 1

    Photomicrographs of ultrasound-guided fine-needle aspirate samples obtained from a firm mass (approx 13 X 15 X 3 cm) in the neck of a 14-year-old castrated Plott Hound evaluated for a 3-week history of progressive inappetence, weight loss, and coughing or gagging. A, B, and C—Examples of atypical, round to spindle-shaped cells appearing in epithelioid aggregates. There is evidence of erythrophagia in the atypical cell population (arrow). D—A large, multinucleated cell. E—A separate population of neuroendocrine-like, epithelioid cells with minimal cytologic atypia. Modified Wright-Giemsa stain; bar = 10 µm (500X; A, B, and E) or 20 µm (1,000X; C and D).

  • Figure 2

    Neoplastic cells are associated with production of osteoid. H&E stain; bar = 100 µm (200X).

  • Figure 3

    Photomicrograph of a cytologic sample from the mass described in Figure 1 showing epithelioid cells with strong cytoplasmic ALP immunoreactivity. Nitroblue tetrazolium chloride and 5-bromo-4-chloro-3-indolyl phosphate toluidine salt-phosphatase substrate; bar = 10 µm.

  • 1.

    Langenbach A, Anderson MA, Dambach DM, Sorenmo KU, Shofer FD. Extraskeletal osteosarcomas in dogs: a retrospective study of 169 cases (1986-1996). J Am Anim Hosp Assoc. 1998;34(2):113120. doi:10.5326/15473317-34-2-113

    • Search Google Scholar
    • Export Citation
  • 2.

    Duffy D, Selmic LE, Kendall AR, Powers BE. Outcome following treatment of soft tissue and visceral extraskeletal osteosarcoma in 33 dogs: 2008-2013. Vet Comp Oncol. 2017;15(1):4654. doi:10.1111/vco.12141

    • Search Google Scholar
    • Export Citation
  • 3.

    Patnaik AK. Canine extraskeletal osteosarcoma and chondrosarcoma: a clinicopathologic study of 14 cases. Vet Pathol. 1990;27(1):4655. doi:10.1177/030098589002700107

    • Search Google Scholar
    • Export Citation
  • 4.

    Kuntz CA, Dernell WS, Powers BE, Withrow S. Extraskeletal osteosarcomas in dogs: 14 cases. J Am Anim Hosp Assoc. 1998;34(1):2630. doi:10.5326/15473317-34-1-26

    • Search Google Scholar
    • Export Citation
  • 5.

    Barger A, Graca R, Bailey K, et al. Use of alkaline phosphatase staining to differentiate canine osteosarcoma from other vimentin-positive tumors. Vet Pathol. 2005;42(2):161165. doi:10.1354/vp.42-2-161

    • Search Google Scholar
    • Export Citation

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