Melanoma

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Cutaneous malignant melanoma in a German shepherd dog[1]
Oral malignant melanoma in a German shepherd dog[2]
Histological appearance of a locally invasive mucocutaneous melanoma within the mammary gland of a 11-year-old spayed Yorkshire Terrier[3]

Canine melanoma are a malignant round cell neoplasia of epithelial melanocytes (pigment cells) in the oral cavity, nail bed, eye[4], foot pad and mucocutaneous junctions (e.g. mammary gland)[5].

Melanoma is relatively common in dogs, accounting for 3% of all neoplasms and up to 7% of all malignant tumors[6]. They are usually found in older dogs.

Canine oral melanomas are virtually always considered malignant tumors, whereas more than 95% of cutaneous melanocytic lesions are benign[7]. Many are locally aggressive and metastasize early, leading to many cases being diagnosed later in the disease progression. Malignant melanoma also have a propensity for migrating along anatomical structures such as nerves (neurotropism) and skin appendages and therefore, diagnosis can be ascertained relatively late in the disease[8].

The metabolic difference between benign and malignant melanocytes appears to correlate well with COX-2 expression, with benign melanocytomas appearing to be less productive of this inflammatory mediator compared with melanomas, suggesting that possible chronic inflammation may be an initiator in the transformation from benign to malignant status[9].

Diagnosis is usually based on visualization of a deeply-pigmented non-pruritic lesion in the skin, mucocutaneous junctions or eye, however, histological analysis is essential for diagnosis. The histological characteristics of malignant melanomas include metastasis, high mitotic index, nuclear atypia, increased cellular size/volume, the presence of deep inflammation, and intralesional necrosis[10].

Malignant melanomas must be distinguished both visually and histologically from benign melanocytomas, which are a pigmented macule, papule or plaque or pedunculated mass that are usually just an incidental finding but may alarm some clients and clinicians.

Malignant melanomas appear different to melanocytomas, and have a raised, swollen and ulcerated appearance that is variably pigmented, often with underlying skin, nail or bone destruction.

Micro RNA assays have been developed as both diagnostic and prognostic tests for canine melanoma[11].

Treatment is usually a combination of wide-margin excision of the localized tumour, with digit amputation or rim mandibulectomy (with oral melanomas).

In concert with surgical excision, a combination of radiation therapy and/or chemotherapy is usually implemented to augment patient longevity.

A number of chemotherapy drugs have been trialed including carboplatin with piroxicam[12], tolfenamic acid[13] or acemannan[14].

With advanced disease (WHO stage II, III, or IV) oral melanomas have survival times of <5 months with aggressive local excision[15][16].

Unfortunately, response rates to chemotherapy in dogs with advanced melanoma range from 8% to 28% with little evidence that treatment improves survival[17].

Recently, a human tyrosinase DNA vaccine has been developed which shows promise against canine oral melanoma[18].

References

  1. Intechopen
  2. Flick River
  3. Yang HJ et al (2011) Angiotropic metastatic malignant melanoma in a canine mammary gland. Lab Anim Res 27(4):353-356
  4. Steinmetz A et al (2012) Oculocardiac reflex in a dog caused by a choroidal melanoma with orbital extension. J Am Anim Hosp Assoc 48(1):66-70
  5. Brockley L et al (2012) Malignant melanoma in 63 dogs (2001-2011): the effect of carboplatin chemotherapy on survival. N Z Vet J Aug 23
  6. Bostock DE (1979) Prognosis after surgical excision of canine melanomas. Vet Pathol 16(1):32–40
  7. Smith SH et al (2002) A comparative review of melanocytic neoplasms. Vet Pathol 39(6):651–678
  8. Barnhill RL (2001) The biology of melanoma micrometastases. Recent Results Cancer Res 158:3–13
  9. Pires I et al (2010) COX-1 and COX-2 expression in canine cutaneous, oral and ocular melanocytic tumours. J Comp Pathol 143(2-3):142-149
  10. Spangler WL & Kass PH (2006) The histologic and epidemiologic bases for prognostic considerations in canine melanocytic neoplasia. Vet Pathol 43(2):136-149
  11. Noguchi S et al (2011) MicroRNAs as tumour suppressors in canine and human melanoma cells and as a prognostic factor in canine melanomas. Vet Comp Oncol Dec 8
  12. Dank G et al (2012) Use of adjuvant carboplatin for treatment of dogs with oral malignant melanoma following surgical excision. Vet Comp Oncol Jun 28
  13. Wilson H et al (2012) Effect of tolfenamic acid on canine cancer cell proliferation, specificity protein (sp) transcription factors, and sp-regulated proteins in canine osteosarcoma, mammary carcinoma, and melanoma cells. J Vet Intern Med 26(4):977-986
  14. Kruth SA (1998) Biological response modifiers: interferons, interleukins, recombinant products, liposomal products. Vet Clin North Am Small Anim Pract 28(2):269-295
  15. Harvey HJ et al (1981) Prognostic criteria for dogs with oral melanoma. J Am Vet Med Assoc 178(6):580–582
  16. MacEwen EG et al (1986) Canine oral melanoma: comparison of surgery versus surgery plus Corynebacterium parvum. Cancer Invest 4(5):397–402
  17. Rassnick KM et al (2001) Use of carboplatin for treatment of dogs with malignant melanoma: 27 casses (1989-2000). J Am Vet Med Assoc 218(9):1444–1448
  18. Grosenbaugh DA et al (2011) Safety and efficacy of a xenogeneic DNA vaccine encoding for human tyrosinase as adjunctive treatment for oral malignant melanoma in dogs following surgical excision of the primary tumor. Am J Vet Res 72(12):1631-1638
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