+ Biologic Behavior

  • Malignant melanoma is the most common oral tumor in dogs with an incidence of 31%-42%
  • Age: mean 12 years
  • Sex predilection: males with a male-to-female ratio of 1.4-6.0:1
  • No breed predisposition, but Cocker Spaniel may be over-represented and more common in smaller dogs
  • Dogs with heavily pigmented oral mucosa are predisposed to malignant melanoma
  • Site predilection: gingiva (42%-63%), buccal or labial mucosa (15%-33%), and lips
  • Gross appearance: firm and black, but can be unpigmented in up to 33% cases
  • Surface ulceration and necrosis is uncommon
  • 57% of dogs have radiographic evidence of bone involvement
  • Metastasis to the regional lymph node in 58%-74%, lungs in 14%-67%, and tonsils in 65% dogs


  • Diagnosis can be difficult if biopsy does not contain melanin (30% are amelanotic)
  • Melanoma should be suspected if histologic diagnosis is anaplastic or undifferentiated sarcoma or carcinoma
  • Regional lymph nodes should be aspirated or biopsied as lymph node size is an inaccurate indication of metastasis:
  • 40% dogs with normal sized lymph nodes have microscopic evidence of metastasis
  • 70% dogs with lymph node metastasis have enlarged lymph nodes and 30% dogs had normal sized nodes
  • Lymph node size as a predictor of metastasis has a 70% sensitivity, 51% specificity, 62% positive-predictive value, and 60% negative-predictive value


+ Surgery

  • Surgical techniques: mandibulectomy and maxillectomy
  • MST for both mandibular and maxillary oral melanoma following surgical resection: 8.0-9.5 months with 12-month survival rate 35%, and local recurrence rate 25%-59%
  • MST following mandibulectomy: 9-11 months with 12-month survival rate 21% and local recurrence rate 22%
  • MST following maxillectomy: 4.5-10 months with 12-month survival rate 27% and local recurrence rate 48%
  • Aggressive surgical approach, regardless of completeness of margins, is associated with significantly longer DFI and survival time than other treatment modalities
  • MST is also stage dependent with MST 20 months for stage I-II and 6 months for stage III-IV
  • MST for surgery alone is 318 days
  • MST for surgery and chemotherapy is 1,120 days

Radiation Therapy

+ Curative-Intent Radiation Therapy

  • Malignant melanoma responds well to course fractionation with a total of 6 fractions (once weekly for 6 weeks or twice weekly for 3 weeks):
  • Overall response rate 83%-94%, with up to 70% CR
  • 15% local tumor recurrence rate with median time to local recurrence of 139 days
  • Median DFI 150-235 days
  • 51% metastatic rate with median time to metastasis of 311 days
  • MST 210-363 days, with 1-year survival rate 45%-48% and 2-year survival rate 21%
  • Time to local recurrence and survival are significantly improved with rostral tumor location, no radiographic evidence of bone lysis, and microscopic disease

+ Palliative Radiation Therapy

  • Palliative radiation therapy for disseminated or advanced oral malignant melanoma
  • Overall response rate 100%, with 69% (25/36) CR and 31% (11/36) PR


+ General Considerations

  • Chemotherapy is indicated for dogs with malignant melanoma because of the high metastatic rate (up to 75%)
  • Chemotherapy can be administered either intralesional or systemically
  • MST for surgery and chemotherapy is 1,120 days

+ Intralesional Chemotherapy

  • Intralesional cisplatin implants associated with 70% (14/20) PR
  • MST is significantly improved in dogs showing a local response to cisplatin (51 weeks v 10 weeks)
  • Implant complications (i.e., mild local necrosis) were common in 85% (17/20) dogs

+ Systemic Chemotherapy

  • Platinum drugs have the best clinical activity against oral malignant melanoma
  • Carboplatin (300 mg/m 2 q 3 weeks) is associated with an overall response rate of 28% (7/25), including 4% (1/25) CR and 24% (6/25) PR and a further 36% (9/25) with SD, with median duration of PR 165 days
  • Cisplatin and piroxicam: 18% (2/11) CR with 41% renal toxicity
  • Melphalan associated with an overall response rate of 27% with a median duration of response of 4 months

+ Immunotherapy

  • Immunotherapy is the most promising adjunctive treatment for dogs with oral malignant melanomas
  • Bacillus Calmette-Guérrin (BCG) and levamisole do not improve survival times or rates
  • Corynebacterium parvum combined with surgical resection provides a mild survival advantage compared to only surgery
  • Intralesional granulocyte-monocyte colony stimulating factor is associated with an overall response rate of 100% and prolongs survival time compared to historical controls
  • Liposome muramyl tripeptide-phosphatidylethanolamine combined with surgery significantly improves survival time and rate compared to surgery alone in dogs with stage I disease, but not stage II or III disease (2-year survival rate 80% v 25%)
  • IL-2 and IFN-λ are promising agents in veterinary medicine as melanomas are highly immunogenic tumors and these agents induce natural killer cells and lymphokine-activated killer cells and augment antibody-dependent cellular cytotoxicity
  • Immunotherapy and radiation therapy may be synergistic


+ General Considerations

  • Prognosis is guarded to poor with metastatic disease in up to 95%
  • Prognostic indicators: size, stage, and local tumor recurrence
  • Age, breed, sex, degree of pigmentation, microscopic appearance, and DNA ploidy are not prognostic
  • Metastatic rate is site, size, and stage dependent
  • Small pedunculated malignant melanoma on gingival margin or lip may not be as malignant
  • MST reported include:
  • 65 days with no treatment
  • 240-318 days with surgery
  • 240-363 days with radiation therapy
  • 1,120 days with surgery and chemotherapy

+ Tumor Size

  • Size of primary lesion is prognostic for metastasis and survival
  • Malignant melanoma < 2 cm (i.e., stage I) has MST of 511 days
  • Malignant melanoma > 2 cm or metastatic malignant melanoma (i.e., stage II-III) has MST of 164 days

+ Tumor Location

  • Mandibular has a better prognosis than maxillary melanoma in dogs treated with intralesional cisplatin
  • Rostral mandibular and caudal maxillary melanoma have a better prognosis

+ Histologic Features

Malignant melanoma with a mitotic index ≤ 3 is associated with a better prognosis




I Tumor diameter less than 2 cm and no regional lymph node or distant metastasis
II Tumor diameter between 2-4 cm and no regional lymph node or distant metastasis
III Tumor diameter > 4 cm or any sized tumor with regional lymph node or distant metastasis