GENERAL CONSIDERATIONS
+ 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
- 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
TREATMENT
+ 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
Chemotherapy
+ 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
PROGNOSIS
+ 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
ORAL MALIGNANT MELANOMA
Stages
| 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 |