Oral Melanoma

GENERAL CONSIDERATIONS

Biologic Behaviour

•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

General Considerations

•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

Clinical Staging

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