Veterinary Society of
Surgical Oncology

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
  • 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

Stage

Description

I

Tumor diameter < 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

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