I. Overview
Malignant melanoma (MM) is formed by the malignant transformation of melanocytes located at the base of the epidermis, mostly developed from nevi or pigmented spots.
Early stage MM can be cured by 95%-100% after expanded surgical excision. Therefore, early detection and early diagnosis are very important.
Early clinical manifestations are: rapid enlargement of the nevus or pigmented spot, elevation, unhealed rupture, uneven edges or cut marks, jagged teeth, color change, local formation of blisters, itching, stinging, etc.
MM prognosis: women are better than men, and the prognosis of head and neck is the worst. The 5-year survival rate of lymph nodes with 1 metastasis is 75%; 3 is 15%; the depth of infiltration is 90%, and >4.5mm is 30%.
II. Epidemiology and etiology
MM is the fastest growing tumor among all malignant tumors, with an annual growth rate of about 3-5%.
The etiology is mainly thought to be related to sun exposure. ua (ultraviolet light) burns the skin to DNA mutation. uva and uvb, uvb is the main cause of damage to a certain gene in melanocytes and induces morbidity. Mutations in p16 or CDKN2A, located on the short arm of chromosome 9, are the main cause of high genetic susceptibility to melanoma.
Inappropriate treatments have the potential to induce rapid growth of MM, such as knife cuts, rope strangulation, salt pickling, laser and freezing treatments.
III. Types of pathology
Common pathological types of MM are: superficial spreading, nodular, and malignant freckle-like melanoma.
Less common types are: epithelioid, pro-fibroproliferative, malignant anaplastic nevus, balloon-like cells, spindle cell and malignant melanoma of giant nevus nigricans.
Superficial diffuse type is most common in Caucasians, while yellow and black races are more common with extremity freckle-like melanoma.
IV. Common patterns of pathological reports
(1) Common pathological diagnostic elements
Tumor site
Pathological histological diagnosis, histological type, tumor size (maximum diameter)
(2) Morphological prognostic indicators
Epidermal melanoma report tumor infiltration depth (Clark infiltration level)
Epidermal melanoma report tumor thickness (Breslow thickness)
Whether there is ulcer formation
Nuclear division image of tumor cells
Tumor cell infiltration of lymph nodes (+ small amount; +++ large amount)
Lymphovascular infiltration
Microscopic satellite foci
whether there is tumor involvement at the tumor cut edge
(3) Immunophenotype
Differentiation markers, progression markers and other markers are selected and reported according to the actual situation.
V. Treatment process or principles
(1) Clear diagnosis and staging
1.If nevus and pigmented spots have malignant tendency, complete excision should be done immediately (the cut edge is usually 1-3mm)
2.Pathology report
3. Whole body physical examination to determine the stage of tumor. Pay attention to lymph nodes.
(II) Sentinel lymph node biopsy (SLNB)
(iii) Extended resection of the primary tumor: The extent of extended resection is decided according to the maximum thickness of the tumor in the pathology report. According to NCCN guidelines and evidence-based medical evidence, the maximum thickness of the lesion ≤1.0mm, the expanded resection range is 1cm at the margin; the maximum thickness of the lesion 1.01-2.0mm, the expanded resection range is 2cm at the margin; the margin should be greater than 4mm when the thickness is >2mm, and many scholars believe that the margin should be at least 3cm, but there is no consensus on this point.
(iv) Regional lymph node dissection.
Patients with lymph node metastasis confirmed by ultrasound in SLNB or superficial lymph nodes should undergo regional lymph node dissection. The number of lymph node dissection in the neck should be at least 15.
(V) Decide the next treatment plan according to the staging
1.If surgery can achieve tumor-free status, (including stage IV patients), surgery should be performed to remove all lesions.
2. If surgery cannot achieve tumor-free status, surgery should not be performed, but systemic treatment should be performed.
The recommended first and second line treatment options include clinical trials of
Dacarbazine (DTIC), Temozolomide (TMZ), high dose IL-2, DTIC or TMZ based combination chemotherapy/biochemotherapy (including cisplatin and vincristine with or without il-2, α-IFN), paclitaxel (or in combination with cisplatin/carboplatin) and best supportive therapy.
VI. Adjuvant therapy
Patients with AJCC stage IA-IIIA fall under the category of postoperative adjuvant therapy.
Patients with stage IA-IB are low-risk patients, and surgical treatment is 95-100% curable without postoperative adjuvant therapy mainly based on etiological prevention.
Patients with IIA-IIIA are medium- to high-risk patients, with a risk of recurrence and death in about 25% of cases.
The postoperative tendency to do adjuvant therapy with evidence is high-dose interferon (IFNa-2b).
Recommendations for high-dose IFNα-2b in Chinese patients.
Use 300wu-600wu-900wu dose creep with a regular daily dose of 1800-2200wu, 5 days per week for 4 weeks. This is followed by a change to 900wu, 3 times/week for 11 months.
VII. Surgical treatment
(I) Stages I and II: The decision to extend resection was based on the maximum thickness of the tumor in the pathology report. If tumor biopsy or marginal resection had been performed, expanded resection should be performed and biopsy of anterior lymph nodes should be considered.
The facial area should be enlarged and resected fully before considering the cosmetic and function, avoiding skin grafting and adjacent skin flap transfer repair.
(B) Stage III: Expanded resection of the primary foci and regional lymph node dissection should be performed at the same time.
If it is difficult to resect, ILP isolated limb perfusion chemotherapy can be considered: Separate the blood vessels to establish chemotherapy access to perfuse Marfan and TNFα.
The efficiency of stage III MM is 80%.
(iii) Stage IV: complete surgical resection of the primary foci and metastases can achieve better than expected survival rates.
VIII. Radiotherapy
It is generally considered insensitive to radiotherapy, but in patients with bone metastases, brain metastases, residual or recurrent lymph node dissection and head and neck MM (especially nasopharyngeal MM).
Head and neck are best treated with stereotactic conformal radiotherapy or intensity-modulated radiotherapy. In the case of specific segmentation, head and neck MM is sensitive to radiotherapy.
For melanoma brain metastases, stereotactic radiotherapy (gamma knife) and surgery are recommended as the first choice
IX. Systemic treatment
The prognosis of advanced melanoma is poor, and individualized and comprehensive treatment is the principle.
(i) Chemotherapy
Single agent: dacarbazine (leading drug), temozolomide, platinum, vincristine, paclitaxel (PTX), formolastine. The effectiveness rate was less than 20%.
Temozolomide and formolastine can cross the blood-brain barrier and are first-line treatments in Europe and North America.
Combination of drugs: no significant increase in efficacy compared with single drugs. PC regimen (PTX, CBP AUC) is one of the options for NCCN.
(ii) Biochemotherapy
Combination il-2 and or IFN efficacy is higher than conventional chemotherapy. However, there is no survival advantage.
Currently TMZ combined with IFN has entered phase III.
(iii) Immunotherapy
1, IFNα is not recommended for stage IV monotherapy.
2. High-dose IL-2 is still a better choice for stage IV melanoma.
(600,000-720,000 IU/Kg) intravenously every 8 hours for a total of 14 doses, repeated after 9 days of rest, requiring hospitalization.
Approximately half of the effective patients are able to sustain complete remission for up to 5 years.
How to predict which patients will benefit is the focus of the current study. Low-dose regimens are not recommended for the treatment of patients with stage IV melanoma.
3. Dendritic cell (DC) vaccines can be tried
In February 2005, the FDA approved the dendritic cell vaccine DC-Melvac for the treatment of patients with stage IV melanoma.
4.Targeted therapy is the main direction of future research
In the treatment of advanced malignant melanoma, DTIC is the gold standard, and targeted therapy is the future trend. Treatment should be mainly multidisciplinary and comprehensive, and individualized therapy is the future treatment trend.
X. Follow up
Annual skin examination is recommended for stage 0 and in situ cancer.
Stage IA, follow-up every 3-12 months, monthly patient self-examination of skin and lymph nodes.
Stage IB and II, follow-up every 3-6 months for the first 3 years. Every 4-12 months for the next 2 years; at least once a year thereafter. Monthly patient self-examination of skin and lymph nodes.
Stages IIA-III recommend CT, ultrasound of superficial lymph nodes, LDH, liver function, and blood work reviewed every 4-6 months. Brain CT (or MRI) as well as bone scan are reviewed every 12 months.
Stage IV is similar to stage III.