Major Topic Malignant Melanoma Plastic and Reconstructive Surgery R3 陸尊惠 /VS 吳瑞星
Patient Data Name: OOO Age: 70 Gender: Male Date of admission: Day 1
Chief Complaint Black skin tumor at the back of the knee, noted for two months
Present Illness Dark brown, blackish patch at the back of the right knee noted for 2 months No itching or bleeding, asymptomatic Visited our dermatology department Biopsy: Melanoma Proliferation of hyperchromatic atypical epithelioid neoplastic cells growing in nests in the epidermis and dermis Immunostain: positive for HMB-45 and MITF Tumor invades and expands the papillary dermis (Clark level III) and measures less than 1mm in thickness Ulceration, vascular space permeation and perineural invasion are not found
Past History Cardiac dysrhythmia, with regular OPD follow-up and medical control (Warfarin 4mg/day) No operation history Non-smoker, occasional social drinking No food or drug allergies
Physical Examination Conscious clear E4M6V5 Body height: 177cm, weight: 70kg Vital signs: BP 128/70, HR 64, RR 20, BT 36 HEENT: grossly normal, conjunctiva pink, sclera anicteric, pupils isocoric, neck supple, no LAP Chest: symmetric expansion, clear breathing,sound, regular heart beat, no murmur Abdomen: flat, soft, no tenderness, bowel sound normoactive, no flank knocking pain Extremities: freely movable, sutures at right popliteal region, wound clear, no palpable lymph nodes at inguinal region
Laboratory Data WBC: 5140/mm3, Seg 49.7%, Lym 38.3% Hb: 14.3 g/dl PLT: 145000/mm3 GOT/GPT: 19/18 IU/L BUN/Cr: 15/1.1 mg/dl Na/K: 139/3.6 mmol/l PT: 14.9/11.9 sec aptt: 35.7/31.0 sec INR: 1.51
Positron Emission Tomography Scan Regionally increased radiotracer uptake in nasal cavity, oropharynx, colon, rectum and testes. The regional radiotracer uptake persisted in the delayed images acquired about 3 hours postinjection. The focal glucose hypermetabolism cannot be ascertained solely by FDG PET result. It may be due to normal physiological glucose metabolism and without clinical significance Otherwise, no other obvious abnormally increased radiotracer uptake is identified elsewhere in the body
Op Wide excision + elective lymph node dissection + split thickness skin graft 2.5cm surgical margin Intraoperative frozen section: Circumferential and basal margins free of malignancy
Pathology Skin, posterior knee, popliteal fossa, right, status post biopsy, wide excision for frozen section --- residual melanoma, Clark level III, 1mm in thickness, without ulceration Surgical margin, basal and circumferential --- free of malignancy Lymph node, inguinal area, right --- free of metastasis (0/11)
Discussion Malignant Melanoma
Introduction Malignant transformation of melanocyte Can occur anywhere melanocytes are present Most common tissue in which melanomas arise is the skin Incidence: varies widely, reflective of variation in genetic, phenotypic, and ultraviolet exposure risk factors US: 15 per 100,000 Australia: 45 per 100,000 China: <1 per 100,000
Risk Factors Exposure to UV radiation Intermittent, damaging exposure History of severe sunburn (blistering or pain for more than 2 days) confers a twofold increase in risk Chronic and occupational exposure confers less of a risk for melanoma, more of a risk for basal or squamous cell cancers Genetic predisposition Fair skin, blue eyes, red hair, easy freckling
Diagnosis Biopsy of a clinically suspicious lesion High-risk lesion (ABCDE Criteria) Asymmetry Border irregularity Color variegation Diameter >6mm Evolution 5% of melanomas are nonpigmented In earliest stages of development, most melanomas are <6mm in diameter Recent change or bleeding or itching: high risk
Workup Chest radiograph, serum lactic dehydrogenase (LDH) Head and neck primary lesion: head and neck CT or PET scan Clinically positive nodes in head or neck or groin: CT Distant metastasis: complete blood count, alkaline phosphatase, LDH, creatinine, CT of chest, abdomen, pelvis; MRI of brain; bone scan if symptomatic
Staging Revised American Joint Committee on Cancer (AJCC) staging system published in August 2001 Major changes: T classification breakpoints of whole-integer thichness Tumor ulceration is included as a factor in the T classification and presence of ulceration upstages patients with stages I, II and III disease Clark level is now used only to subclassify T1 (<1mm) tumors Number of metastatic lymph nodes is prognostically significant Site of distant metastasis and presence of elevated LDH are used to subclassify M stage
5-Year Survival Rates Stage I: 92% Stage II: 68% Stage III: 45% Stage IV: 10%
Management Primary treatment for virtually all melanomas is surgical Wide excision of primary tumor Removal of regional lymph nodes that are involved or at high risk for involvement
Wide Local Excision 5-cm standard margin (normal-appearing skin around the lesion, soft tissue down to, and including, muscle fascia) was the standard of care through most of 20 th century Late 1970s: series of retrospective reviews suggested narrower margins do not lead to significantly higher mortality or local recurrence rates
Archives of Surgery 2007 Excision Margins for Primary Cutaneous Melanoma: Updated Pooled Analysis of Randomized Controlled Trials Meta-analysis of 5 published prospective randomized trials evaluating the effect of width of excision margins on survival and recurrence
Results Total 3313 patients 1639 narrow excision 1674 wide excision 2220 had tumors less than 2mm None of the 5 trials demonstrated a survival advantage for wide excision margins Overall mortality was no significantly improved by performing wide excision margins No statistically significant difference in prevalence of locoregional recurrence between the two groups No statistically significant difference in incidence of local recurrence
WHO Melanoma Program Randomized patients with melanomas <2mm thick to receive wide local excision with 1 vs. 3 cm margin 612 patients, mean follow-up of 55 months No significant differences in disease-free survival, overall survival, or subsequent development of metastatic disease 3 patients developed local recurrence, all were in the 1- cm excision group and each had a primary lesion with a thickness > 1mm Authors concluded that for patients with primary lesions <1mm, a 1-cm margin excision is safe and effective
Intergroup Melanoma Trial Randomized patients with melanomas between 1 and 4 mm thick to receive excision with 2 vs. 4-cm margin 486 patients, median follow-up 6 years No significant difference in local recurrence, metastases, or 5-year survival Authors conclude that for 1 to 4mm thick melanoma patients, margin of excision could be safely reduced to 2 cm
British Trial Randomized 900 patients with melanomas >2mm to receive 1 vs. 3 cm margin wide excisions Median follow-up 60 months Significantly higher locoregional recurrence (37% vs. 32%) and disease-specific mortality (28% vs. 23%) in the group with narrower margins Limitations of study: most of the difference results from a higher nodal recurrence rate in the narrow margin group; there was no difference in local recurrence rate Overall survival was unaffected Authors conclude that to optimize disease-specific survival, use of a 1-cm margin should be avoided in patients with melanoma >2mm
There are no randomized trials to guide treatment standards for patients with thick melanomas (>4mm) A wider margin should be used unless it unduly increases morbidity Generally, a margin of 2 to 3cm is recommended for patients with melanomas >4mm in thickness
Current Recommendations
Lymphadenectomy Controversial Disagreement regarding excision of clinically uninvolved nodes Potential benefit of elective lymph node dissection is based on the dogma of sequential spread of metastatic disease to the regional lymph node prior to distant organs
Intergroup Melanoma Surgical Trial 740 patients randomized to receive ELND vs. observation, average follow-up of 7.4 years Patients with melanomas <1mm and >4mm were excluded from study There was no significant difference in survival There was significant survival advantage conferred by ELND in patients younger than 60 and for tumors between 1 and 2mm thick without ulceration Data suggest that there may be survival advantages for ELND in certain subgroups
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