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CutaneousCutaneous MelanomaMelanomaSurgical ManagementSurgical Management
EMAD KANDIL, MD EMAD KANDIL, MD
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
Case Presentaion• 71 y.o female was scheduled for re-
excision of L shoulder melanoma.
• PMHx:Afib, HTN, osteoprosis, depression• PSHx: Resection of L shoulder melanoma
1m ago with a satellite lesion @ peripheral margin with 1.2mm depth.
• Meds: Coumadin, metoprolol, lenoxin, buspirone and zoloft.
• NKDA• Social Hx: denies smoking, alcohol or
IVDA.
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PE
• A&OX3• Cardiac: S1/S2 RRR• Lungs: CTA B/L• Abdominal exam:soft, NT, ND, +BS• Ext:L arm 1cm scar • Neurological exam: no focal abnormalities, intact cranial
nerves, nystagmus, abnormal ocular movements or peripheral neuropathy
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Labs• WBC 5.1• Hct 39.4• Plt 227• PTT 55• INR: 1.0
• Na 143 • K 4.7• Cl 106 • CO2 28• BUN/Cr 20/0.8• Glu 85• Alb=4.0
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OR
• Lymphazurin blue was administrated intradermallyinto old incsion.
• Eliptical skin incision with 13mm margin @all sides
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OR• Intraop hand held gamma
probe was used.• Axillary dissection:
• Axillary vein was visualized
• Long thoracic and thoracodorsal nerves were identified.
• Single LN was identified as sentinle LN @ level 1
• Specimen included axillary LNs @level1&2
• The area between the injection site and sentinel node bed(s) was also surveyed for in-transit nodes.
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Pathology
• Skin:• No residual malig melanoma• FB giant cell reaction
• LN: • Sentinle LN : neg• 11 LN :neg
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Post-op Course
• Started on heparin drip.
• POD#3 L arm hematoma (5cm X 7cm)
• POD#7 D/C Home
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CutaneousCutaneous MelanomaMelanomaSurgical ManagementSurgical Management
EMAD KANDIL, MD EMAD KANDIL, MD
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
Incidence
• In 2004, an estimated 55,000 Americans received a diagnosis of cutaneous melanoma, and 7900 will die from the disease.• 5th in incidence among men • 7th among women • 1/100 persons in US can expect to
develop this cancer in a lifetime.
• MC cancer among women 20-29 y of age.• Jemal A, Tiwari RC, Murray T, et al. Cancer statistics,
2004. CA Cancer J Clin 2004;54:8-29
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Identification of High-Risk Persons
• Light complexions• Inability to tan• Blond or red hair, or blue
eyes • Inherited mutations in the
melanocortin-1 receptor• Having many pigmented
lesions, and or atypical moles
• Severe sunburns, especially during childhood
• Use of tanning beds Bliss JM, Ford D, Swerdlow AJ, et al. Risk of cutaneous melanoma associated with pigmentation characteristics and freckling: systematic overview of 10 case-control studies. Int J Cancer 1995;62:367-376mm
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Risk Factors
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Bevona, C. et al. Arch Dermatol 2003;139:1620-1624.
Distribution of melanomas by age groupDistribution of Melanomas by age group
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Bevona, C. et al. Arch Dermatol 2003;139:1620-1624.
% of Melanomas associated with nevi by age group
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MelanomaSuperficial Spreading Melanoma
Nodular Melanoma
Lentigo Maligna Melanoma
Acrolentiginous Melanoma
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Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
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Bevona, C. et al. Arch Dermatol 2003;139:1620-1624.
% melanomas associated with nevi by anatomic location
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Bevona, C. et al. Arch Dermatol 2003;139:1620-1624.
% melanomas associated with nevi by anatomic location and sex
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Is Physician Detection Associated With Thinner Melanomas?
Table 2. Classification of Melanoma Pathologic Thickness Level Grouped by Detection Pattern
Darin S. Epstein; etal,JAMA. 1999;281:640-643mm
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Dermoscopy
• Argenziano G, Soyer HP. Dermoscopy of pigmented skin lesions -- a valuable tool for early diagnosis of melanoma. Lancet Oncol 2001;2:443-449
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Ordinary Mole & Malig Melanoma
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Dermoscopy
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Clark WH Jr, From L, Bernadino EA, et al: The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res 29:705–727, 1969.
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Relationship between the Stage of Melanoma and Survival
Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 2001;19:3635-3648
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Relationship between thickness of Melanoma and Survival
Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 2001;19:3635-3648
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Balch, C. M. et al. J Clin Oncol; 19:3635-3648 2001
One-year survival rates from the AJCC melanoma staging database comparing the different M categories
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Regional node evaluation
• Malignant melanoma metastasizes through lymphatic channels to regional LN(most important prognostic factor for patients with clinically node negative melanoma.
• PE is often inaccurate:• 20% of clinically node-negative
patients have metastatic deposits
• 20% of clinically node-positive patients have pathologically negative nodes.
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Ultrasonography
• US aspect of axillary lymph node metastasis(oval , hypoechoic, enlarged node with no hyperechoic hilum)
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Saiag, P. et al. Arch Dermatol 2005;141:183-189.
Summary of Studies Comparing Palpation and Ultrasonography to Diagnose Melanoma Nodal Metastasis
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2 cm vs 4 cm radial margin of surgical excision
Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 2001;19:3635-3648
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Thomas JM, Newton-Bishop J,. N Engl J Med 2004;350:757-766
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Thomas JM, Newton-Bishop J,. N Engl J Med 2004;350:757-766
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ELND for subclinical disease
• Rationale : • Cancers spread first to lymph
nodes and only afterwards to the bloodstream.
• Removal of subclinical regional disease in patients with melanoma should provide a survival benefit over delayed resection after the disease becomes clinically evident.???
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Complications
• Long-term include lymphedema and paresthesias.
• Lymphedema is more common after groin dissection.
• It is preferable to avoid deep groin dissection; this will reduce the lymphedemarate from 67 to 18%.
• compression support stockings for at least 6 m.
• Borgstein, PJ, Meijer, S, van Diest, PJ. Are locoregional cutaneous metastases in melanoma predictable? Ann Surg Oncol 1999; 6:315.
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WHO Trial
• 1st randomized study was the World Health Organization (WHO) Melanoma Group trial.
• 533 pt were randomized to wide excision plus either ELND or delayed lymph node dissection when clinical involved nodes were detected at routine 3 m f/u exam.
Kuvshinoff, BW, Kurtz, C, Coit, DG . Computed tomography in evaluation of patients with stage III melanoma. Ann Surg Oncol 1997; 4:252.
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WHO Trial
• Limitations:• Only patients with melanomas on the distal 2/3 of an
extremity were included and 85% were female. • Female patients with distal extremity primary
melanomas have a highly favorable prognosis, making it difficult to demonstrate a benefit from ELND.
• Melanomas of all thickness levels were included and the trial was not stratified for thickness or ulceration, features now known to be important prognostic factors.
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Intergroup melanoma trial
• 740 patients with melanoma 1-4 mm thick were randomly assigned to immediate ELND or wide excision only.
• Patients with truncal lesions underwent lymphoscintigraphy to be certain that the proper node basins were dissected.
• The patients were stratified for thickness, site, and ulceration.
Balch, CM, Soong, S, Ross, MI, Urist, MM. Long-term results of a multi-institutional randomized trial comparing prognostic factors and surgical results for intermediate thickness melanomas (1.0 to 4.0 mm). Intergroup Melanoma Surgical Trial. Ann Surg Oncol 2000; 7:87.
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Intergroup melanoma trial
• Subgroups that benefited from ELND included :• tumor thickness between 1
and 2 mm• tumor without ulceration• patients < 60 y of age
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Gershenwald, J. E. et al. J Clin Oncol; 17:976 1999
Kaplan-Meier survival for patients undergoing successful lymphatic mapping and SLN biopsy stratified by SLN status
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Lymphatic mapping and SLNB
• Tumor cells migrating from a primary tumor colonize the first node(s) receiving lymphatic drainage from the primary tumor site (the sentinel node[s]) before involving other nodes.
• The concept of the SLN was initially developed for squamous cell penile cancer
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Leong SP. Sentinel lymph node mapping and selective lymphadenectomy: the standard of care for melanoma. Curr Treat Options Oncol. 2004;5:185-194
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Technique
• Intradermal injection of a radiolabeled tracer(isosulfanblue dye).
• Proper injection is accompanied by the development of a tense wheal as the tracer is injected.
• Because the tracer is injected intradermally, many patients experience an uncomfortable burning at the site of injection for several seconds.
• Well-tolerated by most patients.
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Technique• Because lymphatic drainage is
variable, images should usually include both axillary and inguinal node beds when the primary lesion is located anywhere on the trunk.
• The area between the injection site and sentinel node bed(s) should also be surveyed for in-transit nodes.
• For extremity lesions, crossover to contralateral node beds is rare, but in-transit nodes should again be considered when obtaining images.
• Care must be taken to image all nodal basins (SLNs in more than one nodal basin are common)
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Hand-held Gamma Probe
• The tracer is subsequently picked up by the lymphatic channels and is deposited in the nodal tissue receiving lymphatic flow from the site of injection.
• The SLN is often detected within 10-30 min of injection.
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SLNB
• All nodes with radioactive counts greater than 10% of the hottest node be resectedfor analysis
• If the sentinel node is negative for metastasis, the remaining regional nodes are also very likely to be negative.
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Lymphoscintigram
• Lateral view of a patient with a primary melanoma of the back.
• Note 3 parallel lymphatic vascular pathways leading to the axillary SLN.
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SLN Bx
• False negative rate is typically 5% or less.
• Causes include:• inadequate pathologic
examination of the SLN• poor tracer injection technique• imaging the wrong nodal
basin• not imaging all possible nodal
basins
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Copyright © 2004 Pearson Education, Inc., publishing as Benjamin CummingsCopyright © American Society of Clinical Oncology
Gershenwald, J. E. et al. J Clin Oncol; 17:976 1999
Kaplan-Meier survival for patients undergoing successful lymphatic mapping and SLN biopsy stratified by SLN status
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Gershenwald, J. E. et al. J Clin Oncol; 17:976 1999
Surgical management of 612 stage I or II melanoma patients eligible for lymphatic mapping and SLN biopsy
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Kirkwood, J. M. et al. J Clin Oncol; 18:2444-2458 2000
Post-relapse survival for the Obs arm (relapsed patients only) with and without IFN{alpha}-containing salvage therapy
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Manola, J. et al. J Clin Oncol; 18:3782-3793 2000
Overall survival by protocol
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Gollob, J. A. et al. J Clin Oncol; 21:2564-2573 2003
Dosing schedule for first 6-week cycle of interleukin-12 (IL-12) + IL-2
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Gollob, J. A. et al. J Clin Oncol; 21:2564-2573 2003
Fig 6. (ABiopsy of cutaneous metastasis in melanoma patient before & after start of interleukin-12 (IL-12)/IL-2
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Isolated limb perfusion (ILP)
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• Surgical isolation of the vascular inflow and outflow of an extremity to separate the circulation of the affected limb from that of the remainder of the body.
Isolated limb perfusion (ILP)
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Isolated limb perfusion (ILP)
• By connecting the limb vasculature to a bypass circuit, high conc. of chemotherapy can be circulated locally without exposing the rest of the body.
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• The isolated extremity can also be subjected to mild hyperthermia (eg 40ºC) to improve antineoplastic efficacy without subjecting the entire body to the risks of hyperthermia.
• Nitrogen mustard • Melphalan• TNFa
Isolated limb perfusion (ILP)
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• Tsao H, Atkins MB, Sober AJ. Management of cutaneous melanoma. N Engl J Med 2004; 351:998-1012