Surgical Management Of Primary Melanoma Research Articles

Primary Melanoma: from History to Actual Debates.

This review describes the long scientific background followed to design guidelines and everyday clinical practice applied to melanoma patients. Surgery is the first option to cure melanoma patients (PTS) at initial diagnosis, since primary cutaneous lesions are usually easily resectable. An excisional biopsy of the lesion, with minimal clear margins, can be obtained in the vast majority of cases. Punch biopsies may be proposed only in case of large lesions located on specific cosmetic or functional areas like the face, extremities, or genitals where a mutilating complete resection would not be performed without prior histological diagnosis. After the histologic confirmation of melanoma, definite surgical excision of the scar and surrounding tissue is planned, to obtain microsatellite free margins. The width of these margins has been identified following the results of several clinical trials and it is either 1 or 2cm, depending on the Breslow thickness of the primary tumor. Following the latest staging system proposed by the American Joint Cancer commission (AJCC), a sentinel node biopsy (SNB) is usually performed in case of a primary lesion > 0.8mm thickness or for high-risk thinner lesions, if no evidence of nodal involvement has been identified clinically or radiographically. Surgical management of primary melanoma is well established. There is debate on the optimal surgical margins for 1-2mm melanomas. There are specific considerations for special primaries (bulky, extremity, mucosal). Sentinel node (SN) evaluation does not improve survival, but is routinely used as staging.

Impact of genomics on the surgical management of melanoma.

Although surgery for early-stage melanoma offers the best chance of cure, recent advances in molecular medicine have revolutionized the management of late-stage melanoma, leading to significant improvements in clinical outcomes. Research into the genomic drivers of disease and cancer immunology has not only ushered in a new era of targeted and immune-based therapies for patients with metastatic melanoma, but has also provided new tools for monitoring disease recurrence and selecting therapeutic strategies. These advances present new opportunities and challenges to the surgeon treating patients with melanoma. The literature was reviewed to evaluate diagnostic and therapeutic advances in the management of cutaneous melanoma, and to highlight the impact of these advances on surgical decision-making. Genomic testing is not required in the surgical management of primary melanoma, although it can provide useful information in some situations. Circulating nucleic acids from melanoma cells can be detected in peripheral blood to predict disease recurrence before it manifests clinically, but validation is required before routine clinical application. BRAF mutation testing is the standard of care for all patients with advanced disease to guide therapy, including the planning of surgery in adjuvant and neoadjuvant settings. Surgery remains central for managing primary melanoma, and is an important element of integrated multidisciplinary care in advanced disease, particularly for patients with resectable metastases. The field will undergo further change as clinical trials address the relationships between surgery, radiotherapy and systemic therapy for patients with high-risk, early-stage and advanced melanoma.

Current standards of surgical management in primary melanoma.

Melanoma accounts for the majority of skin cancer-related deaths, and its incidence continues to rise worldwide. While advanced disease has historically been associated with poor long-term survival, early-stage disease has a favorable prognosis and therefore, early diagnosis is paramount. Resection of primary melanoma requires a balance of maximizing oncological outcome while minimizing morbidity. Wide excision with 1-2 cm margins, depending on depth of the tumor, is the standard of care for surgical treatment of primary, invasive melanoma. Sentinel lymph node biopsy is indicated for patients with clinically node-negative, intermediate-thickness primary melanomas but should also be considered in selected patients with thin and thick primaries. In this article, historical perspectives and key clinical trials regarding the current guidelines for the surgical management of primary melanoma are discussed.

Identification of metastasis-suppressive microRNAs in primary melanoma.

Surgical management of primary melanoma is curative for most patients with clinically localized disease at diagnosis; however, a substantial number of patients recur and progress to advanced disease. Understanding molecular alterations that influence differential tumor progression of histopathologically similar lesions may lead to improved prognosis and therapies to slow or prevent metastasis. We examined microRNA dysregulation by expression profiling of primary melanoma tumors from 92 patients. We screened candidate microRNAs selected by differential expression between recurrent and nonrecurrent tumors or associated with primary tumor thickness (Student's t test, Benjamini-Hochberg False Discovery Rate [FDR] < 0.05), in in vitro invasion assays. We performed in vivo metastasis assays, matrix remodeling experiments, and molecular studies to identify metastasis-regulating microRNAs and their cellular and molecular mechanisms. All statistical tests were two-sided. We identified two microRNAs (hsa-miR-382, hsa-miR-516b) whose expression was lower in aggressive vs nonaggressive primary tumors, which suppressed invasion in vitro and metastasis in vivo (mean metastatic foci: control: 37.9, 95% confidence interval [CI] = 25.6 to 50.2; miR-382: 19.5, 95% CI = 12.2 to 26.9, P = .009; miR-516b: 12.5, 95% CI = 7.7 to 17.4, P < .001, Student's t test). Mechanistically, miR-382 overexpression inhibits extracellular matrix degradation by melanoma cells. Moreover, we identified actin regulators CTTN, RAC1, and ARPC2 as direct targets of miR-382. Depletion of CTTN partially recapitulates miR-382 effects on matrix remodeling, invasion, and metastasis. Inhibition of miR-382 in a weakly tumorigenic melanoma cell line increased tumor progression and metastasis in vivo. Aberrant expression of specific microRNAs that can functionally impact progression of primary melanoma occurs as an early event of melanomagenesis.

Update and Review on the Surgical Management of Primary Cutaneous Melanoma.

The surgical management of malignant melanoma historically called for wide excision of skin and subcutaneous tissue for any given lesion, but has evolved to be rationally-based on pathological staging. Breslow and Clark independently described level and thickness as determinant in prognosis and margin of excision. The American Joint Committee of Cancer (AJCC) in 1988 combined features from each of these histologic classifications, generating a new system, which is continuously updated and improved. The National Comprehensive Cancer Network (NCCN) has also combined several large randomized prospective trials to generate current guidelines for melanoma excision as well. In this article, we reviewed: (1) Breslow and Clark classifications, AJCC and NCCN guidelines, the World Health Organization’s 1988 study, and the Intergroup Melanoma Surgical Trial; (2) Experimental use of Mohs surgery for in situ melanoma; and (3) Surgical margins and utility and indications for sentinel lymph node biopsy (SLNB) and lymphadenectomy. Current guidelines for the surgical management of a primary melanoma of the skin is based on Breslow microstaging and call for cutaneous margins of resection of 0.5 cm for MIS, 1.0 cm for melanomas ≤1.0 mm thick, 1–2 cm for melanoma thickness of 1.01–2 mm, 2 cm margins for melanoma thickness of 2.01–4 mm, and 2 cm margins for melanomas >4 mm thick. Although the role of SLNB, CLND, and TLND continue to be studied, current recommendations include SLNB for Stage IB (includes T1b lesions ≤1.0 with the adverse features of ulceration or ≥1 mitoses/mm2) and Stage II melanomas. CLND is recommended when sentinel nodes contain metastatic deposits.

Surgery and radiotherapy in the treatment of cutaneous melanoma

Adequate surgical management of primary melanoma and regional lymph node metastasis, and rarely distant metastasis, is the only established curative treatment. Surgical management of primary melanomas consists of excisions with 1–2 cm margins and primary closure. The recommended method of biopsy is excisional biopsy with a 2 mm margin and a small amount of subcutaneous fat. In specific situations (very large lesions or certain anatomical areas), full-thickness incisional or punch biopsy may be acceptable. Sentinel lymph node biopsy provides accurate staging information for patients with clinically unaffected regional nodes and without distant metastases, although survival benefit has not been proved. In cases of positive sentinel node biopsy or clinically detected regional nodal metastases (palpable, positive cytology or histopathology), radical removal of lymph nodes of the involved basin is indicated. For resectable local/in-transit recurrences, excision with a clear margin is recommended. For numerous or unresectable in-transit metastases of the extremities, isolated limb perfusion or infusion with melphalan should be considered. Decisions about surgery of distant metastases should be based on individual circumstances. Radiotherapy is indicated as a treatment option in select patients with lentigo maligna melanoma and as an adjuvant in select patients with regional metastatic disease. Radiotherapy is also indicated for palliation, especially in bone and brain metastases.

Surgical management of primary melanoma.

Melanoma precursor lesions and stage I malignant melanomas are preferentially removed by excisional surgery. Several studies have supported the concept of a more conservative excision strategy. Reduced safety margins with a maximum of 2-3 cm enable us to cover most defects by simple skin flap techniques. In critical anatomical sites and in lentigo maligna melanoma micrographic surgery has recently gained importance. The value of adjuvant surgical procedures remains controversial. Possibly, the technique of sentinel-node-biopsy provides a better approach towards a more selective use of lymphadenectomy in patients with clinically occult micrometastases.

Surgical management of primary melanoma.

A significant proportion of the general population is diagnosed with malignant melanoma each year, and more people die of melanoma now than at any time in the past. Consequently, treatment of melanoma at all stages of development is an important clinical issue. A variety of management options are discussed here, including biopsy techniques and treatment of the primary melanoma. The latter include lymphatic mapping and sentinel lymph node biopsy, hyperthermic isolated limb perfusion, and surgery for stage IV melanoma patients. Procedure-associated benefits and possible complications associated with each modality are also summarized.

Surgical management of primary melanoma.

The outline of the surgical treatment of a primary cutaneous malignant melanoma may be divided into the problems of biopsy, definitive excision and reconstruction of the defect. An excisional, in contrast to an incisional, biopsy provides the full scope of prognostic parameters and should be used whenever possible. General anesthesia is not necessary, and frozen-section examination is inaccurate. An immediate excision biopsy should therefore be performed under local anesthesia as an outpatient procedure. Whenever possible, a margin of 10 mm should be used, as this would mean an adequate and definitive treatment in melanomas up to 1 mm, and possibly 2 mm, in Breslow thickness. In melanomas more than 1-2 mm in thickness a 3-cm free margin instead of a 5-cm free margin is recommended. Many patients, especially those with trunk lesions with a 3-cm free margin may not need a complicated repair, such as a skin graft or a flap. The excision in depth is recommended to be carried perpendicular to the skin and inclusion of underlying fascia is optional, as no study has proved it to be beneficial. The defect after the excision should whenever possible be closed directly. If this is not possible the defect is covered with either a skin graft or a flap and the latter is recommended from both a cosmetic and a functional point of view. If a skin graft has been used, the secondary defect may be reconstructed with a skin expansion technique.