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Malignant Melanoma

»What is melanoma?
»How common is malignant melanoma in the United States?
»What causes melanoma?
»What groups have a genetic predisposition to familial melanoma?
»List the risk factors for melanoma.
»List the high-risk groups for developing melanoma.
»Do all melanomas develop from atypical nevi?
»What are cancer stem cells?
»Is melanoma a single disease?
»What are the molecular pathways in melanoma?
»Is there a host immune response to melanoma?
»Describe the clinical appearance of melanoma.
»What are the ABCDEs of melanoma?
»What is dermoscopy?
»Where on the body does melanoma most commonly arise?
»Are there different types of melanoma?
»What are Clark’s levels?
»What is Breslow’s depth?
»What other findings should be reported in the histopathologic diagnosis of melanoma?
»What are the common immunohistochemical (IHC) markers utilized in the diagnosis of melanoma?
»Are there other factors with prognostic impact in patients with melanoma?
»How are patients with melanoma evaluated after the initial diagnosis?
»What is the most current system for staging melanoma?
»How is melanoma treated?
»How wide should surgical margins be?
»What is the most important risk factor for local recurrence of primary melanoma?
»Does a biopsy of melanoma increase the risk of spreading tumor cells or causing metastases?
»Describe the recommended follow-up for a patient with melanoma.
»Which tests or examinations are conducted during the routine follow-up of patients who have had melanoma?
»Does local tumor recurrence influence overall survival?
»What is elective lymph node dissection (ELND)? When is it indicated?
»What is sentinel lymph node biopsy? When is it indicated?
»What is linear melanonychia?
»What is Hutchinson’s sign?
»What is Hutchinson’s freckle?
»Are there any new ways to assess prognosis in patients with melanoma?
»What forms of chemotherapy are used in the treatment of metastatic melanoma?
»Is radiation therapy effective for melanoma?
»How effective is immunotherapy in malignant melanoma?
»Does gene therapy offer any better results?
»How about local perfusion?
»What are some newer targeted therapies for melanoma?

 
 
 
 

What is sentinel lymph node biopsy? When is it indicated?

In 1990, Morton introduced intraoperative lymphatic mapping and selective lymph node dissection or sentinel lymph node biopsy (SLNB) as an alternative to ELND for melanoma patients. He showed that the histology of the SLN reflects the histology of the entire lymph node basin, because when it is negative, the other lymph nodes within that basin are almost always also negative. The initial data from large series show substantial differences in the survival curves of patients, depending on their SLN status, and, in multivariate analysis, the status of the SLN has been confirmed as the most important prognostic factor for patients with primary melanoma.

SLNB are now being performed in clinical practice in many centers in the United States and abroad. The status of the SLN often guides further therapeutic interventions including complete lymphadenectomy and adjuvant chemotherapy or radiation therapy. Nevertheless, like ELND the theoretical value of SLNB dissection is based on the notion that melanoma cells migrate in an orderly fashion toward the draining lymph node.

To date there is little evidence that early dissection in SLN positive patients improves their survival compared to patients who receive nodal dissection when clinically detectable nodes develop. SLN remains a very controversial topic, and several points need to be emphasized. First, there is little evidence to suggest that melanoma cells migrate in an orderly fashion toward the draining lymph node, and the presence of melanoma cells within a lymph node may merely be an indicator of systemic metastatic disease. Second, surgical alteration of a patient’s regional lymphatic structure may impair the body’s immune response to melanoma. Third, at present we are unable to determine what constitutes relevant nodal disease. In this regard, 60% of patients with primary melanoma <1.0 mm in depth demonstrate positive SLN through polymerase chain reaction (PCR) analysis. These patients have a very favorable survival rate and rarely go on to develop nodal disease. Therefore, the presence of microscopic metastases does not correlate with the clinical course. Fourth, SLN biopsies require close collaboration between the nuclear radiologist, surgeon, and pathologist. Patient selection is also paramount. This procedure is less reliable if a wide excision has been performed; therefore, patients considered candidates should be referred for this procedure prior to the wide excision, which can be carried out simultaneously with the SLNB. Fifth, lymphatic flow is markedly varied in different persons, and it is difficult to predict with any degree of certainty which nodal basin serves a particular area of skin. Lastly, proponents of SLNB argue that SLN may identify patients who may be candidates for adjuvant therapy (see below). Nevertheless, to date no effective adjuvant therapy exists for metastatic melanoma.


Despite the controversies surrounding SNL, the AJCC recommends that all patients with primary melanoma >1 mm in tumor thickness have SNL biopsy performed prior to entry into melanoma clinical trials.

Amersi F, Morton DL: The role of sentinel lymph node biopsy in the management of melanoma, Adv Surg 41:241–256, 2007.

Medalie NS, Ackerman AB: Sentinel lymph node biopsy has no benefit for patients with primary cutaneous melanoma metastatic to a lymph node: an assertion based on comprehensive, critical analysis: part I, Am J Dermatopathol 25:399–417, 2003.

Medalie NS, Ackerman AB: Sentinel lymph node biopsy has no benefit for patients with primary cutaneous melanoma metastatic to a lymph node: an assertion based on comprehensive, critical analysis: part II, Am J Dermatopathol 25:473–484, 2003.

Zitelli JA: Sentinel lymph node biopsy: an alternate view, Dermatol Surg 34:544–549, 2008.