eMedicine Specialties > Otolaryngology and Facial Plastic Surgery > Head & Neck Surgery

Sentinel Lymph Node Biopsy in Patients With Melanoma

Author: Nafisa K Kuwajerwala, MD, Staff Surgeon, Breast Oncology, William Beaumont Hospital
Coauthor(s): Amit Dwivedi, MD, Assistant Professor of Surgery, University of Louisville; Thabet Abbarah, MD, FACS, Consulting Staff, Department of Otolaryngology, North Oakland Medical Centers; Dhananjay A Chitale, MBBS, MD, Diagnostic Molecular Pathology Fellow, Memorial Sloan-Kettering Cancer Center; Venkata Subramanian Kanthimathinathan, MD, Staff Physician, Department of General Surgery, Loma Linda University Medical Center
Contributor Information and Disclosures

Updated: May 22, 2008

Introduction

Melanoma represents 4-5% of skin malignancies. The actual incidence of melanoma is increasing more rapidly than that of any other malignancy, with more than 40,000 cases of invasive melanoma diagnosed each year in the United States. Australia has the highest per capita incidence of melanoma. In general, melanoma is more common in white persons than in Asian or black persons. Melanoma is slightly more common in men than in women, and the prognosis for men is somewhat poorer than for women with equivalent lesions.

Annually, an estimated 51,400 patients in the United States are diagnosed with malignant melanoma, and, in 2001, 7800 died of this disease. Involvement of the regional lymph nodes is the most important prognostic factor in patients with melanoma. Indeed, the presence of lymph node metastases decreases the 5-year survival rate of patients by approximately 40%, independent of other prognostic factors of the primary tumor.

History of the Procedure

Management of the regional lymph nodes in early-stage melanoma has remained controversial throughout the last century. The debate is based on the hypothesis that metastatic melanoma progresses sequentially from the primary tumor to the regional lymph nodes and then to more distant sites. The proponents of elective lymph node dissection (ELND) claim that removing the regional lymph nodes early in the natural history of the disease can halt the metastatic cascade. If so, then patients treated by ELND should have a survival advantage compared with individuals whose lymph nodes are removed only after clinical or pathologic documentation of regional metastasis (delayed therapeutic dissection).

Multiple retrospective, nonrandomized, prospective clinical trials have failed to demonstrate an overall benefit for ELND, thereby supporting the opposing concept (ie, that regional lymph node metastases may be markers for systemic disease). Metastasis to distant sites may even occur without involving the regional lymph nodes. Results of the most recently completed Intergroup Melanoma Trial have fueled the controversy by demonstrating an unexpected survival advantage with ELND for patients with intermediate-thickness primary tumors.¹ Unfortunately, neither ELND nor delayed therapeutic dissection of the regional lymph nodes has been universally accepted for the care of patients with melanoma.

As a result of this controversy regarding the management of the regional lymph nodes, Morton et al devised intraoperative lymphatic mapping, sentinel lymphadenectomy, and selective complete lymph node dissection as an alternative to either ELND or delayed dissection.² This procedure is based on the hypothesis that melanoma metastasizes to the regional lymph nodes via a defined connection of dermal lymphatic vessels that can be followed from the skin of the primary tumor to the first or sentinel lymph nodes in the regional basin, which has the highest risk of harboring micrometastatic disease. Sentinel comes from the French word sentinelle, which means to guard over or vigilance. Hence, a sentinel node (SN) is the guard node that filters all the lymphatics before it drains to the other nodes in that lymphatic basin.

Experiments with cutaneous lymphoscintigraphy and subsequent work with several vital dyes in an animal model showed that the SN could be identified in the draining nodal basin. Hence, biopsy of the sentinel lymph node (SLN) has become widely accepted as a method of staging the regional lymph nodes in patients with melanoma.

Biopsy of the SLN has clarified the natural progression of melanoma metastasis. Data from initial trials using SLN mapping demonstrate an apparent orderly progression of disease with failure to observe lymph node metastases in nodes adjacent to negative SLNs. Cabanas first described a biopsy of the SN in a case of penile cancer as a means to prevent the morbidity of bilateral inguinal lymph node dissection. The concept is that discrete areas of skin initially drain to specific nodes within the lymph node basin(s) that may or may not be proximate anatomical basins. The identification of such initially draining nodes allows for a more detailed pathologic assessment. Although many surgeons believe that biopsy of the SLN is the current criterion standard, the true role and benefit of SLN mapping is yet to be determined.

Indications

Role of elective nodal dissection

In almost all solid tumors (except for low-risk, well-differentiated thyroid cancers and carcinoid tumors), lymph node status is accepted as one of the most important prognostic factors. The presence or absence of regional lymph nodal metastases remains the most significant predictor of outcome for melanoma; the 5-year survival rate is consistently less than 50% for patients with node-positive disease. Traditionally, regional lymph node dissection has been recommended in patients with these cancers for staging, regional control, and prevention of regional and systemic recurrence. Thus, a controversy arose regarding the need for lymph node dissection that benefited approximately 15-20% of patients, while the rest of them experienced morbidity without any therapeutic benefit.

The high likelihood of occult nodal metastases at the time of initial diagnosis prompted the use of ELND as a therapeutic modality intended to prevent subsequent regional and distant dissemination. However, most retrospective and prospective studies were not able to prove any survival advantage with ELND. The therapeutic value of ELND is questionable because the risk of nodal metastases is not more common than distant metastases among patients with intermediate-thickness melanomas. Only 15-20% of patients who have undergone ELND had positive nodes, and ELND does not prevent recurrent nodal disease in the dissected basin. (The recurrence rate is estimated to be 3-4% in the nodal basin after ELND.) Approximately 80% of patients would have negative lymph node status, and patients with positive nodes did poorly in spite of extensive lymph node dissection.

No impact on survival is evident among patients who have undergone ELND. ELND has the potential for substantial morbidity that includes chronic lymphedema, pain, paresthesias, cosmetic deformity, and wound complications (eg, skin-edge necrosis), especially in the groin area. Morbidity may occur in up to 67% of patients.

The usefulness of ELND has been debated for decades because of conflicting trials of various qualities. Multiple trials suggest that therapeutic lymph node dissection, in which a patient has clinically evident nodes, does not jeopardize the probability of cure and prevents the need for difficult toilet operations.

In 1996, initial results of the Intergroup Melanoma Trials were reported. The trial randomized 740 subjects with intermediate-thickness lesions to undergo ELND. Although no difference was noted in the survival rate of the entire group, an apparent survival benefit was observed in a post hoc analysis of a subgroup of subjects. Male subjects younger than 60 years, with tumor thickness of 1.1-2 mm and without ulceration, experienced a significant improvement in their 5-year survival rate (96% vs 84% [P = .007]), which was confirmed in a multivariate analysis. The subgroup of subjects of any age, with tumor thickness of 1.1-2 mm, who underwent an ELND also experienced a significantly better 5-year survival rate than the observation group.

Cascinelli et al suggested a role for prophylactic dissection in a randomized study of subjects with trunk melanoma, comparing elective dissection with delayed dissection, noting that only subjects with positive lymph nodes benefited from lymphadenectomy.³ This data became important with the advent of biopsy of the SN and subsequent complete lymph node dissection (CLND). (A lymphadenectomy after intraoperative lymphatic mapping and biopsy of the SLN is termed CLND.) Now, a large percentage (80%) of patients who may not benefit from lymph node dissection may be spared the procedure, while patients who may benefit are identified.

Lesions of the head and neck are more troublesome than lesions on the extremities because radical neck dissections have more associated morbidity and cosmetic disfigurement. With the advent of biopsy of the SLN, the elective staging of clinically negative lymph nodes has become less morbid and more accurate.

Relevant Anatomy

Lymphatic draining patterns vary. Sappey originally injected mercury into the skin of cadavers and showed that a line drawn just above the umbilicus would differentiate inguinal drainage and axillary drainage.⁴ Lesions within 2 cm of this line had bidirectional drainage. With the use of these techniques, drainage patterns not predicted by Sappey's original description of the cutaneous watershed areas have been frequently observed. However, with the advent of lymphoscintigraphy, Sappey's guide to lymphatic flow has been modified.

Most patients have multiple draining nodes demonstrated by pharmaceutical tracer, and the nodes nearest to the primary melanoma are not necessarily the ones affected by metastatic spread. This is because any node receiving direct drainage from the primary site is a potential site for metastases. A channel can traverse node groups in the upper neck and pass directly to an SN in the lower neck.

Discordance from classic drainage patterns is especially common in the head, neck, and trunk; 60% of the head and neck and 32% of the trunk drain into unpredicted sites. The prevalence rate of nodal metastases to atypical basins is 6%, and the prevalence rate of contralateral nodal metastases is 10-12%, which reflects the variability of lymphatic drainage patterns among individuals with lesions in the head and neck.

With lymphatic mapping, operative intervention changes in almost 50% of patients. Even with lesions on the distal extremities in which lymphatic drainage is seemingly obvious, lymphoscintigraphy may identify popliteal or epitrochlear nodes. Thus, with the unpredictable draining nodes identified, the routine use of ELND based on classic anatomical guidelines is inappropriate.

Contraindications

Contraindications to a SLN biopsy are a palpable lymph node, tumors larger than 4-5 cm, disruption of lymphatic drainage, prior extensive surgery (eg, dissection of the neck), previous radiation to the head and the neck, and allergy to dye.

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