Introduction

The local management of patients with primary melanoma is not controversial. The primary tumor is excised with an adequate margin of surrounding normal skin. In contrast, there has been a long-standing debate as to whether and when the regional lymph nodes should be removed in patients with high-risk (deep, thick) primary melanomas. One school considers that nodes should be excised at the time that the primary is removed: elective or prophylactic lymphadenec-tomy [1-4]. In favor of this approach is the better survival of patients with melanoma confined to the primary site, relative to patients with regional nodal involvement and the fact that 20-30% of patients with clinically uninvolved nodes have melanoma in the excised nodes on examination by histology and immunohisto-chemistry [5]. Against this approach is the fact that if all individuals with high-risk melanoma are so treated, 70-80% of patients will be subjected to an unnecessary surgical operation that carries potential significant morbidity and mortality. The other school considers that lymphadenectomy should be performed only when patients develop clinical evidence of tumor in the nodes—tharapeutic lymphadenectomy [6-10]. This avoids unnecessary operations, but delay of definitive therapy until a relatively advanced stage of disease may deprive these individuals of their best chance of cure.

We have long considered that a proportion of patients with high-risk primary melanoma will benefit from elective nodal dissection. These patients are likely to have limited nodal metastases and no or minimal systemic spread. Because in the past we could not identify this subset of individuals, this dictated lymphadenectomy for all patients with high-risk melanoma, imposing an unnecessary operation on many patients.

We have, therefore, developed techniques to identify those specific individuals likely to benefit from lymphadenectomy. The first priority was to be able to identify small numbers of tumor cells in tissues, including lymph nodes. This became straightforward with our development of S-100 protein as a marker for melanocytic tumors [11-16] and the development of antibodies to melanoma-associated epitopes, such as HMB-45 and NKI/C3 [17,18]. Using these markers, we demonstrated that conventional histology underestimates by 14% the number of tumor-containing lymph nodes in lymphadenectomy specimens from patients with clinically localized primary melanoma [5]. Conventional histology also underestimates tumor positivity by 30% in patients with ostensibly tumor-free nodes [19]. In patients with nodal tumor identifiable only by immunohistology, the number of nodes containing occult tumor cells was small (usually one or two) and the number of tumor cells present was low. Consideration of the anatomic orientation of these nodes carefully related to the location of the primary tumor (in a study examining the relative immune reactivity of nodes near to and remote from tumor) revealed that the nodes that contained occult tumor were those closest to the primary lesion site [20,21].

To develop an alternative approach to the management of high-risk primary melanoma, we needed to be able to identify in vivo the nodes most likely to contain tumor. Identification of the node group to which lymph drains from a particular site is possible using lymphoscintigraphy with technetium-99m (99mTc)-labeled albumin or dextran [22]. The identification of the individual nodes within that node group that are most likely to contain tumor is more difficult. In animals, a marker dye injected intradermally passed reliably from comparable areas of skin to a predictable regional lymph node [23].

Application of this approach to humans showed that we could identify blue coloration of the afferent lymphatics and one or more sentinel lymph nodes in a high proportion of patients (lymphatic mapping). From these initial steps, we developed the techniques of lymphatic mapping and selective lymph node dissection [24]. The sentinel node, identified by lymphatic mapping, is evaluated by histology and immunohistochemistry for the presence of metastatic melanoma. If the sentinel node contains tumor, a complete lymphadenectomy is undertaken. If melanoma is not identified, no further surgery is performed and the patient is observed.

This technique has generated intense interest in the surgical oncology community and there are increasingly frequent reports of its successful application.

A multicenter prospective randomized trial is in progress under the auspices of the U.S. National Cancer Institute, comparing selective lymph node dissection with a ''watch and wait'' approach after wide excision.

Surgical pathologists are increasingly called upon to evaluate tissues removed during this type of procedure. To assist those asked to provide such evaluations, this chapter describes our experience of the pathological aspects of selective lymph node dissection and summarizes our recommendations.

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