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Michigan Oncology Journal Summer 2000

Lymphatic Mapping in Melanoma

Alan M. Yahanda, M.D. Alan M. Yahanda, M.D.,
Assistant Professor, Department of Surgery
Division of Surgical Oncology

The presence or absence of regional lymph node metastases is the single most important prognostic factor in cutaneous melanoma. This fact, taken together with the findings of the Eastern Cooperative Oncology Group trial 1684, in which patients with node-positive melanoma had an improvement of both disease-free and overall survival if they received high-dose adjuvant Interferon alpha, has stirred a new interest in identifying those patients with early stage melanoma who harbor regional lymph node metastases (1,2).

In the past, the only means of identifying patients with regional nodal metastases was to perform a complete lymph node dissection. These operations are associated with significant morbidity, and in only a minority of patients, will lymph node metastases be found. Thus, the majority of patients so treated would be subjected to the morbidity and cost of a surgery from which they will gain some prognostic information, but will not derive any therapeutic benefit.

The Concept of Lymphatic Mapping

In the late 1980s, Morton from the John Wayne Cancer Institute developed and described the technique of lymphatic mapping in melanoma (3). This was based on the concept that the dermal lymphatics for a given area of skin will drain first to a specific lymph node or lymph nodes in a draining lymphatic basin. This first draining node was termed the sentinel node. Furthermore, geographically different regions of the body would drain to distinct sentinel nodes (Figure 1). If one could identify and biopsy these sentinel nodes, one could accurately assess whether or not metastases to the lymph basin had occurred.

The sentinel lymph node is identified by a combination of a blue dye and radiolabeled sulfur colloid. Both of these agents are injected into the dermis around the melanoma or melanoma-biopsy site, are taken up by the dermal lymphatic channels, and flow to the sentinel node. A preoperative lymphoscintigram is imperative in order to identify all nodal basins to which the melanoma drains and to find any aberrant or unusual drainage patterns (4). At the time of surgery, a hand-held gamma probe is used to interrogate the lymphatic basin and to identify areas of increased radioactivity. A small biopsy incision is made over this area, and the sentinel node is found by either identifying a blue lymph node visually, or a radioactive node using the gamma probe. Once identified, the node is excised and subjected to careful pathologic evaluation. Additional sentinel nodes are found by either surveying the basin with the gamma probe to identify any other areas with increased radioactive counts or by finding a blue-stained lymph node.

Lymphatic Mapping Enables Selective Lymphadenectomy

Lymphatic mapping has become an invaluable technique to identify those patients who harbor lymph node metastases. By documenting which patients with early stage melanoma have nodal disease, surgeons are now able to perform a selective lymphadenectomy, that is, perform formal lymph node dissections on only those patients who have documented metastatic disease, while leaving intact the basins of those who do not (5,6). In most series of lymphatic mapping, occult metastatic disease is found in 15 to 21% of patients. Consequently, approximately 80% of patients will have their regional lymph nodes accurately staged without being subjected to the morbidity of a formal lymphadenectomy. Those patients found to have nodal metastases undergo a formal lymphadenectomy and are referred for adjuvant therapy.

In their initial clinical report, Morton and colleagues performed lymphatic mapping in 223 patients with early stage melanoma. In all patients both the sentinel lymph node biopsy and a formal lymphadenectomy were performed to document that the sentinel node accurately reflected the status of the remainder of the lymph nodes in the basin. Of the 40 lymphadenectomies that contained metastatic disease, 38 contained tumor in the sentinel node, for a false negative rate of 5% (3). Subsequently, multiple institutions have reported their experiences with this technique and have corroborated Morton's conclusions: lymphatic mapping is a safe, accurate and reliable means of staging the regional lymph node basins (3, 7-10).

The important question yet to be answered is if lymphatic mapping and selective lymphadenectomy will have any impact on patient survival. As of now, there are no reports which have compared, in a prospective, randomized fashion, the survival of patients managed with lymphatic mapping versus that of patients managed with expectant observation of their nodal basins. Theoretically, one would expect that early attention to the lymph nodes and early institution of adjuvant therapy would be advantageous, but we currently have no data to support this belief. Several multi-institutional studies are being conducted to address this question, but any meaningful data will not be available for several more years.

Who is Eligible?

At the University of Michigan, and at most institutions around the country, lymphatic mapping is offered to any patient with a primary cutaneous melanoma with a Breslow depth ≥1 cm and with no clinical evidence of regional or distant metastatic disease (11). Patients who have had a previous wide local excision are not good candidates for subsequent mapping. The lymphatic drainage of the skin surrounding the excision scar may not be the same as the drainage of the excised patch of skin where the melanoma had been located. Thus, any sentinel lymph node removed may not be the correct sentinel node for the melanoma. Accordingly, we emphasize that any skin lesion suspicious for melanoma should be biopsied with a narrow margin excision that is oriented parallel to the direction of the dermal lymphatics. Furthermore, patients with medical co-morbidities that make them poor candidates for adjuvant interferon therapy may not be offered mapping, as the results of the sentinel node biopsy would have no impact on their subsequent treatment. In these cases, a discussion of eligibility should be held between the medical oncologists and surgeons in the setting of a multidisciplinary clinic.

If you would like to learn more about the technique of lymphatic mapping, the Division of Surgical Oncology and the Comprehensive Cancer Center offer a monthly preceptorship that is open to all health care professionals. For more information, contact Cancer AnswerLine™ 800-865-1125.

References

1. Morton DL, Ollila DW: Critical review of the sentinel node hypothesis. Surgery 1999;126:815-819.

2. Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH: Interferon Alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol 1996;14:7-17.

3. Morton DL, Wen D-R, Wond JH, et al: Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 1992;127:392-399.

4. Thompson JF, Uren RF, Shaw HM, et al: Location of sentinel lymph nodes in patients with cutaneous melanoma: new insights into lymphatic anatomy. J Am Coll Surg 1999;189:195-206.

5. Ross MI, Reintgen DS, Balch CM: Selective lymphadenectomy: emerging role for lymphatic mapping and sentinel node biopsy in the management of early stage melanoma. Sem Surg Oncol 1993;9:219-223.

6. Glass LF, Fenske NA, Messina JL, et al: The role of selective lymphadenectomy in the management of patients with malignant melanoma. Dermatol Surg 1995;21:979-983.

7. Reintgen D, Cruse CW, Wells K, et al: The orderly progression of melanoma nodal metastases. Ann Surg 1994;220:759-767.

8. Thompson JF, McCarthy WH, Bosch CM, et al: Sentinel lymph node status as an indicator of the presence of metastatic melanoma in regional lymph nodes. Melanoma Res 1995;5:255-260.

9. Haddad FF, Stall A, Messina J, Brobeil A, et al: The progression of melanoma nodal metastasis is dependent of tumor thickness of the primary lesion. Ann Surg Oncol 1999;6:144-149.

10. Gershenwald JE, Thompson W, Mansfield PF, et al: Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage I and II melanoma patients. J Clin Oncol 1999;17:976-983.

11. NCCN melanoma practice guidelines. Oncology 1998;12:153177.

Figure 1: Concept of lymphatic mapping: the dermal lymphatics for every region of the skin will drain first to a specific lymph node, the sentinel lymph node. Geographically distinct regions of the skin will drain to distinct lymph nodes in the regional lymphatic basin.

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