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Lymphatic Mapping and Sentinel Lymphadenectomy for Early-Stage Melanoma: Therapeutic Utility and Implications of Nodal Microanatomy and Molecular Staging for Improving the Accuracy of Detection of Nodal Micrometastases

Morton, Donald L. MD; Hoon, Dave S. B. PhD; Cochran, Alistair J. MD; Turner, Roderick R. MD; Essner, Richard MD; Takeuchi, Hiroya MD, PhD; Wanek, Leslie A. Dr. PhH; Glass, Edwin MD; Foshag, Leland J. MD; Hsueh, Eddy C. MD; Bilchik, Anton J. MD, PhD; Elashoff, David PhD; Elashoff, Robert PhD

doi: 10.1097/01.sla.0000086543.45557.cb
Original Papers and Discussions

Objective: Lymphatic mapping and sentinel lymphadenectomy (LM/SL) have been applied to virtually all solid neoplasms since our original description of LM/SL for melanoma. Our objectives were to determine the diagnostic and therapeutic utility of LM/SL, investigate carbon dye for mapping the microanatomy of lymphatic flow within the sentinel node (SN), and determine the prognostic accuracy of molecular assessment of the SN.

Methods: Since 1985, 1599 patients with AJCC Stage I/II melanoma have been treated by LM/SL at our institution and 4590 have been treated by wide excision (WE) without nodal staging. We examined the incidence of clinical nodal recurrence after WE alone, the incidence of subclinical nodal metastases found by LM/SL, and the incidence of nodal recurrence in basins with histopathology-negative SNs.

Results: In 1514 LM/SL patients with a primary of known Breslow thickness, the incidence of metastasis in nodes claimed to be sentinel was 7.3%, 19.7%, 33.2%, and 39.7% for primary lesions ≤1.0, 1.01–2.0, 2.01–4.0, and >4.0 mm, respectively. In 3652 WE-only patients, the corresponding rates of nodal recurrence were 12.0%, 32.0%, 34.4%, and 30.1%. Thus, LM/SL detected only 60% of expected nodal metastases from primary melanomas <2.01 mm. Forty of 1599 (3.1%) patients developed recurrence in basins with immunohistochemistry (IH)-negative SNs. To determine whether nonrandom intranodal distribution of tumor cells could explain missed SN metastases, we coinjected carbon particles and blue dye during LM/SL in 166 patients: 25 (16%) patients had nodal metastases, all of which were found only in nodal subsectors containing carbon particles. When paraffin-embedded SNs from a subset of 162 IH-negative patients were re-examined by quantitative multimarker reverse-transcriptase polymerase chain reaction (qRT) assay, 49 (30%) gave positive signals. These patients had a significantly higher risk of disease recurrence and death than did patients whose IH and qRT results were negative (p < 0.0001). Comparison of 287 prognostically matched pairs of patients who underwent immediate (after LM/SL) versus delayed (after observation) dissection of nodal metastases revealed 5-, 10-, and 15-year survival rates of 73%, 69%, and 69% versus 51%, 37%, and 32%, respectively (P ≤ 0.001).

Conclusions: SN assessment based on intranodal compartmentalization of lymphatic flow (carbon dye mapping) should increase the accuracy of IH and, in combination with multimarker qRT assessment, will allow confident identification of most patients for whom surgery alone is curative. Our data suggest a significant therapeutic benefit for immediate dissection based on identification of a tumor-involved SN.

Sentinel node assessment based on the intranodal comparmentalization of lymphatic flow and on multimarker molecular as well as immunohistochemical techniques increases the accuracy of lymphatic mapping and allows confident identification of patients for whom surgery is likely to be curative without adjuvant therapy.

From the Roy E. Coats Research Laboratories of the John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA, and the David Geffen School of Medicine at the University of California, Los Angeles (Dr. Cochran).

Supported by grant CA 29605 from the National Cancer Institute and by funding from the Harold McAlister Charitable Foundation, Los Angeles, CA, the Amyx Foundation, Inc., Boise, ID, and Mrs. Alice Johnson McKinney.

Reprints: Donald L. Morton, MD, John Wayne Cancer Institute, 2200 Santa Monica Blvd., Santa Monica, CA 90404. E-mail:

Presented at the 123rd Annual Meeting of the American Surgical Association, April 24–26, 2003, Washington, DC.

© 2003 Lippincott Williams & Wilkins, Inc.