Annals of Surgical Oncology 10:196-200 (2003)
© 2003 Society of Surgical Oncology
Delayed Harvesting of Sentinel Lymph Nodes After Previous Wide Local Excision of Extremity Melanoma
Stanley P. L. Leong, MD,
Marylou C. Thelmo, MD,
Robert P. Kim, MD,
Rahul Gokhale, MD,
Jennifer Y. Rhee, BA,
Theodore A. Achtem, BS,
Eugene Morita, MD,
Robert E. Allen, Jr, MD,
Mohammed Kashani-Sabet, MD and
Richard W. Sagebiel, MD
From the Departments of Surgery (SPLL, MCT, RPK, RG, JYR, TAA, REA), Nuclear Medicine (EM), and Dermatology (MK-S, RWS), Melanoma Center, University of California, San Francisco Medical Center at Mount Zion and University of California, San Francisco Comprehensive Cancer Center, San Francisco, California.
Correspondence: Address correspondence and reprint requests to: Stanley P. L. Leong, MD, Department of Surgery, Box 1674, UCSF Medical Center at Mt. Zion/UCSF Comprehensive Cancer Center, 1600 Divisadero Street, #C333, San Francisco, CA 94143-1674; Fax: 415-353-7721; E-mail: leongs{at}surgery.ucsf.edu
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ABSTRACT
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Background: Harvesting the sentinel lymph node (SLN) is important in the management of patients with primary cutaneous melanoma. Selective sentinel lymphadenectomy (SSL) is generally performed at the time of wide local excision (WLE). The aim of our study was to determine whether delayed SSL is useful in detecting micrometastasis to the regional basin in patients with previous WLE of an extremity melanoma.
Methods: Of 203 patients with a primary melanoma site located on the upper or lower extremity seen at the University of California, San Francisco/Mount Zion Melanoma Center from May 17, 1994, to March 23, 1999, 24 patients had a WLE of their extremity melanoma with adequate margins before referral. SSL was performed to assess micrometastasis in the regional lymph node basin after preoperative lymphoscintigraphy.
Results: At least 1 SLN was identified in all 24 patients. At a median follow-up of 3 years, two patients showed micrometastasis in the SLNs. One of these two patients developed recurrence, and all remaining patients showed no evidence of disease.
Conclusions: Although it is generally advised that WLE should be performed simultaneously with SSL, delayed SSL after WLE of an extremity melanoma can still provide valuable staging information, which is critical for management of the patient.
Key Words: Extremity • Melanoma • Previous wide excision • Sentinel lymph node
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INTRODUCTION
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Regional lymph node status is recognized as one of the most important prognostic factors in patients with malignant melanoma.1 Selective sentinel lymphadenectomy (SSL) has become a widely accepted approach for identifying the presence of occult metastasis to the regional lymph node basin in patients with American Joint Committee on Cancer stage I and II disease.2–6 Because the techniques of pre- and intraoperative lymphatic mapping rely on the cutaneous lymphatic channels draining the primary melanoma site, SSL should ideally be performed at the time of wide local excision (WLE) of the primary melanoma site. A WLE before lymphatic mapping may disrupt the surrounding lymphatic channels and result in erroneous drainage patterns. However, most studies suggest that SSL may be performed with success in melanoma patients and provide valuable staging information.7–10
In this study, we focused on 24 patients with extremity melanoma who had a WLE before their referral to the University of California, San Francisco/Mount Zion Melanoma Center from May 17, 1994, to March 23, 1999. We omitted cases of primary melanoma sites on the head, neck, and trunk areas because these regions often exhibit ambiguous drainage patterns.11,12 Thus, given the more predictable lymphatic drainage pattern present in the extremities,12 it is plausible to identify the sentinel lymph node (SLN) even after the WLE has been performed.
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PATIENTS AND METHODS
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A total of 24 patients were included in this study from a database of 203 consecutive patients with extremity melanoma who underwent SSL at the University of California, San Francisco Medical Center at Mount Zion from May 17, 1994, to March 23, 1999. The study group consisted of 10 men and 14 women ranging in age from 24 to 76 years, with a mean age of 50 years. Eighteen patients had primary melanomas situated on the lower extremity, and six patients had a primary melanoma on the upper extremity. Twelve of 24 patients had primary closure, and the rest had skin grafting. The characteristics of this group of patients are listed in Table 1. The median Breslow thickness was 2.0 mm (mean, 3.1 mm). All other patients underwent a standard WLE of 1 cm for lesions <1 mm thick, 1 to 2 cm for 1- to 2-mm-thick lesions, and 2 to 3 cm for >2-mm-thick lesions at the time of SSL. Immediate preoperative lymphoscintigraphy was performed by injection of 99mTc-labeled sulfur colloid intradermally around the biopsy scar, as described previously.13 The sulfur colloid was prepared by a hydrogen sulfide technique and was filtered through a 22-µm filter to remove any large particles.14 For patients with previous primary closure of the WLE, the 99mTc sulfur colloid dose was injected in four spots within 1 cm of the center of the scar. Injection did not occur directly into the scar. Ten patients had a skin graft closure of the WLE site, and injection occurred in four wheals spaced equally around the edge of the graft. Dynamic imaging was performed to visualize the lymphatic channels, and static imaging was performed to determine the number and location of focal 99mTc sulfur colloid uptake by the SLNs. A combination of radiotracer and Lymphazurin (isosulfan blue; Hirsch Industries Inc., Richmond, VA) was injected into six of these patients. Lymphazurin was not injected in general because, since no further WLE would be performed, the skin at the injection site would remain discolored. Furthermore, recent reports also indicate that the use of Lymphazurin can lead to a potentially anaphylactic reaction with associated bradycardia and hypotension.15–17 SLNs were identified in vivo by blue color, increased gamma radiation, or both, as detected by a handheld gamma probe (Neoprobe Corp., Dublin, OH). A "hot" SLN was defined as one that was >3 to 1 of the background activity within the operative field of the nodal basin or if it was >10% of the highest lymph node count. Complications of SSL were minor. All patients were discharged from the hospital on the day of surgery or the following day. Micrometastasis to the SLNs was determined by hematoxylin and eosin staining and was confirmed with specific S-100 and HMB-45 immunohistochemical stains. Various statistical tests were used to compare several parameters between the group with WLE followed by delayed SSL and the group with simultaneous SSL (Table 2).
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TABLE 1. Summary of melanoma patients undergoing selective sentinel lymph node (SLN) dissection after previous wide local excision (WLE)
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TABLE 2. Summary of melanoma patients undergoing delayed SSL after WLE versus patients undergoing SSL at the time of WLE
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RESULTS
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All 24 patients with prior WLE had drainage from the injection site to a regional lymph node basin and had at least one sentinel lymph node harvested. In two patients with primary melanomas on the lower extremities, drainage was noted to the popliteal area in addition to drainage to the inguinal basin. In one patient with an upper-extremity melanoma site, drainage was noted to an epitrochlear node, as well as to the axillary basin. Two patients exhibited SLNs that contained occult metastases. In patient L, drainage from a primary melanoma on the left foot was noted to both the popliteal and inguinal areas. The three SLNs that were positive were all located in the inguinal area. A subsequent completion lymph node dissection revealed 16 lymph nodes, all negative for micrometastasis. For patient U, the primary melanoma was located in the left upper calf. She had a 3-cm WLE with a split-thickness skin graft measuring 7 x 3 cm. The superior edge of the skin graft was 5 cm inferior to the popliteal fossa. No adenopathy was appreciated by physical examination in either the left popliteal or the inguinal region, which may have been due to the patient’s obesity. Lymphoscintigraphy revealed two lymphatic channels draining to the left groin on dynamic images and a single very intense node and three less intense adjacent nodes on static images. Dynamic images of the popliteal region were not performed because of the technical difficulty of capturing two different areas during the 10-minute window of visualization. Static images of the popliteal region were taken and failed to identify an SLN. One inguinal SLN was harvested that contained metastasis. Additionally, a non-SLN (no increased gamma radioactivity reading) that was adjacent to the SLN was grossly positive for metastatic melanoma. Subsequent completion lymph node dissection revealed that 1 of 13 nodes were positive for occult metastases.
The length of follow-up for these 24 patients ranged from 1.0 to 6.2 years, with a mean of 2.9 years and a median of 3 years. At the time of last contact, 21 patients with negative SLNs had no evidence of disease recurrence, and 1 patient had died of non-melanoma-related causes. Patient L had shown no evidence of disease, with a follow-up of 1.9 years. Patient U had a recurrence in her left popliteal regional lymph node basin and underwent subsequent resection. This patient is currently without evidence of disease 2 years after her initial selective SSL and 1.6 years after her popliteal recurrence was excised.
For patients undergoing delayed SSL after WLE and those undergoing SSL at the time of WLE, there was no significance in mean Breslow thickness, number of nodal basins per patient, number of SLNs per patient, or incidence of positive SLNs. However, the percentage of patients with positive SLNs in the delayed group was significantly lower than that in the simultaneous group (Table 2).
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DISCUSSION
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It has been noted that drainage of the upper and lower extremities to the axillary and femoral lymph nodes, respectively, is relatively predictable.18 In our recent study analyzing discordancy between standard clinical predictions of SLN location and the actual location of the SLNs, it was found that lesions in the upper and lower extremity had at least one sentinel lymph node outside the predicted basin in 14% and 5% of cases, respectively.12 In contrast, the head and neck region and the trunk showed a discordancy rate of 37% and 25%, respectively. In addition, primary melanoma sites in the extremities usually drain via a single lymphatic channel, with only 9% showing multiple channel lymphatic drainage, compared with approximately 60% in the head, neck, and trunk regions (S. P. L. Leong, MD, unpublished data, August 2001). The ambiguous draining patterns of these regions have been corroborated by other investigators.19–21 For these reasons, we elected to harvest SLNs for patients who had a primary extremity malignant melanoma with WLE before SSL. In a recent study by Keleman et al.,8 most of their patients undergoing SSL after WLE also had extremity lesions.
This study shows that SSL can be performed after WLE in a select group of patients with extremity melanoma. All 24 patients in our study had successful harvesting of SLNs. Comparing the delayed group with the simultaneous group, there was no difference in the mean Breslow thickness, number of nodal basins per patient, number of SLNs per patient, or percentage of positive SLNs (Table 2). Although the incidence of micrometastasis in the delayed group was 8.3%, which is lower than that of the simultaneous group (19.6%), as shown in Table 2, this difference may disappear if the total number of patients in the delayed group increases. Furthermore, in a retrospective comparison between the two groups by Whitman et al.,9 SSL performed after WLE in melanoma patients was statistically equivalent to SSL performed at the same time as WLE. There was not an increase in SLNs per patient or lymph node basins per patient. The incidence of metastatic disease in SLN was actually higher in the delayed group in their study, probably because these patients had slightly thicker primary lesions and also a higher incidence of ulceration and recurrence, all known risk factors for metastasis. However, Wells et al.7 have shown that lymphatic mapping after WLE increased the number of SLNs per patient, but this was not a statistically significant difference. Patients with a recurrence within the nodal basin were more numerous if the lymphatic mapping was performed after WLE (2.7% vs. 1.9%), but this difference was not statistically significant. There was also no difference in the survival rate between the two groups per the log-rank test (P = .22), with a mean follow-up of 41.9 months. Within the median follow-up period of 2.3 years, approximately 60% to 70% of all the melanoma recurrences would be expected.22 Thus, the fact that no nodal recurrences have been observed in the node-negative population in our delayed group suggests that the true SLNs have probably been removed. There were no regional recurrences in either group among patients with negative SLNs during the period of follow-up in this study. Among the SLN-negative patients in the simultaneous group, there were four recurrences: one local, two in-transit, and one systemic.
Patient U represents a failure of lymphoscintigraphy to identify the second lymph node basin that was also involved. This also stresses the need for close clinical follow-up for all patients undergoing SSL for early identification of regional recurrence.
Given our current understanding of the lymphatic drainage system, it is intuitive to reason that WLE certainly may disrupt these channels and lead to ambiguous or erroneous drainage patterns, although no prospective study is available to substantiate these findings.23 Such a study is unlikely to be performed.24 From the practical point of view and in the best interests of the patient, timing the WLE with the SSL minimizes the patient’s total number of surgical procedures and overall medical expenses.24 Therefore, at most major melanoma centers, it is recommended that patients with stage I or II melanoma have WLE performed in conjunction with SSL. Our study does not dispute this recommendation; however, it shows that SSL in extremity melanoma, even after WLE, can still provide valuable information that can affect the clinical management and eventual outcome of patients. Indeed, 2 of our 24 patients in the delayed group harbored occult disease that would have been missed if SSL had not been attempted. As SSL gains wider acceptance as the standard of care for primary melanoma, fewer patients will present with prior WLE. However, until that time, these patients will continue to present a unique and challenging problem to the management of melanoma. We recommend the following:
- Any suspicious pigmental lesion should be narrowly excised to establish the diagnosis of melanoma. If the thickness is established >1 mm, a WLE should be delayed and should be reserved until the time of SSL.
- In those situations in which WLE is performed, candidates for SSL include patients with lesions in the distal extremity with primary closure or skin graft.
- Patients with head and neck or trunk melanoma after WLE, especially after advanced flap closure, probably should not undergo SLN because of the watershed phenomenon of these anatomical sites and the relative unpredictability of the lymphatic drainage patterns.
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CONCLUSION
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Although it is generally advised that WLE and SSL be performed together, SSL performed after WLE in extremity melanoma can still provide valuable staging information that can help guide clinical decision-making.
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Acknowledgments
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This acknowledgment is available online at www.annalssurgicaloncology.org.
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Footnotes
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In general, it is recommended that selective sentinel lymphadenectomy (SSL) be performed at the time of wide local excision (WLE) of the primary melanoma site. For patients with extremity melanomas with prior WLE, SSL may still provide valuable staging information.
Received for publication August 3, 2001.
Accepted for publication October 7, 2002.
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REFERENCES
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- Morton DL, Wanek L, Nizze JA, et al. Improved long-term survival after lymphadenectomy of melanoma metastatic to regional nodes. Analysis of prognostic factors in 1134 patients from the John Wayne Cancer Clinic. Ann Surg 1991; 214: 491–9;discussion 499–501.
- Leong SPL. The role of sentinel lymph nodes in human solid cancer. In: DeVita VT, Hellman S, Rosenberg SA, eds. PPO Updates: Principles & Practice of Oncology. vol. 12, number 4. Philadelphia: Lippincott, 1998.
- Reintgen DS. Changing standards of surgical care for the melanoma patient. Ann Surg Oncol 1996; 3: 327–8.[CrossRef][Medline]
- Reintgen D. The credentialing of American surgery. Ann Surg Oncol 1997; 4: 99–101.[CrossRef][Medline]
- Emilia JCD, Lawrence W. Sentinel lymph node biopsy in malignant melanoma: the standard of care? J Surg Oncol 1997; 65: 153–4.[CrossRef][Medline]
- Rivers JK, Roof MI. Sentinel lymph-node biopsy in melanoma: is less surgery better? Lancet 1997; 350: 1336–7.[CrossRef][Medline]
- Wells KE, Joseph E, Ross M, et al. Lymphatic Mapping for Melanoma Before and After Wide Local Excision: 4th World Conference on Melanoma. Sydney, Australia: Melanoma Research, 1997: S105.
- Kelemen PR, Essner R, Foshag LJ, et al. Lymphatic mapping and sentinel lymphadenectomy after wide local excision of primary melanoma. J Am Coll Surg 1999; 189: 247–52.[CrossRef][Medline]
- Whitman ED, Yardi P, Boatman A, et al. Sentinel node mapping after wide local excision in melanoma patients at a regional referral center: 2nd International Sentinel Node Congress. Santa Monica, CA, 2000:36.
- Evans HL, Krag DN, Teates J, et al. Lymphoscintigraphy and sentinel node biopsy accurately stages melanoma in patients presenting after wide excision: Society of Surgical Oncology’s Cancer Symposium. Denver, CO, 2002:46.
- Uren R, Howman-Giles R, Shaw H, et al. Lymphoscintigraphy in high risk melanoma of the trunk: predicting draining node groups, defining lymphatic channels and locating the sentinel node. J Nucl Med 1993; 34: 1435–40.[Abstract/Free Full Text]
- Leong SPL, Achtem TA, Habib FA, et al. Discordancy between clinical predictions versus lymphoscintigraphic and intraoperative mapping of sentinel lymph node drainage of primary melanoma. Arch Dermatol 1999; 135: 1472–6.[Abstract/Free Full Text]
- Leong SPL, Steinmetz I, Habib FA, et al. Optimal selective SLN dissection in primary malignant melanoma. Arch Surg 1997; 132: 666–73.[Abstract]
- Kowalsky RJ, Perry JR. Radiopharmaceuticals in Nuclear Medicine Practice. Los Altos, CA: Appleton and Lange, 1987.
- Leong SPL, Donegan E, Heffernon W, et al. Adverse reactions to isosulfan blue during selective sentinel lymph node dissection in melanoma. Ann Surg Oncol 2000; 7: 361–6.[Abstract/Free Full Text]
- Albo D, Wayne J, Hunt K, et al. Anaphylactic reactions to isosulfan blue dye during sentinel lymph node biopsy for breast cancer. Am J Surg 2001; 130: 439–42.
- Cimmino V, Brown A, Szocik J, et al. Allergic reactions to isosulfan blue during sentinel node biopsy—a common event. Surgery 2001; 130: 439–42.[CrossRef][Medline]
- Balch C. The role of elective lymph node dissection in melanoma: rationale, results, and controversies. J Clin Oncol 1998; 6: 163–72.
- Norman J, Cruse C, Espinosa C, et al. Redefinition of cutaneous lymphatic drainage with the use of lymphoscintigraphy for malignant melanoma. Am J Surg 1991; 162: 432–7.[CrossRef][Medline]
- O’Brien C, Uren R, Thompson J, et al. Prediction of potential metastatic sites in cutaneous head and neck melanoma using lymphoscintigraphy. Am J Surg 1995; 170: 461–6.[CrossRef][Medline]
- Kelley MC, Ollila DW, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for melanoma. Semin Surg Oncol 1998; 14: 283–90.[CrossRef][Medline]
- Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 2001; 19: 3535–648.
- Coldiron B. No evidence to support delay in excision of malignant melanoma (letter). Arch Dermatol 2000; 136: 1269–70.[Free Full Text]
- Leong SPL. No evidence to support delay in excision of malignant melanoma (letter, reply). Arch Dermatol 2000; 136: 1269–70.
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TOP
ABSTRACT
INTRODUCTION
