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10.1245/s10434-006-9066-0
Annals of Surgical Oncology 13:1655-1663 (2006)
© 2006 Society of Surgical Oncology
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Original Article

Survival Analysis and Clinicopathological Factors Associated With False-Negative Sentinel Lymph Node Biopsy Findings in Patients with Cutaneous Melanoma

Zbigniew I. Nowecki, MD, PhD1, Piotr Rutkowski, MD, PhD1, Anna Nasierowska-Guttmejer, MD, PhD2 and Wlodzimierz Ruka, MD, PhD1

1 Department of Soft Tissue/Bone Sarcoma, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena Str. 5, 02-781, Warsaw, Poland
2 Department of Pathology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena Str. 5, 02-781, Warsaw, Poland

Correspondence: Address correspondence and reprint requests to: Piotr Rutkowski, MD, PhD; E-mail: rutkowskip{at}coi.waw.pl


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: We analyzed the outcomes and factors associated with false-negative (FN) results of sentinel lymph node (SLN) biopsy findings in patients with cutaneous melanoma. SLN biopsy failure rate was defined as nodal recurrence in the biopsied regional basin without previous local or in-transit recurrence.

Methods: Between April 1997 and December 2004, a total of 1207 patients with cutaneous melanoma with a median Breslow thickness of 2.4 mm underwent SLN biopsy by preoperative and intraoperative lymphoscintigraphy combined with dye injection. In 228 cases, we found positive SLNs; of these, 220 underwent completion lymph node dissection (CLND). Median follow-up was 3 years.

Results: The SLN biopsy failure rate was 5.8% (57 of 979 SLN negative). Median time to occurrence of FN relapse after SLN biopsy was 16 months (range, 3–74 months). The FN SLN biopsy results correlated with primary tumor thickness >4 mm (P = .0012), primary tumor ulceration (P = .0002), primary tumor level of invasion Clark stage IV/V (P = .0005), and nodular melanoma histological type (P = .0375). Five-year overall survival, calculated from the date of primary tumor excision, in the FN group was 53.7%, which was not statistically significantly worse than the CLND group (56.8%; P = .9). The FN group was characterized by a higher ratio of two or more metastatic nodes and extracapsular involvement of lymph nodes after LND compared with the CLND group (P < .0001 and P < .0001, respectively). Additional detailed pathological review of FN SLN revealed metastatic disease in 14 patients, which decreased the SLN biopsy failure rate to 4.4% (43 of 979).

Conclusions: Survival of patients with FN results of SLN biopsy does not differ statistically significantly from that of patients undergoing CLND, although it is slightly lower. The SLN biopsy failure rate is approximately 5.0% in long-term follow-up and is associated mainly with the same factors that indicate a poor prognosis in primary melanoma.

Key Words: Melanoma • Sentinel node • Biopsy • Recurrence • False-negative results


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Sentinel lymph node (SLN) biopsy in many cancer centers is a standard procedure used for the staging of patients with cutaneous melanoma without clinically evident regional lymph node metastases.1–7 The most straightforward definition of SLN is that the SLN is any regional lymph node that receives direct drainage from primary melanoma, and its status indicates the tumor status of the basin.8 Two main factors are applied to assess the success of SLN biopsy: the SLN identification rate and the false-negative (FN) rate. The SLN biopsy failure rate defines the frequency of the SLN being pathologically negative, although clinically overt metastases are detected in the previously biopsied basin during follow-up. Many studies have confirmed the accuracy of SLN biopsy; however, the reported rates of recurrences during long-term follow-up after this procedure are inconsistent. More importantly, the detailed survival outcomes of patients after SLN FN biopsy have never been presented.

The aim of the study was to analyze patient outcomes and factors associated with FN results of SLN biopsy in a large series of patients with cutaneous melanoma with a relatively long-term follow-up. FN findings were defined as nodal recurrence in the biopsied regional basin without previous local or in-transit recurrence.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Between April 1997 and December 2004, a total of 1207 consecutive patients with cutaneous melanoma (474 men and 733 women; median age, 51 years; range, 15–84 years) underwent SLN biopsies at the Department of Soft Tissue/Bone Sarcoma and Melanoma of the M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (CCIO) in Warsaw, Poland. All patients undergoing SLN biopsy met the following criteria: (1) primary focus cutaneous melanoma after excisional biopsy with Breslow thickness ≥.75 mm or ulcerated or Clark stage ≥IV (all histological diagnoses were confirmed in the Department of Pathology, CCIO); (2) clinically nonpalpable regional lymph nodes; (3) absence of distant metastases (confirmed routinely by physical examination, chest x-ray, and abdominal ultrasound); and (4) feasibility for general anesthesia.

The patients had not undergone any other preliminary selection. Each patient provided written informed consent in accordance with institutional regulatory requirements. The study was approved by the Bio-Ethics Committee of the CCIO. The detailed technique of the procedure of SLN biopsy, consisting of preoperative lymphoscintigraphy combined with intraoperative vital blue dye (Patent Blau V), lymphatic mapping, and intraoperative lymphoscintigraphy with hand-held gamma-detecting probe (Neoprobe 1000; Neoprobe Corp., Dublin, OH; or Navigator, RMD Watertown, MA), has been described previously.9 During routine pathologic examination, SLNs were cut serially along the major axis and hilus and stained with hematoxylin and eosin. Intraoperative frozen-section investigation was not performed. Paraffin-embedded specimens were examined by light microscopy at magnifications of x40 and x200. In doubtful cases, additional immunohistochemical staining (S100, HMB 45) was performed. Immunohistochemistry was routinely performed beginning in 2001. For the purpose of this study, all FN SLNs were blindly retrospectively reviewed by the same experienced pathologist (A.N.-G.), who used an extended protocol of serial sectioning and immunohistochemical staining.10

Median Breslow thickness of primary tumors was 2.40 mm (range, .75–35 mm), and median Clark stage of invasion was Clark III. A total of 42% of primary lesions were ulcerated according to the American Joint Committee on Cancer (AJCC) criteria (which defines it as the "absence of an intact epidermis overlying a major portion of the primary melanoma based on microscopic examination of the epidermis," noting that the stratum corneum of the epidermis should not be intact). The minimal margin of repeat excision of primary tumors was 1 cm in all cases. The primary melanoma was localized on the head and neck in 15 cases (1.2%), on the trunk in 517 cases (42.9%), on the upper extremity in 217 cases (18%), and on the lower extremity in 458 (37.9%) cases. Further surgery was performed depending on histopathological results. In all but 8 of the 228 SLN-positive cases (18.9% of the entire group), completion regional lymph node dissection (CLND) was performed 2 or 3 weeks after SLN biopsy.

During the same period, 298 patients with melanoma underwent radical therapeutic lymph node dissection (TLND) as a result of clinically detected (palpable) regional lymph node metastases, which were confirmed pathologically by fine-needle aspiration biopsy.

Detailed patient characteristics for the entire SLN biopsy group, the CLND and FN groups, and patients with true-negative SLN biopsy results (N0 group; SLN group excluding patients with positive SLNs and FN results) are listed in Table 1Go. The only adjuvant therapy used in this group of patients was interferon {alpha}2B, in accordance with the regimen of European Organization for Research and Treatment of Cancer (EORTC) trial 19852. In the CLND group, 68 patients (30.9%) received this therapy; in the FN group, 17 patients (30%; 12 patients after radical LND and 5 patients after initially negative SLN biopsy) received it. We did not observe any statistically significant differences between the two groups.


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  		TABLE 1. Characteristics of patients undergoing SLN biopsya
 
All patients were followed carefully, with a median follow-up time of 35.8 months for survivors (range, 6–108 months). Postoperative follow-up consisted of physical examination and routine imaging investigations (chest x-ray, abdominal ultrasound). Routine surveillance was recommended every 3 months for the first 2 years, every 6 months for years 2 to 5, and annually thereafter. During follow-up, we analyzed the incidence of the recurrences in the nodal basin after SLN biopsy that were not preceded by in-transit or local recurrences.

For statistical analysis of the data, contingency tables were analyzed by the {chi}2 test. For survival analysis and analysis of survival without relapse in the biopsied regional lymphatic basin, the Kaplan-Meier estimator was used with generalized Wilcoxon and log-rank tests for bivariate comparisons. In case of marked difference between the Wilcoxon and log-rank tests, both P values were reported. In multivariate analysis of the factors associated with FN results of SLN biopsy and factors associated with shortened overall survival time, we used the Cox proportional hazard models, applying the stepwise model building procedure including all covariates significant at the 20% level in bivariate analysis. Two-way interactions were then considered in the model. Overall survival time was calculated from the date of primary lesion excision to the date of the most recent follow-up (censored data) or death (observed up to January 30, 2006; death due any cause was set as the end point, because in only seven cases did the patients die of illness other than melanoma). Overall survival was compared between the SLN N0, FN, TLND, and CLND groups adjusted for sex and staging of the primary tumor.

The prognostic value for recurrence after initially negative SLN biopsy in the biopsied basin was examined for clinical and pathological parameters as follows: sex, age (<40 vs. 40–60 vs. >60 years), primary tumor Breslow thickness (dichotomization: ≤4.0 vs. > 4.0 mm or <2.0 vs. 2.0–4.0 vs. ≥4.0 mm), presence of ulceration of primary lesion, primary tumor level of invasion according to Clark stage (II/III vs. IV/V), pathological subtype of primary lesion (nodular melanoma vs. superficial spreading melanoma vs. others), localization of lymphadenectomy (inguinal vs. axillary), number of examined SLNs (one vs. two or more), site of lymphatic basin (inguinal vs. axillary), and number of biopsied nodal basins (1 vs. 2–3). Differences were considered statistically significant at P < .05.

All statistical analyses were performed by SAS Institute software, version 8.2 (SAS Institute, Cary, NC).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
The SLN biopsy failure rate, calculated as the percentage of nodal recurrences in the same biopsied basin, which was found to be negative at the initial pathologic evaluation, was 5.82% (57 nodal recurrences in relation to 979 basins with negative SLN biopsy). We excluded all patients who experienced recurrence of disease in the regional node field preceded by in-transit or local recurrence (11 cases) from this calculation.

Survival Analysis
Five-year overall survival (calculated from the date of primary tumor excision) in the FN group was 53.7% (95% confidence interval [95% CI], 38.8–68.6), which is not statistically significantly worse than in the CLND group (56.8%; 95% CI. 48.5–65.1; P = .877). The 5-year survival in the group with negative SLN biopsy who did not experience a relapse in the biopsied basin (87.9%, 95% CI, 84.9–90.8) was significantly better than in the CLND and FN groups (P < .0001). The survival curves for persons who underwent the SLN biopsy are shown in Fig. 1Go.


Figure 1
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  		FIG. 1. Overall survival (calculated from date of primary tumor excision) of patients with nodal recurrence in lymphatic basin previously biopsied for sentinel lymph node (SLN) (false-negative results—FN), in patients after completion lymph node dissection after positive SLN biopsy (CLND), and in patients with true-negative SLN biopsy result (N0 group).

 
Factors Associated with SLN FN Results and Time to Same Basin Recurrences
The characteristics of FN SLN biopsy group of patients is listed in Table 1Go. The FN group was characterized by higher rate of two or more metastatic nodes (P < .0001) and extracapsular involvement of lymph nodes (after LND) (P < .0001) compared with the CLND group.

The median time to occurrence of the observed FN relapses after SLN biopsy was 16 months (range, 3–74 months). The estimated risk of FN relapse during the 5-year observation time was 8.8% (95% CI 6.3–11.2). The time to recurrence in the same nodal basin after SLN biopsy is illustrated in Fig. 2Go.


Figure 2
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  		FIG. 2. Time curve for recurrences in same nodal basin after sentinel lymph node (SLN) biopsy.

 
As compared with true N0 group after SLN, the FN group was characterized by higher rate of primary tumor thickness >4mm (P = .00005), primary tumor ulceration (P = .006), primary tumor level of invasion Clark stage IV/V (P = .02), nodular melanoma histological type (P = .03), number of identified or excised SLN <2 (P = .08) and inguinal lymphatic basin (P = .07), and lower rate of primary location on an upper extremity (P = .01) (Table 1Go).

In bivariate analysis, the occurrence of FN SLN biopsy results was significantly associated with primary tumor thickness >4mm (P = .0012), primary tumor ulceration (P = .0002), Clark stage IV/V (P = .0005) and histological type nodular melanoma (P = .0375). Additionally, the FN SLN occurred more frequently in the inguinal lymphatic basin (P = .1989). Because no data on histological type were available for a large proportion of cases, this variable was excluded from further analysis. All other factors significant at the 20% level and all two-way interactions were considered in the multivariate analysis. Primary tumor ulceration was identified as the most important independent factor predictive of recurrences in the previously biopsied basin associated with a 2.19 (95% CI, 1.20–3.97) higher risk of recurrence at any time after biopsy. Thickness of melanoma and Clark stage IV or V were found to be marginally statistically significant (Table 2Go).


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  		TABLE 2. Multivariate analysis of factors predictive for recurrence in nodal fielda
 
Pathological Review
Detailed pathological review of SLN slides and tissue blocks performed according to the protocol of the EORTC Melanoma Group, requiring transhilar bivalving, step sections from the central planes, and immunohistochemical analysis,10 has allowed us to detect 14 additional metastatic SLN among those initially evaluated as free of tumor in the case of patients with recurrences in the node field. After excluding these cases, we can estimate the SLN biopsy failure rate to be 4.39% (43 of 979). However, exclusion of these 14 cases did not markedly influence the presented survival analysis or the set of factors that seem to affect recurrence in the previously biopsied basin (FN results) (data not shown).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Sentinel node biopsy is currently a valuable and reliable diagnostic procedure for the precise staging of patients with clinically localized primary cutaneous melanoma. It has already been proven that SLN biopsy offers several benefits in the course of management of patients with melanoma: better staging, avoidance of unnecessary ELND, excellent prognostic information, facilitation of therapeutic lymphadenectomy, homogeneity of patient populations in clinical trials receiving adjuvant therapy, and (from the patient’s point of view) an increase in the feeling of safety and receipt of more accurate care.2,3,7,11,12 The presence of metastases in the SLN has been proven to be the most important prognostic factor influencing clinical outcome in patients with clinically nonpalpable regional lymph nodes.3,7

The important factor for the evaluation of reliability of this procedure is the analysis of the percentage of recurrences in the previously biopsied nodal basin, initially assessed as pathologically free of tumor (FN results). The SLN biopsy failure rate varies in reputable literature reports from .6% to 8%.2,5,13–24 Thus, the rate in our study is not exceptionally high and not very different from presented data (Table 3Go). The SLN biopsy FN results were often reported in patients with a relatively short median follow-up and were presented in two ways: one exactly like that applied by us (failure rate; clinically more meaningful) and the another (FN rate; strict adherence to the mathematical definition) calculated as the rate of the number of the first recurrences in the biopsied basin to the number of true-positive SLN cases plus FN findings.25,26 According to this second method, our FN rate is approximately 20%, which also was within the range reported previously.5,15,17,25,27 We did not consider patients who had developed nodal recurrences in an initially negative lymphatic basin after local or in-transit recurrences as presenting with FN results of SLN biopsy. These recurrences can subsequently metastasize to regional nodes, and therefore, this group of patients does not necessarily represent "true" FN results of the SLN biopsy.


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  		TABLE 3. Review of previous studies of rate of recurrence of disease in nodal field
 
There exist some possible explanations for the FN results of SLN biopsy, including technical, biological, and pathological failure. Some studies emphasize the impact of surgical experience on FN rates. However, early on in the study, between May 1995 and May 1997, we had performed more than 170 SLN biopsies with preoperative lymphoscintigraphy and blue dye only (data not shown). These procedures were almost all performed by the same team of surgeons, who later performed SLN biopsies with the triple technique using intraoperative lymphoscintigraphy, and thus the technical cause should not greatly affect the presented results, although one paper demonstrated that even in experienced hands, FN biopsy results may occur because the wrong node has been removed.28 Another issue is the impact of the number of excised sentinel nodes. It has been shown that removal of multiple (>1) SLNs, if they exist, improves the diagnostic accuracy of SLN biopsy.29,30 It is important to compare the number of removed or detected SLNs with the number of such nodes identified on the preoperative lymphoscintigram. Our rate of FN recurrences may also be explained by the relatively high median Breslow thickness and Clark stage (IV/V) and the high ratio of ulcerated primary lesions in our group of patients because these factors increase the risk of developing FN SLN recurrence.2,19,27 According to our inclusion criteria for SLN biopsy, we included patients with a primary melanoma thickness of >4.0 mm because the presented results support the integral role of SLN biopsy in the management of this patient cohort.26,31 It is suggested that more advanced primary melanomas have different biologic behavior and may more commonly cause obstruction of lymphatics by melanoma cells (e.g., in-transit metastases),21,32–35 thus rerouting lymphatic flow or causing delay in reseeding of the nodal basin.18

Another issue related to regional nodal metastasis in patients with tumor-free SLN is the histopathological sampling error, which omits the identification of micrometastases in the SLN. SLN positivity in most studies reaches approximately 20% and is clearly related to primary tumor thickness and ulceration,16,17,23,27 but an article by van Akkooi et al.36 reveals a higher detection rate when the more extensive EORTC Melanoma Group protocol of pathological examination of SLNs is followed.10 The analysis of multiple levels of the lymph node increases the sensitivity of the examination. Further improvement of the diagnostic sensitivity of detecting occult tumor cells may be achieved with the use of immunohistochemical techniques; the most common are S-100 protein and HMB-45 antigen. Re-evaluation of initially negative SLNs by immunohistochemistry and serial sectioning may allow detection of micrometastatic disease in some patients.2,15,37 Several detailed protocols of pathological and molecular examination of sentinel nodes exist,38–47 but the balance between reasonable effort, cost, maximum detection rate, and accuracy is debatable, and thus the optimal assessment of the SLN remains controversial.

Yet another problem is the clinical significance of such micrometastases.37,48 Of course, from a cost-benefit perspective, such an extensive histological examination of SLN is difficult to justify in the course of routine practice.30 In our study, we have identified additional 14 metastatic nodes in 57 re-examined cases (24.5%), which had recurred in biopsied basin and which were negative at initial evaluation. But it may suggest that mechanisms other than imprecise histopathologic examination contribute to the failure of the SLN biopsy method in most patients. This is supported by the results of Yee et al.26 from the Sydney Melanoma Unit. Here, we analyze the rate of FN results of SLN biopsy in a large series of patients with a relatively long follow-up. However, to determine the true nodal-basin failure rate, a longer follow-up is required because regional metastases may not become clinically apparent for more than 5 years; for example, in our study, we identified three FN cases that recurred after 5 years.

The second objective of our study was to analyze the survival of patients with cutaneous melanoma with nodal recurrences in the previously biopsied basin assessed initially as tumor-free. To our knowledge, this is the first study to present a detailed analysis of the survival outcomes of patients with FN nodal recurrences after SLN biopsy. Our results indicate that FN recurrence in patients with melanoma after SLN biopsy does not greatly change the biology of the disease, because survival (calculated from the date of primary tumor excision) is almost the same as in case of positive SLN biopsy results. Additionally, we compared overall survival in the FN group with the group of patients with clinically detected regional lymph node metastases confirmed by fine-needle aspiration biopsy followed by TLND, and we found it better over a longer observation time, although it did not attain statistical significance (log-rank test, P = .177; Fig. 3Go).


Figure 3
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  		FIG. 3. Overall survival (calculated from date of primary tumor excision) in patients with nodal recurrence in lymphatic basins who previously underwent sentinel lymph node (SLN) biopsy (false-negative results—FN group) and in patients after therapeutic lymph node dissection due to clinical nodal involvement (TLND group).

 
Our data suggest that the rate of FN recurrences after negative SLN biopsies is approximately 5.0% in long-term follow-up and is mainly associated with the same factors that indicate a worse prognosis in the primary tumor, including increased Breslow thickness and the presence of ulceration. We conclude that even recurrence in the initially negative nodal basin after SLN biopsy does not markedly worsen the outcomes of patients who undergo this procedure.


   ACKNOWLEDGMENTS
 
We thank M. Rosinska, MD, for statistical advice and M. Symonides, MD, PhD, for English-language assistance.


   FOOTNOTES
 
Preliminary results of this study were presented as an oral presentation during the Melanoma Session on the 59th Annual Cancer Symposium of the Society of Surgical Oncology, San Diego, CA, March 23–25, 2006.

Received for publication July 3, 2006. Accepted for publication July 4, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Morton DL, Wen DR, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 1992; 127:392–9.[Abstract/Free Full Text]
  2. 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 or II melanoma patients. J Clin Oncol 1999; 17:976–83.[Abstract/Free Full Text]
  3. Statius Muller MG, van Leeuwen PA, de Lange-De Klerk ES, et al. The sentinel lymph node status is an important factor for predicting clinical outcome in patients with stage I or II cutaneous melanoma. Cancer 2001; 91:2401–8.[CrossRef][Medline]
  4. Cascinelli N. WHO declares lymphatic mapping to be standard of care for melanoma. Oncology 1999; 13:288.
  5. Cascinelli N, Belli F, Santinami M, et al. Sentinel lymph node biopsy in cutaneous melanoma: the WHO Melanoma Program experience. Ann Surg Oncol 2000; 7:469–74.[Abstract]
  6. Balch Ch M, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 2001; 19:3635–48.[Abstract/Free Full Text]
  7. Morton DL, Thompson JF, Essner R, et al. Validation of the accuracy of intraoperative lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma—a multicenter trial. Ann Surg 1999; 4:453–65.
  8. Morton DL, Thompson JF, Cochran AJ, Essner R, Elashoff R. Interim results of the Multicenter Selective Lymphadenectomy Trial (MSLT-I) in clinical stage I melanoma (abstract 7500). J Clin Oncol 2005; 23(suppl):710s.
  9. Nowecki ZI, Rutkowski P, Nasierowska-Guttmejer A, Ruka W. Sentinel lymph node biopsy in clinically N0 melanoma patients—one institution experience. Melanoma Res 2003; 13:35–43.[CrossRef][Medline]
  10. Cook MG, Green Ma, Anderson B, et al. The development of optimal assessment of sentinel lymph nodes for melanoma. J Pathol 2003; 200:314–9.[CrossRef][Medline]
  11. McMasters KM, Reintgen DS, Ross MI, et al. Sentinel lymph node biopsy for melanoma: controversy despite widespread agreement. J Clin Oncol 2001; 19:2851–5.[Abstract/Free Full Text]
  12. Morton D, Chan A. Current status of intraoperative lymphatic mapping and sentinel lymphadenectomy for melanoma: is it standard of care?. J Am Coll Surg 1999; 189:214–23.[CrossRef][Medline]
  13. Fincher TR, McCarthy TM, Fischer TL, et al. Patterns of recurrence after sentinel lymph node biopsy for cutaneous melanoma. Am J Surg 2003; 186:675–81.[CrossRef][Medline]
  14. Wagner JD, Ranieri J, Evdokimow DZ, et al. Patterns of initial recurrence and prognosis after sentinel lymph node biopsy and selective lymphadenectomy for melanoma. Plast Reconstr Surg 2003; 112:486–97.[CrossRef][Medline]
  15. Gershenwald JE, Colome MI, Lee JE, et al. Patterns of recurrence following a negative sentinel node biopsy in 243 patients with stage I or II melanoma. J Clin Oncol 1998; 16:2253–60.[Abstract]
  16. Clary BM, Mann B, Brady MS, Lewis JL, Coit DG. Early recurrence after lymphatic mapping and sentinel node biopsy with primary extremity melanoma: a comparison with elective lymph node dissection. Ann Surg Oncol 2001; 8:328–37.[Abstract/Free Full Text]
  17. Jacobs IA, Chevinsky AH, Swayne LC, Magidson JG, Britto EJ, Smith TJ. Gamma probe-directed lymphatic mapping and sentinel lymphadenectomy in primary melanoma: reliability of the procedure and analysis of failures after long-term follow-up. J Surg Oncol 2001; 77:157–64.[CrossRef][Medline]
  18. Statius Muller MG, Borgenstein PJ, Pipjers R, et al. Reliability of the sentinel node procedure in melanoma patients: analysis of failures after long-term follow-up. Ann Surg Oncol 2000; 7:461–8.[Abstract]
  19. Vuylsteke RJCLM, van Leeuwen PAM, Statius Muller MG, Gietema HA, Kragt DR, Meijer S. Clinical outcome of stage I/II melanoma patients after selective lymph node dissection: long term follow-up results. J Clin Oncol 2003; 21:1057–65.[Abstract/Free Full Text]
  20. Gadd MA, Cosimi AB, Yu J, et al. Outcome of patients with melanoma and histologically negative sentinel lymph nodes. Arch Surg 1999; 134:381–7.[Abstract/Free Full Text]
  21. Chao C, Wong SL, Ross MI, et al. Patterns of recurrence after sentinel lymph node biopsy for melanoma. Am J Surg 2002; 184:520–5.[CrossRef][Medline]
  22. Statius-Mueller MG, van Leeuwen PA, Van Diest PJ, et al. Pattern and incidence of the first site recurrences following sentinel node procedure in melanoma patients. World J Surg 2002; 26:1405–11.[CrossRef][Medline]
  23. Duprat JP, Silva DC, Coimbra FJ, et al. Sentinel lymph node biopsy in cutaneous melanoma: analysis of 240 consecutive cases. Plast Reconstr Surg 2005; 115:1944–51; discussion 1952–3.[CrossRef][Medline]
  24. Jansen L, Nieweg OE, Peterse JL, Hoefnagel CA, Olmos RA, Kroon BB. Reliability of sentinel lymph node biopsy for staging melanoma. Br J Surg 2000; 87:484–9.[CrossRef][Medline]
  25. Estourgie SH, Nieweg OE, Valdes Olmos RA, Hoefnagel CA, Kroon BB. Review and evaluation of sentinel node procedures in 250 melanoma patients with median follow-up of 6 years. Ann Surg Oncol 2003; 10:681–8.[Abstract/Free Full Text]
  26. Yee VS, Thompson JF, McKinnon JG, et al. Outcome in 846 cutaneous melanoma patients from a single center after a negative sentinel node biopsy. Ann Surg Oncol 2005; 12:429–39.[Abstract/Free Full Text]
  27. Doting MHE, Hoekstra HJ, Plukker JThM, et al. Is sentinel node biopsy beneficial in melanoma patients? A report on 200 patients with cutaneous melanoma. Eur J Surg Oncol 2002; 28:673–678.[CrossRef][Medline]
  28. Scolyer RA, Thompson JF, Li LX, et al. Failure to remove true sentinel nodes can cause failure of the sentinel node biopsy technique: evidence from antimony concentrations in false-negative sentinel nodes from melanoma patients. Ann Surg Oncol 2004; 11(3 suppl):174S–8S.[Abstract/Free Full Text]
  29. Stewart LE, Tyler DS, Vollmer RT. The importance of total number of sentinel lymph nodes in patients with stage N0 cutaneous melanoma. Am J Clin Pathol 2005; 124:77–82.[CrossRef][Medline]
  30. Porter G, Ross MI, Berman RS, et al. How many lymph nodes are enough during sentinel lymphadenectomy for primary melanoma? Surgery 2000; 128:306–11.[CrossRef][Medline]
  31. Gershenwald JE, Mansfield PF, Lee JF, Ross MI. Role for lymphatic mapping an sentinel lymph node biopsy in patients with thick (≥4 mm) primary melanoma. Ann Surg Oncol 2000; 7:160–5.[Abstract]
  32. Pawlik TM, Ross MI, Thompson JF, Eggermont AMM, Gershenwald JE. The risk of in-transit melanoma metastasis depends on tumor biology and not the surgical approach to regional lymph nodes. J Clin Oncol 2005; 23:4588–90.[Free Full Text]
  33. Rutkowski P, Nowecki ZI, Zurawski Z, et al. In-transit/local recurrences in melanoma patients after sentinel node biopsy and therapeutic lymph node dissection. Eur J Cancer 2006; 42:159–64.[CrossRef][Medline]
  34. Pawlik TM, Ross MI, Johnson MM, et al. Predictors and natural history of in-transit melanoma after sentinel lymphadenectomy. Ann Surg Oncol 2005; 12:587–96.[Abstract/Free Full Text]
  35. Niakosari F, Kahn HJ, Marks A, From L. Detection of lymphatic invasion in primary melanoma with monoclonal antibody D2–40: a selective immunohistochemical marker of lymphatic endothelium. Arch Dermatol 2005; 141:440–4.[Abstract/Free Full Text]
  36. van Akkooi ACJ, de Wilt JHW, Verhoef C, et al. High positive sentinel node identification rate by EORTC Melanoma Group protocol: prognostic indicators of metastatic patterns after sentinel node biopsy in melanoma. Eur J Cancer 2006; 42:372–80.[CrossRef][Medline]
  37. Li LX, Scolyer RA, Ka VS, et al. Pathologic review of negative sentinel lymph nodes in melanoma patients with regional recurrence: a clinicopathologic study of 1152 patients undergoing sentinel lymph node biopsy. Am J Surg Pathol 2003; 27:1197–202.[Medline]
  38. Starz H. Pathology of the sentinel lymph node in melanoma. Semin Oncol 2004; 31:357–62.[CrossRef][Medline]
  39. Roberts AA, Cochran AJ. Pathologic analysis of sentinel lymph nodes in melanoma patients: current and future trends. J Surg Oncol 2004; 85:152–61.[CrossRef][Medline]
  40. Ruiter DJ, Spatz A, van der Oord JJ, Cook MG. Pathologic staging of melanoma. Semin Oncol 2002; 29:370–81.[CrossRef][Medline]
  41. Cochran AJ, Balda BR, Starz H, et al. The Augsburg Consensus—techniques of lymphatic mapping, sentinel lymphadenectomy and completion lymphadenectomy in cutaneous malignancies. Cancer 2000; 89:236–41.[CrossRef][Medline]
  42. Kuo CT, Hoon DS, Takeuchi H, et al. Prediction of disease outcome in melanoma patients by molecular analysis of paraffin-embedded sentinel lymph nodes. J Clin Oncol 2003; 21:3566–72.[Abstract/Free Full Text]
  43. Li W, Stall A, Shivers SC, Lin et al. Clinical relevance of molecular staging for melanoma: comparison of RT-PCR and immunohistochemistry staining in sentinel lymph nodes of patients with melanoma. Ann Surg 2000; 231:795–803.[CrossRef][Medline]
  44. Sung J, Wenbin L, Shivers S, Reintgen D. Molecular analysis in evaluating the sentinel node in malignant melanoma. Ann Surg Oncol 2001; 8(9 suppl):29–30.
  45. Cochrane AJ, Wen D-R, Morton DL. Occult tumor cells in the lymph nodes of patients with pathological stage I malignant melanoma: an immunohistochemical study. Am Surg Pathol 1988; 12:612–8.
  46. Cochran AJ, Huang RR, Guo J, Wen D-R. Current practice and future directions in pathology and laboratory evaluation in the sentinel node. Ann Surg Oncol 2001; 8(suppl):13–7.[Abstract/Free Full Text]
  47. McMasters KM, Noyes RD, Reintgen DS, et al. Lessons learned from the Sunbelt Melanoma Trial. J Surg Oncol 2004; 86:212–23.[CrossRef][Medline]
  48. Shen J, Wallace AM, Bouvet M. The role of sentinel lymph node biopsy for melanoma. Semin Oncol 2002; 29:341–52.[CrossRef][Medline]



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