Sentinel Lymph Node Biopsy in Cutaneous Melanoma: The WHO Melanoma Program Experience

Background: We report the experience of the World Health Organization (WHO) Melanoma Program concerning sentinel lymph node (SLN) biopsy for detecting patients with occult regional nodal metastases to submit to selective regional node dissection.Methods: From February 1994 to August 1998, in 12 centers of the WHO Melanoma Program, 892 SLN biopsies were performed in 829 patients with clinical stage I melanoma (male: 370; female: 459; median age: 50 years old). The location of the primary melanoma was as follows: trunk, 35%; lower limbs, 45%; upper limbs, 18%; and head and neck, 2%. Blue dye injection for SLN identification was performed in all cases; preoperative lymphoscintigraphy was one in 440 patients, and an intra-operative probe for a radio-guided biopsy was used in 141 cases. Overall, the SLN identification rate was 88%. In 68% of the patients, only one SLN was identified, whereas two and three or more SLN were detected in 24% and 8% of the remaining cases, respectively.Results: Overall SLN positivity rate was 18%. Intra-operative frozen section examination was performed in 39% of the cases and was helpful in detecting occult localizations only in 47% of the positive SLNs. Distribution of positive cases by primary thickness was as follows:,1mm: 2%; 1–1.99 mm: 7%; 2–2.99 mm: 13%; and 3 mm: 31%. Positive nonsentinel lymph nodes were found in 22% of cases with positive SLN submitted for selective dissection. No complications due to the procedure were registered. Of 710 patients who were evaluated, 40 (6%) presented a regional nodal relapse after a negative SLN biopsy and underwent a delayed therapeutic dissection. From the 710 enrolled cases, 638 (88.5%) were alive without evidence of disease at the time of this writing. A multivariate analysis showed SLN status as one of the most significant prognostic factors (P 5 .000) along with thickness (P 5 .001) and ulceration (P 5 .015) of primary tumor.Conclusions: These data confirm the feasibility and safety of the SLN technique for selecting patients to submit to a radical node dissection. The data represent the basis for a future trial by the WHO Melanoma Program in this field to evaluate the most appropriate surgical approach for treating patients with occult regional nodal metastases.     

Impact of False-Negative Sentinel Lymph Node Biopsy on Survival in Patients with Cutaneous Melanoma

Background and Objectives Sentinel lymph node biopsy is widely accepted as standard care in melanoma despite lack of pertinent randomized trials results. A possible pitfall of this procedure is the inaccurate identification of the sentinel lymph node leading to biopsy and analysis of a nonsentinel node. Such a technical failure may yield a different prognosis. The purpose of this study is to analyze the incidence of false negativity and its impact on clinical outcome and to try to understand its causes. Methods The Melanoma Data Base at National Cancer Institute of Naples was analyzed comparing results between false-negative and tumor-positive sentinel node patients focusing on overall survival and prognostic factors influencing the clinical outcome. Results One hundred fifty-one cases were diagnosed to be tumor-positive after sentinel lymph node biopsy and were subjected to complete lymph node dissection. Thirty-four (18.4%)patients with tumor-negative sentinel node subsequently developed lymph node metastases in the basin site of the sentinel procedure. With a median follow-up of 42.8 months the 5-year overall survival was 48.4% and 66.3% for false-negative and tumor-positive group respectively with significant statistical differences (P < .03). Conclusions The sensitivity of sentinel lymph node biopsy was 81.6%, and a regional nodal basin recurrence after negative-sentinel node biopsy means a worse prognosis, compared with patients submitted to complete lymph node dissection after a positive sentinel biopsy. The evidence of higher number of tumor-positive nodes after delayed lymphadenectomy in false-negative group compared with tumor-positive sentinel node cases, confirmed the importance of an early staging of lymph nodal involvement. Further data will better clarify the role of prognostic factors to identify cases with a more aggressive biological behavior of the disease.     

Sentinel Lymph Node Biopsy for Patients With Cutaneous Desmoplastic Melanoma

Background: Although desmoplastic melanoma (DM) often presents at a locally advanced stage, nodal metastases are rare. We describe our experience with lymphatic mapping and sentinel lymph node biopsy (SLNB) in patients with DM to characterize the biological behavior of these tumors.Methods: Twenty-seven patients with cutaneous DM underwent wide excision and attempted SLNB between 1996 and 2001. All pathology was reviewed by a single dermatopathologist (KB). Clinical and histological features were recorded.Results: There were 20 male and 7 female patients. The median age was 64 years (range, 35–83 years). The head and neck was the most commonly involved anatomical region (n = 14). The median Breslow thickness was 2.2 mm. Twenty-four patients underwent successful SLNB. No patient had a positive sentinel node. At a median follow-up of 27 months, five patients recurred (four systemic and one local); all five had undergone successful SLNB. Two of these patients died of disease, two are alive with disease, and one remains alive and disease free. No patient experienced failure in a regional nodal basin.Conclusions:DM is a biologically distinct form of melanoma, with a very low incidence of regional lymph node metastases, either at presentation or in long-term follow-up. This biology should be considered when designing rational treatment strategies for these patients.     

Significance of Multiple Lymphatic Basin Drainage in Truncal Melanoma Patients Undergoing Sentinel Lymph Node Biopsy

Background Truncal melanoma involving metastases to multiple lymph node basins has a much worse prognosis than tumor involvement of a single lymph node basin. Recent results also suggest that, independently of the status of lymph node involvement, patients with multiple lymphatic basin drainage (MLBD) on lymphoscintigraphy have an increased risk of lymph node metastasis and a worse prognosis than those with a single lymphatic drainage basin. Because published reports have conflicting results, the authors compared their experience at the University of Michigan Comprehensive Cancer Center with recently published findings.Methods The authors searched a prospectively maintained melanoma database at the University of Michigan for patients with primary truncal melanoma who underwent lymphoscintigraphy and sentinel lymph node biopsy between 1997 and 2004. The association of MLBD with the clinical and pathologic characteristics collected and the presence of regional metastases was tested by using contingency tables and the χ² test statistic and by using the Fisher’s exact test statistic when cell frequencies were small. The product-limit method of Kaplan and Meier was used to estimate disease-free and overall survival probabilities.Results Of 423 patients with primary truncal melanoma who underwent sentinel lymph node biopsy, 123 (29%) had a positive result, and 98 patients (23.2%) had MLBD. Patients with tumors located in the middle of the trunk and tumor ulceration were more likely to have MLBD (P < .0001 and P = .045, respectively). Patients with a single lymphatic drainage basin and MLBD had a similar risk of lymph node metastasis and similar disease-free and overall survival.Conclusions Patients with truncal melanomas tend to have MLBD when the tumor is located in the middle of the trunk or when ulceration is present. In our experience, drainage to multiple lymphatic basins was not an independent risk factor for sentinel lymph node metastasis and has no independent prognostic significance.     

Patterns of First-Recurrence and Post-recurrence Survival in Patients with Primary Cutaneous Melanoma After Sentinel Lymph Node Biopsy

Background Sentinel lymph node biopsy (SLNB) has become well accepted in management of patients with primary cutaneous melanoma. An understanding of the pattern of recurrence after SLNB is helpful in coordinating a rational plan of follow-up in these patients. We sought to determine the site and timing of initial recurrence and post-recurrence survival after SLNB. Methods Stage I/II melanoma patients who underwent SLNB during 1991–2004 were identified from a prospective single-institution database. Site and date of first recurrence after SLNB were recorded. Patterns of recurrence after SLNB and post-recurrence survival were analyzed. Results One thousand and forty-six patients underwent SLNB. The sentinel lymph node (SLN) was positive in 164 patients (16%). Median follow-up was 36 months for survivors. Median and 3-year relapse-free survival for SLN-positive patients were 41 months and 56%, and for SLN-negative patients were not reached and 87%, respectively (P < .0001). Of the SLN-positive patients, 47% experienced recurrence, compared with 14% SLN-negative patients. The pattern of recurrence stratified by SLN status was similar between the two groups (P = NS). After recurrence, the site of recurrence was the only significant prognostic factor influencing survival (P < .0001). Conclusions Although SLN-positive patients experience recurrence far earlier and more frequently than SLN-negative patients, the pattern of recurrence is similar. After recurrence, its site is the primary determinant of survival.     

A Randomized Study Comparing the Effectiveness of Methylene Blue Dye with Lymphazurin Blue Dye in Sentinel Lymph Node Biopsy for the Treatment of Cutaneous Melanoma

Background  Radioactive colloid with a gamma probe is the most effective method of identifying sentinel lymph nodes (SLN). Nevertheless, since vital blue dyes are also helpful for visually identifying SLN during surgical dissection, they are often used together with radioactive colloid. There has occasionally been a shortage of lymphazurin blue (LB) dye for use in sentinel lymph node biopsies (SLNB). There have also been reports of anaphylactic reactions to the use of LB dye. Therefore, we were interested in using methylene (MB) blue dye to aid in the visualization of the SLN for biopsy because of its ready availability and greater safety. The purpose of this study of SLN biopsies was to compare the effectiveness of MB with that of LB dye. Study Design  We randomly assigned 159 consecutive patients with intermediate and high-risk melanomas, who were treated by a single surgeon at the Yale Melanoma Unit between January 10, 2005, and June 13, 2007 with SLN biopsy, with radioactive colloid and either LB or MB. Results  A total of 443 SLN were identified and removed from these 159 consecutive patients. MB dye was found to be as effective as LB dye in visually identifying SLN: blue dye was visible in 62% of SLN in the MB group compared with 58% in the LB group. When the SLN were separated into three anatomic locations the visualization results were LB 36% and MB 72% (P = 0.010) for head and neck, LB 65% and MB 61% (P = 0.919) for axilla, and LB 59% and MB 67% (P = 0.001) for groin. Conclusion  SLN were identified in all 158 patients. Approximately 60% of these SLN were also visibly blue. In the cervical and groin regions, MB dye was more visible in the SLN than was the LB dye, and in the axilla the SLN were equally stained blue by both dyes. Generally, if surgeons wish to use intradermal injections of vital blue dye to help visualize SLN, we have found in this study that MB is at least as effective as LB for the visualization of these SLN. The cost of MB is less than that of LB.     

Significance of Multiple Nodal Basin Drainage in Truncal Melanoma Patients Undergoing Sentinel Lymph Node Biopsy

Background: Although previous studies have demonstrated that truncal site is associated with an adverse prognosis, explanations for such risk are lacking. In addition, the number of nodal basins as well as the number of lymph nodes containing regional metastases are important prognostic factors in these patients. Because the lymphatic drainage pattern of truncal melanoma often includes more than one basin, we designed a study to evaluate (1) whether patients with multiple nodal basin drainage (MNBD) were at an increased risk of lymph node metastases identified by sentinel lymph node (SLN) biopsy, and (2) whether the histological status of an individual basin reliably predicted the status of the other draining basins in patients with MNBD.Methods: The records of 295 consecutive truncal melanoma patients who were managed primarily with intraoperative lymphatic mapping and SLN biopsy, between 1991 and 1997, were reviewed. All patients underwent preoperative lymphoscintigraphy, which established the number and location of draining nodal basins. Univariate and multivariate analyses of relevant clinicopathological factors were performed to assess which factors may predict the presence of a pathologically positive SLN.Results: At least one SLN was identified in 281 patients. MNBD was present in 86 (31%) patients, and a pathologically positive SLN was found in 56 (20%) patients. By multivariate analysis, the presence of MNBD (relative risk = 1.9; P = .03), tumor thickness (P = .007), and tumor ulceration (relative risk = 2.4; P = .01) were significant independent risk factors for the presence of at least one pathologically positive SLN. SLN pathology in one basin did not predict the histology of other basins in 19 (22%) of 86 patients with MNBD.Conclusions: MNBD is independently associated with an increased risk of nodal metastases in truncal melanoma patients. Because the histological status of an individual basin did not reliably predict the status of the other draining basins in patients with MNBD, it is important to adequately identify and completely assess all nodal basins at risk, as defined by lymphoscintigraphy, in truncal melanoma patients.Presented at the 52nd Annual Meeting of the Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999.     

Sentinel Lymph Node Biopsy in Cutaneous Melanoma: A Case-Control Study

Abstarct Background Sentinel lymph node biopsy (SLNB) is the most precise method for staging invasive cutaneous melanoma, but its therapeutic effect has been difficult to assess, and SLNB is not routinely used in all melanoma treatment centers. Methods This case-control study of 305 prospective SLNB patients compared them with 616 retrospective patients who had not undergone invasive nodal staging at diagnosis. Thin melanomas were included in both study groups. Results A total of 50 SLNB patients were sentinel positive (16.4%) and 255 were sentinel negative (83.6%). A total of 49 of the 50 sentinel-positive patients underwent completion lymph node dissection, and 9 of them (18%) had additional metastases in the nonsentinel nodes. The false-negative rate was 1.6% (five same-basin nodal recurrences during follow-up). There was a significant difference in melanoma-related overall survival (OS) between sentinel-positive and sentinel-negative patients (P < .001). The tumor burden of the sentinel nodes was a significant prognostic factor for melanoma-related OS (P < .001). There was no significant difference in melanoma-related OS or disease-free survival between the study groups, but the nodal disease-free survival was significantly longer among the SLNB patients (P = .004). Conclusions SLNB is recommended for routine use in the treatment of cutaneous melanoma because the sentinel node status carries unique prognostic information on the survival of melanoma patient. Improved regional disease control is an obvious therapeutic advantage of SLNB and immediate completion lymph node dissection.     

Sentinel Node Biopsy Provides More Accurate Staging Than Elective Lymph Node Dissection in Patients With Cutaneous Melanoma

Background: In most major melanoma treatment centers, sentinel node biopsy (SNB), with complete regional lymph node dissection when a positive sentinel node is found, has now replaced elective lymph node dissection (ELND) for patients with primary cutaneous melanomas who are considered to be at moderate to high risk of nodal recurrence. As for ELND, however, no overall survival benefit for the SNB procedure has yet been demonstrated. The objective of this study was to compare the nodal staging accuracy and duration of survival for SNB and ELND.Methods: A retrospective cohort study was conducted among patients with American Joint Committee on Cancer (AJCC) stage II disease treated at a single center between 1983 and 2000 with either SNB (n = 672) or ELND (n = 793). Multivariate analyses were performed using the logistic regression model for nodal staging accuracy and Coxs proportional hazards regression model for survival.Results: Patient factors that influenced nodal positivity included age, Breslow thickness, ulceration, head or neck primary, and operation type (SNB or ELND). SNB was superior to ELND in the detection of micrometastases (odds ratio 1.23, 95% CI, 1.06 – 1.43) but operation type did not influence survival (P = .24).Conclusions: Sentinel node biopsy identified more nodal micrometastases than ELND but did not influence survival, although complete regional node dissection was performed in all patients who were SNB positive. This increase in staging accuracy likely results from the reliable identification of the appropriate lymph node field by preoperative lymphoscintigraphy, along with more detailed pathologic examination of the nodes removed by SNB.Presented to the Society of Surgical Oncology, New York, March 2004     

Ultrasound-guided Fine Needle Aspiration Cytology prior to Sentinel Lymph Node Biopsy in Melanoma Patients

Background Sentinel lymph node biopsy (SLNB) allows early detection of metastases, thereby enabling early treatment in melanoma patients likely to benefit from adjuvant therapies. This prospective study analyzes the possible benefits of additional ultrasound (US) and fine needle aspiration cytology (FNAC) of sentinel nodes (SN) prior to SLNB.Method Over a 2-year period 127 melanoma patients with 151 SN were scheduled for SLNB. All SN were initially identified with lymphoscintigraphy, then identified and evaluated by US and the cells aspirated for cytology (FNAC). US findings and FNAC results were compared to surgical findings.Results Of 127 patients, 114 had one SN each, 12 had two, and one had three. In vivo US achieved a sensitivity of 79% (95% CI: 62–91%) and a specificity of 72% (95% CI: 62–81%). FNAC showed a sensitivity of 59% (95% CI: 41–76%) and a specificity of 100% (95% CI: 95–100%). The combination of these two in vivo methods achieved an overall sensitivity of 82% (95% CI: 65–93%) and an overall specificity of 72% [95% CI: 62–81%].Conclusion Combined US and FNAC provides important information prior to SLNB in that both procedures identify metastases in the lymph nodes (sensitivity > 80%). Patients with positive FNAC may proceed directly to complete lymph node dissection (cLND) instead of having initial SLNB. Thus, combined US and FNAC may prevent unnecessary anesthesia and surgical management as well reduce costs. In our study 16% (19/121) fewer SLNB procedures were carried out, subsequently replaced by cLND. For patients with a negative combination of in vivo US and FNAC, SLNB remains the best diagnostic option.Part of this work was presented in May 2003 at the Melanoma session of the 39^th Annual Meeting of the American Society of Clinical Oncology in Chicago, Illinois, and at the Oral Melanoma Poster Discussion session of the 40^th Annual Meeting of the American Society of Clinical Oncology in New Orleans, Louisiana.     

Ultrasonography and Fine-needle Aspiration Cytology in the Preoperative Evaluation of Melanoma Patients Eligible for Sentinel Node Biopsy

Background Ultrasonography with fine-needle aspiration cytology (FNAC) has proven to be a valuable diagnostic tool in the preoperative workup of patients with breast cancer or penile cancer eligible for sentinel lymph node biopsy. The aim of this study was to evaluate the use of this technique in the initial assessment of patients with primary cutaneous melanoma.Methods A total of 107 patients with cutaneous melanoma eligible for sentinel node biopsy with clinically negative nodes were studied prospectively. Patients underwent ultrasonography of potentially involved basins and FNAC in case of a suspicious lymph node. The sentinel node procedure was omitted in patients with tumour-positive lymph nodes in lieu of lymph node dissection.Results Ultrasonography with FNAC correctly identified disease preoperatively in two of the 107 patients (2%). Thirteen of the 22 patients (59%) with a suspicious node on ultrasonographic imaging but a tumour-negative fine-needle aspirate were shown to have involved nodes. Of the 85 patients with ultrasonographically normal nodes, 25 (29%) were shown to have metastases. Of the total of 43 involved basins, 16 contained metastases > 2 mm and 25 ≤ 2 mm.Conclusions In our hands, the sensitivity and specificity of preoperative ultrasonography to detect lymph node involvement in patients with melanoma are 34% and 87%, respectively. In combination with FNAC, this is 4.7% and 100%, respectively. This yield is insufficient for this technique to be used as a routine diagnostic tool in the selection of patients eligible for sentinel node biopsy.     

Role of Sentinel Lymph Node Biopsy in Patients With Thin (<1 mm) Primary Melanoma

Background: Thin melanomas have become increasingly prevalent, and lesions 1 mm in thickness are frequently diagnosed. They are considered highly curable when treated solely with wide local excision, with reported 5-year disease-free survivals of 95% to 98%. However, thin Clark level III and IV melanomas may have increased potentials for metastasizing and late recurrences because of dermal lymphatics located at the interface of the papillary and reticular dermis. We have addressed this controversial area by reviewing the outcomes of patients with invasive thin melanomas.Methods: We performed 266 sentinel lymph node biopsy procedures, using both radioisotope and blue dye, over a 5-year period. Sixty-five of the 266 invasive melanomas were thin and were treated by wide local excision and sentinel lymph node biopsy.Results: Two (3%) of the 65 thin melanomas were found to have a positive sentinel lymph node. In melanomas thinner than .75 mm, no positive sentinel lymph node was found. Therefore, only 3% of patients may benefit from tumor upstaging by sentinel lymph node biopsy.Conclusions: The occurrence of regional lymph node metastases in thin melanomas is rather low. Our data suggest that sentinel lymph node biopsy may not justified in patients with melanoma <.75 mm thick.     

Sentinel Node Biopsy Before Neoadjuvant Chemotherapy Spares Breast Cancer Patients Axillary Lymph Node Dissection

Background Neoadjuvant chemotherapy in breast cancer patients is a valuable method to determine the efficacy of chemotherapy and potentially downsize the primary tumor, which facilitates breast-conserving therapy. In 18 studies published about sentinel node biopsy after neoadjuvant chemotherapy, the sentinel node was identified in on average 89%, and the false-negative rate was on average 10%. Because of these mediocre results, no author dares to omit axillary clearance just yet. In our institute, sentinel lymph node biopsy is performed before neoadjuvant chemotherapy. The aim of this study was to evaluate our experience with this approach. Methods Sentinel node biopsy was performed before neoadjuvant chemotherapy in 25 T2N0 patients by using lymphoscintigraphy, a gamma ray detection probe, and patent blue dye. Axillary lymph node dissection was performed after chemotherapy if the sentinel node contained metastases. Results Ten patients had a tumor-positive axillary sentinel node, and one patient had an involved lateral intramammary node. Four patients had additional involved nodes in the completion lymph node dissection specimen. The other 14 patients (56%) had a tumor-negative sentinel node and did not undergo axillary lymph node dissection. No recurrences have been observed after a median follow-up of 18 months. Conclusions Fourteen (56%) of the 25 patients were spared axillary lymph node dissection when the sentinel node was found to be disease free. Performing sentinel node biopsy before neoadjuvant chemotherapy seems successful and reliable in patients with T2N0 breast cancer.     

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

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.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.     

Factors Predictive of Nonsentinel Lymph Node Involvement and Clinical Outcome in Melanoma Patients With Metastatic Sentinel Lymph Node

BACKGROUND: Identification of melanoma patients who need completion lymphadenectomy and adjuvant treatment after positive sentinel lymph node (SLN) biopsy would be a fundamental step forward toward personalized medicine. This study tested the hypothesis that the microscopic features of metastatic SLNs might predict not only nonsentinel lymph node (NSLN) status, but also patients' clinical outcomes. METHODS: A retrospective analysis was performed on 96 consecutive melanoma patients who underwent completion lymphadenectomy after positive SLN biopsy. Patients' age and sex, primary tumor Breslow thickness, number of positive SLNs, the largest diameter and depth of invasion of metastatic deposits in the SLN, S stage, and pattern of nodal involvement were correlated with the presence of metastatic disease in NSLNs as well as with the likelihood of tumor recurrence and patient death. RESULTS: At pathological examination, 20 patients (20.8%) had metastatic melanoma in the NSLN. Pattern of nodal involvement, depth of invasion of SLN by metastatic disease, and S stage were statistically significantly associated with the presence of metastatic disease in NSLN. Multivariate analysis revealed that only the SLN depth of invasion was an independent predictor of NSLN status (P = .0035). This parameter was also significantly associated with disease-free and overall survival, both by univariate (P < .0001 and P = .0006, respectively) and multivariate (P < .0001 and P = .0013, respectively) survival analysis. CONCLUSIONS: These findings support further investigation of SLN depth of invasion as a predictive factor of potential clinical use to select patients as candidates for completion lymphadenectomy and adjuvant treatment.     

Primary Cutaneous Melanoma with Regression Does not Require a Lower Threshold for Sentinel Lymph Node Biopsy

Introduction Histological evidence of primary tumor regression (RG) is observed in 35% or fewer patients with cutaneous melanoma. Some advocate a lower threshold for sentinel lymph node (SLN) biopsy when RG is present. Methods We identified 1,349 patients presenting to our center with clinically localized cutaneous melanoma between 1995 and 2004. Of these, 344 demonstrated histological RG in their primary melanoma. A retrospective analysis of their medical records was performed to obtain clinical and pathological information. Results The median Breslow depth for the 344 patients with RG was 1.1 mm versus 1.5 mm for 1,005 patients with no regression (NRG) (P < 0.005). SLN biopsy was performed in 64% of patients with RG and 72% without. Positive SLN was more common in those with NRG than in those with RG (18% vs 10%, P = 0.005). Only one RG patient with thin melanoma (≤1 mm, Clark IV) had a positive SLN. When stratified by Breslow depth, patients with RG had lower rates of SLN positivity in all groups (≤1.0mm, >1.0 and ≤2.0mm, >2 and ≤4 mm, and >4.0 mm). Recurrence was more common in patients with NRG (21% vs 12%; P < 0.005). Both local and systemic recurrence occurred more commonly in patients with NRG (4% vs 1%, P = 0.002 and 8% vs 3%, P < 0.005, respectively) Conclusions The presence of histological RG in a primary melanoma predicts neither SLN positivity when stratified by Breslow depth nor increased risk of recurrence when compared with melanomas with NRG.     

Outcome in 846 Cutaneous Melanoma Patients From a Single Center After a Negative Sentinel Node Biopsy

Background A negative sentinel node biopsy (SNB) implies a good prognosis for melanoma patients. The purpose of this study was to determine the long-term outcome for melanoma patients with a negative SNB.Methods Survival and prognostic factors were analyzed for 836 SNB-negative patients. All patients with a node field recurrence were reviewed, and sentinel node (SN) tissue was reexamined.Results The median tumor thickness was 1.7 mm, and 23.8% were ulcerated. The median follow-up was 42.1 months. Melanoma specific survival at 5 years was 90%, compared with 56% for SN-positive patients (P < .001). On multivariate analysis, only thickness and ulceration retained significance for disease-free and disease-specific survival. Five-year survival for patients with nonulcerated lesions was 94% vs. 78% with ulceration. Eighty-three patients (9.9%) had a recurrence. Twenty-seven patients developed recurrence in the regional node field, and in 22 of these, it was the first recurrence site. Six developed local recurrence, 17 an in-transit metastasis, and 58 distant disease. The false-negative rate was 13.2%. SN slides and tissue blocks were further examined in 18 patients with recurrence in the node field, and metastatic disease was found in 3 of them.Conclusions This large, single-center study confirms that patients with a negative SNB have a significantly better prognosis than those with positive SNs. In those with a negative SNB, primary tumor thickness and ulceration are independent predictors of survival. Incorrect pathologic diagnosis contributed to only a minority of the false-negative results in this study.     

Complete Lymph Node Dissection for Sentinel Node-Positive Melanoma: Assessment of Practice Patterns in the United States

Background Currently, complete lymph node dissection (CLND) is recommended after identification of a metastatic lymph node by sentinel lymph node biopsy (SLNB). Guidelines suggest that CLND should be performed as a separate procedure, and a sufficient number of nodes should be examined. Our objective was to examine the utilization, timing, and adequacy of CLND for melanoma in the United States. Methods From the National Cancer Data Base, patients diagnosed with stage I to III melanoma during 2004–2005 were identified. Multiple logistic regression was used to assess factors associated with CLND utilization, timing (separate operation from SLNB), and adequacy (examination of ≥10 nodes). Results Of the 44,548 patients identified, 47.5% were pathologic stage IA, 23.8% stage IB, 14.1% stage II, and 14.6% stage III. Of the 17% (2942 of 17,524) with nodal metastases on SLNB, only 50% underwent a CLND. Patients were significantly less likely to undergo a CLND after SLNB if >75 years old or had lower extremity melanomas. Of the patients who underwent a CLND, only 42% underwent the CLND at a separate procedure after the SLNB. Of those who underwent a CLND, 69.2% had ≥10 nodes examined. Patients were significantly less likely to have ≥10 nodes examined if they were >75 years old or had lower extremity melanomas. Patients treated at NCCN/NCI-designated centers were significantly more likely to undergo nodal evaluation in concordance with established guidelines. Conclusions Only half of patients with sentinel node-positive melanoma underwent CLND. Quality surveillance measures are needed to monitor, standardize, and improve the care of patients with malignant melanoma. Presented in part at the Society of Surgical Oncology Annual Meeting, March 14, 2008, Chicago, IL.     

Sentinel Lymph Node Tumor Load: An Independent Predictor of Additional Lymph Node Involvement and Survival in Melanoma

Background Even though 60% to 80% of melanoma patients with a positive sentinel lymph node (SLN) have no positive additional lymph nodes (ALNs), all these patients are subjected to an ALN dissection (ALND) with its associated morbidity. The aim of this study was to predict the absence of ALN metastases in patients with a positive SLN by using features of the primary melanoma and SLN tumor load.Methods Of 71 SLN-positive patients, 52 had metastasis limited to the SLN (group 1), and 19 had 1 positive ALN after ALND (group 2). The tumor load of the SLN was assessed by measuring the total surface area by computerized morphometry. Breslow thickness, ulceration and lymphatic invasion of the primary tumor, and total SLN metastatic area were tested as covariates predicting the absence of positive ALNs.Results The mean SLN metastatic area was 1.18 mm² (group 1) and 3.39 mm² (group 2) (P = .003) and was the only significant and independent factor after multivariate analysis (P = .02). None of the patients with both a Breslow thickness <2.5 mm and an SLN metastatic area <.3 mm² had a positive ALN.Conclusions SLN metastatic area can be used to predict the absence of positive ALNs in melanoma patients. In this study, patients with a Breslow thickness <2.5 mm and an SLN tumor load <.3 mm² seemed to have no positive ALN and had excellent survival. We hypothesize that this subgroup might not benefit from ALND. Prospective larger trials, using this model and randomizing between ALND and no ALND, should confirm this hypothesis.Published by Springer Science+Business Media, Inc. © 2005 The Society of Surgical Oncology, Inc.