Sentinel lymph node biopsy for melanoma and other melanocytic tumors in adolescents

Background/Purpose

Melanoma is rare, accounting for only 1% of all pediatric malignancies. The management of pediatric melanoma is controversial but largely parallels that of an adult occurrence. Sentinel lymph node biopsy (SLNBX) has become a standard of care for adults with melanoma, but the role of this procedure in the staging of pediatric patients remains to be established. The goal of this study was to determine outcomes and complications of children and adolescent patients undergoing SLNBX at the authors' institution.

Methods

A retrospective review of patients younger than 21 years (N = 20) undergoing SLNBX for melanoma or other melanocytic skin lesions at the University of Colorado Health Science Center between 1996 and 2003 was conducted.

Results

Sentinel lymph node biopsy was successful in all 20 patients, and 8 patients (40%) were found to have metastases within the sentinel node. As in adults, the sentinel node status correlates with primary tumor depth. No complications occurred in patients undergoing SLNBX, but 4 clinically significant complications (57%) occurred in the 7 patients undergoing a completion lymph node dissection. At 33 months median follow-up, all patients were disease free.

Conclusions

Sentinel lymph node biopsy can be successfully and safely performed in pediatric patients for melanoma and atypical nevi. However, the prognostic information and therapeutic implications of SLNBX results for children and adolescents remain unclear. Completion lymph node dissection for microscopic disease is a morbid procedure with uncertain benefit to pediatric or adult patients with a positive SLNBX result. Long-term follow-up data are needed before SLNBX can become a standard of care in pediatric melanoma or as a diagnostic tool to distinguish the atypical Spitz nevus from melanoma.     

Sentinel lymph node biopsy in melanoma: The Oxford ten year clinical experience

Sentinel lymph node biopsy (SLNB) has become an established investigation for assessing microscopic nodal metastasis in melanoma. The American Joint Committee on Cancer (AJCC) incorporates the sentinel node status in its staging criteria for melanoma.We present our clinical evaluation of performing SLNB in a single UK centre between 1998 and 2008. There were 697 patients with a mean age 53 years (range 13–92). We were able to surgically harvest at least one sentinel node in 694 patients of which 532 (76%) were negative. Of the 162 positive patients, 129 underwent further completion lymphadenectomy with 29 showing further pathologically positive nodes. At median follow up of 46 months, mortality from melanoma for SLN positive and negative patients was 32% and 4%, respectively. Disease recurrence was noted in 10% of the SLN negative group. Survival curves showed significant difference (p < 0.001) in outcomes for patients grouped by Breslow thickness. Postoperative complications were noted in 6% of patients. No life-threatening complications were noted.Our results are comparable to other national and international studies. We await the outcomes of ongoing trials to assess the therapeutic value of SLNB for melanoma.     

乳腺癌前哨淋巴结活检

目的 评价前哨淋巴结活检预测腋窝淋巴结有无肿瘤转移的准确性及其临床意义。方法 用^99m锝－硫胶体作为示踪剂,用γ探测仪导向,对70例临床分期为T1－2N0M0的乳腺癌患者进行前哨淋巴结活检,所有的患者均同时行腋窝淋巴结清扫,HE染色阴性的前哨淋巴结再切片,用CK8、CK19、KP－1行免疫组织化学染色。结果 70例患者中成功发现前哨淋巴结的有67例,发现率为95.7%（67／70）。前哨淋巴结的数量为1－5枚,平均每例1.6枚。非前哨淋巴结5－20枚,平均例12.3枚。67例前哨淋巴结活检成功的患者中,29例患者（43.3%）有腋窝淋巴结转移,其中前哨淋巴结有转移者24例（35.8%）,前哨淋巴结未发现转移而非前哨淋巴结有转移者5例（7.5%）。7例患者（10.4%）只有有淋巴结为阳性淋巴结,前哨淋巴结活检的准确性为100％。43例患者的65枚HE染色阴性一的前哨淋巴结,CK8及CK19免疫组织化学染色均为阴性。结论 前哨淋巴结检能较准确地预测腋窝淋巴结转移情况,对原发灶为T1的乳腺癌,前哨淋巴结活检的准确性为100％。同一层面切片行免疫组织化学染色并不能提高淋巴结微转移癌的发现率。     

Sentinel node biopsy site used as full thickness skin graft donor for cutaneous melanoma

BACKGROUND: Wound defects after wide local excision (WLE) for cutaneous melanoma can occasionally require the use of skin grafts for closure. Harvesting the skin graft can result in an additional wound. METHODS: The increasing use of sentinel lymph node (SLN) biopsy in cutaneous melanoma at our institution has facilitated the development of an alternative technique for obtaining donor skin. The proposed method utilizes the skin overlying the SLN as the skin graft donor site. Sixteen patients underwent WLE of intermediate to thick melanomas with SLN biopsy and full thickness skin graft harvested from the SLN biopsy site. RESULTS: After a median follow-up of 12 months, there were no graft failures. There were 2 partial graft losses. There were no wound complications. There were no melanoma recurrences. CONCLUSIONS: In cases where primary closure is not technically feasible or cosmetically favorable, the use of the SLN incision site as a skin graft donor provides the surgeon with an effective repair and spares the patient an additional skin graft donor site defect.     

Utility of frozen-section analysis of sentinel lymph node biopsy specimens for melanoma in surgical decision making

Background

Debate exists whether frozen-section analysis of sentinel lymph nodes (SLNs) for melanoma is an accurate method to detect disease that has metastasized to the lymph nodes. The purpose of this study was to evaluate the utility of intraoperative frozen section for SLNs in melanoma.

Methods

We reviewed 133 patients (271 nodes) who underwent SLN biopsy with frozen section for melanoma between April 2003 and September 2007. Frozen-section diagnosis was compared with final diagnosis to determine concordance between intraoperative and postsurgical diagnosis.

Results

A total of 11 nodes (8% of patients) were found to have metastatic disease. All patients underwent lymph node dissections at the time of SLN biopsy. No false-positive SLNs were found on frozen section. The false-negative rate for SLN biopsy frozen section was 8% (1 of 133 patients).

Conclusions

Intraoperative frozen section can be an accurate and reliable tool in the right setting for analysis of sentinel nodes in cutaneous melanoma and deserves further study.     

Sentinel lymph node biopsy in the pediatric population

Background

Sentinel lymph node biopsy (SLNB) has only been recently used for childhood neoplasms.

Methods

We reviewed all patients younger than 19 years who underwent SLNB for 5 years.

Results

Twenty patients were identified (11 male, 9 female). Sentinel lymph node biopsy was performed for 10 sarcomas (5 synovial, 3 rhabdomyosarcoma, 1 epitheliod, 1 other); 9 skin neoplasms (4 melanomas, 3 Spitz nevi, 2 melanocytomas); and 1 acinic cell carcinoma. All patients underwent Technetium 99m sulfur microcolloid injection and 4-quadrant subdermal injection with Lymphazurin 1% (Autosuture, Norwalk, Conn). Six patients required either sedation for lymphoscintigraphy. Intraoperative gamma probe was used. Primary lesions were found in lower extremity (n = 8), upper extremity (n = 6), trunk (n = 3), and head and neck (n = 3). The lymphatic basins were inguinal (n = 8), axilla (n = 8), neck (n = 3), and both inguinal and axilla (n = 1). At least one lymph node was identified in each procedure. Of 20 patients, 5 (25%) had metastatic disease (4 skin neoplasms and 1 sarcoma). There were no complications in our series, and all patients are alive with no recurrence at an average follow-up of 2.2 years.

Conclusions

Sentinel lymph node biopsy allows for an accurate biopsy in children. However, some younger patients may require sedation, and it may be more challenging to isolate the sentinel node.     

Sentinel lymph node staging of cutaneous melanoma: predictors and outcomes

Background

The authors updated their experience with sentinel lymph node (SLN) biopsy of clinically node negative (N0) melanoma to clarify indications, predictive factors, and outcomes.

Methods

A review of patients from the authors' institution's prospective database (n = 397) was performed; survival statistics were obtained from the institutional tumor registry.

Results

The SLN-positive (SLN+) rate was 16% (47 of 282) for lesions >1 mm thick; only 2 of 105 T1 lesions were SLN+. Thickness >2 mm, upper extremity primary, and ulceration predicted SLN+ status. Most SLN+ patients underwent completion node dissection; 12% had additional positive nodes. The false-negative SLN biopsy rate was 4.0%; the majority involved lower extremity and head and neck primaries. The overall complication rate was 26%; all were minor and resolved within 6 months. Overall 5-year survival rates were 73% and 92% for SLN+ and SLN-negative patients, respectively. SLN status was the most significant predictor of survival.

Conclusions

SLN status, the most important determinant of outcome for clinically N0 melanoma, correlated with T stage, ulceration, and site. Staging of T1 lesions had low yield. A minority of completion node dissections yielded additional positive nodes.     

Sentinel node biopsy for cutaneous melanoma in the head and neck

Background: Selective sentinel lymphadenectomy has gained widespread acceptance for staging of melanomas arising in the trunk and extremities, but the complex lymphatic drainage of the head and neck area has limited its application in this area.Methods: We performed a retrospective analysis of patients who underwent selective sentinel lymphadenectomy for cutaneous melanoma of the head and neck at the University of Alabama at Birmingham from 1997 through 2000, by using a standard technique of preoperative lymphoscintigram and biopsy guided with blue dye injection and a handheld gamma probe. Complete lymph node dissection was recommended only for tumor-positive sentinel lymph nodes (SLNs). Survival curves were constructed with the Kaplan-Meier method. Fishers exact test was used for comparisons. Significance was defined as P < .05.Results: Thirty-eight patients underwent selective sentinel lymphadenectomy with the standard technique during the study period. A majority (82%) of patients were men with a median age of 55 years. The most common site of the primary tumor was the face (44%), followed by the scalp (24%). Mean tumor thickness was 2.5 mm. The sentinel node was identified during surgery in 35 patients (92%). Before the use of the handheld gamma probe, the identification rate of the SLN was only 56%. A single SLN was identified in 53% of cases. The incidence of metastases in SLN was 11.4%. With a mean follow-up of 17 months, the actuarial 3-year overall survival was 92%. The accuracy of the selective sentinel lymphadenectomy in this series was 80%.Conclusions: Selective sentinel lymphadenectomy in the head and neck region is a technically demanding procedure, but the combined use of blue dye and gamma-probe radiolocalization can be a reliable method of staging regional lymph nodes and determining the need for elective lymphadenectomy.     

Performance of models predicting residual lymph node disease in melanoma patients following sentinel lymph node biopsy

BackgroundAmong melanoma patients with a tumor-positive sentinel node biopsy (SNB), approximately 20% harbor disease in non-sentinel nodes (nSN), as determined by a completion lymph node dissection (CLND). CLND lacks a survival benefit and has high morbidity. This study assesses predictive factors for nSN metastasis and validates five models predicting nSN metastasis.MethodsPatients with invasive melanoma were identified from the BC Cancer Agency (2005–2015). Clinicopathological data were collected from 296 patients who underwent a CLND after a positive SNB. Multivariate analysis was completed to assess predictive variables in the study population. Five models were externally validated using overall model performance (Brier score [calibration and discrimination]) and discrimination (area under the ROC curve [AUC]).ResultsSeventy-three patients had nSN metastasis at the time of CLND. The variable most predictive of nSN involvement was lymphovascular invasion (odds ratio [OR] 3.99; 95% confidence interval [CI] 1.67–9.54; p = 0.002). The highest discrimination was Lee et al. (2004) (AUC 0.68 [95% CI 0.61–0.75]), Rossi et al. (2018) (AUC 0.68 [95% CI 0.57–0.77]), and Bertolli et al. (2019) (AUC 0.68 [95% CI 0.60–0.75]). Rossi et al. (2018) had the lowest overall model performance (Brier score 0.44). Rossi et al. (2018) and Bertolli et al. (2019) had the ability to stratify patients to a risk of nSN involvement up to 99% and 95%, respectively.ConclusionBertolli et al. (2019) had amongst the highest overall model performance, was the most clinically meaningful and is recommended as the preferred model for predicting nSN metastasis.     

Assessment of value of the sentinel lymph node biopsy in melanoma in children and adolescents and applicability of subcutaneous infusion anesthesia

Background/Purpose

The management of pediatric melanoma is controversial but equates that of adults. Lymphatic mapping with sentinel lymph node (SLN) biopsy is proposed as standard of care for patients with primary melanoma. The operation can be done with general or local anesthesia in adults. The goal of this study was to determine the applicability of subcutaneous infusion anesthesia (SIA) for SLN biopsy in children and adolescents, as well as to assess complications of this procedure and to document outcome of patients with melanoma in this particular age group after SLN biopsy.

Methods

Charts of patients with melanomas on the trunk and extremities who underwent lymphatic mapping and SLN biopsy in SIA between November 2000 and January 2006 revealed 13 patients with age 21 years or less. Tumescent solutions with lidocaine (0.2%) were used for SLN biopsy. Patient demographics, tumor thickness, Clark level, location of primary melanoma, ulceration, number of SLNs, number of positive nodes, and follow-up of patients were included.

Results

In 13 patients (age range, 12-21), SLN biopsy was performed. Mean tumor thickness was 1.8 mm (range, 1.0-7.0), none of these melanomas showed ulceration. The operation was tolerated in SIA by all patients; none had any associated complications. Of 13 patients, 5 (38.5%) had positive sentinel nodes. Three patients underwent completion lymph node dissection, and no further positive nodes were found. After a mean follow-up of 29.2 months (range, 13-68), all patients were found disease-free.

Conclusions

Sentinel lymph node biopsy in SIA can safely be performed in children and adolescents with primary melanomas. Further studies are necessary to determine the prognostic information and therapeutic implications of SLN biopsy in this patient group.     

The effect of time to sentinel lymph node biopsy on cutaneous melanoma survival

Background

Whether timing of sentinel lymph node biopsy (SLNB) in cutaneous melanoma improves survival is not yet clear. The aim of this study was to investigate if the timing of SLNB influences long-term melanoma mortality.

Methods

A 10-year retrospective cohort study was conducted on 748 cutaneous melanoma patients who underwent excision of the SLN. Hazard ratios and 95% confidence intervals were estimated from Cox proportional hazards models.

Results

After adjusting for sex, age, Breslow thickness, mitotic rate, ulceration, and histologic type, patients who underwent early SLNB (≤30 days) and resulted positive on final pathology had a 3 times decreased risk of melanoma mortality (hazard ratio = .29; 95%confidence interval = .11 to .77) in comparison to patients who underwent delayed SLNB (≥31 days) and resulted positive on final pathology.

Conclusions

Our findings suggest that early SLNB (≤30 days) improves melanoma survival.     

Sentinel lymph node biopsy in thick malignant melanoma: A 10-year single unit experience

Between the years 2000-2010, 195 patients were diagnosed with ≥4?mm Breslow thickness malignant melanoma in our unit. Median follow-up was 36.8 months. 49% of patients were male and 51% were female. Median age was 74 years. The commonest melanoma type was nodular (55%). The commonest tumour location was on the extremity (45%). 64% of tumours were ulcerated. Median mitotic rate was 9. Median Breslow thickness was 7?mm 66 patients underwent sentinel lymph node biopsy. 44 (67%) patients had negative results and the remaining 22 (33%) patients were positive for metastatic melanoma. There was no statistically significant correlation between any of the patient or tumour variables (age, sex, melanoma type, melanoma site, Clark level, Breslow thickness, mitotic rate, ulceration) and sentinel lymph node status. Patients with Breslow thickness melanoma of <6?mm had a significantly better 5-year disease free and overall survival compared with those patients with >6?mm Breslow thickness melanoma (63.5% vs. 32.9%; P?=?0.004 and 73.9% vs. 54.7%; P?=?0.02 respectively). Recurrence rate was 50% in those with positive sentinel lymph node biopsy compared to 23% in those with negative results. Distant recurrence was the commonest in both groups. 5-year disease free survival was 64.1% in the SLNB -ve group and 35.4% in the SLNB +ve group (P?=?0.01). There was no significant difference in overall survival between the SLNB -ve and SLNB +ve groups (70.3% vs. 63.7% respectively; P?=?0.66). We conclude that sentinel lymph node biopsy in our unit has provided no survival benefit in those with thick melanoma over the past 10 years but is an important predictor of recurrence free survival. Breslow thickness remains an important predictor of disease free and overall survival in thick melanoma.     

Complications associated with sentinel lymph node biopsy for melanoma

Background: Sentinel lymph node (SLN) biopsy has become widely accepted as a method of staging the regional lymph nodes for patients with melanoma. Although it is often stated that SLN biopsy is a minimally invasive procedure associated with few complications, a paucity of data exists to specifically determine the morbidity associated with this procedure. This analysis was performed to evaluate the morbidity associated with SLN biopsy compared with completion lymph node dissection (CLND).Methods: Patients were enrolled in the Sunbelt Melanoma Trial, a prospective multi-institutional study of SLN biopsy for melanoma. Patients underwent SLN biopsy and were prospectively followed up for the development of complications associated with this technique. Patients who had evidence of nodal metastasis in the SLN underwent CLND. Complications associated with SLN biopsy alone were compared with those associated with SLN biopsy plus CLND.Results: A total of 2120 patients were evaluated, with a median follow-up of 16 months. Overall, 96 (4.6%) of 2120 patients developed major or minor complications associated with SLN biopsy, whereas 103 (23.2%) of 444 patients experienced complications associated with SLN biopsy plus CLND. There were no deaths associated with either procedure.Conclusions: SLN biopsy alone is associated with significantly less morbidity compared with SLN biopsy plus CLND.W.W.R. and S.L.W. contributed equally to this work.     

Predictors of positive sentinel lymph node in thin melanoma

Background

The treatment of thin melanoma (Breslow thickness <1.0 mm) may include sentinel lymph node (SLN) biopsy (SLNB). The validity of SLNB for thin melanoma remains widely debated. The purpose of this study was to elucidate pathologic factors that are predictive of SLN positivity.

Methods

A retrospective analysis of a prospective database revealed 1,199 patients diagnosed with primary cutaneous melanoma. Multiple logistic regression was used to determine an association between pathologic factors and SLN positivity.

Results

Thin melanomas were identified in 469 patients (39%). Of these, 147 patients (31%) underwent SLNB. Positive SLNs were found in 16 patients (11%). Multiple logistic regression demonstrated that both ulceration (odds ratio, 5.27; P = .047) and thickness (odds ratio, 46.69; P = .022) were associated with SLN positivity.

Conclusions

Patients with thin melanomas >.75 mm and/or ulceration should be considered for SLNB.     

Criteria in Sentinel Lymph Nodes of Melanoma Patients that Predict Involvement of Nonsentinel Lymph Nodes

Background Previous studies described various criteria in sentinel lymph nodes (SLN) of melanoma patients that predict the involvement of further, nonsentinel lymph nodes (NSLN). Such criteria may facilitate the selection of patients who might benefit from a completion lymph node dissection (CLND). However, it is currently unclear which parameters are most important. Methods A total of 180 melanoma patients with positive SLNB and subsequent CLND were investigated. Histopathologic parameters in the SLN were systematically evaluated and compared with regard to NSLN positivity. Twenty-eight of these patients (16.0%) had positive NSLN. Results By univariate analysis several criteria with regard to tumor burden and location of melanoma cells in the SLN correlated with NSLN involvement, such as positivity by hematoxylin-eosin (H&E) staining (P < .001), largest diameter of clusters (P < .001), capsular involvement (P = .001), extranodal extension (P < .001), and tumor penetrative depth (P < .001). Multivariate analysis revealed three independent parameters: (1) positivity of the SLN by H&E staining (versus by immunohistochemistry alone), (2) relative tumor burden >10% of total lymph node tissue, and (3) perinodal intralymphatic tumor. In 23 of 28 patients with positive NSLN the SLN was positive by H&E staining, in 15 of 28 patients the relative tumor burden was >10%, and 13 of 28 showed perinodal intralymphatic tumor. In 5 of 28 patients with NSLN involvement, these three parameters were negative. Conclusions Histopathologic examination of the SLN can identify patients at risk for NSLN positivity.     

Demonstration of second-tier lymph nodes during preoperative lymphoscintigraphy for melanoma: Incidence varies with primary tumor site

Background: Preoperative cutaneous lymphoscintigraphy (LS) to identify sentinel (first-tier) lymph nodes was performed in 250 consecutive melanoma patients before wide local excision only or wide local excision with sentinel node biopsy. Methods: The location of the sentinel nodes was marked on the overlying skin in all patients. Whether or not tracer was present in second-tier lymph nodes on the delayed scans was recorded for each patient and related to the lesion site at which the tracer had initially been injected. For 100 consecutive patients the rate of tracer movement through the lymphatic channels was compared to the incidence of second-tier drainage. Results: Second-tier nodes were visualized in all patients with melanomas on the leg and thigh, and in almost all patients with melanomas on the forearm and hand, but were seen less often in patients with more centrally located melanomas. There was a significant correlation between the rate of lymph flow and the incidence of demonstrable second-tier drainage. Conclusion: The results suggest that the physiology of the lymphatic system varies depending on the origin of the lymphatic vessel. These findings have important implications for application of the sentinel node biopsy technique in individual patients.     

Melanoma in children and the use of sentinel lymph node biopsy

Background

The rarity of pediatric melanoma prompted our review of sentinel lymph node biopsy (SLNB) and associated prognosis.

Methods

A chart review from 1989 to 2004 revealed 12 cases of cutaneous melanoma. Variables analyzed included demographics, site, histology, tumor characteristics, nodal status, and distant metastasis (TMN status), SLNB and/or therapeutic lymph node dissection (TLND), adjuvant treatment, disease-free survival, and overall survival.

Results

Mean age at diagnosis was 8.5 years with 7 of 12 patients younger than 10 years (range, 0.3-17.9 years). Site distribution was the extremity (7), trunk (4), and head and neck (1). All patients had wide local excision and primary closure or skin graft. Breslow's thickness averaged 3.5 mm (range, 0.8-6 mm). Only patients diagnosed after 2000 with melanomas thicker than 1 mm were offered SLNB (extremity = 2, trunk = 1, head and neck = 1). Two patients had positive sentinel lymph node: one received TLND and interferon and one is followed closely (unclear pathology). Disease-free survival and overall survival by stage were stage I (n = 2, 3.9 years, 100%), stage II (n = 6, 7.7 years, 83%), stage III (n = 4, 2.6 years, 75%), and stage IV (n = 0). A stage II patient with negative SLNB, adjuvant chemotherapy, and interferon died 26 months after diagnosis, and a stage III patient with clinically and pathologically positive nodes after TLND died 15 months after diagnosis.

Conclusion

Although a negative SLNB does not guarantee a favorable prognosis, its increasing use will further define its role in pediatric melanoma.     

Sentinel node biopsy prior to neoadjuvant chemotherapy

BACKGROUND: Several studies have explored sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy, but false negative rates and the loss of pretreatment nodal staging are limitations. Sentinel lymph node biopsy prior to induction chemotherapy may address both. METHODS: Sentinel lymph node biopsy was performed in clinically node negative patients prior to initiating chemotherapy. Standard level I/II axillary lymph node dissection (ALND) was performed at the time of surgery in those patients who had metastases in the sentinel lymph node (SLN). RESULTS: Twenty-five patients had 26 SLNB prior to the initiation of chemotherapy. The SLN was identified in all cases (100%). Twelve patients (48%) were found to be node negative and did not require axillary node dissection after chemotherapy. Of the patients who were SLN positive and underwent completion ALND, residual nodal disease was identified in 60%. There were no surgical complications or delay of chemotherapy. CONCLUSIONS: Sentinel lymph node biopsy prior to neoadjuvant chemotherapy can avoid the morbidity of ALND without compromising the accuracy of axillary staging. It allows for identification of node positive patients subsequently rendered disease free in the regional nodes, which can assist in planning additional chemotherapy or radiation.