Lymphatic drainage from the skin of the back to retroperitoneal and paravertebral lymph nodes in melanoma patients

Background: Preoperative lymphoscintigraphy (LS) with^99mTc antimony sulphide colloid is now part of the routine management of patients with intermediate thickness melanoma at the Sydney Melanoma Unit. Over a 13-year period, 1375 patients have been examined using LS, and we have observed many unusual lymphatic drainage pathways, including direct drainage through the body wall to retroperitoneal and paravertebral lymph nodes from the skin of the back. The aim of this study was to determine the incidence of such drainage in the 542 patients who had primary melanoma sites on the posterior trunk. Methods: The lymphoscintigrams performed on these patients were examined for the presence of direct lymphatic drainage through the posterior body wall to sentinel nodes in the retroperitoneal and paravertebral regions. Results: Lymphatic drainage directly through the body wall to such lymph nodes occurred in 14 of these 542 patients. Conclusions: Preoperative knowledge of the presence of this lymph drainage pattern may influence surgical management, and follow-up investigations in these patients can be tailored to ensure that the relevant areas are examined with anatomic imaging or F18-FDG PET scans.     

Correlation of lymphoscintigraphy with the number of sentinel lymph nodes identified intraoperatively in patients with breast cancer

BACKGROUND: Numerous studies have evaluated the benefit of performing lymphoscintigraphy for the sentinel lymph node procedure in breast cancer patients. The purpose of this study is to determine if lymphoscintigraphy accurately predicts the number of radioactive sentinel lymph nodes (SLNs) identified during surgery for breast cancer patients. METHODS: From October 2001 to June 2004, SLN biopsy was attempted in 112 patients with breast cancer using a combination of blue dye and radioisotope. Lymphoscintigraphy was performed in 98 of the patients. A lymph node was considered an SLN when it was stained with blue dye, had a blue lymphatic afferent, had increased radioactivity, or was abnormal by palpation. RESULTS: Lymphoscintigraphy accurately predicted the number of radioactive SLN identified intraoperatively in 47 patients. In 44 of the patients who did not have concordance, there were more SLN identified intraoperatively than were seen on lymphoscintigraphy. In the other 8 patients, there were fewer SLN identified intraoperatively than seen on lymphoscintigraphy. CONCLUSIONS: Lymphoscintigraphy accurately predicted the number of SLN identified intraoperatively in only 47% of the patients in this study. In a majority of the patients in whom the lymphoscintigraphy was not concordant, the number of SLN identified intraoperatively was underestimated. Thus, although lymphoscintigraphy is beneficial in showing that at least 1 radioactive SLN will be identified intraoperatively, it does not accurately predict the number.     

Epitrochlear lymph nodes as a site of melanoma metastasis

Background: The incidence of epitrochlear lymph node metastasis for patients with melanomas on the hand or forearm is disputed, and management guidelines for these nodes are unclear. Methods: The records of 13,139 consecutive melanoma patients were reviewed to document the incidence of metastatic disease in epitrochlear nodes. The frequency of direct lymphatic drainage to epitrochlear nodes was determined for 109 patients with melanomas of the distal upper limb who had undergone preoperative lymphoscintigraphy. Results: Nine of 801 patients (1.1%) with upper limb primary melanomas developed metastatic disease in an epitrochlear node, and one other patient with an occult primary tumor did so. Six of these ten patients underwent elective axillary node dissection at the time of surgery for epitrochlear node disease, and three were found to have metastatic disease in an axillary node. Epitrochlear node metastasis occurred in only two of 83 (2.4%) patients with upper extremity melanoma who underwent therapeutic axillary dissection. Of the 109 patients who underwent lymphoscintigraphy, four (3.7%) demonstrated lymphatic drainage to an epitrochlear node. Conclusions: Epitrochlear nodal involvement from melanoma of the distal upper extremity is rare, and routine epitrochlear node clearance at the time of either elective or therapeutic axillary dissection for upper extremity melanoma is not indicated. However, it is desirable to perform an axillary dissection whenever surgery for metastatic disease in an epitrochlear node is performed.     

Reliability of Lymphatic Mapping After Wide Local Excision of Cutaneous Melanoma

Background Since the advent of sentinel lymph node (SLN) biopsy, patients with cutaneous melanoma have been referred to surgeons for consideration for SLN biopsy, sometimes even after the wide local excision (WLE) of the primary melanoma has been performed. This has raised the question of the reliability and validity of a lymphoscintigram performed for lymphatic mapping of the SLN after there has been anatomic rearrangement of the skin following the WLE of this primary melanoma. Methods We conducted a prospective study of 20 consecutive patients with cutaneous melanomas with thickness less than 1.00 mm, who volunteered to undergo preoperative and postoperative lymphatic mapping to determine if there were any changes in the lymph nodes that were identified following the WLE of the primary melanoma. Each of the patients had a resection with a minimum of 1.0 cm margin, and closure of their wounds with either transposition flap or double advancement flaps. Results Lymphatic mapping was clearly identified in all 20 patients. One patient declined to undergo postoperative lymphatic mapping. Postoperative lymphatic mapping performed in the remaining 19 patients 2–4 weeks following WLE was identical to the preoperative mapping in 13 patients (68%), showed additional lymph nodes in 4–5 patients (21–26%), and showed fewer lymph nodes in 1–2 patients (5–10%). Conclusions Lymphatic mapping performed after a WLE of a primary cutaneous melanoma should be as reliable in identifying the SLN as a preoperative lymphatic mapping in 90% of the patients. This investigation was supported by NIH Research Grant CA-16359 from the National Cancer Institute.     

OX40 (CD134) expression in sentinel lymph nodes correlates with prognostic features of primary melanomas

BACKGROUND: The expression of OX40 (CD134) on activated CD4+ T cells has been associated with favorable cancer patient outcomes. Because of recent reports that sentinel lymph nodes (SLNs) may represent an immunosuppressive environment, we investigated the expression of OX40 in SLNs from patients with primary cutaneous melanoma. METHODS: Samples of peripheral blood lymphocytes and a section of 71 SLNs from 53 patients with clinically node negative melanoma were purified for CD4+ T cells, stained for OX40, and analyzed by flow cytometry. RESULTS: The mean percentage of OX40 on CD4 T cells in the SLNs versus peripheral blood lymphocytes was related indirectly to the T stage of the primary tumor and was decreased in ulcerated primary tumors and positive sentinel nodes. CONCLUSIONS: The expression of OX40 on CD4+ T cells in SLNs draining primary melanomas decreased with more advanced tumor features (higher T stage, ulceration) and nodal involvement, suggesting that such tumors may have an immunosuppressive effect on the SLN microenvironment.     

Failure to harvest sentinel lymph nodes identified by preoperative lymphoscintigraphy in breast cancer patients

Abstract: Selective sentinel lymphadenectomy dissection has been demonstrated to have high predictive value for axillary staging in breast cancer patients. Preoperative lymphoscintigraphy can localize and facilitate the harvesting of sentinel lymph nodes (SNLs) with a high success rate. The failure rate of selective sentinel lymphodenectomy ranges between 2% and 8%. Details of the failures were seldom addressed. This study analyzes the causes of failure to harvest SLNs in spite of positive preoperative lymphoscintigraphy. From November 1997 through November 2000, 201 female patients with histologically confirmed and operable breast carcinoma underwent selective sentinel lymphadenectomy at the University of California, San Francisco (UCSF) Carol Franc Buck Breast Care Center. Among these patients, 183 (91%) received preoperative lymphoscintigraphy to identify axillary lymph nodes. The causes of failure to harvest the SLNs in this group of patients despite successful preoperative lymphoscintigraphy were analyzed. In our series, the failure rate of SLN identification was 7.0% (14/201). The failure rate for our first year was 11.1% (6/54), second year 9.1% (7/77), and third year 1.4% (1/70). The incidence of failure in spite of positive preoperative lymphoscintigraphy was 3.5% (6/170). The shine-through effect of the primary injection site and failure to visualize a blue lymph node were the main reasons for technical failure. Most of these cases occurred during our learning curve of the procedure. The possibility of failure to get the SLN should be explained to patients before surgery. Axillary lymph node dissection (ALND) should be done if selective SLN dissection is not successful.      

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.     

Determinants of outcome in elderly patients with positive sentinel lymph nodes

Background

Older women are less likely to receive standard of care treatment for breast cancer.

Methods

We examined variables that affected the outcome of elderly patients ≥70 years old among 1,470 patients with invasive cancer with positive sentinel lymph nodes (SLNs).

Results

Elderly patients were less likely to undergo mastectomy, completion axillary node dissection (ALND), adjuvant chemotherapy, and radiotherapy (RT) following breast-conserving therapy (BCT) compared with patients <70 years old. The 5-year risk of disease progression and cumulative incidence of breast cancer–specific deaths were not significantly different for both groups. On multivariate analysis, hormone receptor–negative status, number of metastatic lymph nodes, high nuclear grade, and tumor size were the factors independently associated with increased risk of disease progression.

Conclusions

Tumor factors were the primary determinants of breast cancer outcomes in our cohort. Elderly patients are less likely to receive aggressive surgical interventions and adjuvant therapy because of perceived life expectancy.     

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.     

Improved sentinel node localisation by pre-operative node depth measurement using lymphoscintigraphy and ultrasound in patients with primary melanoma

Sentinel node biopsy has become an integral part of staging metastatic spread from neoplasia such as malignant melanoma and breast cancer. This study aims to optimize localization of sentinel node(s) in patients with primary melanoma by improved pre-operative measurement of their position. Forty-three patients with primary melanoma underwent sentinel node biopsy. Pre-operatively, patients underwent assessment of their sentinel nodes including depth measurements using lymphoscintigraphy and ultrasound. At the time of operation, the sentinel node was identified using blue dye injected into the site of the primary melanoma as well as by application of the gamma probe. The blinded observer noted the depth of the node. Pre-operative and operative sentinel node depth measurements were compared to assess the accuracy of the predicted depth. The results showed a good correlation between the predicted and actual depth measurements. Pre-operative assessment of depth is therefore a reliable means of predicting sentinel node depth. This provides useful information for the surgeon in identifying nodes, especially where there are multiple sentinel nodes or when nodes appear in unexpected sites.     

Predicting residual lymph node basin disease in melanoma patients with sentinel lymph node metastases

BACKGROUND: The incidence of residual occult disease in nonsentinel lymph nodes (NSLN) after a positive sentinel lymph node (SLN) biopsy in patients with melanoma is relatively low. The purpose of this study is to identify factors that may be predictive of occult NSLN metastases after positive SLN biopsy. METHODS: Fifty-six consecutive melanoma patients with positive sentinel nodes who subsequently underwent complete lymph node dissection (CLND) were evaluated. RESULTS: Only the number of positive SLN predicted the status on NSLN by univariate (P = 0.008) and multivariate (P = 0.028) analyses. None of the other variables (characteristics of SLN metastases, number of draining nodal basins, age, sex, thickness, Clark level, ulceration, number of mitoses/mm(2), histological subtype, and location of the primary) significantly predicted CLND results. CONCLUSIONS: Identifying patients with residual lymph node basin disease remains difficult. Thus, lymph node dissection should be performed in all patients after positive sentinel node biopsy.     

Sentinel node biopsy in vulvar and vaginal melanoma: presentation of six cases and a literature review

Background Urogenital melanoma is a rare neoplasm with poor prognosis. Its management in the past involved radical vulvectomy and complete bilateral inguinofemoral lymphadenectomy. Sentinel lymph node biopsy is an accurate low-morbidity procedure when used in the context of cutaneous melanoma. However, prophylactic lymphadenectomy has not been shown to improve survival of melanoma patients. We wanted to determine the feasibility of sentinel lymph node biopsy in patients with female urogenital melanoma as a staging procedure. Methods Six patients with vulvar or vaginal melanomas underwent preoperative lymphatic mapping with^99mTc-labeled sulfur colloid followed by sentinel lymphadenectomy. In addition, we reviewed the literature on the application of sentinel lymph node biopsy in urogenital tract melanomas. Results One or more sentinel nodes were identified in all six patients by lymphoscintigraphy. All patients underwent sentinel lymphadenectomy, except for one patient with a deep vaginal melanoma that drained to pelvic nodes. The five successful cases had unilateral drainage patterns. None of the sentinel lymph nodes excised had tumor invasion. Combined with five other patients from the published literature, the success rate of localizing sentinel lymph nodes in the patients with urogenital melanoma approaches 100%. Conclusions This experience, plus reports of a small number of patients from three similar studies, supports the impression that sentinel lymph node biopsy is feasible for vulvar and vaginal melanoma.     

Reliability of lymphoscintigraphy in indicating the number of sentinel nodes in melanoma patients

Background: This study was undertaken to establish the reliability of lymphoscintigraphy in indicating the number of sentinel nodes in patients with melanoma. Methods: Lymphoscintigraphy was performed with dynamic imaging after injection of 60 MBq^99mTc-nanocolloid (1.6 mCi) and static imaging after 2 hours in 200 patients with clinically localized primary melanoma of the skin. The following day, sentinel nodes were retrieved with the blue dye technique and a gamma detection probe (Neoprobe 1000/1500). The discrepancies between the number of sentinel nodes indicated by lymphoscintigraphy and the actual number of sentinel nodes as established by the surgeon were evaluated. Results: Lymphoscintigraphy showed drainage to 393 sentinel nodes in 255 lymphatic fields in 199 patients. In 48 lymphatic fields (19%) in 46 patients (23%), the number of sentinel nodes was different from the number that was visualized with scintigraphy. Additional sentinel nodes were found by the surgeon because a lymphatic vessel was not seen on the lymphoscintigraphy (43%), because a sentinel node was not visualized separately from other hot nodes or vessels or the injection site (36%), or because a sentinel node was blue and not hot (4%). Fewer sentinel nodes were found than suggested by scintigraphy because a lymphangioma was mistaken for a sentinel node (4%) or because a single elongated node was depicted as two hot spots (6%). Conclusions: Although lymphoscintigraphy is indispensable for lymphatic mapping, the predicted number of sentinel nodes is accurate in only 81% of lymph node fields. The limited discriminating power of the gamma camera is an important cause of discrepancies. Presented at the 4th World Conference on Melanoma, Sydney, Australia, June 10–14, 1997, and the First World Congress of Surgical Oncology, WFSOS/SSO meeting, San Diego, California, March 26–29, 1998.     

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.     

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.     

结直肠癌前哨淋巴结转移相关蛋白的蛋白组学研究

目的 筛选前哨淋巴结(SLN)中与结直肠癌早期转移相关的蛋白质.方法 术中取43名结直肠癌早期患者的SLN及对应的正常淋巴结(NLN).提取SLN和NLN两组总蛋白后行双向凝胶电泳和质谱法对差异蛋白进行筛选和鉴定.用蛋白质印迹法和免疫组织化学法对其中的转移相关蛋白行进一步研究.结果 两组间检测出40种差异表达的蛋白质,SLN中表达升高且与转移相关的蛋白分别为核不均一核糖核蛋白A1( hnRNP A1)、埃兹蛋白(Fzrin)、微管蛋白β-2C (tubulin β-2C)和膜联蛋白A1(Annexin A1).蛋白定量结果显示两组间4种蛋白表达差异有统计学意义(P＜0.05).结论 结直肠癌SLN与NLN蛋白表达存在差异.筛选出的4种转移相关蛋白可能成为结直肠癌早期淋巴转移的标志物.     

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.     

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.