Gamma probe-directed lymphatic mapping and sentinel lymphadenectomy in primary melanoma: Reliability of the procedure and analysis of failures after long-term follow-up.

BACKGROUND AND OBJECTIVES: Some patients presenting with cutaneous malignant melanoma without palpable adenopathy have regional metastatic disease. The results of a prospective clinical study of gamma probe-directed sentinel lymph node (SLN) biopsy are presented. METHODS: Over a 3-year period, 103 patients with a diagnosis of invasive primary cutaneous malignant melanoma (Breslow > 0.12 mm or > Clark level II) underwent preoperative lymphoscintigraphy with technetium sulfur colloid followed by gamma-probe-guided sentinel lymphadenectomy. There were 46 women and 57 men with a mean age of 55.7 years (range, 19-91). RESULTS: Mean Breslow thickness was 2.3 mm (range, 0.12-10 mm). Primary locations were head and neck in 12, trunk 46, upper extremity 19, and lower extremity in 26. One hundred sixteen lymph node basins were mapped in 103 patients. Axillary, inguinal, and cervical nodal basins comprised 55, 34, and 11% of the total basins evaluated, respectively. Sixty-eight patients (66%) underwent lymphatic mapping of one regional nodal basin, 27 patients (26%) underwent synchronous lymphatic mapping of 2 regional nodal basins, 6 patients (6%) underwent synchronous lymphatic mapping of 3 regional nodal basins, and 2 patients (2%) underwent synchronous lymphatic mapping of 4 regional nodal basins. Seroma or infection did not occur in any patients. Micrometastatic disease was identified in 15 sentinel lymph node biopsy sites in 13 (10%) patients. Of 10 patients undergoing lymph node dissection, 9(90%) had no additional pathological lymph node involvement. We achieved 99% success rate, 1% rate of failed sentinel node procedure, and 8% false-negative rate after median follow-up for 2 years. CONCLUSIONS: We concluded that gamma probe-directed sentinel lymph node biopsy is a straightforward procedure which can be done in the outpatient setting and facilitates management of patients with cutaneous malignant melanoma. It allows the surgeon to identify all basins at risk for metastatic disease and the location of the sentinel node(s) in relation to the basin.     

Sentinel node identification by scintigraphic methods in cutaneous melanoma

In melanoma patients lymph node metastasis is an important prognostic factor that indicates the need for therapeutic lymph node dissection. Preoperative lymphoscintigraphy mapping associated with radioguided sentinel lymph node biopsy has become a well established procedure for cutaneous melanoma patients without clinically detectable lymph node metastases (stage I, II). This technique is a versatile way of characterizing the lymphatic basin at risk for metastases and identifying involved lymph nodes. The purpose of the present study was to examine the reproducibility of lymphoscintigraphy and sentinel lymph node biopsy in detecting micro metastases in cutaneous melanoma. The study was a single-institution prospective analysis of 74 melanoma patients, with primary tumors having Breslow thickness > 0.7 mm, who underwent lymphoscintigraphies between May 2002 and September 2003. Technetium-99m sulfur colloid was injected intradermally at the primary tumor site and dynamic images were obtained for 40 minutes. Two observers evaluated the images. One to two weeks after the first lymphoscintigraphy, radioguided lymph node biopsy was performed. For the biopsy, technetium-99m sulfer colloid was injected intradermally in the same manner as performed before. Lymph nodes were identified and removed with the aid of a gamma ray detecting probe (GDP), and were submitted to histopathological analysis. The histopathological analysis of the sentinel lymph nodes collected during surgery was performed in a sequential manner. First, frozen sections were analyzed during surgery. The lymph nodes considered negative by frozen section were analyzed by H&E staining. Subsequently, the slides considered negative with H&E were sent for immunohistochemical analysis. Lymphoscintigraphy identified at least one sentinel lymph node in all patients. Sentinel node biopsy detected metastases in 20 patients (27.2%). In all cases the lymph node basins identified during lymphoscintigraphy were found to have at least one sentinel lymph node during surgery. Frozen section analysis of the lymph node was only able to identify the disease in 35% of the patients eventually found to have micrometastases with H&E and immunohistochemistry. Two lymph nodes were negative with H&E and positive with immunohistochemical analysis. In conclusion, lymphoscintigraphy is a simple procedure that is well tolerated by patients. It is useful in locating sentinel lymph nodes in patients with melanoma and is an important tool in the clinical practice of oncology. We recommend performing H&E, and if necessary, immunohistochemical analysis of all sentinel lymph nodes because of the high rate of false negative results with frozen sections alone.     

Lymphoscintigraphic and intraoperative detection of the sentinel lymph node in breast cancer patients: the nuclear medicine perspective

The concept of sentinel lymph node biopsy in breast cancer surgery relates to the fact that the tumor drains in a logical way via the lymphatic system, from the first to upper levels. Therefore, (1) the first lymph node met (the sentinel node) will most likely be the first one affected by metastasis, and (2) a negative sentinel node makes it highly unlikely that other nodes are affected. Sentinel lymph node biopsy would represent a significant advantage as a mini-invasive procedure, considering that, after operation, about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidity. Although the pattern of lymphatic drainage from a breast cancer can be very variable, the mammary gland and the overlying skin can be considered as a biologic unit in which lymphatics tend to follow the vasculature. Considering that tumor lymphatics are disorganized and relatively ineffective, subdermal, and peritumoral injection of small aliquots of radiotracer is preferred to intratumoral administration. (99m)Tc-labeled colloids with most of the particles in the 100-200 nm size range would be ideal for radioguided sentinel node biopsy in breast cancer. Lymphoscintigraphy is an essential part of radioguided sentinel lymph node biopsy, as images are used to direct the surgeon to the site of the node. The sentinel lymph node should have a significantly higher count than background. After removal of the sentinel node, the axilla must be re-examined to ensure all radioactive sites are identified and removed for analysis. The success rate of radioguidance in localizing the sentinel lymph node in breast cancer surgery is about 94-97% in Institutions where a high number of procedures are performed, approaching 99% when combined with the vital blue dye technique. At present, there is no definite evidence that a negative sentinel lymph node biopsy is invariably correlated with a negative axillary status, except perhaps for T(1a-b) breast cancers, with size < or =1 cm. Randomized clinical trials should elucidate the impact of avoiding axillary node dissection in patients with a negative sentinel lymph node on the long-term clinical outcome of patients.     

Should all melanoma patients undergo sentinel lymph node biopsy?

PURPOSE OF REVIEW: It is now well established that sentinel lymph node biopsy is a powerful test to predict prognosis for melanoma patients. Controversy exists, however, regarding the appropriate selection of patients for sentinel lymph node biopsy, especially among patients with thin melanomas (< 1 mm Breslow thickness), thick melanomas (> 4 mm Breslow thickness), or locally recurrent melanoma. RECENT FINDINGS: The majority of the studies in the past 2 years regarding sentinel lymph node biopsy have been concerned with identifying factors that can better predict regional nodal metastasis and survival. Other studies have proposed a better risk stratification model, which includes these factors, to best select those patients at increased risk of nodal positivity. SUMMARY: Although much research has been done to select appropriate patients for sentinel lymph node biopsy based on multiple prognostic factors, further studies are necessary to completely define the indications for this procedure in patients with thin, thick and locally recurrent melanomas.     

Lymphatic mapping and sentinel lymph node biopsy in the management of primary cutaneous melanoma: report of a single-centre experience

AIMS AND BACKGROUND: Lymphatic mapping and sentinel lymph node biopsy provide important prognostic data in patients with early stage melanoma and are crucial in guiding the management of the tumor. We report our experience with lymphatic mapping and sentinel lymph node biopsy in a group of patients with primary cutaneous melanoma and discuss recent concepts and controversies on its use. PATIENTS AND METHODS: A total of 111 patients with stage I-II AJCC primary cutaneous melanoma underwent lymphatic mapping and sentinel lymph node biopsy from December 1999 through December 2004 using a standardized technique of preoperative lymphoscintigraphy and biopsy guided by blue dye injection in addition to a hand-held gamma probe. After removal, sentinel lymph nodes were submitted to serial sectioning and permanent preparations for histological and immunohistochemical examination. Complete lymph node dissection was performed only in patients with tumor-positive sentinel lymph nodes. RESULTS: Sentinel lymph nodes were identified and removed in all patients (detection rate of 100%), and metastases were found in 17 cases (15.3%).The incidence of metastasis in sentinel lymph nodes was 2.1%, 15.9%, 35.2%, and 41.6% for melanomas < or 1.0, 1.01-2.0, 2.01-4.0, and > 4.0 mm in thickness, respectively. Complete lymph node dissection was performed in 15 of 17 patients with positive sentinel lymph nodes, and metastases in non-sentinel lymph nodes were detected in only 2 cases (11.7%). Recurrences were more frequently observed in patients with a positive than in those with negative sentinel lymph node (41.1% vs. 5.3% at a median follow-up of 31.5 months, P < 0.001). The false-negative rate was 2.1%. CONCLUSIONS: Our study confirms that lymphatic mapping and sentinel lymph node biopsy allow accurate staging and yield relevant prognostic information in patients with early stage melanoma.     

Sentinel node-guided evaluation of drainage patterns for melanoma of the helix of the ear

The head and neck region, and especially the ear and its helix, is notorious for its ambiguous pattern of lymphatic drainage. Therefore, the primary nodal drainage basins in melanoma of the helix of the ear are often unpredictable. The aim of the study was to examine the value of sentinel lymph node biopsy in melanoma of the helix of the ear and to describe the natural history of the disease. Fifteen consecutive patients (14 men) with primary melanoma of the helix of the ear (median thickness, 1.2 mm; range, 0.7-10.0) underwent preoperative lymphoscintigraphy, followed by intraoperative lymphatic mapping, using blue dye in combination with a hand-held gamma probe and sentinel lymphadenectomy. The melanomas were characterized by low mitotic rate, low lymphocytic infiltrate, low spontaneous-regression rate, and mostly epitheloid cell type. In one patient, preoperative lymphoscintigraphy failed to demonstrate the draining nodes. The sentinel lymph nodes were identified and retrieved in all patients during surgery. In 13 patients (87%), they were found in the upper jugular lymphatic basin (level IIA); none were found in the retroauricular region. All sentinel lymph nodes were tumor-negative. At a median follow-up of 39 months (range, 12-73), all 15 patients were disease-free. In conclusion, sentinel lymph node biopsy for helix melanoma is an excellent alternative to elective lymph node neck dissection and superficial parotidectomy, with a high success rate and low morbidity. Melanoma of the helix of the ear has an indolent natural history.     

Sentinel node biopsy for thin melanomas: which patients should be considered?

BACKGROUND: As the incidence of melanoma increases, thin melanomas are being diagnosed at an increasingly frequent rate. Currently available prognostic factors are limited in their ability to reliably discriminate which patients will manifest regional nodal metastasis and would be identified early through sentinel node biopsy. METHODS: We summarized our experience with sentinel node biopsy for patients with cutaneous melanomas less than 1.00 mm in Breslow thickness, with evaluation of Clark level as a predictor of positive sentinel node metastasis. RESULTS: Among the 409 patients identified, micrometastases were found in the sentinel node in 20 patients, for an overall incidence of nodal progression of 4.9%. A total of 252 (62%) were Clark level II or III (11 of whom had a positive sentinel node) and 157 (38%) were Clark level IV (9 of whom had a positive sentinel node). We reviewed the literature to identify reliable indicators that might be helpful in determining which patients with "thin melanomas" would be likely to manifest regional progression to warrant routinely undergoing a preoperative lymphoscintigraphy followed by a sentinel node biopsy. CONCLUSIONS: Based on available data, patients with melanomas between 0.75 and 1.00 mm are appropriate candidates to be considered for sentinel node biopsy after discussing the likelihood of finding evidence of nodal progression, the risks of sentinel node biopsy (including the risk of a false-negative result), and the lack of proven survival benefit from any form of surgical nodal staging.     

Immunohistochemical detection of incipient melanoma micrometastases. Relationship with sentinel lymph node involvement

It is acknowledged that tumour thickness, ulceration and lymph node invasion are the most important prognostic factors for cutaneous melanomas. Other histopathological features may also be informative. The aim of this study was to ascertain whether immunohistochemical methods can improve the detection of satellite micrometastases in primary melanoma patients. In addition, the predictive value of cutaneous satellite micrometastases for sentinel lymph node involvement was evaluated. A total of 265 primary cutaneous melanomas and 68 of the respective sentinel nodes were studied using a panel of seven antibodies directed against melanocyte-related antigens. In 12.4% of the 265 cases, small satellite micrometastases were detected by immunohistochemistry. Sentinel lymph node metastases were found in 14% of the 68 cases. Invasion of the sentinel lymph node correlated with the presence of cutaneous satellite micrometastases. It is concluded that the presence of cutaneous satellite micrometastases may be an indication for the performance of sentinel lymph node biopsy, and this finding calls for a closer follow-up of these patients.     

Are there factors that predict the result of selective sentinel lymph-node biopsy in melanoma?

Background

Sentinel lymph node biopsy is an appropriate method to assess lymphatic involvement in cutaneous melanoma. We collated clinical and histo-pathological parameters of primary tumours to assess their predictive value of sentinel lymph node involvement.

Patients and methods

Factors such as age, gender, histology subtype, site, Breslow index, lesion size, and the presence of ulceration, signs of regression, lympho-vascular invasion and/or inflammatory infiltration of the primary lesion were collated from 142 patients diagnosed with cutaneous melanoma. During the scheduled surgery, a selective sentinel lymph node biopsy was taken. The procedure was successful in terms of localisation with scintigraphy, detection and surgical removal. Univariate and multivariate statistical analyses were applied to the variables in relation to the sentinel lymph node biopsy results.

Results

There were significant differences with respect to size (p=0.046), the presence of ulceration in the primary lesion (p=0.0146), the Breslow index (p=0.0001) and lympho-vascular invasion in the primary lesion (p=0.00005). Logistic regression showed an independent predictive value for sentinel lymph node involvement.

Conclusions

The data indicate that, apart from Breslow index, the presence of lymphatic invasion in the primary tumour, the size of the melanoma, and the presence of ulceration are independent factors predictive of a positive result of selective sentinel lymph node biopsy in cutaneous melanoma. Although prospective studies are still awaited, these variables need to be taken into account when such biopsies are proposed, even with less thick tumours.     

Update on the use of sentinel node biopsy in patients with melanoma: who and how

This review highlights the utility of sentinel lymph node biopsy for melanoma. The histopathologic status of the sentinel lymph node is acknowledged as the most powerful indicator of prognosis. Changes by the American Joint Committee for Cancer have not only incorporated the importance of ulceration in cutaneous melanoma, but have focused on the number of metastatic lymph nodes as well as whether the disease is macro- or micrometastatic. Specific technical aspects of the sentinel lymph node procedure are discussed, with emphasis on practical guidelines to minimize incorrect nodal staging.     

Sentinel lymph node biopsy: A new perspective in head and neck mucosal melanoma?

Sentinel lymph node biopsy in patients with head and neck mucosal melanomas has not been performed so far. Therefore, this method as a staging tool was tested in a pilot study. In two consecutive patients, a lymphoscintigraphy, elective neck dissection with radio-guided sentinel lymph node identification, and resection of the primary were performed. The histopathological status of the sentinel lymph node was compared with the lymphadenectomy specimen and with the clinical course. Patient no. 1, in whom both the sentinel lymph node and the lymphadenectomy specimen were found to be free of tumour, is well and with no evidence of disease, the follow-up interval being 19 months. Patient no. 2, with the sentinel lymph node and remaining lymphatic basin being positive and negative, respectively, developed hematogenous dissemination 3 months after the primary treatment, and he was started on palliative chemotherapy. In mucosal melanoma, the prognostic significance of clinical nodal status is controversial, resulting in the lack of an official, applicable TNM classification and also of therapeutic guidelines. The presence of microscopic metastatic focus in the sentinel lymph node was associated with an early hematogenous dissemination. Therefore, sentinel lymph node biopsy, which represents a potentially efficient staging tool, warrants further investigation.     

The place of lymphatic mapping and sentinel node biopsy in oncology

The techniques of sentinel lymphatic mapping (LM) and sentinel lymph node biopsy (SLNB) have become almost routine for the staging of clinically node-negative patients with high-risk cutaneous melanoma. The techniques are also widely applied to staging of the axilla in breast cancer. Investigations of the use of LM and SLNB for other solid malignancies have also shown promise. LM/SLNB requires a multidisciplinary effort involving experienced surgeons, nuclear medicine physicians, and surgical pathologists. The techniques require a learning curve for all involved personnel, requiring experience with at least 30 cases followed by complete nodal dissection after SLNB to achieve full competency. Surgical pathologists play a pivotal role in determining optimum sentinel node analysis. The techniques have lower morbidity and greater accuracy than traditional complete regional node dissection. Pathologists are receiving increasing numbers of SLN specimens and are expected to evaluate the results of the application of the LM/SLNB techniques to a range of solid tumors. We have reviewed LM/SLNB in regard to melanoma and breast cancer and other types of malignancies. The techniques have much to offer, but despite their seeming simplicity, need considerable technical skill and clinical judgment if they are to be effectively applied. They also provide unique opportunities for basic and translational research.     

Ultrasound assessment of lymph nodes in the management of early-stage melanoma

It has been suggested that ultrasound examination of regional lymph nodes provides staging and prognostic information that is as accurate as sentinel node biopsy in patients who present with cutaneous melanoma. However, in most studies the sensitivity of ultrasound in detecting nodal metastasis has been low (23% in a recent large series). For the present, sentinel node biopsy remains the most accurate method of regional node staging in patients with newly diagnosed melanoma.     

Contrast-enhanced ultrasound: a filter role in AJCC stage I/II melanoma patients

One of the most significant advances in melanoma staging is sentinel lymph node biopsy (SLNB). It is a surgical technique to detect occult nonpalpable micrometastases in regional lymph nodes. Recently, contrast-enhanced ultrasound (CEUS) was introduced as a noninvasive procedure, in spite of SLNB, for the detection of SLNs in patients with cutaneous melanoma. The main purpose of this study was to evaluate the diagnostic accuracy of CEUS in the diagnostic workup of patients with melanoma in comparison with the final histology of SLNs detected through preoperative lymphoscintigraphy. Fifteen patients with cutaneous melanoma underwent prompt excisional biopsy with narrow margins in order to avoid impairment of the melanoma lymphatic basin and were referred for SLNB according to routine indications between January and February 2009. In our study CEUS showed, albeit based on a small patient sample, a negative predictive value of 100%, that means that all negative results were confirmed by negative SLN histopathological examination; all ultrasonographically negative lymph nodes corresponded to nonmetastatic sentinel nodes.     

Lymphatic mapping for staging of head and neck cancer

Lymphatic mapping with sentinel lymph node (SLN) biopsy can accurately stage the nodal basins in patients with melanoma of the trunk and extremities and has become a routine, well-accepted diagnostic method for melanoma at these anatomic locations. Melanoma of the head and neck (16% of all cases of melanoma) is complex and difficult to manage because of the rich abundant interlacing lymphatic drainage patterns, as well as watershed areas, which can lead to unusual and unexpected drainage patterns. Radioguided surgery in combination with blue dye facilitates localization of the SLN in the head and neck; however, this type of radioguided surgery is an evolving technique of some difficulty and thus requires careful coordination among the surgeon, nuclear medicine physician, and pathologist. Applications of this technique to other sites in the head and neck are currently being investigated for conditions including squamous cell carcinoma (SCC) of the oral cavity, thyroid cancer, and Merkel cell cancer. More studies of patients with head and neck cancer are needed--and technical issues must be resolved--before radioguided surgery can be recommended as the standard of care for these patients.     

The new staging system for cutaneous melanoma in the era of lymphatic mapping

In 2002, the American Joint Committee on Cancer (AJCC) revised the staging system for cutaneous melanoma on the basis of a survival analysis of important melanoma prognostic factors. Features of the revised system include new strata for primary tumor thickness, incorporation of primary tumor ulceration as an important staging criterion in both the tumor (T) and node (N) classifications, revision of the N classification to reflect the prognostic significance of regional nodal tumor burden, and new categories for distant metastatic disease. These changes reflect evolving insight into melanoma arising from the results of numerous clinical investigations and database analyses. One of the most important recent changes in melanoma care is the establishment of lymphatic mapping and sentinel lymph node (SLN) biopsy as a highly accurate and minimally morbid technique for pathologic regional nodal staging. In this article, the salient features of the revised melanoma staging system are examined, with specific attention paid to its use in this era of lymphatic mapping and SLN biopsy.     

Controversies in the management of regional nodes in melanoma

The surgical management of the regional lymph node basin of melanoma has undergone significant changes in the past 2 decades, most of which have been guided by prospective randomized trials. Historically, routine elective lymph node dissection was recommended for the management of melanoma regardless of clinical nodal involvement. Subsequent randomized trials failed to show a clear benefit for all patients, and sentinel lymph node (SLN) biopsy emerged as an alternative. Although the prognostic value of SLN biopsy in intermediate-thickness melanoma is well accepted, its value for patients with thin and thick lesions is debated. The therapeutic advantage of removing an involved SLN, and the need for a completion lymph node dissection after the identification of a positive SLN, are areas of continued controversy. This article discusses these issues in the management of the regional lymph node basin in patients with melanoma.     

Clinical utilities and biological characteristics of melanoma sentinel lymph nodes

An estimated 73870 people will be diagnosed with melanoma in the United States in 2015, resulting in 9940 deaths. The majority of patients with cutaneous melanomas are cured with wide local excision. However, current evidence supports the use of sentinel lymph node biopsy (SLNB) given the 15%-20% of patients who harbor regional node metastasis. More importantly, the presence or absence of nodal micrometastases has been found to be the most important prognostic factor in early-stage melanoma, particularly in intermediate thickness melanoma. This review examines the development of SLNB for melanoma as a means to determine a patient’s nodal status, the efficacy of SLNB in patients with melanoma, and the biology of melanoma metastatic to sentinel lymph nodes. Prospective randomized trials have guided the development of practice guidelines for use of SLNB for melanoma and have shown the prognostic value of SLNB. Given the rapidly advancing molecular and surgical technologies, the technical aspects of diagnosis, identification, and management of regional lymph nodes in melanoma continues to evolve and to improve. Additionally, there is ongoing research examining both the role of SLNB for specific clinical scenarios and the ways to identify patients who may benefit from completion lymphadenectomy for a positive SLN. Until further data provides sufficient evidence to alter national consensus-based guidelines, SLNB with completion lymphadenectomy remains the standard of care for clinically node-negative patients found to have a positive SLN.     

前哨淋巴结活检在皮肤恶性黑色素瘤中的应用现状及进展

前哨淋巴结活检（sentinel lymph node biopsy,SLNB）是皮肤恶性黑色素瘤诊治过程中不可或缺的手段,在进行准确分期、预后判断以及治疗指导等方面都发挥着重要的作用。SLNB的操作方法已基本成熟,但在适应症的选择方面还存在一定的争议,仍无足够的证据表明前哨淋巴结活检联合区域淋巴结清扫（complete lymph node biopsy,CLND）能够延长转移患者的生存。此外,由于国内恶性黑色素瘤的发病率较低,SLNB尚未得到广泛开展,相关的操作方法也较为落后。近年来,随着恶性黑色素瘤发病率增高,其外科治疗也受到越来越多的关注。本文通过总结分析近年来的相关文献,对SLNB在皮肤恶性黑色素瘤中的应用现状和进展进行综述。      

The evolution of the management of regional lymph nodes in melanoma

The last two decades have seen sweeping changes in the surgical approach to melanoma. Traditionally, patients without evidence of nodal metastases were considered for elective lymph node dissection. This approach placed many patients at risk of morbidity while many derived no benefit. As investigators gained a deeper understanding of melanoma and lymphatic biology, newer methods of managing regional lymph nodes were sought. The advent of sentinel node biopsy has radically changed the approach to melanoma.