Lymphatic mapping and sentinel node analysis: current concepts and applications

Since the introduction of sentinel node biopsy in 1990 as a minimally invasive surgical technique for the diagnosis of melanoma lymphatic metastases, the number of applications has expanded. We review applications and the current status of sentinel node biopsy in melanoma, breast, colon, gastric, esophageal, head and neck, thyroid, and lung cancer. Variations on techniques specific to each organ are explained, and the current role of sentinel node biopsy in diagnosis and treatment is discussed.     

Population-based assessment of surgical treatment trends for patients with melanoma in the era of sentinel lymph node biopsy.

PURPOSE: The surgical staging of melanoma dramatically changed with the introduction of sentinel lymph node (SLN) biopsy. In this study, Surveillance, Epidemiology, and End Results (SEER) data were examined to determine how surgical treatment is being carried out and whether SLN biopsy is being performed in melanoma patients in conformance with National Comprehensive Cancer Network (NCCN) guidelines. PATIENTS AND METHODS: The SEER database (1998 to 2001) was searched for all patients with invasive melanoma. NCCN guidelines were used to define optimal stage-specific surgical treatment. Treatment trends in patients with stages I to III disease were summarized, and multivariate analyses were performed to identify factors associated with nonadherence with treatment guidelines. RESULTS: A total of 21,867 melanoma patients were identified; 18,499 of these patients met the inclusion criteria. The number of patients diagnosed with stage III melanoma increased by 55.7% over the study period, and this corresponded to a 53% increase in the number of SLN biopsies performed annually. The odds ratios for nonadherence were 2.32, 2.27, and 1.54 for stages IB, II, and III disease, respectively, compared with stage IA melanoma. Multivariate analyses revealed that age more than 65 years, marital status, minority populations, and primary tumor location were associated with nonadherence with guidelines. Treatment patterns among tumor registries also varied significantly. CONCLUSION: Stage migration is evident in the SEER registries in consort with increasing use of SLN biopsy. Although treatment trends are improving, SLN biopsy continues to be underused, particularly in the elderly and minority populations, in patients with truncal and head/neck melanomas, and also in some geographic regions of the United States.     

The effect of delay time between primary melanoma biopsy and sentinel lymph node dissection on sentinel node status, recurrence, and survival

For primary melanoma, there is a delay between the initial skin biopsy and sentinel lymph node dissection, which may cause anxiety for the patient. The consequences of this delay on disease progression are unknown. The goal of this study was to determine whether delay time for sentinel node dissection from the initial cutaneous melanoma biopsy affects patient outcomes. A retrospective analysis of 492 patients with melanoma who underwent a sentinel node dissection between 1993 and 1999 was carried out. The endpoints assessed were sentinel node tumor status, recurrence, and mortality. Time to sentinel node dissection was compared between patients with positive and negative sentinel nodes. Long-term survival and recurrence were evaluated in relation to the time between the cutaneous biopsy and the sentinel node dissection (delay time), comparing less than 40 days with at least 40 days. In total, 15.9% of patients had positive sentinel nodes. The median follow-up was 11.7 years. Positive sentinel node patients had a median delay of 35 days between the primary melanoma biopsy and the sentinel node dissection compared with 41 days for negative sentinel node patients (P=0.5). Kaplan-Meier survival curves showed that a delay time of less than 40 days versus at least 40 days was not related to recurrence of melanoma (log-rank P=0.13) or overall survival (log-rank P=0.14). On multivariate analysis of age, thickness, ulceration, and sentinel node status, there was no difference in disease-free survival (P=0.58) or overall survival (P=0.53) between the less than 40 days and the at least 40 days groups. A modest delay in sentinel node dissection from the initial melanoma biopsy does not adversely affect sentinel node status, recurrence, nor survival.     

Head and neck melanoma.

BACKGROUND: Melanoma of the head and neck and its treatment are complex issues. The behavior of head and neck melanoma is aggressive, and it has an overall poorer prognosis than that of other skin sites. METHODS: The authors review current data on the treatment of head and neck melanoma, including both cutaneous and mucosal melanoma. RESULTS: Current understanding of the behavior of head and neck melanoma is reviewed and treatment stratagems are presented. Controversies in treatment include lymphoscintigraphy with sentinel node biopsy, nodal dissection, margin size, role of radiation therapy, and reconstruction. The management goal is to treat melanoma aggressively while minimizing the effects of treatment on patient quality of life. CONCLUSIONS: Due to its aggressiveness, head and neck melanoma should be treated aggressively when morbidity is not significantly increased. Patient specific treatment is imperative.     

Intraoperative evaluation of sentinel lymph nodes for metastatic melanoma by imprint cytology

BACKGROUND: Sentinel lymph node (SLN) biopsy has revolutionized lymph node staging in patients with malignant melanoma. Intraoperative evaluation is a new addition to the SLN procedure that allows for a one-step regional lymph node dissection to be performed when the SLN biopsy findings are positive. To date, several studies have evaluated the use of intraoperative frozen sectioning to evaluate the SLN in patients with melanoma. The literature pertaining to the use of intraoperative imprint cytology (IIC) to evaluate the SLN in melanoma patients is scant and to the authors' knowledge studies published to date are relatively small. The purpose of the current study was to evaluate the utility of IIC in patients undergoing SLN for melanoma. METHODS: A total of 235 SLN biopsies from 93 patients with malignant melanoma and 3 patients with atypical Spitz nevi were examined by IIC after SLN biopsy using a double indicator technique. The SLNs were bisected and a pair of imprints were made from each half. One imprint from each half was stained with hematoxylin and eosin (H & E) whereas its counterpart was stained with Diff-Quik. Paraffin-embedded permanent sections were examined using multiple H & E stained sections from the SLNs in conjunction with immunohistochemical staining for S-100 and HMB-45 proteins. RESULTS: A total of 235 SLNs were excised from 93 patients (2.5 SLNs per patient). On a per patient basis, metastases were identified in 21 patients (23%) on permanent section evaluation. Of these 21 patients, 8 were detected by IIC (sensitivity of 38%). The negative predictive value was 85%. No false-positive results were identified (specificity of 100%). The positive predictive value was 100%. The overall accuracy of the intraoperative evaluation was 86%. Patients found to have positive SLNs by IIC went on to undergo lymphadenectomy under the same anesthetic. CONCLUSIONS: The sensitivity and specificity of IIC are similar to those of intraoperative frozen-section evaluation. Therefore, IIC appears to be a viable alternative to frozen sectioning when intraoperative evaluation is required. IIC evaluation of SLN makes a single surgical procedure possible for patients with malignant melanoma who are undergoing SLN.     

Sentinel lymph node biopsy for melanoma: controversy despite widespread agreement.

Although sentinel lymph node (SLN) biopsy for melanoma has been adopted throughout the United States and abroad as a standard method of determining the pathologic status of the regional lymph nodes, some controversy still exists regarding the validity and utility of this procedure. SLN biopsy is a minimally invasive procedure, performed on an outpatient basis at the time of wide local excision of the melanoma, with little morbidity. Numerous studies have documented the accuracy of this procedure for identifying nodal metastases. There are four major reasons to perform SLN biopsy. First, SLN biopsy improves the accuracy of staging and provides valuable prognostic information for patients and physicians to guide subsequent treatment decisions. Second, SLN biopsy facilitates early therapeutic lymph node dissection for those patients with nodal metastases. Third, SLN biopsy identifies patients who are candidates for adjuvant therapy with interferon alfa-2b. Fourth, SLN biopsy identifies homogeneous patient populations for entry onto clinical trials of novel adjuvant therapy agents. Overall, the benefit of accurate nodal staging obtained by SLN biopsy far outweighs the risks and has important implications for patient management.     

Primary malignant melanoma of the penis: a case report

We present the case of a patient with malignant melanoma of the glans penis and urethral meatus, which was found in a 60-year-old man with non-healing ulcerative penile lesion and bilateral clinically palpable inguinal lymphadenopathies at diagnosis. A diagnostic biopsy showed the characteristics of a malignant melanoma. Incisional biopsies from the cutaneous lesions on his glans penis and urethra were performed. Histopathological examination of both specimens showed generally ulceronecrotic surface and numerous atypical melanocytic cells. The diagnosis of giant cell melanoma was made. Two months later, bilateral inguinal lymph nodes dissection was performed. Histopathological examination of both specimens demonstrated malignant melanoma metastasis. Three months after the diagnosis, the patient underwent partial penectomy. High-dose interferon-alpha-2b treatment was started. Early diagnosis is of paramount importance, as the prognosis becomes very poor with an advanced tumor stage.     

Rapid detection of metastatic melanoma in lymph nodes using proton magnetic resonance spectroscopy of fine needle aspiration biopsy specimens

Accurate staging of patients with primary cutaneous melanoma includes assessment of regional lymph nodes for the presence of micrometastatic disease. Sentinel lymph node biopsy is highly accurate but is an invasive surgical procedure with a 5-10% complication rate, and requires labour-intensive and expensive histological examination to identify disease. A rapid, accurate and cost-effective non-surgical technique able to detect micrometastatic deposits of melanoma in regional lymph nodes would be of great benefit. Fine needle aspiration biopsies and tissue specimens were obtained from lymph nodes from 18 patients undergoing node resection for metastatic melanoma and five patients undergoing radical retropubic prostatectomy. One-dimensional proton magnetic resonance spectroscopy was undertaken at 360 MHz (8.5 T). Lymph nodes were cut into 3 mm thick slices and embedded. Four sequential 5 microm tissue sections were cut from each block and stained, with haematoxylin and eosin, for S100 protein, for HMB45, and again with haematoxylin and eosin, respectively. Proton magnetic resonance spectroscopy distinguished between benign and malignant lymph node tissue (P < 0.001, separate t-test) and benign and malignant lymph node fine needle aspiration biopsy (P < 0.012) based on the ratio of the integrals of resonances from lipid/other metabolites (1.8-2.5 p.p.m. region) and 'choline' (3.1-3.3 p.p.m. region). In conclusion, one-dimensional proton magnetic resonance spectroscopy on a simple fine needle aspiration biopsy can distinguish lymph nodes containing metastatic melanoma from uninvolved nodes, providing a rapid, accurate and cost-effective non-surgical technique to assess regional lymph nodes in patients with melanoma.     

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。      

Management of Clitoral Melanoma Presenting as an Exophytic Clitoral Mass: A Case Report and Review of the Literature

Primary mucosal melanomas of the female genital tract account for one percent or less of all cases of melanoma with even fewer originating in the clitoris. Given the rarity of diagnosis of clitoral melanoma, there is a paucity of data guiding management. There is no supporting evidence that radical vulvectomy (with or without inguinal lymphadenopathy) is associated with improved disease-free or overall survival compared to partial vulvectomy or wide local excision. Additionally, there is no data to evaluate the role of sentinel lymph node biopsy or extensive lymphadenectomy in clitoral melanoma, however previous evidence demonstrates the utility of regional lymph node sampling in predicting survival in women with female genital tract mucosal melanoma. Adjuvant therapy considerations are often extrapolated from their use in treating cutaneous melanomas, including immune checkpoint inhibitors and other immunotherapy agents. Adjuvant radiation therapy has limited utility except in cases of bulky, unresectable disease, or when inguinal lymph nodes are positive for metastasis. The 52 year-old patient presented in this review was diagnosed with locally invasive advanced stage clitoral melanoma presenting as an exophytic clitoral mass. She underwent diagnostic primary tumor resection, which demonstrated ulcerative melanoma with spindle cell features extending to a Breslow depth of at least 28 mm. She subsequently underwent secondary wide local excision with groin sentinel lymph node biopsy, and adjuvant treatment with pembrolizumab. This article also emphasizes the importance of a multidisciplinary team involving gynecologic oncology, medical oncology, radiology, and pathology for management of this rare type of primary mucosal melanoma of the female genital tract.     

Diagnostic biopsy of cutaneous melanoma,sentinel lymph node biopsy and indications for lymphadenectomy

The incidence of cutaneous melanoma appears to be increasing worldwide and this is attributed to solar radiation exposure. Early diagnosis is a challenging task. Any clinically suspected lesion must be assessed by complete diagnostic excision biopsy (margins 1-2 mm); however, there are other biopsy techniques that are less commonly used. Melanomas are characterized by Breslow thickness as thin (< 1 mm), intermediate (1-4 mm) and thick (> 4 mm). This thickness determines their biological behavior, therapy, prognosis and survival. If the biopsy is positive, a wide local excision (margins 1-2 cm) is finally performed. However, metastasis to regional lymph nodes is the most accurate prognostic determinant. Therefore, sentinel lymph node biopsy (SLNB) for diagnosed melanoma plays a pivotal role in the management strategy. Complete lymph node clearance has undoubted advantages and is recommended in all cases of positive SLN biopsy. A PET-CT (positron emission tomography-computed tomography) scan is necessary for staging and follow-up after treatment. Novel targeted therapies and immunotherapies have shown improved outcomes in advanced cases.     

Cutaneous melanoma and sentinel lymph node biopsy: where are we today?

Malignant cutaneous melanoma is the cancer which has the most increased these last ten years. His prognose is linked with melanoma thickness, tumoral ulceration and lymph node metastasis. The research of these node metastasis is important for the prognosis and the treatment. The sentinel lymph node biopsy is used since 1991 and is now considered as a reliable choice for the patient staging. However, his therapeutic interest remains discussed. We discussed the used of the sentinel lymph node biopsy for malignant cutaneous melanoma with the last publications.     

Melanoma in the young: differences and similarities with adult melanoma: a case-matched controlled analysis

BACKGROUND: Melanoma in the first 2 decades of life is rare and is less well characterized than melanoma in adults. Previously published comparisons of melanoma of the young (age 13 years. CONCLUSIONS: Melanoma of the young had some important differences and similarities relative to adult melanoma. Lymph node metastases were more prevalent in young patients with melanoma compared with adult (thickness-matched) control patients; however, the 5- and 10-year survival rates were similar.     

前哨淋巴结活检在皮肤型和肢端型黑色素瘤临床诊疗中的价值

背景与目的：前哨淋巴结活检（sentinel lymph node biopsy,SLNB）是评估皮肤型和肢端型黑色素瘤区域淋巴结转移情况及病理学分期的重要手段。SLNB作为外科诊疗规范的重要环节,已在各大诊疗指南中被推荐,也已在中国临床应用近10年。自2017年靶向和免疫治疗应用于中国黑色素瘤治疗领域,患者预后得到显著改善。本研究旨在分析复旦大学附属肿瘤医院近5年恶性黑色素瘤患者的临床资料,评估在新药治疗时代前哨淋巴结（sentinel lymph node,SLN）状态在临床应用的价值和对预后的影响。方法：对2017—2021年在复旦大学附属肿瘤医院黑色素瘤诊治中心接受诊治的381例恶性黑色素瘤患者的临床资料进行回顾性分析。每例患者均接受原发灶扩大切除和相应的SLNB,手术后随访至少6个月。SLN定位使用美兰染色或同位素示踪。结果：本研究共入组381例恶性黑色素瘤患者,平均Breslow浸润深度为3.10 mm,69.8%为肢端型,溃疡率为57.1%,SLN阳性率为34.6%,中位无复发生存率（relapse-free survival,RFS）为17个月。SLN状态是显著影响患者预后的独立危险因素。在N_1a和T₄亚组,SLN活检数>2枚的患者具有更好的RFS。接受完整的区域淋巴结清扫（complete lymph node dissection,CLND）和未清扫患者的RFS差异无统计学意义,在SLN活检数>2枚和SLN微转移直径<1 mm的亚组未清扫者反而具有更优的RFS。结论：SLN状态仍是影响临床无显性转移的黑色素瘤预后的重要因素,对于恶性黑色素瘤患者应常规开展SLNB,在保证微创的前提下,提高SLN定位的准确性,保证SLNB充分。SLN阳性后行即刻CLND对于皮肤型和肢端型黑色素瘤患者未能带来进一步的预后改善。     

Evidence and interdisciplinary consensus-based German guidelines: surgical treatment and radiotherapy of melanoma

The primary treatment of a melanoma is surgical excision. An excisional biopsy is preferred, and safety margins of 1 cm for tumor thickness up to 2 mm and 2 cm for higher tumor thickness should be applied either at primary excision or in a two-step procedure. When dealing with facial, acral or anogenital melanomas, micrographic control of the surgical margins may be preferable to allow reduced safety margins and conservation of tissue. The sentinel lymph node biopsy should be performed in patients whose primary melanoma is thicker than 1.0 mm and this operation should be performed in centers where both the operative and nuclear medicine teams are experienced. In clinically identified lymph node metastases, radical lymph node dissection is considered standard therapy. If distant metastases involve just one internal organ and operative removal is feasible, then surgery should be seen as therapy of choice. Radiation therapy for the primary treatment of melanoma is indicated only in those cases in which surgery is impossible or not reasonable. In regional lymph nodes, radiation therapy is usually recommended when excision is not complete (R1 resection) or if the nodes are inoperable. In distant metastases, radiation therapy is particularly indicated in bone metastases, brain metastases and soft tissue metastases.     

A proposal for the timing of management of patients with melanoma presenting during pregnancy

The treatment of melanoma during and immediately after pregnancy poses a significant challenge to surgeons, oncologists, and patients alike. With the overall increase in incidence of melanoma in the United States and worldwide, it is likely that more surgeons will be faced with management decisions regarding pregnant patients with melanoma. We report on five patients who presented to the Yale Melanoma Unit with melanoma during their pregnancy. We propose the management option of resection of the primary tumor under local anesthesia, and postponing of the sentinel lymph node biopsy until after the birth of the child. The completion lymphadenectomy can be performed if these nodes are found to be harboring metastases. We further discuss treatment options and propose an algorithm for management of patients diagnosed with melanoma while pregnant.     

Melanoma metastatic to “lipomata”

Three patients presented with solitary melanoma metastases that mimicked a simple “lipomata.” On further investigation each patient had a discrete fatty tissue tumor mass surrounding a melanoma metastasis. The presence of an enlarging mass in patients with a history of melanoma should be viewed with suspicion and a biopsy should be performed.     

Mélanome multiple polymétastatique sur cicatrice de brûlure

Malignant changes in burn scars are common. The most frequent cancer arising from an old burn scar is squamous cell carcinoma, while melanoma is extremely rare. We report a case of a patient with a multiple polymetatasic malignant melanoma arising from a burn scar areas and a review of literature. A 67-year-old patient who had been burned, the upper portion of her anterior trunk, at age 6 years. Nodular pigmented lesions were noted, on the burned areas 5 years before consultation. The biopsy was reported as malignant melanoma. Multiple metastases were noted.     

The possibility of performing an incisional biopsy in skin melanomas during pulsed laser radiation treatment

A procedure for stage I skin melanoma treatment using pulsed laser radiation was developed and employed in 94 patients. At first, a delimiting barrier around tumor was formed with laser beam. It was followed by incision biopsy of melanoma under local anesthesia to morphologically assess level of invasion (after Clark) and thickness of tumor (according to Breslow). Finally, tumor was destroyed with laser beam. The observed rates of metastasis development and 5-year survival and duration of metastasis-free period suggest that the treatment did not provoke tumor dissemination. Moreover, the procedure offered certain advantages over other therapeutic modalities for skin melanoma employing pulsed laser radiation.     

Management of primary cutaneous melanoma of the head and neck: The University of Colorado experience and a review of the literature.

BACKGROUND: While elective lymph node dissection (ELND), adjuvant radiation therapy and sentinel lymph node biopsy have all been advocated in the routine management of primary cutaneous melanoma arising in the head and neck, the optimal management has not been defined. METHODS: We have reviewed our experience of 273 patients with primary melanoma of the head and neck entered into a prospective database at the University of Colorado Health Sciences Center (UCHSC) from 1978 through 1998 and contrasted this with other reports in the literature. RESULTS: A total of 168 patients were identified that received their initial management at UCHSC and had no clinical evidence of distant disease. Only nine patients (5%) underwent ELND, and no patients received adjuvant radiation therapy. The local recurrence rate and 5-year melanoma specific survival, according to Breslow thickness, were similar to centers where adjuvant radiation therapy or ELND are routinely performed. Our preliminary experience and a review of the literature suggests that the technique of sentinel lymph node biopsy is an accurate and low risk procedure that provides valuable prognostic information useful in the further management of these patients. CONCLUSIONS: There is no clear indication that either ELND or adjuvant radiation therapy impacts on the outcome of patients with primary melanoma of the head and neck. Sentinel lymph node biopsy, in appropriate cases, is becoming the standard of care.