Prognostic Significance and Management of Sentinel Nodes in the Triangular Intermuscular Space of Patients with Melanoma.

BACKGROUND: The clinical significance of sentinel nodes (SNs) in the triangular intermuscular space (TIS) of patients with melanoma is poorly understood. This study aimed to determine their incidence and positivity rate, and to report their management and patient outcomes. METHODS: This was a single-institution retrospective cohort study of patients with unilateral or bilateral TIS SNs on lymphoscintigraphy treated between 1992 and 2017. Recurrence-free survival was analyzed. RESULTS: Lymphoscintigraphy identified TIS SNs in 266 patients. They were bilateral in 17 patients. Of the 2296 patients with a melanoma on the upper back, 259 (11%) had TIS SNs. Procurement of SNs was not attempted in 122 (43%) of the 283 cases and failed in 11 cases (7%). An SN was successfully retrieved from the TIS in 145 patients (53%) and contained metastasis in 18 of 150 TIS SNs. This was the only positive SN in 12 patients (8%), upstaging all of them. Of the 18 patients with a positive SN in the TIS, 9 (50%) underwent completion axillary lymph node dissection, but no additional involved nodes were found in any of these patients. Recurrence in the TIS was observed in six patients (5%), none of whom had their TIS SN surgically pursued previously. CONCLUSIONS: Lymphoscintigraphy showed TIS SNs in 11% of patients with melanomas on their upper back. In such cases, retrieval of TIS SNs is required for accurate staging and to minimize the risk of TIS recurrence.

Preoperative Ultrasound Assessment of Regional Lymph Nodes in Melanoma Patients Does not Provide Reliable Nodal Staging: Results From a Large Multicenter Trial.

OBJECTIVE: To assess whether preoperative ultrasound (US) assessment of regional lymph nodes in patients who present with primary cutaneous melanoma provides accurate staging. BACKGROUND: It has been suggested that preoperative US could avoid the need for sentinel node (SN) biopsy, but in most single-institution reports, the sensitivity of preoperative US has been low. METHODS: Preoperative US data and SNB results were analyzed for patients enrolled at 20 centers participating in the screening phase of the second Multicenter Selective Lymphadenectomy Trial. Excised SNs were histopathologically assessed and considered positive if any melanoma was seen. RESULTS: SNs were identified and removed from 2859 patients who had preoperative US evaluation. Among those patients, 548 had SN metastases. US was positive (abnormal) in 87 patients (3.0%). Among SN-positive patients, 39 (7.1%) had an abnormal US. When analyzed by lymph node basin, 3302 basins were evaluated, and 38 were true positive (1.2%). By basin, the sensitivity of US was 6.6% (95% confidence interval: 4.6-8.7) and the specificity 98.0% (95% CI: 97.5-98.5). Median cross-sectional area of all SN metastases was 0.13 mm2; in US true-positive nodes, it was 6.8 mm2. US sensitivity increased with increasing Breslow thickness of the primary melanoma (0% for ≤1 mm thickness, 11.9% for >4 mm thickness). US sensitivity was not significantly greater with higher trial center volume or with pre-US lymphoscintigraphy. CONCLUSION: In the MSLT-II screening phase population, SN tumor volume was usually too small to be reliably detected by US. For accurate nodal staging to guide the management of melanoma patients, US is not an effective substitute for SN biopsy.

Ultrasound Examination of the Lymphatic Drainage Area and Regional Lymph Nodes in Melanoma Patients with In-Transit Metastases.

BACKGROUND: In-transit metastases (ITMs) are cutaneous or subcutaneous regional metastases that may occur in patients with melanoma. ITMs are often multiple and new lesions tend to appear over time. Ultrasonography can detect impalpable subcutaneous tumors. OBJECTIVE: The aim of this study was to assess the value of ultrasound examination in detecting additional, non-palpable ITMs and to determine their relevance. METHODS: Melanoma patients with ITMs who underwent regional ultrasound examination of the skin and subcutaneous tissue between the wide excision scar of the primary melanoma and the regional lymph node field were identified. In most, ultrasound assessment also included the regional lymph node field. Relevant data were collected and analyzed. RESULTS: Twenty-eight patients presenting with a total of 40 ITMs were included. Ultrasound examination identified additional ITMs in 15 patients (54%). No nodal recurrences were detected. Most additional lesions were found closer to the regional lymph nodes than the original ITMs. Management was influenced by the ultrasound findings in nine patients (32%), five of whom had more extensive surgery, three received systemic drug therapy instead of surgery, and in one patient surgery was delayed and follow-up intensified. In one patient, only subcutaneous fat was found in the excised specimen and the ultrasound was classified as false-positive. CONCLUSION: In melanoma patients with ITMs, ultrasonography of the lymphatic drainage area provided valuable information, as additional ITMs were identified in more than half of these patients and management was influenced in one-third.

Sentinel Node Biopsy for Melanoma Patients with a Local Recurrence or In-Transit Metastasis.

BACKGROUND: Sentinel node (SN) biopsy (SNB) is not routinely performed for melanoma patients with local recurrence (LR) or in-transit metastasis (ITM). This study aimed to describe the technique, findings, and prognostic value of this procedure, and the outcome for such patients at our institution. METHODS: Prospectively collected data were obtained from the Melanoma Institute Australia database. Patients who had SNB for LR or ITM between 1992 and 2015 were included in the study. Patient and primary tumor characteristics, lymphoscintigrams, SNB results, and follow-up data were analyzed. RESULTS: Overall, 7999 patients underwent SNB, 128 (1.6%) of whom met the selection criteria. The SNB procedure was performed for 85 of 1516 patients with LR (6%), 17 of 1671 patients with ITM from a known primary tumor (1%), and 26 of 170 patients who presented with ITM from an unknown primary site (15%). The SN identification rate was 100%. Metastatic melanoma was identified in an SN from 16 of the 128 patients (13%). Follow-up data were available for 114 patients. The false-negative rate was 27%. The SN-positive patients had significantly worse overall survival than the SN-negative patients, with respective 5-year survival rates of 54% and 81% (P = 0.01). CONCLUSION: The SNB procedure was performed infrequently for LR or ITM. The SNs were positive for 13% of the patients with LR or ITM. Positive SNs were associated with worse overall survival. Despite the false-negative rate of 27%, the procedure yielded information that was relevant for staging and prognosis. The SNB procedure should be considered for patients with LR or ITM.

Current management of patients with melanoma who are found to be sentinel node-positive.

BACKGROUND: The results of the DeCOG-SLT and MSLT-II studies, published in 2016 and mid-2017, indicated no survival benefit from completion lymph node dissection (CLND) in melanoma patients with positive sentinel nodes (SNs). Subsequently, several studies have been published reporting a benefit of adjuvant systemic therapy in patients with stage III melanoma. The current study assessed how these findings influenced management of SN-positive patients in a dedicated melanoma treatment centre. METHODS: SN-positive patients treated at Melanoma Institute Australia between July 2017 and December 2018 were prospectively identified. Surgeons completed a questionnaire documenting the management of each patient. Information on patients, primary tumours, SNs, further treatment and follow-up was collected from patient files, the institutional research database and pathology reports. RESULTS: During the 18-month study period, 483 patients underwent SN biopsy. A positive SN was found in 61 (13%). Two patients (3%) requested CLND because of anxiety about observation in view of unfavourable primary tumour and SN characteristics. The other 59 patients (97%) were followed with a four-monthly ultrasound examination of the relevant lymph node field(s). Two of them (3%) developed an isolated nodal recurrence after 4 and 11 months of follow-up. Fifty-seven patients (93%) were seen following the publication of the first two adjuvant systemic therapy studies in November 2017; 46 (81%) were referred to a medical oncologist to discuss adjuvant systemic therapy, which 32 (70%) chose to receive. CONCLUSION: At Melanoma Institute Australia most patients with an involved SN are now managed without CLND. The majority are referred to a medical oncologist and receive adjuvant systemic therapy.

Focused Ultrasound Surveillance of Lymph Nodes Following Lymphoscintigraphy Without Sentinel Node Biopsy: A Useful and Safe Strategy in Elderly or Frail Melanoma Patients.

BACKGROUND: Sentinel node (SN) biopsy (SNB) has become standard of care in clinically localized melanoma patients. Although it is minimally invasive, advanced age and/or comorbidities may render SNB inadvisable in some patients. Focused ultrasound follow-up of SNs identified by preoperative lymphoscintigraphy may be an alternative in these patients. This study examines the outcomes in patients managed in this way at a major melanoma treatment center. METHODS: All patients with clinically localized cutaneous melanoma who underwent lymphoscintigraphy and in whom SNB was intentionally not performed due to advanced age and/or comorbidities were included. RESULTS: Between 2000 and 2009, 160 patients (5.2% of the total) underwent lymphoscintigraphy without SNB because of advanced age and/or comorbidities. Compared with the 2945 patients who had a SNB, the 160 patients were older, had thicker melanomas that were more often located in the head and neck region, and had more SNs in more nodal regions. Of the 160 patients, 150 (94%) were followed with ultrasound examination of their SNs at each follow-up visit; this identified 33% of the nodal recurrences before they became clinically apparent. Compared with SN-positive patients who were treated by completion lymph node dissection, observed patients who developed nodal recurrence had more involved nodes when a delayed lymphadenectomy was performed. Melanoma-specific survival, recurrence-free survival, and distant recurrence-free survival rates were similar, while regional lymph node-free survival was worse. CONCLUSIONS: Lymphoscintigraphy with focused ultrasound follow-up of SNs is a reasonable management alternative to SNB in patients who are elderly and/or have substantial comorbidities.

Clinical importance and surgical management of sentinel lymph nodes in the popliteal fossa of melanoma patients.

BACKGROUND AND PURPOSE: Patients with a primary melanoma below the knee may have lymphatic drainage to a sentinel node (SN) in the popliteal fossa. The purpose of this study was to analyze lymphatic drainage to this site and to describe clinical features and surgical management of SNs in the popliteal fossa. METHODS: Patients with a primary melanoma below the knee presenting to Melanoma Institute Australia between 1992 and 2013 were analyzed. Those found to have a popliteal SN were evaluated. Data on imaging, SN biopsy, completion lymph node dissection, morbidity and follow-up were analyzed. RESULTS: Lymphoscintigraphy showed drainage to a popliteal SN in 176 of 3902 cases of melanoma below the knee (4.5%). In 96 of these patients (55%) a popliteal SN biopsy was attempted. The procedure failed to identify the node(s) in seventeen of them (18%). Thirteen of the 79 patients (17%) had a positive popliteal SN and in eight (10%) this was the only positive node. The tumor stage of ten patients (13%) changed as a result of the popliteal node biopsy. A positive popliteal node was associated with an increased risk of recurrence and diminished overall survival. Popliteal SN biopsy did not improve regional control or survival. CONCLUSION: Melanomas below the knee infrequently drain to lymph nodes in the popliteal fossa. Although popliteal SN biopsy can be challenging, it is worthwhile, providing improved staging and guiding subsequent management.

Outcome of Melanoma Patients Who Did Not Proceed to Sentinel Node Biopsy After Preoperative Lymphoscintigraphy.

BACKGROUND: At our institution, a planned sentinel node biopsy (SNB) procedure is occasionally canceled after preoperative lymphoscintigraphy. This study reports the frequency of this, the reasons, and the management and outcomes of these patients. METHODS: All patients with clinically localized cutaneous melanoma treated at Melanoma Institute Australia between 2000 and 2009 whose planned SNB procedure was not undertaken after lymphoscintigraphy were included in this retrospective study. RESULTS: Of the 3148 patients in whom the procedure had been planned, 203 patients (6.4 %) did not have a SNB. The main reason for not proceeding with SNB (in 84 % of cases) was the lymphoscintigraphic demonstration of multiple drainage fields and/or multiple sentinel nodes (SNs). Patients who did not proceed to SNB were significantly older than those who did, more often had melanomas of the head or neck, and had more SNs and more nodal drainage fields. Of the 203 patients, 181 (89 %) were followed with high-resolution ultrasound of their SNs, which identified 33 % of the nodal recurrences before they were clinically apparent. Patients whose SNB was canceled had significantly worse recurrence-free survival and regional node disease-free survival, but melanoma-specific survival was similar. Compared to SN-positive patients, node-positive patients without SNB had significantly more involved nodes when a delayed lymphadenectomy was performed, but melanoma-specific survival was not significantly different after a median follow-up of 42 months. CONCLUSIONS: Lymphoscintigraphy with ultrasound follow-up of previously identified SNs is an acceptable management strategy for patients in whom a SNB procedure is likely to be challenging.

Sentinel Lymph Node Biopsy: Evolution of the Technique Since the Original Description by Morton et al. in 1992.

Donald Morton was a truly amazing man: a remarkable scientist and an outstanding, inspirational surgical oncologist. For those of us who had the great fortune to know him personally, it was an experience that we will always remember with warmth and gratitude. Hundreds of thousands, possibly millions, of patients in the future will also be grateful to him when they benefit from his original but simple idea that has so dramatically improved the surgical approach to patients with cancers that may metastasize to regional lymph nodes: the sentinel lymph node biopsy concept.

Prospective study of sentinel node biopsy for high-risk cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: Nodal metastasis from cutaneous squamous cell carcinoma (SCC) is poorly predicted clinically and is associated with a high mortality rate. METHODS: From 2010 to 2013, patients with high-risk cutaneous SCC were assessed with sentinel node biopsy (SNB) either at the time of primary cutaneous tumor resection or at secondary wide local excision. RESULTS: Of 57 patients, 8 (14%) had nodal metastasis. Significant predictors of metastasis are the number of high-risk factors (p = .008), perineural invasion (PNI; p = .05), and lymphovascular invasion (LVI; p = .05). During a mean of 19.4 months, 9 patients developed recurrence and 6 died of cutaneous SCC, indicating that over 1300 patients would be required for a randomized controlled trial with 80% power to detect a significant difference in disease-free survival. CONCLUSION: Lymph node metastasis occurs in 14% of patients with high-risk cutaneous SCC. Larger studies will be required to identify which "high-risk" factors should be considered as an indication for surgical assessment of the nodal basin. © 2015 Wiley Periodicals, Inc. Head Neck 38: E884-E889, 2016.

EANM practice guidelines for lymphoscintigraphy and sentinel lymph node biopsy in melanoma.

PURPOSE: Sentinel lymph node biopsy is an essential staging tool in patients with clinically localized melanoma. The harvesting of a sentinel lymph node entails a sequence of procedures with participation of specialists in nuclear medicine, radiology, surgery and pathology. The aim of this document is to provide guidelines for nuclear medicine physicians performing lymphoscintigraphy for sentinel lymph node detection in patients with melanoma. METHODS: These practice guidelines were written and have been approved by the European Association of Nuclear Medicine (EANM) to promote high-quality lymphoscintigraphy. The final result has been discussed by distinguished experts from the EANM Oncology Committee, national nuclear medicine societies, the European Society of Surgical Oncology (ESSO) and the European Association for Research and Treatment of Cancer (EORTC) melanoma group. The document has been endorsed by the Society of Nuclear Medicine and Molecular Imaging (SNMMI). CONCLUSION: The present practice guidelines will help nuclear medicine practitioners play their essential role in providing high-quality lymphatic mapping for the care of melanoma patients.

Identification of the sentinel lymph node in the SNAC-1 trial.

BACKGROUND: A combination of scintigraphy and a lymphotropic dye (patent blue dye (BD)) is the recommended technique to detect the sentinel lymph node (SLN) in early breast cancer. This study determined the effect of clinical factors on SLN identification in the sentinel node biopsy versus axillary clearance (SNAC) trial. METHODS: A total of 1088 women were registered. Lymphatic mapping was performed using preoperative lymphoscintigraphy (LSG) and gamma probe (GP) combined with peritumoural injection of patent BD (971 patients) or BD alone (106 patients). RESULTS: SLNs were identified in 1024 women (94%), localized with LSG in 779 (81.4%), and were identified by GP in 879 (91.8%). The BD identified SLNs in 890 of 1073 (82%) women. Three patients had allergic reactions. BD detected the SLNs in 141 of 178 women with negative LSG mapping and in 44 of 79 women with no hot SLNs detected intraoperatively. Age, body mass index (BMI) and tumour presentation (screen detected versus symptomatic) were significantly related to the identification of the SLN. For BD, the primary tumour location was significantly related to identification rate. The detection of blue SLN was significantly lower in women with inner quadrant tumours. CONCLUSION: The combined technique resulted in a high identification rate. BD contributed to the identification of the SLNs in patients where LSG and GP failed to identify the sentinel node. Special attention to these techniques is needed in particular groups of patients such as those with high BMI, screen-detected primary tumours and tumour located in the inner quadrants.

The history of sentinel lymph node biopsy.

The sentinel node biopsy technique, developed by Drs Donald Morton and Alistair Cochran and reported in 1992, undoubtedly constitutes the most important recent development in surgical oncology. This article describes the evolution of the procedure and its contribution to the evolution of modern multidisciplinary cancer care and discusses its present role in the management of patients with melanoma, breast cancer, and a wide range of other malignancies.

Imaging sentinel lymph nodes.

As the technique of sentinel lymph node (SLN) biopsy has evolved over the last 22 years, it has become increasingly evident that accurate SLN imaging is vital to allow surgical removal of only the true SLN(s) and not other nodes. Identifying the lymphatic collectors draining a tumor site and following them to the draining SLNs defines which nodes need to be removed for careful histologic examination. Current technology allows the exact location of each SLN to be defined. This allows the full benefits of SLN biopsy to be achieved, that is, highly accurate lymph node staging with minimal morbidity. In melanoma and breast cancer, the current practice of preoperative lymphoscintigraphy (LS) using peritumoral injections of tracer or injection adjacent to an excision biopsy site with dynamic imaging to visualize the lymphatic collectors and delayed imaging including single-photon emission computed tomography/computed tomography gives the best results. This information informs the surgical approach and allows rapid excision of the SLNs at surgery.In patients with visceral tumors where the primary cancer site is difficult to access, it appears that using fluorophores that are fluorescent under near-infrared light, injected during surgery, is evolving as the preferred technique.

Lymphatic drainage patterns from primary cutaneous tumours of the forehead: refining the recommendations for selective neck dissection.

BACKGROUND: Recommended selective neck dissections for primary cutaneous tumours on the head and neck are based largely on clinical recurrence data acquired prior to the era of lymphatic mapping and sentinel lymph node (SLN) biopsy. This study aimed to examine lymphatic drainage patterns from the forehead in order to provide evidence upon which to base recommendations regarding the extent of neck dissection. METHODS: Data were collected prospectively from all patients undergoing lymphoscintigraphy following diagnosis of a primary cutaneous tumour on the forehead. The site of injection of radioisotope was documented using a co-ordinate-based mapping system. The forehead was divided into glabellar, supra-orbital and anterior temple zones. The location of all SLNs was recorded and drainage patterns were analysed. RESULTS: Between 1994 and 2006, 152 patients underwent lymphoscintigraphy for primary cutaneous tumours on the forehead. Drainage was to 3.0 SLNs in 2.1 lymph node fields (mean values). Drainage was to ipsilateral SLNs in 85% of cases. Between zones there were significant differences in drainage patterns and the frequency of bilateral drainage. From the glabellar zone, drainage was more frequently to a higher number of SLNs and SLN fields, and to level I nodes. CONCLUSIONS: The forehead can be divided into zones with patterns of lymphatic drainage that vary significantly in terms of number of SLNs, number of SLN sites, likelihood of drainage to contralateral SLNs and predictability of drainage pattern. Drainage to level 1 nodes from the anterior temple is rare, suggesting that it may be safe to exclude this level when performing a selective neck dissection for tumours in this zone.

Sentinel lymph node mapping for defining site and extent of elective radiotherapy management of regional nodes in Merkel cell carcinoma: a pilot case series.

Merkel cell carcinoma is a rare and aggressive skin malignancy. We discuss sentinel lymph node mapping which is a valuable decision aid for radiotherapy management and planning of treatment volumes as illustrated by four cases.

Outcome following sentinel node biopsy plus wide local excision versus wide local excision only for primary cutaneous melanoma: analysis of 5840 patients treated at a single institution.

OBJECTIVE: Worldwide, sentinel node biopsy (SNB) is now a standard staging procedure for most patients with melanomas 1 mm or more in thickness, but its therapeutic benefit is not clear, pending randomized trial results. This study sought to assess the therapeutic benefit of SNB in a large, nonrandomized patient cohort. METHODS: Patients with primary melanomas 1.00 mm or more thick or with adverse prognostic features treated with wide local excision (WLE) at a single institution between 1992 and 2008 were identified. The outcomes for those who underwent WLE plus SNB (n = 2909) were compared with the outcomes for patients in an observation (OBS) group who had WLE only (n = 2931). Median follow-up was 42 months. RESULTS: Melanoma-specific survival (MSS) was not significantly different for patients in the SNB and OBS groups. However, a stratified univariate analysis of MSS for different thickness subgroups indicated a significantly better MSS for SNB patients with T2 and T3 melanomas (>1.0 to 4.0 mm thick) (P = 0.011), but this was not independently significant in multivariate analysis. Compared with OBS patients, SNB patients demonstrated improved disease-free survival (DFS) (P < 0.001) and regional recurrence-free survival (P < 0.001). There was also an improvement in distant metastasis-free survival (DMFS) for SNB patients with T2 and T3 melanomas (P = 0.041). CONCLUSIONS: In this study, the outcome for the overall cohort after WLE alone did not differ significantly from the outcome after additional SNB. However, the outcome for the subgroup of patients with melanomas more than 1.0 to 4.0 mm in thickness was improved if they had a SNB, with significantly improved disease-free and DMFS.

Sentinel node biopsy and large (≥3 cm) breast cancer.

BACKGROUND: Sentinel node biopsy is an accurate method for staging the axilla in early (small) breast cancers. However, data for the role of this technique for large breast cancers remain limited. METHOD: From the Royal Adelaide Hospital Sentinel Node database and the SNAC trial database, 100 subjects were identified with clinically node negative, large (≥3 cm) primary breast cancer who had undergone sentinel node biopsy and immediate axillary clearance. The pathology results from the sentinel node and axillary specimens were analysed. RESULTS: Average tumour size was 3.91 cm (range 3-10 cm) and 65 of 100 cases had metastatic disease in the axillary nodes. A sentinel node was successfully identified in 93 out of 100 cases with an average of 1.75 sentinel nodes sampled. Sixty-two per cent (58 out of 93) were sentinel node positive and 43% (43 out of 100) had a positive non-sentinel node. The false negative rate following successful sentinel node identification was 4.9% (3 out of 61). CONCLUSION: Sentinel node biopsy was an accurate tool for staging the axilla with a false negative rate comparable to that seen in small tumours. However, given the increased incidence of metastases with larger cancers, further prospective investigation is warranted.