Melanoma Sentinel Lymph Node Research Articles

Sentinel Lymph Node in Melanoma – a Study Conducted in the South of Brazil

The presence or absence of lymph node metastases is a very important prognostic factor for survival and recurrence in patients with cutaneous melanoma. Controversies remain among specialists about whether it is advisable or not to perform a sentinel lymph node biopsy in patients with melanoma, although it is currently supported by most standard guidelines. We performed this study to identify which patients are more prone to having a positive lymph node test result in a population with high melanoma rates in the south of Brazil. We performed the study with 62 consecutive patients who underwent sentinel lymph node biopsies from 2003 to the early months of 2015 in the city of Blumenau - Santa Catarina, Brazil. Breslow thickness, ulceration, nodular subtype, and Clark level IV were associated with positive sentinel lymph node group status (p 0.05). Although there is still a controversy over whether or not this procedure should be performed, most guidelines still support its application. To lower the economical and physical impact, however, it is worthwhile to determine which patients are more prone to acquiring positive lymph node at presentation and, perhaps, in the future, indicate surgery for this particular group, who could benefit most from further treatment options. melanoma - sentinel lymph node biopsy - prognosis.

Clinical significance of intra-nodal naevi in sentinel node biopsies for malignant melanoma

BackgroundIntra-nodal naevi (INN) identified during assessment of a sentinel lymph node for melanoma are not an uncommon finding. Little is known about their clinical significance. Patients with INN are treated as sentinel node biopsy (SNB) negative currently. Our aim was to assess the significance of INN in patients who undergo SNB for melanoma. Methods353 melanoma patients who underwent a SNB between November 1999 and June 2012 were retrospectively analysed from a prospectively collected database. The patients were divided into SNB negative, INN, isolated tumour cells (ITC) and SNB positive groups. Outcome measures of nodal recurrence, distal recurrence and survival were used to assess the differences between the groups. Results203 patients were SNB negative, 103 were positive of which 13 had ITC, 47 had INN (13%). Overall median follow up was 2.3 years (range 0.1–14.1 years). Our data demonstrated a statistically significant survival benefit for patients who had an INN compared to the SNB positive and ITC group. INN patients also had significantly better nodal and regional recurrence compared to SNB positive patients. There was no difference between INN and SNB negative patients. ConclusionWe have clinically demonstrated that patients with INN on SNB can be adequately treated as SNB negative patients.

Localization of the Sentinel Lymph Node in Melanoma Without Blue Dye.

The purpose of this study was to assess regional recurrence rates of patients who underwent sentinel lymph node biopsy (SLNB) using radiocolloid guidance alone. Isosulfan blue dye is commonly used along with Tc99-labeled radiocolloid localization in SLNB for melanoma. Blue dye has, however, been associated with allergic reactions, long-term staining of skin, and increased cost. We hypothesized that the rate of regional recurrence when SLNB is performed with radiocolloid alone would be comparable to established reports using both radiocolloid and blue dye. A prospectively collected database was retrospectively queried for patients who underwent SLNB for melanoma during the years 2005 through 2008. Data collected included patient demographics, primary lesion characteristics, operative details, and recurrence. The primary outcome was the rate of recurrence within the biopsied basin after negative SLNB's performed without isosulfan blue dye. In 215 patients, 279 nodal basins were identified. All patients underwent successful radiocolloid localization, and positive sentinel nodes were found in 40 patients (18.6%). Six of 175 patients with a negative SLNB developed a regional node recurrence as the first site of metastasis (3.4%). Among all 215 patients, 44 experienced recurrence of any kind (20.5%). Higher mitotic rate and Breslow depth were significantly associated with likelihood of recurrence. Success rates, node positivity rates, and rates of regional recurrence after SLNB for melanoma using radiocolloid alone are acceptable and similar to those of prior reports using blue dye plus radiocolloid.

Hard Copy Durable Patient Cancer Education Materials: Do They Still Matter?

Traditional hard copy information materials are still present in our cancer clinics. While their actual impact on patient care often goes un-assessed, it is important to understand their role in today's electronic age where information can easily be obtained from various sources. It has remained the practice in our melanoma clinic to provide an information booklet to all of our new patients. The purpose of this study was to evaluate how useful this booklet was, as well as determine the current resources our patients use to gather cancer information. All patients referred to the clinic in the previous 3years were pooled from our prospective, IRB-approved, melanoma sentinel node database. Of these 205 patients, a valid email address was listed for 147. A ten-question survey was emailed to all of these patients, who were not told ahead of time that their experience with the booklet would be studied. Seventy-seven of the 147 (52%) patients polled responded. Fifty-eight (75%) remembered receiving the booklet at their initial consultation. Forty-four (76%) of those patients rated it as extremely or very useful, and no patients reported the booklet as not useful at all. Eighty-eight percent of respondents found the information to be clear and helpful. Sixty-four percent remembered the provider reviewing the material with them, and nearly all of these patients found that helpful. When asked to rank the importance of the various resources for obtaining cancer information, providers were ranked as most important, followed by the information booklet and Internet information sites. Internet blogs and friends and family were rated as the least important sources of information. Even in the current electronic age, our results indicate that information shared by providers, including the hard copy education booklet, was the most important source of information for our newly referred melanoma patients.

Frequency of level II and III axillary nodes metastases in patients with positive sentinel lymph nodes in melanoma: a multi-institutional study in Japan

Axillary lymph node dissection (ALND) has been recommended to include levels I-III for melanoma patients who have evidence of metastasis in the axillary sentinel lymph node (SLN). The extent of the subsequent axillary dissection is in debate. The objective of this study was to determine the frequency of metastasis of level III nodes in addition to that of level II nodes in this setting. A multi-institutional retrospective study was undertaken in 14 melanoma treatment centers in Japan. Between 2007 and 2012, 69 patients with involved axillary SLNs underwent a subsequent ALND and 55 underwent level I and II dissections. Level III metastatic nodes, which is our primary endpoint, were seen in only 1 patient (1.5%). The level II metastatic rate was 4.4%. Our study sample size was small, but melanoma patients with positive SLN rarely had level III disease, suggesting that level III dissection may be unnecessary. We also found that level II metastasis was not so frequent. More evidence is needed to standardize the extent of ALND and to identify the patients who would have the most benefit with undergoing level II dissection for positive axillary SLNs.

Sentinel lymph node scintigraphy in cutaneous melanoma using a planar calibration phantom filled with Tc-99m pertechnetate solution for body contouring.

Background and aimsMelanoma is a disease that has an increasing incidence worldwide. Sentinel lymph node scintigraphy is a diagnostic tool that offers important information regarding the localization of the sentinel lymph nodes offering important input data to establish a pertinent and personalized therapeutic strategy. The golden standard in body contouring for sentinel lymph node scintigraphy is to use a planar flood source of Cobalt-57 (Co-57) placed behind the patients, against the gamma camera. The purpose of the study was to determine the performance of the procedure using a flood calibration planar phantom filled with aqueous solution of Technetion-99m (Tc-99m) in comparison with the published data in literature where the gold standard was used.MethodsThe study was conducted in the Department of Nuclear Medicine of Oncology Institute “Prof. Dr. Ion Chiricuţă” Cluj-Napoca in 95 patients, 31 males and 64 females. The localization of the lesions was grouped by anatomical regions as follows: 23 on lower limbs, 17 on upper limbs, 45 on thorax and 10 on abdomen. The calibration flood phantom containing aqueous solution of Tc-99m pertechnetate was used as planar source to visualize the body contour of the patients for a proper anatomic localization of detected sentinel lymph nodes. The radiopharmaceutical uptake in sentinel lymph nodes has been recorded in serial images following peritumoral injection of 1 ml solution of Tc-99m albumin nanocolloids with an activity of 1 mCi (37 MBq). The used protocol consisted in early acquired planar images within 15 minutes post-injection and delayed images at 2–3 hours and when necessary, additional images at 6–7 hours. The acquisition matrix used was 128×128 pixels for an acquisition time of 5 – 7 minutes. The skin projection of the sentinel lymph nodes was marked on the skin and surgical removal of detected sentinel lymph nodes was performed the next day using a gamma probe for detection and measurements.ResultsThe sentinel lymph nodes were detected in 92 cases and confirmed with the gamma probe during the surgical procedure. The localization of the lymph nodes was as follows: for the tumors localized on lower limb 23 lymph nodes were localized in inguinal region, for the tumors localized on upper limb, 17 lymph nodes were localized in axilla, for the tumors localized on the thorax, 40 lymph nodes were localized in axilla and 3 were localized in the inguinal region; for the tumors localized on the abdomen, 1 lymph node was localized in axilla and 8 lymph nodes was localized in inguinal region. Regarding the negative sentinel lymph node cases, 2 cases were registered for primarily lesions localized on thorax and 1 for a lesion localized on abdomen. According to histology, 26 cases revealed lymphatic metastatic invasion. Dose rates measured at 1m from the calibrator phantom had an average value of 3.46 μSv/h (SD 0.19) and at 1.4m, the value was 2.57 μSv/h (SD 0.22). Dose rates measured at the same distances from the Co-57 planar flood source had a average values of 32.5μSv/h (SD 0.11) respectively 24.1 μSv/h (SD 0.14).ConclusionThe planar calibration flood phantom is an effective tool for body contouring in sentinel lymph node scintigraphy and offers accurate anatomical information to efficiently localize the detected sentinel lymph nodes in melanoma, being for the first time used and mentioned as a pertinent alternative in our department.

Can SOX-10 or KBA.62 Replace S100 Protein in Immunohistochemical Evaluation of Sentinel Lymph Nodes for Metastatic Melanoma?

Microscopic evaluation of sentinel lymph nodes for metastatic melanoma relies, in part, on the use of immunohistochemical analysis to identify minute metastatic deposits that may be overlooked on routine microscopy. At present S100 protein is widely used in this role, in large part for its superior sensitivity; however, interpretation is hampered by the presence of benign S100 protein-positive cellular elements present in every lymph node, leading to reduced specificity and consequent difficulties in interpretation. In recent years, multiple melanocytic markers have emerged that promise superior sensitivity and specificity, including KBA.62 and SOX-10. SOX-10 shows a nuclear pattern of staining. In normal tissue it is expressed in Schwann cells, melanocytes, and myoepithelial cells of salivary, bronchial, and mammary glands. KBA.62 is also specific except for staining of endothelial cells and shows a membranous staining pattern. This study was undertaken to determine whether KBA.62 or SOX-10 could equal (or surpass) the sensitivity of S100 protein while offering superior specificity in the immunohistochemical evaluation of sentinel lymph nodes for metastatic melanoma. In this study we performed immunohistochemical stains for S100 protein, Sox-10, and KBA.62 on 50 lymph nodes with proven metastatic melanoma. SOX-10 detected all cases of metastatic melanoma (50 of 50 cases; 100%) compared with S100 protein (48 of 50 cases; 96%) and KBA.62 (37 of 50 cases; 74%). There was no "background" staining of normal cellular elements with SOX-10 or KBA.62. In contrast, S100 protein was expressed in scattered dendritic interdigitating reticulum cells in the paracortex of lymph nodes, showing cytoplasmic and nuclear positivity, sometimes posing significant difficulty in differentiating benign reticulum cells from single cell metastatic melanoma. Our findings suggest that SOX-10 may be superior to S100 protein for identifying metastatic melanoma in a lymph node. KBA.62 was less sensitive than either marker, although more specific than S100 protein.

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.

Metastatic status of sentinel lymph nodes in melanoma determined noninvasively with multispectral optoacoustic imaging.

Sentinel lymph node (SLN) excision is included in various cancer guidelines to identify microscopic metastatic disease. Although effective, SLN excision is an invasive procedure requiring radioactive tracing. Novel imaging approaches assessing SLN metastatic status could improve or replace conventional lymph node excision protocols. In our first-in-human study, we used noninvasive multispectral optoacoustic tomography (MSOT) to image SLNs ex vivo and in vivo in patients with melanoma, to determine metastatic status. MSOT significantly improved the tumor metastasis detection rate in excised SLN (506 SLNs from 214 melanoma patients) compared with the conventional EORTC (European Organisation for Research and Treatment of Cancer) Melanoma Group protocol (22.9% versus 14.2%). MSOT combined with the near-infrared fluorophore indocyanine green reliably visualized SLNs in vivo in 20 patients, up to 5-cm penetration and with 100% concordance with (99m)Tc-marked SLN lymphoscintigraphy. MSOT identified cancer-free SLNs in vivo and ex vivo without a single false negative (189 total lymph nodes), with 100% sensitivity and 48 to 62% specificity. Our findings indicate that a noninvasive, nonradioactive MSOT-based approach can identify and determine SLN status and confidently rule out the presence of metastasis. The study further demonstrates that optoacoustic imaging strategies can improve the identification of SLN metastasis as an alternative to current invasive SLN excision protocols.

Tumor PD-L1 expression, immune cell correlates and PD-1+ lymphocytes in sentinel lymph node melanoma metastases

Melanoma patients with sentinel lymph node metastases have variable 5-year survival rates (39–70%). The prognostic significance of tumor-infiltrating lymphocytes in sentinel lymph node metastases from such patients is currently unknown. Anti-PD-1/PD-L1 inhibitors have significantly improved clinical outcome in unresectable AJCC stage IIIC/IV metastatic melanoma patients, and are being trialed in the adjuvant setting in advanced stage disease, however, their role in early stage (sentinel lymph node positive) metastatic disease remains unclear. The aims of this study were to characterize, in sentinel lymph nodes, the subpopulations of lymphocytes that interact with metastatic melanoma cells and analyze their associations with outcome, and to determine tumor PD-L1 expression as this may provide a rational scientific basis for the administration of adjuvant anti-PD-1/PD-L1 inhibitors in sentinel lymph node positive metastatic melanoma patients. Sentinel lymph nodes containing metastatic melanoma from 60 treatment-naive patients were analyzed for CD3, CD4, CD8, FOXP3, PD-1, and PD-L1 using immunohistochemistry on serial sections. The results were correlated with clinicopathologic features and outcome. Positive correlations between recurrence-free/overall survival with the number of CD3+ tumor-infiltrating lymphocytes (hazard ratio=0.36 (0.17–0.76), P=0.005; hazard ratio=0.29 (0.14–0.61), P=0.0005, respectively), the number of CD4+ tumor-infiltrating lymphocytes (hazard ratio=0.34 (0.15–0.77), P=0.007; hazard ratio=0.32 (0.14–0.74), P=0.005, respectively), and the number of CD8+ tumor-infiltrating lymphocytes (hazard ratio =0.42 (0.21–0.85), P=0.013; hazard ratio =0.32 (0.19–0.78), P=0.006, respectively) were observed. There was also a negative correlation with the number of peritumoral PD-1+ lymphocytes (hazard ratio=2.67 (1.17–6.13), P=0.016; hazard ratio=2.74 (1.14–6.76), P=0.019, respectively). Tumoral PD-L1 expression was present in 26 cases (43%) but did not correlate with outcome. The findings suggest that T-cell subsets in sentinel lymph node metastases can predict melanoma patient outcome. In addition, the relatively high number of PD-L1 positive sentinel lymph node melanoma metastases provides a rationale for anti-PD-1 therapy trials in sentinel lymph node positive melanoma patients, particularly those with peritumoral PD-1+ lymphocytes.

Predictors and Survival Impact of False-Negative Sentinel Nodes in Melanoma

The status of the sentinel lymph node in melanoma is an important prognostic factor. The clinical predictors and implications of false-negative (FN) biopsy remain debatable. We compared patients with positive sentinel lymph node biopsy (SNB) [true positive (TP)] and negative SNB with and without regional recurrence [FN, true negative (TN)] from our prospective institutional database. Among 2986 patients (84 FN, 494 TP, and 2408 TN; median follow-up 93 months), the incidence of FN-SNB was 2.8%. While calculated FN rate was 14.5% [84 FN/(494 TP + 84 FN) × 100], when we accounted for local/in-transit recurrence (LITR) this rate was 8.5% [46 FN/(494 TP + 46 FN) × 100 %]. On multivariate analysis, male gender (OR 2.0, 95% CI 1.1-3.6, p = 0.018), head/neck primaries (OR 2.5, 95% CI 1.3-4.8, p < 0.006), and LITR (OR 3.5, 95% CI 2.1-5.8, p < 0.001) were associated with FN-SNB. Melanoma-specific survival (MSS) for the FN group was similar to the TP group at 5 years (68 vs. 73%, p = 0.539). However, MSS declined more for the FN group with a longer follow up and was significantly worse at 10 years (44 vs. 64%, p < 0.001). On multivariate analysis, FN-SNB was a significant predictor of worse MSS in melanomas <4 mm in Breslow thickness (HR 1.6; 95% CI 1.1-2.5, p = 0.021). Male gender, LITR, and head and neck tumors were associated with FN-SNB. FN-SNB was an independent predictor of worse MSS in melanomas <4 mm in thickness, but this survival difference did not become apparent until after 5 years of follow-up.

Abstract 454: Evaluating the progression of cutaneous melanoma by the molecular immune response of the sentinel lymph node

Abstract Introduction: The sentinel node (SN) has become the standard diagnostic tool for staging melanoma. With the recent development of several potent immunotherapies we hypothesized that the early immune events in melanoma maybe first seen in the SN. Methods: 81 SN from 79 patients were evaluated with microarray technology, qPCR, routine H&amp;E &amp; IHC. We identified immune genes that are present by qPCR in SNs from a random section of the SN, away from the blue dye. Statistical analysis assessed the utility of these markers to predict tumor progression by increasing primary thickness and tumor-positive SN. Results: Of the 79 patients, 48 (61%) were men. Median age was 59 (range 6-95 years). Primary melanomas were most commonly from the trunk (51%) and extremities (40%). The median thickness of the primaries was 0.95mm. In 7 cases the tumor thickness was not measured. 13% of the patients had ulcerated primaries. 29% of the primary tumors had at least 1 mitosis/mm2. 9 (11%) patients had SN metastasis, as determined by conventional H&amp;E and IHC. The incidence of SN positivity was directly related to tumor thickness; the higher the T-stage the greater percentage of SN positivity: 2% T1, 19% T2, 20% T3 and 60% T4 melanoma. 33% of ulcerated primaries and 30% with increased mitotic rate had a tumor-positive SN. Increased mitotic rate (&amp;gt;1 mitosis/mm2) and decreased gene expression of CD80 and ARG2 correlated with T3/4 primaries. By univariate analyses: age (p&amp;lt;0.001), primary site (&amp;lt;0.001), mitotic rate and increasing gene expression of CTLA-4 (p&amp;lt;0.001) and PD-1 (p&amp;lt;0.001) in SN were predictive of SN positivity. Multivariate analysis demonstrates mitoses in the primary and CTLA-4 and PD-1 gene expression in the SN were predictive of metastases in the SN. The up-regulation of CTLA-4 and PD-1 gene expression, in combination with increased mitoses was an accurate determinate of SN metastasis. The AUC values of CTLA-4 and PD-1 expression and increased mitoses at the primary site were 0.8 and 0.73. The positive and negative predictive values of the assays varied with level of gene expression but approached 100% and 90% respectively. Conclusions: The immune molecular profile of the sentinel lymph node in melanoma is altered in the presence or absence of metastases in the lymph node and by progression of the primary melanoma. These alterations in immune profiles may be important for distinguishing the patterns of metastases and ultimately the response to therapy in melanoma. Citation Format: Richard Essner, Alexandra Gangi, David Kaufman, Ke Wei Gong, Myung Sim, Dennis Slamon. Evaluating the progression of cutaneous melanoma by the molecular immune response of the sentinel lymph node. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 454. doi:10.1158/1538-7445.AM2015-454

Evidence of Th2 polarization of the sentinel lymph node (SLN) in melanoma

Melanoma has a propensity for lymphatogenous metastasis. Improved understanding of the sentinel lymph node (SLN) immunological environment may improve outcomes. The immune phenotype of fresh melanoma SLNs (n = 13) were compared to fresh control lymph nodes (n = 13) using flow cytometry. RNA was isolated from CD4+ T cells of the SLN and control lymph node and assessed for Th1/Th2 gene expression pathways using qRT-PCR. In addition, VEGF expression was compared between primary melanoma (n = 6) and benign nevi (n = 6) using immunohistochemistry. Melanoma SLNs had fewer CD8+ T cells compared to controls (9.2% vs. 19.5%, p = 0.0005). The CD8+ T cells within the SLN appeared to have an exhausted phenotype demonstrated by increased PD-1 mRNA expression (2.2% vs. 0.8%, p = 0.004) and a five-fold increase in CTLA-4 mRNA expression. The SLN also contained an increased number of CD14 (22.7% vs. 7.7%, p = 0.009) and CD68 (9.3% vs. 2.7%, p = 0.001) macrophages, and CD20 B cells (31.1% vs. 20.7%, p = 0.008), suggesting chronic inflammation. RT-PCR demonstrated a significant Th2 bias within the SLN. In vitro studies demonstrated a similar Th2 polarization with VEGF treatment of control lymph nodes. The primary melanoma demonstrated strong VEGF expression and an increase in VEGFR1 within the SLN. Melanoma is associated with Th2-mediated “chronic inflammation,” fewer cytotoxic T cells, and an exhausted T cell phenotype within the SLN combined with VEGF overproduction by the primary melanoma. These immunologic changes precede nodal metastasis and suggests consideration of VEGF inhibitors in future immunotherapy studies.

The Utility of Intraoperative Handheld Gamma Camera for Detection of Sentinel Lymph Nodes in Melanoma.

Accurate identification of the sentinel lymph node (SLN) is an important prognostic factor for melanoma. In a minority of cases drainage to interval nodal basins, such as the epitrochlear region, are possible. Intraoperative handheld gamma cameras have been used to detect SLNs which are located in different anatomical localizations. In this case we report the utility of an intraoperative handheld gamma camera in the localization of epitrochlear drainage of distal upper extremity melanoma and its impact on surgical procedure.

Sentinel lymph node in melanoma: present aspects and future trends

In melanoma, the sentinel lymph node (SLN) status is the most important factor determining overall survival. Lymphoscintigraphy is a current practice evolving since more than 20 years. It represents the standard practice in detecting SLN and includes dynamic imaging and SPECT/CT. This article reviews the different technical aspects of lymphoscintigraphy with their advantages. It also reviews the main other ways of SLN imaging in melanoma, including more specific techniques, some of them representing a field of research. A PUBMED (MeSH) search was performed with the following keywords: sentinel lymph node melanoma imaging and reviewed relevant articles. We excluded case reports, publications with an Impact Factor lower than 2 and older than 10 years. The use of dynamic and delayed images combined with preoperative SPECT/CT and blue dye during surgery remains the method of choice in sentinel lymph node melanoma detection. SPECT/CT provides several advantages, in particular a higher rate of node detection, better nodes localization and reduction of operative time, with significantly reducing costs. To provide longer retention in lymphatic nodes, some targeted agents are developed but their clinical use is limited. Lymphatic staging with imaging contrast agents could directly assess nodal status without surgery and could be a promising method for the future.

Clinical significance of microscopic melanoma metastases in the nonhottest sentinel lymph nodes.

A practice gap exists in the surgical removal of sentinel lymph nodes, from removal of only the most radioactive (hottest) lymph node to removal of all lymph nodes with radioactivity greater than 10% of the hottest lymph node. To determine the clinical significance of melanoma in sentinel lymph nodes that are not the hottest sentinel node and to determine the risk for disease progression based on sentinel lymph node status and primary tumor characteristics. Consecutive patients with cutaneous melanoma with sentinel lymph nodes resected from January 5, 2004, to June 30, 2008, with a mean follow-up of 59 months, at Massachusetts General Hospital were included in this retrospective review. The last year of follow-up was 2012. The operative protocol led to resection of all sentinel lymph nodes with radioactivity greater than 10% of the hottest lymph node. The number of lymph nodes removed, technetium-99m counts for each sentinel lymph node, presence or absence of sentinel lymph node metastases, primary tumor characteristics, disease progression, and melanoma-specific survival were recorded. Microscopic melanoma metastases in the hottest and nonhottest sentinel lymph nodes and factors that correlate with disease progression and mortality. A total of 1575 sentinel lymph nodes were analyzed in 475 patients. Ninety-one patients (19%) had positive sentinel lymph nodes. Of these, 72 (79%) had metastases in the hottest sentinel lymph node. Of 19 cases with tumor present, but not in the hottest sentinel lymph node, counts ranged from 26% to 97% of the hottest node. Progression occurred in 43% of patients with sentinel node metastasis, regardless of whether the hottest lymph node was positive. In patients with negative sentinel lymph nodes, 11% developed metastases beyond the sentinel lymph node basin and 3.4% recurred in the basin. Mitogenicity of the primary tumor was associated with mortality (odds ratio, 2.435; 95% CI, 1.351-4.391; P < .001). Removing only the hottest sentinel lymph node would have led to false-negative results in 19 of 475 (4%) of all patients and 19 of 91 patients (21%) with positive sentinel lymph nodes. The 8-year survival in patients with at least 1 positive sentinel lymph node was less than 55%. The presence of more than 1 mitosis per square millimeter in the primary cutaneous melanoma was associated with decreased survival. Microscopic melanoma metastases was associated with disease progression and mortality, whether present in the hottest sentinel lymph node or not. These observations emphasize the importance of removing the less hot nodes, addressing a practice gap in the surgical approach to patients with melanoma.

Selective biopsy of sentinel node in melanoma. Survey results of nuclear medicine services in Spain

Selective biopsy of sentinel node in melanoma. Survey results of nuclear medicine services in Spain

Selective biopsy of sentinel node in melanoma. Survey results of nuclear medicine services in Spain

of Radio-guided Surgery (RGS) of the Spanish Society of Nuclear Medicineand Molecular Imaging (SEMNIM) analyzed the data obtained witha survey carried out in the Departments of Nuclear Medicine of ourcountrywiththeaimofevaluatingtheuniformityofthecriteriaandtechniques used in selective sentinel lymph node biopsy (SSLNB)in malignant melanoma (MM).The survey collected data regarding: the year of techniqueimplementation, the number of cases, inclusion criteria, previousultrasonography of lymph node regions, rate of scintigraphic andsurgical localization and the false negative rate in both the vali-dation and application phases. The survey also included questionsrelated to the injection site, radiotracer used, the imaging protocolperformed, the use of SPECT and/or SPECT-CT, the use of a portablegamma camera and dyes, the histological studies carried out andthe role of nuclear medicine staff in the operating room.The survey was sent to 135 centers with Nuclear MedicineDepartments and response was obtained from 42 centers, 38 ofwhich provided data.ResultsValidation phaseThe validation phase was carried out in 17 centers, with only 11having data in this phase which included 10–50 patients (mean:15).The rates of scintigraphic and surgical localization ranged from95% to 100% and the false negative rate in axillary lymph nodedissection was of 0–5%.

Sentinel node in melanoma and breast cancer. Current considerations

The main objectives of sentinel node (SN) biopsy are to avoid unnecessary lymphadenectomies and to identify the 20–25% of patients with occult regional metastatic involvement. This technique reduces the associated morbidity from lymphadenectomy and increases the occult lymphatic metastases identification rate by offering the pathologist the lymph nodes with the highest probability of containing metastatic cells. Pre-surgical lymphoscintigraphy is considered a “road map” to guide the surgeon toward the sentinel nodes and to localize unpredictable lymphatic drainage patterns. The SPECT/CT advantages include a better SN detection rate than planar images, the ability to detect SNs in difficult to interpret studies, better SN depiction, especially in sites closer to the injection site and better anatomic localization. These advantages may result in a change in the patient's clinical management both in melanoma and breast cancer. The correct SN evaluation by pathology implies a tumoral load stratification and further prognostic implication. The use of intraoperative imaging devices allows the surgeon a better surgical approach and precise SN localization. Several studies report the added value of such devices for more sentinel nodes excision and a complete monitoring of the whole procedure. New techniques, by using fluorescent or hybrid tracers, are currently being developed.

Sentinel node in melanoma and breast cancer. Current considerations

The main objectives of sentinel node (SN) biopsy is to avoid unnecessary lymphadenectomies and to identify the 20-25% of patients with occult regional metastatic involvement. This technique reduces the associated morbidity from lymphadenectomy and increases the occult lymphatic metastases identification rate by offering the pathologist the or those lymph nodes with the highest probability of containing metastatic cells. Pre-surgical lymphoscintigraphy is considered a "road map" to guide the surgeon towards the sentinel nodes and to localize unpredictable lymphatic drainage patterns. The SPECT/CT advantages include a better SN detection rate than planar images, the ability to detect SNs in difficult to interpret studies, better SN depiction, especially in sites closer to the injection site and better anatomic localization. These advantages may result in a change in the patient's clinical management both in melanoma and breast cancer. The correct SN evaluation by pathology implies a tumoral load stratification and further prognostic implication. The use of intraoperative imaging devices allows the surgeon a better surgical approach and precise SN localization. Several studies reports the added value of such devices for more sentinel nodes excision and a complete monitoring of the whole procedure. New techniques, by using fluorescent or hybrid tracers, are currently being developed.