Selective Sentinel Lymph Node Dissection Research Articles

Endometrial stripe thickness: a preoperative marker to identify patients with endometrial intraepithelial neoplasia who may benefit from sentinel lymph node mapping and biopsy

ObjectivesThe goal of our study was to identify preoperative factors in patients with endometrial intraepithelial neoplasia that are associated with concurrent endometrial cancer to select patients who may benefit from...

Is Head and Neck Melanoma Different from Trunk and Extremity Melanomas with Respect to Sentinel Lymph Node Status and Clinical Outcome?

Previous studies showed conflicting and inconsistent results regarding the effect of anatomic location of the melanoma on sentinel lymph node (SLN) positivity and/or survival. This study was conducted to evaluate and compare the effect of the anatomic locations of primary melanoma on long-term clinical outcomes. All consecutive cutaneous melanoma patients (n=2,079) who underwent selective SLN dissection (SLND) from 1993 to 2009 in a single academic tertiary-care medical center were included. SLN positive rate, disease-free survival (DFS), and overall survival (OS) were determined. Kaplan-Meier survival, univariate, and multivariate analyses were performed to determine predictive factors for SLN status, DFS, and OS. Head and neck melanoma (HNM) had the lowest SLN-positive rate at 10.8% (16.8% for extremity and 19.3% for trunk; P=0.002) but had the worst 5-year DFS (P<0.0001) and 5-year OS (P<0.0001) compared with other sites. Tumor thickness (P<0.001), ulceration (P<0.001), HNM location (P=0.001), mitotic rate (P<0.001), and decreasing age (P<0.001) were independent predictive factors for SLN-positivity. HNM with T3 or T4 thickness had significantly lower SLN positive rate compared with other locations (P≤0.05). Also, on multivariate analysis, HNM location versus other anatomic sites was independently predictive of decreased DFS and OS (P<0.001). By Kaplan-Meier analysis, HNM was associated significantly with the worst DFS and OS. Primary melanoma anatomic location is an independent predictor of SLN status and survival. Although HNM has a decreased SLN-positivity rate, it shows a significantly increased risk of recurrence and death as compared with other sites.

Selective sentinel lymph node dissection in head and neck cutaneous melanoma

Sentinel lymph node biopsy accuracy and prognostic value in the head and neck region has been established. The article describes the current indications for the procedure, lymph node localization using lymphoscintigraphy and intra-operative blue dye injection, the surgical technique, and important recommendations to avoid complications in this very important anatomic region.

In-Transit Intramammary Sentinel Lymph Nodes From Malignant Melanoma of the Trunk

Our goal was to determine the incidence and outcomes of intramammary in-transit sentinel lymph nodes (IMSLN) from primary malignant melanoma (MM) of the trunk. We hypothesize that regional metastasis to the breast from anterior trunk MM also occurs via the lymphatic system to these intramammary in-transit sentinel lymph nodes. MM is the most common solid tumor metastasis to the breast. The mechanism of intramammary (IM) metastasis is generally attributed to hematogenous rather than lymphatic spread. We retrospectively reviewed medical records from all patients who underwent selective sentinel lymph node dissection at the UCSF Melanoma Center from 1993 to 2008 after the approval of UCSF Committee on Human Research. Of the 1911 cases, we found 614 patients with primary MM located on the trunk, and queried their medical records for in-transit SLN and SLNs in the breast. Data from preoperative lymphoscintigraphy, intraoperative lymphatic mapping, operative notes, and pathology and clinic notes were gathered. Of the 1911 patients with MM, 169 (8.9%) and 420 (22.0%) had anterior and posterior trunk lesions, respectively, and 25 patients (1.3%) with flank lesions (lateral abdominal wall below the rib cage, above the iliac crest). Of the anterior trunk population, 18 patients had in-transit SLNs. The vast majority of these patients (14 of 18, 77.8%) had in-transit IMSLN. Of patients with posterior trunk melanoma, 27 patients had in-transit nodes with 1 patient having IMSLNs. Of patients with flank melanomas, 3 patients had in-transit nodes with 1 patient having IMSLNs. Interestingly, all patients with IMSLNs had primary lesions located inferior to the breasts. Two of the 16 patients with IMSLNs had micrometastasis to IMSLN; 1 patient died and the other currently is disease free 4 years after initial SLND. Four of the 32 patients with non-IM in-transit nodes had micrometastases to these in-transit nodes. Of all patients with trunk melanomas, 4 patients had micrometastases to axillary SLNs (AxSLNs). Three of the 4 patients with positive AxSLNs also had positive in-transit nodes whereas only half of the patients with positive in-transit SLNs had positive AxSLNs. IMSLNs exist in the breast. Our results establish an anatomic basis for lymphatic metastasis to the breast from primary cutaneous melanoma mainly from the anterior trunk inferior to the breasts. For anterior trunk melanomas, IMSLNs should not be overlooked during SLND as they may harbor micrometastasis.

Role of selective sentinel lymph node dissection in head and neck melanoma

Selective sentinel lymph node dissection (SLND) plays an important role in the staging of the regional nodal basins for head and neck (H&N) melanoma. Preoperative lymphoscintigraphy is mandatory to identify the regional nodal basin(s) accurately for a newly diagnosed H&N primary melanoma of at least 1mm or greater. A wide local excision should be delayed if SLN mapping is indicated, to minimize watershed effect and maximize accuracy in identifying the "true" SLN because of the complex lymphatic network in the H&N region. An experienced multidisciplinary team is required for optimal identification of H&N SLNs. In general, selective SLND can replace ELND to minimize the complications of a neck dissection. Completion lymph node dissection is only indicated when the SLN is positive. A nerve stimulator should be used during selective SLND in the parotid and posterior triangle to minimize the injury to the facial and spinal accessory nerve.

Selective Sentinel Lymph Node Dissection for Melanoma: Importance of Harvesting Nodes with Lower Radioactive Counts without the Need for Blue Dye

Determining how many sentinel lymph nodes (SLNs) should be removed for melanoma is important. The purpose of this study is to determine the frequency at which nodes that are less radioactive than the "hottest" node (which is negative) are positive for melanoma, how low of a radioactivity should warrant harvest, and if isosulfan blue is necessary. We reviewed 1,152 melanoma patients who underwent lymphoscintigraphy with technetium, with or without blue dye, and SLN dissection from 1996 to 2008. SLNs with radioactivity ≥10% of the "hottest" SLN, all blue nodes, and all suspicious nodes were removed and analyzed. The miss rate was calculated as the proportion of node positive cases in which the "hottest" SLN was negative. SLNs were identified in 1,520 nodal basins in 1,152 patients. SLN micrometastases were detected in 218 basins (14%) in 204 patients (18%). In 16% of SLN-positive patients (33/204 patients), the positive SLN was found to have a lower radioactive count than the "hottest" SLN, which was negative. In 21 of these cases, the positive SLNs had radioactivity ≤50% of the "hottest" SLN. The 10% rule significantly reduced the miss rate to 2.5% compared with removal of only the "hottest" SLN (miss rate = 16%). Also, blue dye did not significantly decrease the miss rate compared with radiocolloid alone using the 10% rule. To decrease the miss rate, all SLNs with ≥10% of the ex vivo radioactivity of the "hottest" SLN should be removed and blue dye is not essential.

Utility of Computed Tomography and Magnetic Resonance Imaging Staging Before Completion Lymphadenectomy in Sentinel Lymph Node–Positive Melanoma

TO THE EDITOR: In their excellent study, Aloia et al have confirmed our results that modern computed tomography and magnetic resonance imaging do not detect distant metastases in patients with melanoma metastatic to sentinel lymph nodes. With the addition of their 314 patients to the 185 already reported, the detectable distant metastasis rate in stage III melanoma patients at the time of selective sentinel lymph node dissection (SLND) can be more accurately estimated at approximately 1.2% (range, 0.5% to 1.9%). Furthermore, because Aloia et al had several patients with distant metastases, the risk factors for detectable distant metastasis within 3 months of SLND have been further refined to include patients with very thick ( 3.5 mm) ulcerated melanomas with large tumor burdens metastatic to regional lymph node basins. Conversely, these data should not be interpreted in a way that results in tumors that are thick or ulcerated or have high regional tumor burden being classified as needing further imaging via computed tomography or magnetic resonance imaging. False-positive rates of 12% to 14% make this a potentially dangerous treatment protocol (for example, although ulceration was shown to be an independent risk factor for distant metastasis; P .018; 107 of 112; 96%; ulcerated melanomas were negative for distant metastasis). What would be particularly interesting is to know whether or not any of the five patients with distant metastases were symptomatic. In our original study, only asymptomatic patients received SLND. However, when the history of the one patient with true distant metastasis was reviewed, he had developed constitutional symptoms after initial diagnosis but before SLND. If in retrospect these patients were actually symptomatic, a valuable clue would be added to the ones already brought forth by Aloia et al, aiding the discrimination of those patients with stage III disease who do need imaging for staging from the majority who do not.

Matched Skin and Sentinel Lymph Node Samples of Melanoma Patients Reveal Exclusive Migration of Mature Dendritic Cells

Mature and immature myeloid dendritic cells (DCs) are thought to differentially modulate T-cell responses in secondary lymphoid tissues. Although mature DCs are believed to induce T-cell activation under proinflammatory conditions, immature DCs are believed to maintain a state of T-cell tolerance under steady state conditions. However, little is known about the actual activation state of human DCs under these different conditions. Here, we compare the frequency and activation state of human DCs between matched skin and sentinel lymph node (SLN) samples, after intradermal administration of either granulocyte/macrophage colony-stimulating factor (GM-CSF) or saline, at the excision site of stage I primary melanoma. Although DCs remained immature (CD1a+CD83-) and mostly situated in the epidermis of the saline-injected skin (fully consistent with a quiescent steady state), mature (CD1a+CD83+) DC frequencies significantly increased in the GM-CSF-injected skin and correlated with the number of mature DCs in the SLN, indicative of increased DC migration. Interestingly, irrespective of GM-CSF or saline administration, all CD1a+ myeloid DCs in the SLN were phenotypically mature (ie, CD83+). These data are indicative of migration of small numbers of phenotypically mature DCs to lymph nodes under steady state conditions.

Sentinel lymph node dissection in stage I/II melanoma patients: surgical management and clinical follow-up study

Selective sentinel lymph node (SLN) dissection is widely used in the management of cutaneous melanoma patients without clinical evidence of nodal metastases. A series of 274 consecutive melanoma patients who underwent melanoma primary excision and SLN mapping at our institutions since 1998, and were thereafter followed up and eventually treated, is reported in this prospective study. The aim was to analyse the parameters associated with a higher risk of occult nodal metastases, to evaluate the clinical outcome of melanoma patients who underwent SLN procedure, and to identify by means of multivariate analysis the prognostic parameters with independent predictive value on disease-free survival (DFS) in node-positive and negative patients. The SLN was tumour-negative in 228 patients (83.2%). A disease progression occurred in 25 (10.9%); among them, 10 patients in whom the initially identified SLN had been negative, developed a clinically and histologically evident positive lymph node in the same basin during follow-up. Five-year DFS and overall survival were 75% and 82%, respectively. In 46 patients (16.8%), the SLN proved to be tumour positive. The percentage of SLN-positive patients varied according to the primary thickness, from 11.8% in patients with Breslow of 2 mm or lower, to 34.7% in patients with Breslow from 2 to 4 mm, up to 55.9% in patients with Breslow greater than 4 mm (P<0.001). Only two patients with Breslow thickness lower than 1 mm had positive SLN biopsy. Five-year DFS and overall survival (OS) were 42 and 69%, respectively, significantly lower than those of negative SLN-patients (P<0.001). Multivariate analyses showed that the parameters with prognostic independent value on DFS were SLN status (micrometastases or macrometastases; P=0.0001), and to a lesser extent, Breslow thickness (P=0.04). In conclusion, our data support the clinical usefulness of SLN dissection as a reliable and accurate staging method in patients with cutaneous melanoma. SLN-positive patient OS (5-year survival 69%) seems to be superior to that historically reported for stage III patients treated with curative nodal dissection only after the clinical evidence of palpable adenopathies (5-year survival 36%). The prognostic relevance of the pattern of SLN invasion (micrometastases/macrometastases) could be the basis for the planning of adjuvant treatment trials on selected groups of patients.

Clinical Outcome of Stage I/II Melanoma Patients After Selective Sentinel Lymph Node Dissection: Long-Term Follow-Up Results

Although sentinel lymph node (SLN) status is part of the new American Joint Committee on Cancer staging system, there is no final proof that the SLN procedure in melanoma patients influences outcome of disease. This study investigated the accuracy of the SLN procedure and clinical outcome in melanoma patients after at least 60 months of follow-up. Between 1993 and 1996, 209 patients with stage I/II cutaneous melanoma underwent selective SLN dissection by the triple technique. If the SLN contained metastatic disease, a completion lymphadenectomy was performed. Survival analyses were performed using the Kaplan-Meier approach. Factors associated with survival were analyzed using the Cox proportional hazards regression model. The success rate was 99.5%. Median follow-up was 72 months. Forty patients (19%) had a positive SLN. The false-negative rate was 9%. Five-year overall survival was 87% for the entire group and 92% and 67% for SLN-negative and SLN-positive patients (P <.0001), respectively. All patients with a positive SLN and a Breslow thickness < or = 1.00 mm survived, and SLN-positive patients with a Breslow thickness less than 2.00 mm tend to have a better prognosis compared with SLN-negative patients with a Breslow thickness greater than 2.00 mm. SLN status (P =.002), Breslow thickness (P =.002), and lymphatic invasion (P =.0009) were all found to be independent prognostic factors for overall survival. With a success rate of 99.5% and a false-negative rate of 9% after long-term follow-up, the triple-technique SLN procedure is a reliable and accurate method. Survival data seem promising, although a therapeutic effect is still questionable. As shown in this study, not all SLN-positive patients have a poor prognosis.

The role of sentinel lymph node biopsy for melanoma

Regional lymph nodes are a common site of melanoma metastases, and the presence or absence of melanoma in regional lymph nodes is the single most important prognostic factor for predicting survival. Furthermore, identification of metastatic melanoma in lymph nodes and excision of these nodes may enhance survival in a subgroup of patients whose melanoma has metastasized only to their regional lymph nodes and not to distant sites. Sentinel lymph node (SLN) biopsy was developed as a low morbidity technique to stage the lymphatic basin without the potential morbidity of lymphedema and nerve injury. The presence or absence of metastatic melanoma in the SLN accurately predicts the presence or absence of metastatic melanoma in that lymph node basin. When performed by experienced centers, the false-negative rate of SLN biopsy is very low. As such, the nodal basin that contains a negative SLN will usually be free of microscopic disease. Since occult micrometastatic disease affects only 12% to 15% of patients with melanoma, selective SLN dissection allows up to 85% of patients with melanoma to be spared a formal lymph node dissection, thus avoiding the complications usually associated with that procedure. While standard pathologic evaluation of lymph nodes may miss metastatic melanoma cells, more sensitive techniques are developing which may identify micrometastases more accurately. The clinical significance of these micrometastases remains unknown and is the subject of active investigations. Semin Oncol 29:341-352. Copyright 2002, Elsevier Science (USA). All rights reserved.

Cytokine Profiles of Sentinel Lymph Nodes Draining the Primary Melanoma

The sentinel lymph node (SLN) draining the primary melanoma is the first echelon node where micrometastasis is established. SLNs may be the initial sites of antigen presentation associated with immune responses. A portion of each SLN from 68 melanoma patients undergoing selective SLN dissection was processed for enzyme-linked immunospot (ELISPOT) assay determination of interferon gamma (IFN-gamma), interleukin-2 (IL-2), granulocyte macrophage colony-stimulating factor (GM-CSF), and interleukin-10 (IL-10) secretion. The control was the adjacent non-SLN. Lymphocytes were stimulated with staphylococcal enterotoxin A (SEA) prior to ELISPOT assay. No significant difference was noted in the production of IL-10 between the SLNs and non-SLNs. Significant production of IFN-gamma, IL-2, and GM-CSF was noted in the SLNs when compared to the non-SLNs in the overall group. Patients with no micrometastasis (n = 60) had elevated secretion of all cytokines in the SLNs. However, patients harboring lymph node micrometastasis (n = 8) showed no increase of cytokine secretion in the SLNs. Significant Th1 and Th2 response was induced in melanoma-free SLNs. SLNs without micrometastasis may be activated by submicroscopic cells or soluble tumor antigens, while cytokine production may be down-regulated by micrometastasis. Future studies should be directed towards identifying the specific SLN T cells recognizing the tumor antigens.

Early experience with sentinel lymph node mapping for Merkel cell carcinoma

Merkel cell or cutaneous neuroendocrine carcinoma is a malignant tumor with a propensity toward local and systemic recurrence. A new surgical technique, intraoperative lymphatic mapping and selective sentinel lymph node dissection (SSLND), has been demonstrated to have a high predictive value for the detection of metastatic disease in the regional lymphatic basin in cutaneous melanoma. The use of this technology may be particularly useful to accurately stage patients with Merkel cell carcinoma (MCC) because this tumor has a frequent propensity toward regional nodal metastases. Intraoperative lymphatic mapping and SSLND were performed on 6 patients with biopsy-proven MCC. Three patients with MCC had positive disease in the sentinel lymph node(s). SSLND is a feasible technique with minimal procedural morbidity to detect clinically occult disease in patients with MCC. (J Am Acad Dermatol 2001;45:303-8.)

Evaluation of sentinel lymph node status in spindle cell melanomas

Background: The propensity for spindle cell melanoma to metastasize to the lymph node is relatively low despite its relative thick depth. To date, there are no published reports on the sentinel lymph node (SLN) status in patients diagnosed with spindle cell melanoma and desmoplastic malignant melanoma (DMM). Objective: Our purpose was to report our experience on the SLN status in spindle cell melanoma and DMM. Methods: We undertook a retrospective database and medical record review from Oct 21, 1993 to Sept 29, 1999. At the University of California at San Francisco Melanoma Center, patients with tumor thickness greater than 1 mm or less than 1 mm with high-risk features are managed with preoperative lymphoscintigraphy, selective SLN dissection, and wide excision. Results: Of 29 patients diagnosed with spindle cell melanoma and DMM, 28 had negative SLNs and are free of disease except for one patient who experienced splenic, bony, and brain metastases. The mean follow-up in this population was 16.5 and 11 months, respectively. Conclusion: Our preliminary findings show that SLNs from patients diagnosed with spindle cell melanoma and DMM only rarely harbor micrometastasis despite their relative thickness. A larger number of cases from multicenter databases may further define the true biology of SLNs in this melanoma variant. (J Am Acad Dermatol 2001;44:451-5.)

THE ROLE OF SENTINEL LYMPH NODES IN MALIGNANT MELANOMA

Selective sentinel lymph node dissection should be considered a standard approach in the treatment of primary malignant melanoma. With the combination of blue dye and radioisotope mapping, the sentinel lymph nodes (SLNs) can be harvested with pinpoint accuracy. This article compares blue dye and radioisotope mapping techniques. Based on the clinical outcome data of selective sentinel lymph node dissection, micrometastasis to the SLNs carries a poor prognosis for patients with primary invasive melanoma.

THE ROLE OF SELECTIVE SENTINEL LYMPH NODE DISSECTION IN BREAST CANCER

Axillary nodal status continues to be the most statistically significant predictor of survival for patients with breast cancer. Although still providing regional control of axillary disease, axillary dissection is more important as a staging and prognostic tool. Trials are currently underway to investigate the possibility of replacing the current standard treatment of breast cancer, axillary lymph node dissection, with the less invasive lymphatic mapping and sentinel lymph node biopsy. This issue and the technical aspects of sentinel lymph node mapping for breast cancer are discussed in detail in this article.

Multidisciplinary approach to selective sentinel lymph node mapping in breast cancer.

Although the role of axillary lymph node dissection is controversial with respect to survival benefits, its role as a staging procedure has been well established since nodal involvement is the most reliable prognostic indicator for patients with breast cancer. Selective sentinel lymph node (SLN) dissection is gaining acceptance as a useful staging procedure because it is minimally invasive and spares approximately 70-80% of the patients a more extensive axillary lymph node dissection. The evolving techniques for selective SLN dissection using blue dye and radiotracer methods are reviewed in this article. Based on the classic definition of the breast lymphatic drainage and recently published articles addressing the issue of peritumoral and intradermal injections, a possible new and simplified approach using intradermal injection may identify the axillary SLN more quickly and reliably. This article emphasizes the importance of a multidisciplinary approach in the identification of SLNs by preoperative lymphoscintigraphy performed by expert nuclear medicine physicians, the intraoperative mapping and harvesting of SLNs by well trained surgeons and the meticulous examination of SLNs by experienced pathologists. Therefore, to achieve the highest rate of accuracy regarding SLN status, it is imperative that a multidisciplinary team with close communication and cooperation be formed. The clinical significance of SLNs will be determined by results from follow-up and clinical trials.

Linfogammagrafía y estudio del ganglio centinela en el melanoma cutáneo

To evaluate the role of selective sentinel lymph node dissection to reduce the number of unnecessary lymphadenectomies in patients with intermediate risk of melanoma and without clinical evidence of regional node and distant metastases. We studied 65 patients with stage I and II melanoma. Only vital blue dye mapping was carried out in nine patients and combined lymphatic mapping with both blue dye and lymphoscintigraphy was used in the remaining 56 patients. The sentinel node was identified in 63 of 65 patients (97%). Only eighth patients (12%) were found to have metastatic melanoma cells in their sentinel node. Our findings confirm that the intraoperative lymphatic mapping of the sentinel node using both blue dye and radiodetection is an appropriate and simple technique for selecting patients who are more likely to benefit from lymph node dissection.

Patterns of recurrence in primary malignant melanoma following selective sentinel lymph node dissection (SSLND)

Patterns of recurrence in primary malignant melanoma following selective sentinel lymph node dissection (SSLND)