Interval sentinel lymph nodes in melanoma

HYPOTHESIS: For patients with melanoma, interval or in-transit sentinel lymph nodes (SLNs) have the same risk for nodal metastasis as SLN in traditional (ie, cervical, axillary, and inguinal) nodal basins. DESIGN: Prospective clinical trial. SETTING: Multicenter study. PATIENTS: Eligible patients were aged 18 to 70 years with melanomas of at least 1.0-mm Breslow thickness and nodes with clinically negative findings. INTERVENTION: Sentinel lymph node biopsy was guided by preoperative lymphoscintigraphy to identify all SLNs. MAIN OUTCOME MEASURES: We evaluated interval nodal sites, including epitrochlear, popliteal, and subcutaneous or intramuscular nodes outside of traditional basins, for the presence of metastases. RESULTS: The SLNs were identified in 2332 nodal basins from 2000 patients. In 62 patients (3.1%), interval SLNs were identified. We found SLN metastases in 442 (19.5%) of 2270 conventional nodal basins and 13 (21.0%) of 62 interval sites. In 11 (84.6%) of the 13 cases in which we found an interval node that was positive for metastatic disease, it was the only site of nodal metastasis. CONCLUSIONS: Although interval SLNs are identified infrequently, they contain metastatic disease at nearly the same frequency as SLNs in cervical, axillary, and inguinal nodal basins. Positive interval SLNs are likely to be the only site of nodal metastasis. Therefore, detailed preoperative lymphoscintigraphy and meticulous intraoperative search for interval nodes should be performed.     

Outcome of patients with melanoma and histologically negative sentinel lymph nodes

HYPOTHESIS: Patients with melanoma and histologically negative sentinel lymph nodes identified by lymphatic mapping have a very good prognosis. DESIGN: Cohort study with follow-up information obtained from medical records and telephone interviews. SETTING AND PATIENTS: Of all patients with cutaneous melanoma who underwent intraoperative sentinel lymph node mapping between November 15, 1993, and April 18, 1997, at the Massachusetts General Hospital, Boston, 89 were found to have no evidence of melanoma in their sentinel nodes. Forty-six lesions (51%) were on an extremity and 44 (49%) were of axial location. The median tumor thickness was 1.8 mm (range, 0.36-12.0 mm) and 11 tumors (12%) were ulcerated. INTERVENTIONS: Patients underwent intraoperative sentinel lymph node mapping with lymphazurin and radiolabeled sulfur colloid. Sentinel lymph nodes were analyzed by standard hematoxylin-eosin staining. Only 2 patients received adjuvant therapy following wide excision of the primary lesion. MAIN OUTCOME MEASURES: Site of initial recurrence and time to initial recurrence. RESULTS: The median follow-up for all patients was 23 months (range, 2-54 months). Eleven patients (12%) developed melanoma recurrences, and 78 (88%) patients remain disease free. Regional lymph nodes were the initial site of recurrence in 7 (8%) of 89 patients, and 7 (7%) of 106 mapped basins. Four patients had recurrence without involvement of regional lymph nodes: 2 with distant metastases and 2 with in transit metastases. The median time to recurrence was 12 months (range, 2-35 months). Sentinel lymph nodes were reanalyzed using serial sections and immunoperoxidase stains in 7 patients with recurrence and metastatic melanoma was identified in 3 (43%). CONCLUSIONS: The risk for melanoma recurrence is relatively low in patients with histologically negative sentinel nodes identified by lymphatic mapping. Longer follow-up will improve our understanding of the prognostic value of this procedure.     

Aberrant sentinel nodes in malignant melanoma.

The option of sentinel lymph node biopsy for patients with a cutaneous malignant melanoma has allowed an alternative to the traditional approaches to lymph node basin surgery. Lymphatic mapping usually identifies the sentinel node(s) in a recognised lymphatic basin, however aberrant nodes may occasionally be identified outside these areas. The notes of 100 consecutive patients with a localised cutaneous malignant melanoma, who had a sentinel lymph node biopsy in our unit, were reviewed. Lymphatic mapping identified three patients with aberrant sentinel lymph nodes. Failure to remove an aberrant sentinel lymph node harbouring metastatic melanoma may reduce significantly the chance of control or cure of the disease. In order to reduce this risk we advocate lymphatic mapping prior to surgical management of the draining lymph nodes of a cutaneous malignant melanoma.     

Reliability of lymphoscintigraphy in indicating the number of sentinel nodes in melanoma patients

Background: This study was undertaken to establish the reliability of lymphoscintigraphy in indicating the number of sentinel nodes in patients with melanoma. Methods: Lymphoscintigraphy was performed with dynamic imaging after injection of 60 MBq^99mTc-nanocolloid (1.6 mCi) and static imaging after 2 hours in 200 patients with clinically localized primary melanoma of the skin. The following day, sentinel nodes were retrieved with the blue dye technique and a gamma detection probe (Neoprobe 1000/1500). The discrepancies between the number of sentinel nodes indicated by lymphoscintigraphy and the actual number of sentinel nodes as established by the surgeon were evaluated. Results: Lymphoscintigraphy showed drainage to 393 sentinel nodes in 255 lymphatic fields in 199 patients. In 48 lymphatic fields (19%) in 46 patients (23%), the number of sentinel nodes was different from the number that was visualized with scintigraphy. Additional sentinel nodes were found by the surgeon because a lymphatic vessel was not seen on the lymphoscintigraphy (43%), because a sentinel node was not visualized separately from other hot nodes or vessels or the injection site (36%), or because a sentinel node was blue and not hot (4%). Fewer sentinel nodes were found than suggested by scintigraphy because a lymphangioma was mistaken for a sentinel node (4%) or because a single elongated node was depicted as two hot spots (6%). Conclusions: Although lymphoscintigraphy is indispensable for lymphatic mapping, the predicted number of sentinel nodes is accurate in only 81% of lymph node fields. The limited discriminating power of the gamma camera is an important cause of discrepancies. Presented at the 4th World Conference on Melanoma, Sydney, Australia, June 10–14, 1997, and the First World Congress of Surgical Oncology, WFSOS/SSO meeting, San Diego, California, March 26–29, 1998.     

Failure to remove true sentinel nodes can cause failure of the sentinel node biopsy technique: Evidence from antimony concentrations in false-negative sentinel nodes from melanoma patients

We have recently found that antimony (originating from the technetium 99m antimony trisulfide colloid, used for preoperative lymphoscintigraphy) can be measured in tissue sections from archival paraffin blocks of sentinel nodes (SNs) by means of inductively coupled plasma mass spectrometry (ICP-MS) to confirm that removed nodes are ture SNs. We performed a retrospective analysis of antimony concentrations in all our false-negative (FN) SNs to determine whether errors in lymphadenectomy (i.e., failure to remove true SNs) may be a cause of FN SN biopsies (SNBs). Among 27 patients with an FN SNB, metastases were found on histopathologic review of the original slides or additional sections in 7 of 23 patients for which they were available; however, antimony concentrations were low in 5 of 20 presumptive SNs. Our results suggest that an FN SNB can occur because of failure to remove the true SN as well as histopathologic misdiagnosis.     

Results of complete lymph node dissection in 83 melanoma patients with positive sentinel nodes

Background: The technique of sentinel lymph node (SLN) biopsy for melanoma provides accurate staging information because the histology of the SLN reflects the histology of the entire basin, particularly when the SLN is negative. Methods: We combined two mapping techniques, one using vital blue dye and the other using radiolymphoscintigraphy with a hand-held gamma Neoprobe, to identify the SLN in 600 consecutive patients with stage I–II melanoma. The SLNs were examined using conventional histopathology and immunohistochemistry for S-100. Results: Eighty-three (13.9%) patients had micrometastatic disease in the SLNs. Thirty percent of patients with primary melanomas greater than 4.0 mm in thickness had positive SLNs, followed by 48 of 267 (18%) of patients with tumors between 1.5 mm and 4 mm, and 12 of 169 (7%) of those with lesions between 1.0 mm and 1.5 mm. No patient with a tumor less than 0.76 mm in thickness had a positive SLN. Sixty-four of the 83 SLN-positive patients consented to undergo complete lymph node dissection (CLND), and five of 64 (7.8%) of the CLNDs were positive. All patients with positive CLNDs had tumor thicknesses greater than 3.0 mm. Conclusions: The rate of SLN-positive patients increases with increasing thickness of the melanoma. SLN-positive patients with primary lesions less than 1.5 mm in thickness may have disease confined to the SLN, thus rendering higher-level nodes free of disease, and may not require a CLND. Presented at the 50th Annual Cancer Symposium of The Society of Surgical Oncology, Chicago, Illinois, March 20–23, 1997.     

Location of sentinel lymph nodes in patients with cutaneous melanoma: new insights into lymphatic anatomy.

BACKGROUND: Accurate staging of melanoma patients by sentinel node (SN) biopsy can be achieved only if all SNs draining a given melanoma site are identified and removed for detailed histologic examination. Lymphoscintigraphy with a radiolabeled colloid provides an objective and reliable method of locating SNs and demonstrates that confident prediction of their location is not possible on clinical grounds. STUDY DESIGN: Lymphatic drainage pathways demonstrated by preoperative lymphoscintigraphy for 1,759 patients with primary cutaneous melanomas were reviewed, and locations of SNs in these patients were documented. An SN was defined as any node receiving direct lymphatic drainage from a primary melanoma site. RESULTS: In many instances the cutaneous lymphatic drainage pathways were found to be at variance with longheld concepts of lymphatic anatomy. Several new pathways were identified, draining to SNs in unexpected sites. These included triangular intermuscular space SNs (from upper back and, rarely, upper limb primaries), paraaortic and retroperitoneal SNs (from upper and lower back primaries), and costal margin SNs with onward drainage to internal mammary nodes (from periumbilical primaries). Occasional drainage to node fields on the opposite side of the body was noted from head, neck, and trunk primaries, and drainage to interval nodes (by definition, SNs) outside recognized lymph node fields was also observed. CONCLUSIONS: Knowledge of the possibility of these unusual lymphatic drainage patterns and SN sites should help to ensure the accuracy and completeness of SN identification. Preoperative lymphoscintigraphy to definitively locate SNs is recommended for every patient undergoing an SN biopsy procedure.     

Reliability of identification of 655 sentinel lymph nodes in 263 consecutive patients with malignant melanoma

BACKGROUND: The purpose of this study of sentinel lymph node biopsies (SLN) was threefold: to compare the reliability of lymphazurin blue dye to radioactive technetium 99m sulfur colloid (TC); to evaluate the reliability of frozen section examinations of sentinel lymph nodes; and to determine how much SLN dissections prolonged operative time. STUDY DESIGN: We evaluated the records of 263 consecutive patients with intermediate and high-risk melanomas (1.0 mm or thicker, or Clark Level IV or greater), who were treated by a single surgeon at the Yale Melanoma Unit between October 1, 1997, and September 30, 2001, and followed for more than 18 months. RESULTS: A total of 655 SLN were identified and removed from these 263 consecutive patients. Radioactive colloid was found to be more reliable (100%) in identifying the SLN than lymphazurin blue dye (51%) in the nodes of the patients. Twenty-eight patients (11%) had positive sentinel lymph nodes, and 2 patients (7%) had false-negative frozen sections. Three patients (11%) had false-negative frozen sections; tumor was found subsequently on permanent sections only after special immunohistochemical stains were used. The location or removal of SLN did not prolong the operative procedure unreasonably, requiring an average of 7 to 20 minutes for removal of SLN, and 33 minutes for frozen section reports, during which time the primary tumor resection and wound coverage were performed. CONCLUSIONS: SLN were found in all 263 patients. All SLN were identified reliably with radioactive colloid. Because blue dye was found in only half of the radioactive nodes, it is not appropriate to use this as the only marker for locating the SLN. This large series of patients attests to the reliability of frozen sections in identifying SLN harboring metastases, with 82% of the patients with nodal metastases identified in this fashion.     

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.     

Pathologic review of negative sentinel lymph nodes in melanoma patients with regional recurrence: a clinicopathologic study of 1152 patients undergoing sentinel lymph node biopsy

A sentinel lymph node (SLN) that is melanoma negative by pathologic examination implies absence of melanoma metastasis to that regional lymph node field. However, a small proportion of patients develop regional node field recurrence after a negative SLN biopsy. In this study, we reviewed the histopathology of negative SLNs from such patients to determine whether occult melanoma cells were present in the SLNs, to characterize the pathologic features of false-negative SLNs, and to provide recommendations for the histopathologic examination of these specimens. Between March 1992 and June 2001, of 1152 patients who had undergone SLN biopsy for primary melanomas at the Sydney Melanoma Unit, 976 were diagnosed with negative SLNs by initial pathologic examination (using 2 hematoxylin and eosin stained sections, and 2 immunostained sections for S-100 protein and HMB45), and follow-up was available in 957. Of these, 26 (2.7%) developed regional lymph node recurrence during a median follow-up period of 35.7 months. For 22 of them, the original slides and tissue blocks were available for reexamination. The original slides of each block were reviewed. Multiple further sections were cut from each block and stained with hematoxylin and eosin, for S-100, HMB45, and Melan A. Deposits of occult melanoma cells were detected in 7 of the 22 cases (31.8%). In 5 of the 7 cases, deposits of melanoma cells were present only in the recut sections. There were no significant differences in clinical and pathologic variables for those patients in whom occult melanoma cells were found by pathologic reexamination of their SLNs, compared with those in whom no melanoma cells were detected. The detection of melanoma cell deposits in only 7 of 22 false-negative SLNs suggests that mechanisms other than failure of histopathologic examination may contribute to the failure of the SLN biopsy technique in some patients. The failure rate for melanoma detection in SLNs by our routine pathologic examination, using the current protocol at our institution, was <1% (7 of 957 patients). Routinely performing more intensive histopathologic examination of SLNs is difficult to justify from a cost benefit perspective; we therefore recommend examining two hematoxylin and eosin stained sections and two immunostained sections (for S-100 and HMB45) routinely on SLNs from melanoma patients.     

Cytokine profiles of sentinel lymph nodes draining the primary melanoma

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Significant Th1 and Th2 response was induced in melanoma-free SLNs. IMPLICATIONS: 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.     

Evaluation of a method to reduce the number of sentinel nodes removed in melanoma patients: prospective study

INTRODUCTION: Since 1992, sentinel node (SLN) biopsy was generally applied to melanoma for carcinologic staging. Literature points out an increase of nodes removed for each procedure. It means to a high cost for this procedure and it wanders from the defining concept of SLN. The aim of our study was to evaluate whether, we can minimize number of SLN removed, without influencing the reliability of carcinologic staging. MATERIAL AND METHODS: We conducted a prospective study about 50 patients with stage one melanoma. For each patient, the SLN was identified with hand-held gamma probe technique. We removed only the hottest and all nodes greater than 70% of the hottest. We analysed the characteristics of melanoma, the success rate of this procedure, how many nodes have been removed and how many have had micro-metastases. This result was compared to two main studies with chi(2) test. RESULTS: The success rate of this technique was 100%. We dissected 1,3 SLN for each patient, with 22% positive SLN. Statistical analyse pointed out a better selectivity of our study, rate of pathological positivity and recurrence was alike. DISCUSSION: Our technique decreasing number of removed SLN is reliable. A minimal number of nodes doesn't distort sensitivity of carcinologic staging, and reduce cost of the procedure.     

Routine imaging of asymptomatic melanoma patients with metastasis to sentinel lymph nodes rarely identifies systemic disease

HYPOTHESIS: The diagnostic yield of chest radiography; computed tomography (CT) of the chest, abdomen, and pelvis; and CT or magnetic resonance imaging of the brain in the initial evaluation of melanoma with metastasis to sentinel lymph nodes may not identify systemic disease. DESIGN: Retrospective analysis. SETTING: Tertiary care referral center. PATIENTS: Of 1183 patients identified from a database of individuals who underwent selective sentinel lymphadenectomy for primary melanoma (Breslow thickness, 0.2-30 mm), we studied 185 with at least 1 sentinel lymph node positive for metastatic melanoma (Breslow thickness, 0.8-14.5 mm). INTERVENTIONS: Chest radiography; CT of the chest, abdomen, and pelvis; and CT or magnetic resonance imaging of the brain after selective sentinel lymphadenectomy with positive sentinel lymph nodes. The medical records of the 185 patients were systematically reviewed by 4 physician reviewers, and data were extracted primarily from pathology and radiology reports. When medical records were unavailable, information was taken from formal clinic and inpatient progress notes. MAIN OUTCOME MEASURE: Diagnostic yield of imaging studies. RESULTS: The results of 0.5% of the imaging studies were positive for metastatic disease, 86% were negative, and 14% were indeterminate. Indeterminate results were confirmed to be negative by additional studies ranging from repeated imaging to invasive procedures, including thoracotomy and brain biopsy. The yields are as follows: chest radiography, 0%; chest CT, 0.7%; abdominal and pelvic CT, 0.7%; brain CT, 0%; and brain magnetic resonance imaging, 0%. Only 1 patient (0.5%) had detectable metastatic disease, and he had symptoms of systemic disease at the time of imaging. CONCLUSIONS: Computed tomography of the chest, abdomen and pelvis, and brain rarely reveals systemic metastasis at the time of selective sentinel lymphadenectomy. Routine imaging of asymptomatic patients at the time of selective sentinel lymphadenectomy is not indicated.     

Mapping sentinel nodes in patients with early-stage gastric carcinoma

BACKGROUND: Nodal status in gastric carcinoma is related not only to prognosis but also to the extent of nodal dissection. However, a method for accurate assessment of nodal status during operation has not been established. This study aimed to map the sentinel nodes of gastric carcinoma and to estimate the clinical usefulness of sentinel node biopsy. METHODS: Following laparotomy, a vital dye (0.2 ml 2 per cent patent blue) was injected through a gastroscope into the submucosal layer at four sites around a clinical T1 gastric carcinoma. The dye immediately appeared at the serosal surface and stained lymphatic vessels and nodes. The stained nodes were removed and examined by frozen sectioning. RESULTS: The assay was successful in mapping the lymphatic basins in 203 (96.2 per cent) of 211 patients. The dye stained one or more metastatic nodes in 31 patients, but failed to indicate a metastatic node in four patients with a large involved node. Meticulous postoperative examination of all resected nodes in the standard paraffin slices revealed no new metastases. The accuracy of the assay was 98.0 per cent. CONCLUSION: The method was accurate in predicting nodal status in patients with early-stage gastric carcinoma.