Controversial topics in breast lymphatic mapping.

As a result of increased accuracy of staging and decreased patient morbidity, lymphatic mapping and sentinel lymph node (SLN) biopsy for breast cancer has enjoyed a rapid acceptance into clinical practice. Despite the use of lymphatic mapping techniques to obtain nodal staging information, many controversies remain. We have attempted to highlight the major controversies in this report.

Clinical relevance of internal mammary node mapping as a guide to radiation therapy.

BACKGROUND: The surgical management of breast cancer has changed markedly with the development of lymphatic mapping and sentinel lymph node (SLN) biopsy. Lymphatic mapping technique varies with respect to injection method, mapping agent, and surgical technique. The decision to pursue the internal mammary nodes (IMN) is another source of controversy. METHODS: From April 1998 to November 2000, 1,470 patients underwent lymphatic mapping for breast cancer and were prospectively entered into the breast database. The combined technique method was used, consisting of both isosulfan blue dye and technetium-99 labeled sulfur colloid. Patients with inner quadrant lesions and suspicion for internal mammary metastasis had preoperative lymphoscintigraphy. Those with internal mammary radioactivity noted by either lymphoscintigraphy or gamma probe underwent removal of the internal mammary sentinel nodes. RESULTS: Thirty-six of the 1,470 (2.4%) patients mapped had at least 1 internal mammary lymph node removed. Inner quadrant lesions were present in 24 of the 36 (67%) IMN mapped patients. Of the 36 patients mapping to the IM area, 5 (14%) had at least 1 IM node positive. Two of the 5 (40%) had only IM metastasis, with 1 of these patients having 5 of 5 IMN positive and no disease detected in her axilla. A total of 2 of the 5 (40%) IM positive patients had more than 1 IMN positive. Twenty-eight of the 36 (78%) IM node harvested patients had preoperative lymphoscintigraphy, with 18 (64%) IMN appearing on imaging. Complications occurred in 3 of the 36 (8%) IMN mapped patients, without clinical significance. CONCLUSIONS: Mapping to the IMN basin with the finding of metastasis results in N3 disease by the current staging system. The consequence for these patients is radiation therapy to the IMN basin. It is significant to note that 14% (5 of 36) were upstaged as result of IMN detection and 40% (2 of 5) had multiple positive IMNs. Substantial disease was detected in these 5 patients necessitating additional radiation therapy while avoiding IM radiation and its attendant complications in 86% of patients mapping to the IM basin.

Radioguidance for nonpalpable primary lesions and sentinel lymph node(s).

BACKGROUND: Radioguided surgery can also be used for the simultaneous guidance to a nonpalpable primary tumor and sentinel lymph nodes. METHODS: Retrospective review of a prospective database. The surgeon used a gamma probe for guidance to an iodine-125 labeled titanium seed at the primary lesion and technetium-99 labeled sulfur colloid at the sentinel lymph node. RESULTS: Forty-three patients with nonpalpable breast carcinoma underwent dual isotope radioguided surgery. The radioactive seed and primary lesion were retrieved in the first excision in all 44 patients (100%). Eleven patients (25%) had pathologically involved margins. Sentinel lymph node mapping was successful in 42 patients (98%). A mean of 2.4 sentinel nodes were excised and metastatic carcinoma was present in four patients (10%). CONCLUSIONS: Dual isotopes can be effectively used in breast cancer patients for simultaneous radioguidance to both a nonpalpable primary lesion and sentinel lymph node and allows for improved logistics.

Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system.

PURPOSE: The American Joint Committee on Cancer (AJCC) recently proposed major revisions of the tumor-node-metastases (TNM) categories and stage groupings for cutaneous melanoma. Thirteen cancer centers and cancer cooperative groups contributed staging and survival data from a total of 30,450 melanoma patients from their databases in order to validate this staging proposal. PATIENTS AND METHODS: There were 17,600 melanoma patients with complete clinical, pathologic, and follow-up information. Factors predicting melanoma-specific survival rates were analyzed using the Cox proportional hazards regression model. Follow-up survival data for 5 years or longer were available for 73% of the patients. RESULTS: This analysis demonstrated that (1) in the T category, tumor thickness and ulceration were the most powerful predictors of survival, and the level of invasion had a significant impact only within the subgroup of thin (< or = 1 mm) melanomas; (2) in the N category, the following three independent factors were identified: the number of metastatic nodes, whether nodal metastases were clinically occult or clinically apparent, and the presence or absence of primary tumor ulceration; and (3) in the M category, nonvisceral metastases was associated with a better survival compared with visceral metastases. A marked diversity in the natural history of pathologic stage III melanoma was demonstrated by five-fold differences in 5-year survival rates for defined subgroups. This analysis also demonstrated that large and complex data sets could be used effectively to examine prognosis and survival outcome in melanoma patients. CONCLUSION: The results of this evidence-based methodology were incorporated into the AJCC melanoma staging as described in the companion publication.

Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma.

PURPOSE: To revise the staging system for cutaneous melanoma under the auspices of the American Joint Committee on Cancer (AJCC). MATERIALS AND METHODS: The prognostic factors analysis described in the companion publication (this issue), as well as evidence from the published literature, was used to assemble the tumor-node-metastasis criteria and stage grouping for the melanoma staging system. RESULTS: Major changes include (1) melanoma thickness and ulceration but not level of invasion to be used in the T category (except for T1 melanomas); (2) the number of metastatic lymph nodes rather than their gross dimensions and the delineation of clinically occult (ie, microscopic) versus clinically apparent (ie, macroscopic) nodal metastases to be used in the N category; (3) the site of distant metastases and the presence of elevated serum lactic dehydrogenase to be used in the M category; (4) an upstaging of all patients with stage I, II, and III disease when a primary melanoma is ulcerated; (5) a merging of satellite metastases around a primary melanoma and in-transit metastases into a single staging entity that is grouped into stage III disease; and (6) a new convention for defining clinical and pathologic staging so as to take into account the staging information gained from intraoperative lymphatic mapping and sentinel node biopsy. CONCLUSION: This revision will become official with publication of the sixth edition of the AJCC Cancer Staging Manual in the year 2002.

Factors that predict the presence of sentinel lymph node metastasis in patients with melanoma.

BACKGROUND: This analysis was performed to identify prognostic factors that are predictive of sentinel lymph node (SLN) metastasis in melanoma. METHODS: Analysis was performed of a multi-institutional, prospective, randomized trial of SLN biopsy for melanoma. Eligibility criteria included age 18 to 70 years, Breslow thickness of 1.0 mm or more, and clinically negative regional lymph nodes. SLNs were evaluated by serial sectioning and immunohistochemistry for S100. Univariate chi-square and multivariate logistic regression analyses were performed to assess factors predictive of the presence of a positive SLN. Probability values of less than.05 were considered significant. RESULTS: SLNs were identified in 99.7% of patients. A total of 1058 patients were evaluated; 961 patients had complete data and were included in the statistical analysis. SLNs were positive for tumor in 208 of 961 patients (22%). Breslow thickness, Clark level, ulceration, and patient age were factors that were found to be independently predictive of the presence of SLN metastasis. CONCLUSIONS: Increasing Breslow thickness, Clark level of more than III, the presence of ulceration, and patient age of 60 years or less are the most important independent prognostic factors associated with the finding of positive SLN in patients with melanoma.

The process of clinical trials: a model for successful clinical trial participation.

PURPOSE/OBJECTIVES: To present barriers and strategies related to successful clinical trial participation and integrate them into a model for successful trial participation. DATA SOURCES: The proposed model was developed based on a literature review related to clinical trial participation, review of empirical studies related to clinical trials, and experiences with subject participation. DATA SYNTHESIS: Successful clinical trial participation depends on study design, participant factors, issues related to ethnic diversity, the informed consent process, and physician factors. CONCLUSIONS: Clinical trial participation is critical for all disciplines. However, nurses either are researchers or co-investigators with physicians on clinical trials, and it is critical for them to understand specific barriers and success strategies for patient participation. Future studies need to be conducted related to participation in nursing clinical trial research. These study results will facilitate successful nursing clinical trials. IMPLICATIONS FOR NURSING PRACTICE: This model can be used in implementation of clinical trials across disciplines prior to and during enrollment of patients into studies.

Characteristics of the sentinel lymph node in breast cancer predict further involvement of higher-echelon nodes in the axilla: a study to evaluate the need for complete axillary lymph node dissection.

BACKGROUND: Sentinel lymph node (SLN) biopsy techniques provide accurate nodal staging for breast cancer. In the past, complete lymph node dissection (CLND) (levels 1 and 2) was performed for breast cancer staging, although the therapeutic benefit of this more extensive procedure has remained controversial. HYPOTHESIS: It has been demonstrated that if the axillary SLN has no evidence of micrometastases, the nonsentinel lymph nodes (NSLNs) are unlikely to have metastases. OBJECTIVE: To determine which variables predict the probability of NSLN involvement in patients with primary breast carcinoma and SLN metastases. METHODS: An analysis of 101 women with SLN metastases and subsequent CLND was performed. Variables included size of the primary tumor, tumor volume in the SLN, staining techniques used to initially identify the micrometastases (cytokeratin immunohistochemical vs hematoxylin-eosin), number of SLNs harvested, and number of NSLNs involved with the metastases. Tumor size was determined by the invasive component of the primary tumor. Patients with ductal carcinoma in situ who were upstaged with cytokeratin staining were considered to have stage T1a tumors. RESULTS: Sentinel lymph node micrometastases (<2 mm) detected initially by cytokeratin staining were associated with a 7.6% (2/26) incidence of positive CLND compared with a 25% (5/20) incidence when micrometastases were detected initially by routine hematoxylin-eosin staining. Sentinel lymph node micrometastases, regardless of identification technique, inferred a risk of 15.2% (7/46) for NSLN involvement. As the volume of tumor in the SLN increased (ie, <2 mm, >2 mm, grossly visible tumor), so did the risk of NSLN metastases (P<.001). CONCLUSIONS: Our study demonstrated that patients with micrometastases detected initially by cytokeratin staining had low-volume disease in the SLN with a small chance of having metastases in higher-echelon nodes in the regional basin other than the SLN. Characteristics of the SLN can provide information to determine the need for a complete axillary CLND. Complete lymph node dissection may not be necessary in patients with micrometastases detected initially by cytokeratin staining since the disease is confined to the SLN 92.4% of the time. However, the therapeutic value of CLND in breast cancer remains to be determined by further investigation.

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

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

The role of lymphoscintigraphy in the management of the patient with breast cancer.

INTRODUCTION: Regional nodal status is the most powerful predictor of recurrence and survival in women with breast cancer. Lymphatic mapping and sentinel lymph node (SLN) biopsy have been found to accurately predict the regional nodal status. Preoperative lymphoscintigraphy has been used in melanoma patients to identify the basins at risk for metastases when primary sites are located in watershed areas of the body. This study was performed to define the role of lymphoscintigraphy for axillary nodal staging in women with breast cancer. Specifically, can preoperative lymphoscintigraphy define a population of women with breast cancer who have multidirectional drainage or who do not drain to the axilla and need no axillary dissection? METHODS: 516 patients with invasive breast cancer were accrued in a national breast lymphatic mapping trial sponsored by the U.S. Department of Defense. Preoperative lymphoscintigraphy images were produced using filtered technetium-99 sulfur colloid. Lymphatic drainage to axillary and internal mammary sites was noted. RESULTS: Drainage to an axillary SLN was found in 335 (65%) patients, and internal mammary or extra-axillary drainage was noted in 52 (10%) patients. By using sensitive hand-held probes and vital blue dye intraoperatively, the overall success rate of finding an axillary SLN was 85%. Of the 335 patients who had an axillary SLN identified with imaging, all had successful SLN biopsy procedures. Although no SLNs could be imaged in 181 patients, 153 (85%) of these patients had an axillary SLN identified with intraoperative mapping. For 28 patients in which lymphoscintigraphy was negative and intraoperative mapping was unsuccessful, complete axillary node dissection was performed, and 13 (46%) of these patients were found to have metastatic disease in the basin. CONCLUSIONS: Preoperative lymphoscintigraphy can identify those women with primary breast cancers who have extra-axillary regional basin drainage such as internal mammary. The ability to image an axillary SLN was associated with a high success rate of being able to find the node intraoperatively with a combination mapping technique. In a high percentage of patients with negative lymphoscintigraphy, the SLN was identified with more sensitive hand-held probes. Therefore, patients who have a negative preoperative lymphoscintigraphy and intraoperatively are found to have no "hot" spot in the axilla with the hand-held probe still need an axillary node dissection, because 46% of these patients contain metastatic disease in the axilla.

Sentinel lymph node biopsy for melanoma: how many radioactive nodes should be removed?

BACKGROUND: Sentinel lymph node (SLN) biopsy has become a standard method of staging patients with cutaneous melanoma. Sentinel lymph node biopsy usually is performed by intradermal injection of a vital blue dye (isosulfan blue) plus radioactive colloid (technetium sulfur colloid) around the site of the tumor. Intraoperative gamma probe detection has been shown to improve the rate of SLN identification compared to the use of blue dye alone. However, multiple sentinel nodes often are detected using the gamma probe. It is not clear whether these additional lymph nodes represent true sentinel nodes, or second-echelon lymph nodes that have received radiocolloid particles that have passed through the true sentinel node. This analysis was performed to determine the frequency with which these less radioactive lymph nodes contain metastatic disease when the most radioactive, or "hottest," node does not. MATERIALS AND METHODS: In the Sunbelt Melanoma Trial, 1184 patients with cutaneous melanoma of Breslow thickness 1.0 mm or more had sentinel lymph nodes identified. Sentinel lymph node biopsy was performed by injection of technetium sulfur colloid plus isosulfan blue dye in 99% of cases. Intraoperative determination of the degree of radioactivity of sentinel nodes (ex vivo) was measured, as well as the degree of blue dye staining. RESULTS: Sentinel nodes were identified in 1373 nodal basins in 1184 patients. A total of 288 of 1184 patients (24.3%) were found to have sentinel node metastases detected by histology or immunohistochemistry. Nodal metastases were detected in 306 nodal basins in these 288 patients. There were 175 nodal basins from 170 patients in which at least one positive sentinel node was found and more than one sentinel node was harvested. Blue dye staining was found in 86.3% of the histologically positive sentinel nodes and 66.4% of the negative sentinel nodes. In 40 of 306 positive nodal basins (13.1%), the most radioactive sentinel node was negative for tumor when another, less radioactive, sentinel node was positive for tumor. In 20 of 40 cases (50%), the less radioactive positive sentinel node contained 50% or less of the radioactive count of the hottest lymph node. The cervical lymph node basin was associated with an increased likelihood of finding a positive sentinel node other than the hottest node. CONCLUSIONS: If only the most radioactive sentinel node in each basin had been removed, 13.1% of the nodal basins with positive sentinel nodes would have been missed. It is recommended that all blue lymph nodes and all nodes that measure 10% or higher of the ex vivo radioactive count of the hottest sentinel node should be harvested for optimal detection of nodal metastases.

Sentinel lymph node micrometastasis and other histologic factors that predict outcome in patients with thicker melanomas.

BACKGROUND: In patients with melanoma, lymph node staging information is obtainable by the surgical techniques of lymphatic mapping and sentinel lymph node (SLN) biopsy. Although no survival benefit has been proven for the procedure, the staging information is useful in identifying patients who may benefit from further surgery or adjuvant therapy. Currently, however, it is not being recommended for patients with thick melanomas (> 3-4 mm). The risk of hematogenous dissemination is considered too great in these patients. Recent studies indicate, however, that a surprising number of patients with thick melanomas become long-term survivors, and the lymph node status may be predictive. None of the conventional microscopic features used to gauge prognosis in patients with melanoma have proven helpful in distinguishing the survivors with thick melanoma from those who will die of their disease. OBJECTIVE: Our purpose was to evaluate the influence of SLN histology and other microscopic parameters on survival of patients with thick melanomas. METHODS: A computerized patient database at the Cutaneous Oncology Clinic at H. Lee Moffitt Cancer Center was accessed to obtain records on patients with melanomas thicker than 3.0 mm (AJCC T3b). A retrospective analysis was conducted with attention paid to histologic variables, sentinel node status, and survival. Survival curves were constructed with the Kaplan-Meier method, and a Cox-Mantel rank testing was used to establish statistical significance. RESULTS: Between 1991 and 1999, 201 patients were diagnosed with melanoma thicker than 3.0 mm, and 180 were alive at an average follow-up of 51 months. Of these, 166 were alive without disease. The mean overall and disease-free survival rates were 78% and 66%, respectively. There was a statistically significant difference in disease-free survival (3-year) between SLN-positive and SLN-negative patients (37% vs 73%, respectively; P =.02). The overall survival (3-year) for the SLN-positive patients was less than the node-negative patients (70% vs 82%), but it was not statistically significant (P =.08). The disease-free survival for patients with ulcerated lesions was less than for nonulcerated lesions (77% vs 93%, P =.05). None of the other histologic parameters studied, including Breslow thickness, Clark level, mitotic rate, or regression, had an influence on the overall or disease-free survival in this group of patients with thick tumors. CONCLUSIONS: The results indicate that the SLN node status is predictive of disease-free survival for patients with thick melanomas. A surprising number of patients in the study were free of disease after prolonged follow-up. None of the histologic features of the primary tumor were helpful in predicting outcome, except for ulceration. SLN biopsy appears to be justified for prognostic purposes in patients with thick melanomas.

The effects of postinjection massage on the sensitivity of lymphatic mapping in breast cancer.

BACKGROUND: The technique of lymphatic mapping and sentinel lymph node (SLN) biopsy is rapidly becoming the preferred method of staging the axilla of the breast cancer patient. This report describes the impact of postinjection massage on the sensitivity of this surgical technique. STUDY DESIGN: Lymphatic mapping at the H Lee Moffitt Cancer Center is performed using a combination of isosulfan blue dye and Tc99m labeled sulfur colloid. Data describing the rate of SLN identification and the node characteristics from 594 consecutive patients were calculated. Patients who received a 5-minute massage after injection of blue dye and radiocolloid were compared with a control group in which the patients did not receive a postinjection massage. RESULTS: When compared with controls, the proportion of patients who had their SLN identified using blue dye after massage increased from 73.0% to 88.3%, and the proportion of patients who had their SLN identified using radiocolloid after massage increased from 81.7% to 91.3%. The overall rate of SLN identification increased from 93.5% to 97.8%. The proportion of nodes that were stained blue among those removed increased from 73.4% to 79.7% after massage. CONCLUSIONS: As experience increases with this new procedure, the surgical technique of lymphatic mapping continues to evolve. The addition of a postinjection massage significantly improves the uptake of blue dye by SLNs and may also aid in the accumulation of radioactivity in the SLNs, further increasing the sensitivity of this procedure.

The clinical relevance of molecular staging for melanoma.

The presence of metastatic disease in the regional nodal basin is the most important prognostic indicator for patients with malignant melanoma. The metastatic status of the sentinel lymph node (SLN), defined as the first node in the basin to drain a primary tumor, has been shown to represent that of the entire basin. Since routine histologic examination of lymph nodes often underestimates the presence of micrometastatic disease, a more sensitive assay for detecting tumor cells is needed. We have previously shown that a molecular assay based on the reverse transcriptase polymerase chain reaction (RT-PCR) was able to define a population of patients at higher risk for both recurrence and death, compared with routine H&E histology. Recently, we have compared "molecular staging" of patients by RT-PCR with conventional S-100 immunohistochemistry (IHC) staining of the SLNs. In these studies, SLN specimens were bivaled, and half of each specimen was examined by routine histology, including both H&E and S-100 IHC. The other half of each specimen was analyzed by a nested RT-PCR assay. H&E histology alone detected metastatic disease in 36 of 233 (16%) patients tested. Serial sectioning and IHC detected micrometastatic disease in another 16 patients, thus increasing the proportion of patients with nodal disease to 22%. RT-PCR detected micrometastatic disease in 114 of 181 patients who were negative by conventional methods, further increasing the proportion of patients with evidence of nodal disease to 70% overall. The clinical significance of these findings is still uncertain. The value of additional therapy (including elective lymph node dissection and interferon therapy) for patients who are positive only by the molecular method is currently being investigated by the national multi-center Sunbelt Melanoma Trial.

Importance of missed axillary micrometastases in breast cancer patients.

Axillary lymph node metastases dramatically worsen the prognosis of patients with breast cancer. Despite this prognostic significance, routine histologic examination of axillary lymph nodes examines less than 1% of the submitted material. It is therefore obvious that micrometastatic disease is missed with this rather cursory examination, and the question arises as to the significance of this missed disease. Most lines of evidence suggest that missed axillary micrometastases exist and contribute to patient mortality. Most large studies of breast cancer micrometastases have suggested that undetected axillary micrometastases can be identified with more detailed examinations of the regional lymph nodes and that this group of patients has a poorer prognosis than those with no metastases identified. In addition, small-volume nodal disease, too small to be detected by traditional hematoxylin and eosin staining, has been shown to be capable of producing tumors in animal models. Finally, micrometastases have been shown to be of significance in other diseases. This article reviews the lines of evidence and the ongoing studies that are attempting to clarify the significance of micrometastatic disease in patients with breast cancer.

Learning curves for breast cancer sentinel lymph node mapping based on surgical volume analysis.

BACKGROUND: Implementation of new procedures, including lymphatic mapping for breast cancer, must be done and overseen by the medical community in a responsible way to ensure that the procedures are performed correctly. This study addresses the issues of adequacy of training and certification of surgeons performing lymphatic mapping. Ensuring quality in surgical care requires outcomes measures that are described in this study. STUDY DESIGN: Sixteen surgeons performed lymphatic mapping in 2,255 patients with breast cancer using a combination blue dye and Tc99m-labeled sulfur colloid to identify the sentinel lymph nodes (SLNs). All participants were trained in a 2-day CME-accredited course. The Cox learning curve model (total number of mapping failures/total number of mapping cases) for a consecutive series of lymphatic mapping cases is described. The relationship of the Surgical Volume Index, the cases performed in a 30-day period, to the failure rate for each surgeon was modeled as a logistic regression curve (y = e(a+bx)/[1 + e(a+bx)]). RESULTS: Surgeons performing less than three SLN biopsies per month had an average success rate of 86.23% +/- 8.30%. Surgeons performing three to six SLN biopsies per month had a success rate of 88.73% +/- 6.36%. Surgeons performing more than six SLN biopsies per month had a success rate of 97.81% +/- 0.44%. CONCLUSIONS: This experience defines a learning curve for lymphatic mapping in breast cancer patients. Data suggest that increased volumes lead to decreased failure rates. These data provide surgeons performing SLN biopsy with a new paradigm for assessing their skill and adequacy of training and describes the relationship between volume of cases performed and success rate of SLN detection.

Utility of internal mammary lymph node removal when noted by intraoperative gamma probe detection.

BACKGROUND: Lymphatic mapping (LM) for breast cancer has made internal mammary node (IMN) detection practical and dependable. This study demonstrates the necessity of IMN removal when suggested by intraoperative radioguided surgery detection. METHODS: From April 1998 to July 2000, 1273 patients underwent LM for breast cancer. LM was performed using the combined dye and radiocolloid technique. Patients were scanned operatively with a gamma probe over the IMN area, and most underwent preoperative lymphoscintigraphy. Nodes were removed from patients in whom radioactivity was detected in the internal mammary area. RESULTS: Thirty of the 1273 (2.4%) patients mapped had at least one IMN removed. Twenty-two of 30 (73.3%) had inner quadrant lesions. Five of 30 (16.7%) patients had IMNs that were positive for metastatic disease. Three of these five had no metastatic spread to the axillary sentinel lymph node (SLN). One of thirty (3.3%) patients with IMN localization had neither hot nor blue nodes detected in an SLN procedure. CONCLUSIONS: Radioguided SLN detection should be attempted in the IMN basin with all tumors. If an IMN is identified, it should be removed. IMN biopsy is a feasible, low-risk procedure when directed by radioguided LM and provides a guide for radiotherapy for patients with positive IMNs.

A molecular technique useful in the detection of occult metastases in patients with melanoma : rt-PCR analysis of sentinel lymph nodes and peripheral blood.

When cutaneous melanoma is confined to the skin, simple excision with adequate margins will usually cure the patient (1,2). Local recurrences do occur but reexcision still results in a very high cure rate. When cutaneous melanoma spreads beyond the primary site, the metastases are predominantly by way of the lymphatics. If in-transit disease or regional lymph node involvement is present, the 5-yr survival rate drops to approx 60% (1-3). Accurate staging of the locoregional lymphatic basin is thus extremely important. Pre- operative lymphoscintigraphy followed by selective lymphadenectomy has revolutionized the staging of cutaneous melanoma by delivering to the pathologist only those nodes that are most likely to contain metastatic cells (4). A close examination of these sentinel lymph nodes (SLNs) by serial sectioning and immunohistochemical staining can detect very minute quantities of melanoma. This type of detailed examination is impossible in standard lymphadenectomy specimens that can contain 20-40 lymph nodes. The standard technique used to examine large numbers of lymph nodes is to examine only 1-5% of each node using hematoxylin and eosin staining. This can obviously miss micrometastatic disease and understage the patient.