Intraoperative Sentinel Lymph Node Biopsy Research Articles

Sentinel lymph node radiolocalization in clinically negative neck oral cancer

The sentinel node concept has become one of the most interesting topics in the treatment of head and neck cancer. The aim of this article is to report the results of our feasibility study and clinical application of sentinel lymph node (SLN) radiolocalization and biopsy in patients with clinically negative neck oral cancer. Individuals with previously untreated N0 oral cancer participated in the study. The radioactive tracer used was 99m Tc phytate. Lymphoscintigrams were taken in the feasibility study, and fusion images of SPECT and CT were obtained in the clinical SLN biopsy (SLNB) group. In the feasibility study, metastases to SLNs and other nodes were analyzed in permanent specimens. In the clinical application group, we investigated the comparative effectiveness of multi-slice frozen section analysis and imprint cytology for the intraoperative diagnosis of SLNB. Fifteen individuals participated in the feasibility study. Six SLNs in five patients were cancer-positive, and two thirds of the SLNs were micrometastases. The SLN concept was established, and SLNs with the highest to the third highest radioactivity reflected the patients' neck status accurately. Twelve patients participated in the clinical application group of SLNB. Intraoperative diagnosis of the three hottest SLNs correctly predicted the neck status of 10 patients. Three patients underwent modified radical neck dissection on the basis of the intraoperative diagnosis of cancer metastasis to SLNs, whereas neck dissections were spared in patients with no evidence of such metastases. There were two false-negative cases. One involved a failure of the intraoperative diagnosis of SLNB, and the other had cancer-negative SLNs and cancer-positive non-SLNs. Considering intraoperative diagnosis, multi-slice frozen section analysis was found to be superior to imprint cytology in its sensitivity, specificity, and overall accuracy on a lymph node basis. No differences were found in any of these indices of intraoperative SLNB on a patient basis. The fusion images of SPECT and CT proved very useful during intraoperative SLNB. The sentinel node concept was established in the head and neck region. Analyzing the three hottest SLNs suffices to predict a patient's neck status. Multi-slice frozen section analysis was shown to be superior to imprint cytology for detecting micrometastasis to SLN. Intraoperative SLNB based on fusion images of SPECT and CT proved to be an easy, accurate, and reliable method.

Intraoperative lymphatic mapping and sentinel lymph node biopsy using radioactive tracer in gastric cancer

Gastric cancer continues to be a significant health problem around the world. Surgical resection with a lymph node dissection remains the only potentially curative treatment with gastric cancer. Determination of the extent of lymph node dissection required on the basis of actual node involvement in patients with gastric cancer is important as less extensive dissection may reduce postoperative morbidity and mortality rates. The current study examines the feasibility and reliability of sentinel lymph node biopsy in gastric cancer. A total of 32 patients who underwent gastrectomy with extended lymphadenectomy were enrolled in this study. A total volume of 148 MBq (2 mL) technetium-99m-radiolabeled, filtered sulphur colloid solution was injected into the primary lesion under gastroscopy 2 hours before the operation. Lymph nodes were examined as soon as possible by a hand-held gamma probe during the operation, without significant manipulation of the stomach or greater omentum. A sentinel lymph node (SLN) was defined by a level of radioactivity 10 times higher than the background. Thirty-one of 32 patients had successful SLN biopsy, with a success rate of 97%. The sensitivity, specificity, positive predictive value, and negative predictive value of SLN biopsy were 100%, 95%, 90%, and 100%, respectively. SLN biopsy using gamma probe in gastric cancer is a feasible procedure with high sensitivity and accuracy. This technique may be of a great benefit to surgeons in planning the extend of lymph node dissection in gastric cancer.

Glandular structures in an intraoperative axillary sentinel lymph node biopsy: a diagnostic dilemma

Glandular structures in an intraoperative axillary sentinel lymph node biopsy: a diagnostic dilemma

Thorough intraoperative analysis of breast sentinel lymph node biopsies: histologic and immunohistochemical findings

Background We report the use of a thorough intraoperative sentinel lymph node (SLN) biopsy screening procedure for patients with small N0 breast tumors. Methods Sixty-eight consecutive female patients with monofocal stage I or “small” stage II (ie, 2.1-3.0 cm) N0 tumors received intraoperative SLN screening according to a procedure on the basis of comprehensive histologic analysis and cytokeratin immunohistochemical determination (CkID) of adjacent frozen sections of the SLN taken at 50-μm cutting levels. Results The maximum duration of intraoperative analysis including CkID was 40 minutes. Positive SLN were found in 15/68 (22%) patients (always in a single node); they included 5 instances of micrometastasis and 3 of carcinomatous lymphangitis. In the 14 patients who underwent axillary lymph node dissection, no further metastasis was found at histologic analysis or CkID. SLN positivity correlated with histologic type ( P = .044), intratumoral or peritumoral vascular invasion ( P<.001) and Mib1 score ( P = .042). Conclusions It is possible for an experienced team to perform intraoperative SLN screening for T1 or small T2 N0 breast tumors with frozen sections taken at 50-μm cutting levels. This procedure facilitates identification of micrometastasis, as well as of carcinomatous lymphangitis to help understand the biologic implications of these small lesions in the long term. SLN positivity appears to correlate with histologic type, intratumoral/peritumoral vascular invasion and Mib1 score.

The utility of sentinel lymph node biopsy in head and neck melanoma in the pediatric population.

Intraoperative lymph node mapping and sentinel lymph node biopsy have proven beneficial techniques in staging adult patients with melanoma of the head and neck, where there is great variability in lymphatic drainage. This technique has also been applied to pediatric patients with truncal cutaneous melanomas in an effort to determine nodal status without the morbidity associated with complete lymph node dissection. Nevertheless, the utility of sentinel lymph node biopsy in head and neck melanoma in the pediatric population has not been established. The objective of the authors' study was to determine the clinical utility of intraoperative lymph node mapping and sentinel lymph node biopsy of head and neck melanoma in the pediatric population. The authors reviewed the records of seven pediatric patients with head and neck melanoma or borderline melanocytic proliferations of unknown biologic potential who underwent intraoperative lymph node mapping and sentinel lymph node biopsy between 1998 and 2001. All sentinel lymph node specimens were examined by a melanoma dermatopathologist for the presence of metastatic melanoma. The mean operative time for each case was 3 hours, 8 minutes (range, 2 hours, 15 minutes to 3 hours, 50 minutes). All seven pediatric patients who underwent extirpation of a primary head and neck melanoma and preoperative lymphoscintigraphy had unique and identifiable basins of drainage to regional nodal groups. Four of seven patients had at least one positive sentinel lymph node. Overall, five of 19 sentinel nodes (26 percent) resected had evidence of metastatic melanoma. Of the patients with positive sentinel lymph nodes, two of the primary lesions were diagnosed as melanoma while two were initially considered atypical melanocytic proliferations of uncertain biologic potential with melanoma in the differential diagnosis. Sentinel lymph nodes in pediatric patients with melanoma of the head and neck can be successfully mapped and biopsied, as in adult patients. In addition, this procedure can provide critical diagnostic information for those pediatric patients with diagnostically challenging, controversial, or borderline melanocytic lesions.

Intraoperative lymphatic mapping and sentinel lymph node biopsy for Merkel cell carcinoma.

Merkel cell carcinoma is a rare cutaneous neoplasm which commonly spreads to the regional lymph nodes. The feasibility of identifying the sentinel node in patients with clinically node-negative Merkel cell carcinoma was evaluated. Sentinel lymphatic mapping was performed in 18 patients with stage 1 Merkel cell carcinoma using the combination of isosulphan blue dye and 99mTc-radiolabelled sulphur colloid. Patients with tumour metastasis in the sentinel node underwent complete dissection of the remainder of the lymph node basin. Eighteen patients underwent removal of 35 sentinel nodes. Two patients demonstrated metastatic disease in the sentinel lymph nodes; complete dissection of the involved nodal basin revealed no additional positive nodes suggesting that the sentinel lymph node had been identified. The node-negative patients received no further surgical therapy, with no evidence of recurrent disease in the sentinel nodal basin at a median of 7 months' follow-up. Sentinel node biopsy is feasible in patients with Merkel cell carcinoma. It can be used to stage patients and provides important prognostic information. In those with subclinical nodal disease, it may direct early regional lymphadenectomy but the effect of such surgery on survival remains unclear.

Sentinel lymph node biopsy without axillary dissection after an intraoperative negative histological investigation in 358 invasive breast cancer cases.

Sentinel lymph node biopsy (SLNB) is an important treatment option for breast cancer patients, as it can accurately predict axillary status. Our previous study using dye with or without radioisotope showed the accuracy and sensitivity of SLNB to be 97% and 94%, respectively. Based on these results, axillary lymph node dissection (ALND) was eliminated starting in January, 1999 in patients with intraoperatively negative SLNB at our institution. The present study shows the results and outcomes of SLNB as a sole procedure for patients with invasive breast cancer. Three-hundred-fifty-four patients and 358 cases of invasive breast cancer (4 bilateral breast carcinoma) treated with SLNB alone after an intraoperative negative SLNB were studied prospectively from January 1999 to December 2001. The number of the identified SLNs per case ranged from 1 to 8 (mean, 2.5). Of a total of 358 cases, 297 (83%) were treated with hormone therapy and/or chemotherapy, and 281 (78%) were treated with radiotherapy to the conserved breast (50 Gy+/-10 Gy boost), the axilla (50 Gy), or the both sites. After a median follow-up of 21 (range 6-42) months, no patient developed an axillary relapse. Four cases initially recurred in distant organs and one case in the conserved breast. Our results indicate that an intraoperative negative SLNB without further ALND may be a safe procedure when strict SLNB is performed. To better assess the safety, however, may require longer follow-up.

Section 2. Thyroid: Intraoperative lymphatic mapping and sentinel lymph node biopsy in patients with papillary carcinoma of the thyroid gland

We examined the feasibility of sentinel lymph node biopsy for thyroid cancer. Thirty-eight patients with papillary thyroid carcinoma underwent intraoperative lymphatic mapping and sentinel lymph node biopsy. At surgery, we exposed the thyroid gland and used a tuberculin syringe to inject 0.2 ml of 1% patent blue dye directly into the thyroid mass. The lymphatics and the lymph node dyed with blue dyes, was excised as a sentinel lymph node. Modified radical neck dissection was performed following sentinel lymph node biopsy and the diagnostic ability of sentinel lymph node biopsy was examined. A sentinel lymph node was identified successfully in 27 (71%) of 38 patients. Sentinel lymph node biopsy removed one to three lymph nodes (median, two nodes). Eighteen patients had paratracheal sentinel lymph nodes, five patients had jugular sentinel lymph nodes, and four patients had both. Histological nodal metastasis was recognized in 16 of 27 cases. The positive rate of cancer metastases in sentinel lymph nodes was 58%, which was significantly higher than 11% in non-sentinel lymph nodes. Diagnostic ability of sentinel lymph node biopsy showed that accuracy was 89%, sensitivity was 84%, and specificity was 100%. Our preliminary study indicated that sentinel lymph node biopsy was available on detection of non-palpable nodal metastasis in the patients with thyroid cancer; however, further experience and refinement are needed.

A Prospective Study of Intraoperative Lymphatic Mapping for Head and Neck Cutaneous Melanoma

Intraoperative lymphatic mapping and sentinel lymph node biopsy have been used successfully to stage regional lymphatics for trunk and extremity melanomas. However, the accuracy and applicability of these techniques in the head and neck have not been determined conclusively. To report the results of a prospective trial of intraoperative lymphatic mapping and sentinel lymph node identification in patients with head and neck cutaneous melanoma. Using technetium Tc 99m--labeled sulfur colloid and isosulfan blue, intraoperative lymphatic mapping and sentinel lymph node identification were performed in 43 patients with melanomas of intermediate thickness. After the sentinel lymph nodes were identified in situ, an elective dissection of levels I through V or II through V was performed, based on the location of the primary tumor. The parotid, postauricular, and suboccipital lymphatics were dissected as clinically indicated. The sentinel lymph nodes were isolated ex vivo and evaluated pathologically by serial sectioning, and the accuracy of the lymphatic mapping was determined. Intraoperative lymphatic mapping identified 155 sentinel lymph nodes in 94 nodal basins, with a mean of 3.6 sentinel nodes and 2.2 basins per patient. Sentinel nodes were located in the parotid gland in 19 patients (44%), necessitating superficial parotidectomies, and they were distributed throughout nonadjacent nodal basins in 18 patients (42%). Nine patients (21%) had metastatic disease in 1 or more sentinel nodes, 3 of whom had metastatic disease in a nonsentinel node. No patient who had negative sentinel nodes had a positive nonsentinel node (false-negative incidence, 0). Although intraoperative lymphatic mapping accurately identifies sentinel lymph nodes for head and neck cutaneous melanomas, the multiplicity of these nodes, their widespread distribution, and their frequent location within the parotid gland may preclude sentinel lymph node biopsy in many patients. Therefore, we advocate selective lymphadenectomy of sentinel nodal basins, allowing histological staging of the regional lymphatics with limited morbidity. However, further study is necessary to define the true role of sentinel lymph node identification for head and neck cutaneous melanoma.

Lymphatic mapping and sentinel lymph node biopsy in squamous cell carcinoma of the lower lip

Aims: The risk of metastases to the submandibular and submental lymph nodes in squamous cell carcinoma (SCC) of the lower lip is closely related to the primary tumour size and the differentiation of the tumour. In order to determine the feasibility of the technique and the possible metastatic lymph nodes in SCC of the lower lip, intraoperative lymphatic mapping and sentinel lymph node biopsy was performed in patients with tumour size greater than 2 cm (T2) and clinically non-palpable regional lymph nodes (N0). Methods: Intraoperative lymphatic mapping with patent blue dye was performed in 20 patients with SCC of the lower lip. The stained lymph node (sentinel) was identified in each patient and sent for frozen section analysis in order to verify tumour metastasis. All patients had undergone bilateral suprahyoid neck dissection at the same stage. Results: Three of the patients were female and 17 were male. The median age was 66. Sentinel lymph nodes were identified in 18 of the patients (90%). Intraoperative or post-operative histopathologic examination of the sentinel lymph node showed tumour metastasis in three of the patients (16.6%). The histopathologic examination of the remaining 15 patients whose sentinel lymph nodes were free of metastasis, showed no metastasis in the non-sentinel lymph nodes. In two of the three patients with metastatic sentinel lymph nodes, non-sentinel lymph nodes were free of metastases. There were no false negative results and no local or systemic complications of the technique were seen among the patients. Conclusions: Intraoperative lymphatic mapping and sentinel lymph node biopsy is feasible in patients with SCC of the lower lip who have large tumour size and non-palpable regional lymph nodes. The technique may help to avoid neck dissection when the patient has negative sentinel lymph node and when positive provides useful information for more effective radical treatment.

The sentinel node concept in head and neck squamous cell carcinoma--a critical analysis in 100 patients

The value of Sentinel Node (SN) concept is a current issue in clinical oncology. Few investigations deal with SN biopsy in head and neck squamous cell carcinomas (HNSCC). For this reason the SN concept was investigated based on the results of the so far largest group of 100 patients. Three groups of patients were investigated. Group 1: In 30 patients (6 x oral cavity, 24 x oropharynx) a dynamic lymphoscintigraphy was performed. Group 2: 60 previously untreated patients (12 x oral cavity, 23 x oropharynx, 16 x larynx, 9 x hypopharynx); neck lymph node status on ultrasound imaging: 39 x N0, 5 x N1, 16 x N2, intraoperative identification of the SN during neck dissection (ND) accomplished according to the extent of assumed lymphogenic metastatic spread; postoperative comparison of the histological result of the SN with the neck dissection specimen. Group 3: 10 previously treated patients (1 x oral cavity, 5 x oropharynx, 1 x larynx, 3 x hypopharynx) in whom an intraoperative SN biopsy was performed. Group 1: In 20/30 patients a cervical lymph drainage could be visualized on dynamic lymphscintigraphy and an activity enrichment above the mean metastatic region could be identified transcutaneously. Group 2: In 34 patients the tumorfree SN1 reflected the regional lymph node status. In 9 patients an isolated tumor metastasis (pN1) was found in the intraoperatively identified SN1 and in a further patient in the SN2 (pN1). The results of SN biopsy are encouraging in cases of clinical N0-necks. Nevertheless the data demonstrates that extensive investigations followed by a critical analysis of the results are required. The presented results suggest that the value of the SN concept seems to be of minor importance in cases of advanced lymphogenic metastatic spread.

Value of sentinel lymphonodectomy in head and neck cancer patients without evidence of lymphogenic metastatic disease

Objective: Only few communications deal with the value of sentinel node (SN) biopsy for head and neck squamous cell carcinoma (HNSCC). Based on the results of 38 investigated patients with clinically N0-neck the feasibility of SN biopsy in HNSCC is critically discussed. Patients and methods: Thirty-eight previously untreated patients with clinically N0-neck were staged by intraoperative SN biopsy. After intraoperative identification of the hottest node (SN 1) and further less tracer accumulating lymph nodes (SN 2, SN 3), patients were treated by different types of neck dissection (ND), adjusted to the location and extent of the primary tumour. Postoperatively the histologic results of the SN 1–3 and the entire ND specimen were compared. Results: The stage of cervical metastatic disease was demonstrated by a disease-free SN 1 in 32 patients. In five patients an isolated metastasis could be proven in the intraoperatively identified SN 1, while in the remaining patient an isolated metastasis was found in the SN 2. Conclusion: Intraoperative SN biopsy seems to be valuable for the detection of occult lymph node metastases in HNSCC. This method might help to limit the extent of ipsilateral ND, if used as an intraoperative staging procedure to investigate the first draining tracer accumulating lymph nodes (SN 1–3).

Regarding Intraoperative Lymphatic Mapping and Sentinel Lymph Node Biopsy

Regarding Intraoperative Lymphatic Mapping and Sentinel Lymph Node Biopsy

Regarding Intraoperative Lymphatic Mapping and Sentinel Lymph Node Biopsy

Regarding Intraoperative Lymphatic Mapping and Sentinel Lymph Node Biopsy

54. Lymphatic mapping and sentinel lymphnode Biopsy in breast cancer patients in clinical stage T1-T2 NO MO

The authors report the feasibility an accuracy of intraoperative sentinel lymphnode biopsy (SLN) in patients with operable breast cancer to test the hypothesis that the histologic characteristic of SLN predicts the histologic status of remaining lymph nodes in the axilla. In between August 1999 and May 2000 to SLN biopsy there were 124 patients enrolled with median age of 55,2 years of age. All patients had operable breast cancer and all axillary lymphnodes were clinically negative. A day before surgery 4 cc of Nannocol marked with Tc99 was injected subcutuanesly nearby the tumor bed and an hour later the lymphoscyntygraphy was performed to achieve axillary lymphnodes mapping. Then immediately prior to surgery Blue Dye Patent Blau V was injected in the same manner as the radiological marker. Then with the use of hand – held gamma probe the hotspot was defined and marked. Five to ten minutes later first cut was performed over marked hotspot. After visualization of stained lymph vassals the SLN was traced and confirmed with high dose output (using the Neoprobe) and then was harvested for histologic examination. After this all patients were submitted for regular lymphadenectomy regardless main surgery type (mastectomy or BCT). Employing above method we were able to define SLN in 93,3%, only in 6,7% of our patients identification failed. In the group with defined SLN we found cancer cells deposits only in 20%. And in that group remaining lymphnodes had cancer metastasis in almost 80%. We had two cases of false negative results but still our specify rate was over 97%. In conclusion we think that SLN biopsy is quite safe and efficient method to evaluate axillary lymphnodes status in patients with operable early stage breast cancer. Our findings are also confirmed by other authors world wide.

Predictive factors associated with axillary lymph node metastases in T1a and T1b breast carcinomas: analysis in more than 900 patients

Background: Axillary lymph node metastasis (ALNM) represents the single most important prognostic indicator in patients diagnosed with breast cancer. The proportion of ≤ 1-cm (T1a, T1b) invasive breast carcinomas is increasing. The incidence and predictive factors associated with ALNM in patients with ≤ 1-cm tumors remains unclear and the role of axillary lymph node dissection in these patients has been questioned. The purpose of this study was to determine clinical and pathologic factors predictive of ALNM in patients with ≤ 1-cm invasive breast carcinomas by univariate and multivariate analyses. Study Design: Review analysis from a prospective database identified patients with ≤ 1-cm invasive breast cancers treated at our institution between 1990 and 1996. All patients underwent a resection of the primary tumor and axillary lymph node dissections. Routine patient and tumor characteristics evaluated included: age, race, tumor size, histologic grade, estrogen and progesterone receptor status, and lymphatic and vascular invasion. Univariate and multivariate analyses were performed. Adjusted odds ratios (OR) and 95% confidence intervals (CI) are presented. Results: A total of 919 patients were identified in this study with tumors ≤ 1 cm. These included 199 patients (21.7%) with T1a tumors and 720 patients (78.3%) with T1b tumors. ALNM was detected in 165 patients with an overall incidence of 18.0%. Of the ALNM group, 32 patients (19.4%) had T1a tumors and 133 patients (80.6%) had T1b tumors. Four variables were found to be significant in univariate analysis. These included: increasing tumor size, poor histologic grade, presence of lymphatic or vascular invasion, and younger age of the patient. An increase in tumor size was associated with a significant risk of ALNM (OR = 2.66, 95% CI = 1.28 to 5.75; p = 0.01). Poor tumor grade and the presence of lymphatic or vascular invasion were also associated with an increased risk of ALNM (OR = 2.69, p = 0.003 and OR = 5.52, p = 0.0001, respectively). Patients with ALNM were more likely to have a tumor grade of 3 (25.0% ALNM versus 12.5% node-negative, p = 0.004) and lymphatic or vascular invasion (16.9% ALNM versus 3.5% node-negative, p < 0.0001). In multivariate analysis, an increased risk of ALNM was demonstrated with increasing tumor size (0.1-cm increments), poor histologic grade, and younger age. Conclusions: This study investigated clinical and pathologic factors influencing ALNM in patients with T1a and T1b breast carcinomas. We have identified three factors by multivariate analysis as significant independent predictors of ALNM in this group of patients. These include increasing tumor size, poor histologic grade, and younger age. Given the significant amount of ALNM demonstrated in this study (overall 18%) and the inability to identify a subgroup of patients that had an acceptable low risk of ALNM, the complete omission of assessing the axilla for metastatic disease in patients with small breast cancers cannot be advocated. Our recommendation for patients diagnosed with T1a and T1b tumors is to have their axilla investigated for metastatic disease either by traditional axillary lymph node dissections or by intraoperative lymphatic mapping and sentinel lymph node biopsy techniques.

Sentinel lymph node mapping and biopsy for breast cancer: a review of the literature relative to 4791 procedures.

The status of axillary nodes is the most important prognostic factor in breast cancer to select patient subgroups for adjuvant chemotherapy; the current standard of care for surgical management of invasive breast cancer is complete removal of the tumor by either mastectomy or lumpectomy followed by axillary lymph node dissection (ALND). The recent introduction of intraoperative lymphatic mapping and sentinel lymph node biopsy (SLND) represents a major new opportunity for appropriate and less invasive surgical management of many tumors. There is an almost uniformly enthusiasm concerning the potential of this technique in breast carcinoma management, shown by published data. A peculiar attention to the so-called "sentinel node debate" in breast cancer surgery is a constant in the last years issues of the major medical journals. Even patients have become more aware about medical enthusiasm and their request of concise information on the topic and the possibilities of this approach is an increasing reality in medical practice. The aim of this paper is to review recent literature to offer an overview about the main controversial methodological aspects and a wide analysis of reported results. The most significative international literature papers from Medline were retrieved from 1993 to September 1999, and 4782 procedures were analysed. This extensive review of the literature has confirmed accuracy, feasibility and reliability of the SN detecting technique in axillary mapping. Provided a good proficiency in SN localisation and pathological evaluation, human resources and efforts should be mainly focused on its clinical validation as an alternative to ALND instead of on further phase I-lI clinical studies.

Lymphatic Mapping and Sentinel Lymph Node Biopsy

Malignant melanoma--cancer of the pigment cells--has the highest mortality rate of all skin cancers. With early detection and treatment, however, malignant melanoma is highly curable. Recently, diagnostic modalities for nodal involvement have been perfected, reducing the morbidity of elective lymph node dissections and rendering them unnecessary in many cases. Total lymphadenectomy procedures are being replaced by intraoperative lymphatic mapping and sentinel lymph node biopsy using gamma detector probes. This article reviews lymphatic drainage from the primary site to possible lymph node basins and selective lymph node dissection using lymphoscintigraphy and intraoperative mapping as guides. This article also includes a case study, beginning with a diagnosis of malignant melanoma and following a successful postoperative course.

The progression of melanoma nodal metastasis is dependent on tumor thickness of the primary lesion.

Recent results of several clinical trials using the technique of intraoperative lymphatic mapping and sentinel lymph node (SLN) biopsy confirm the validity of the concept of there being an order to the progression of melanoma nodal metastases. This report reviews the H. Lee Moffitt Cancer Center experience with this procedure, one of the largest series described to date. These data demonstrate that the involvement of the SLNs, as well as higher-echelon nodes, is directly proportional to the melanoma tumor thickness, as measured by the method of Breslow. The investigators at the H. Lee Moffitt Cancer Center retrospectively reviewed their experience using lymphatic mapping and SLN biopsies in the treatment of malignant melanoma. All eligible patients with primary malignant melanomas underwent preoperative and intraoperative mapping of the lymphatic drainage of their primary sites, along with SLN biopsies. All patients with positive SLNs underwent complete regional basin nodal dissection. For 20 consecutive patients with one positive SLN, all of the nodes from the complete lymphadenectomy were serially sectioned and examined by S-100 immunohistochemical analysis, to detect additional metastatic disease. Six hundred ninety-three patients consented to undergo lymphatic mapping and SLN biopsy. The SLNs were successfully identified and collected for 688 patients, yielding a 99% success rate. One hundred patients (14.52%) showed evidence of nodal metastasis. The rates of SLN involvement for primary tumors with thicknesses of <0.76 mm, 0.76-1.0 mm, 1.0-1.5 mm, 1.5-4.0 mm, and >4.0 mm were 0%, 5.3%, 8%, 19%, and 29%, respectively. Eighty-one patients underwent complete lymph node dissection after observation of a positive SLN, and only six patients with positive SLNs demonstrated metastatic disease beyond the SLN (7.4%). The tumor thicknesses for these six patients ranged from 2.8 to 6.0 mm. No patient with a tumor thickness of <2.8 mm was found to have evidence of metastatic disease beyond the SLN in complete lymph node dissection. All 20 patients with a positive SLN for whom all of the regional nodes were serially sectioned and examined by S-100 immunohistochemical analysis failed to show additional positive nodes. These results suggest that regional lymph node involvement may be dependent on the thickness of the primary tumor. As the primary tumor thickness increases, so does the likelihood of involvement of SLNs and higher regional nodes in the basin beyond the positive SLNs.