Positive Sentinel Lymph Node Status Research Articles

Reporting regression in primary cutaneous melanoma. Part 2: prognosis, evaluation and management.

The effect of histological regression on patient prognosis for primary cutaneous melanoma is controversial. Some authors hypothesize that regression indicates a robust systemic immune response and may decrease risk of metastasis. Others argue that histological regression calls into question a T0 diagnosis because there may have been an invasive component of the melanoma that is no longer visible but is still active. The literature to date does not suggest that histological regression is associated with increased risk of positive sentinel lymph node status, metastasis or increased risk of mortality. Thus, the presence of histological regression should not change patient staging, evaluation or management. The criteria used for reporting regression have varied dramatically across studies, and standardized reporting is needed to foster evidence-based practices in the future.

Acral lentiginous melanoma: a single-centre retrospective review of four decades in East-Central Europe.

Acral lentiginous melanoma (ALM) occurs on the palms, soles and subungual surface and has poor prognosis. It is uncommon in the Caucasian population and has remained unreported in East-Central Europe. Our aim was to collect data from East-Central Europe by analysing the demographic and clinicopathologic features of patients with ALM and comparing data with the reports in literature. We conducted a single-centre, retrospective review between 1976 and 2016 at one of the largest melanoma referral centres in Hungary. We identified 176 patients with ALM (3.83%) from 4593 patients with melanoma (mean age: 66.2years). The tumours were mainly located on the lower extremities (88.63%). The mean Breslow tumour thickness was 3.861mm, 37.50% of the tumours were thicker than 4.00mm, and 71.6% exhibited microscopic ulceration. Nearly one-third of the patients underwent sentinel lymph node (SLN) biopsy, and 60.3% of the biopsies were positive for metastasis. The positive SLN status was associated with significantly thick tumours and reduced survival. Patients with ALM had 5- and 10-year overall survival rates of 60.5% and 41.6%, respectively. The mean delay in diagnosis was 18months after the discovery of skin tumours. In multivariate analyses, age, tumour thickness and distant metastasis were independent risk factors for poor survival (P<0.001). Our study, which is the first single-centre report in East-Central Europe focusing on ALM, confirms that patient and tumour characteristics and prognostic factors are similar with previous literature data involving Caucasians; however, tumour thickness and survival suggest even worse prognosis.

Time to Procedure, Nuclear Imaging and Clinicopathological Characteristics as Predictive Factors for Sentinel Lymph Node Metastasis in Cutaneous Melanoma: A Single-Center Analysis.

Sentinel lymph node (SLN) biopsy is a widely accepted staging procedure for cutaneous melanoma patients who are at risk of clinically occult nodal metastases. Numerous predictive factors for regional lymph node metastases have been identified; however, few have been found to be reproducibly significant. Also, the role of blue dye in identification was questioned in recent trials. Time to procedure was also found to be predictive of SLN positivity, but this was not confirmed in other studies. In our study, predictive factors for metastatic involvement of SLN were analyzed, together with the role of addition blue dye in imaging on detection rate and false-negative SLN rate. An impact of time interval to procedure on the rate of SLN positivity was also explored. Data analysis was done in 362 cutaneous melanoma patients who underwent lymphoscintigraphy and SLN biopsy at our institution from 2010 to 2016, with a median follow-up of 29 months (1-98 months). To delineate the relation of each variable (demographical, time to procedure, and clinical and pathological variables, as well as the presence of in-transit nodes, the number of draining basins, and SLN localization on scintigraphy) with positive SLN status, we used univariate logistic regression with odds ratios representing effect size. Metastatic involvement SLN was found in 67 (18.8%) of 356 patients. Detection rate was similar with or without further intraoperative SLN identification with blue dye (98.8% vs 98.17%, P > 0.05). Time to procedure was not associated with higher SLN positivity rate (P > 0.05). In univariate analysis, Breslow thickness (P < 0.001), primary ulceration lesion (P = 0.001), and lymphovascular invasion (P = 0.006) were strongly correlated with SLN positivity, as well as the site of primary tumor (P = 0.024), tumor-infiltrating lymphocytes (TILs) (P = 0.021), and sex (P = 0.026). In multivariate analysis, Breslow thickness and TILs were found to be significant independent predictors of SLN status (P < 0.05). Addition of blue dye did not improve SLN detection rate; time to procedure was not found to be associated with higher SLN biopsy positivity rates. Breslow thickness and TILs, as a marker of immune response to tumor, were consistently found to be significant independent predictors of SLN status.

Regression and Sentinel Lymph Node Status in Melanoma Progression.

BackgroundThe purpose of this study was to assess the role of regression and other clinical and histological features for the prognosis and the progression of cutaneous melanoma.Material/MethodsBetween 2005 and 2016, 403 patients with melanoma were treated and followed at our Department of Dermatology. Of the 403 patients, 173 patients had cutaneous melanoma and underwent sentinel lymph node (SLN) biopsy and thus were included in this study.ResultsHistological regression was found in 37 cases of melanoma (21.3%). It was significantly associated with marked and moderate tumor-infiltrating lymphocyte (TIL) and with negative SLN. Progression of the disease occurred in 42 patients (24.2%). On multivariate analysis, we found that a positive lymph node and a Breslow index higher than 2 mm were independent variables associated with disease free survival (DFS). These variables together with a mild TIL were significantly correlated with overall survival (OS). The presence of regression was not associated with DFS or OS.ConclusionsWe could not demonstrate an association between regression and the outcome of patients with cutaneous melanoma. Tumor thickness greater than 2 mm and a positive SLN were associated with recurrence. Survival was influenced by a Breslow thickness >2 mm, the presence of a mild TIL and a positive SLN status.

Clinical impact of ulceration width, lymphovascular invasion, microscopic satellitosis, perineural invasion, and mitotic rate in patients undergoing sentinel lymph node biopsy for cutaneous melanoma: a retrospective observational study at a comprehensive cancer center.

The prognostic significance of the width of the ulceration in primary melanomas remains unclear, and there is a relative paucity of data for lymphovascular invasion (LVI), microscopic satellitosis (MS), perineural invasion (PNI), and mitotic rate when compared with other pathological elements currently required for reporting. To evaluate the prognostic importance of the ulceration width and other important pathologic measurements, a single‐institutional retrospective study was conducted using records of cutaneous melanoma patients who underwent sentinel lymph node (SLN) biopsy at The University of Texas, MD Anderson Cancer Center between 2003 and 2008. We identified 1898 eligible patients with median tumor thickness of 1.25 mm and median follow‐up of 6.7 years. By multivariable analyses, the strongest risk factor for SLN positivity was high tumor thickness followed by the presence of LVI. The pathologic measures with the strongest influence on recurrence‐free survival (RFS) were tumor thickness and positive SLN status. Ulceration width and presence of MS were also significantly associated with RFS while PNI was not. Factors with the strongest influence on melanoma‐specific survival (MSS) were positive SLN status and mitotic rate. In conclusion, SLN biopsy should probably be offered if the primary tumor has LVI. MS is an adverse prognostic factor for RFS, but its influence on outcome is modest. Ulceration width predicts RFS but loses its independent prognostic significance for MSS when adjusting for currently used clinicopathological factors. In view of its impact on MSS, mitotic rate should be recorded for cutaneous invasive melanomas across all T categories.

Prognostic significance of BRAF and NRAS mutations in melanoma: a German study from routine care

BackgroundHotspot mutations of the oncogenes BRAF and NRAS are the most common genetic alterations in cutaneous melanoma. Specific inhibitors of BRAF and MEK have shown significant survival benefits in large phase III trials. However, the prognostic significance of BRAF and NRAS mutations outside of clinical trials remains unclear.MethodsThe mutational status of BRAF (exon 15) and NRAS (exon 2 and 3) was determined in melanoma samples of 217 patients with pyrosequencing and Sanger sequencing. The genotypes were correlated with clinical outcomes and pathologic features of the primary tumors. Time to disease progression was calculated with the cumulative incidence function. Survival analyses were performed with Kaplan-Meier estimates and Cox proportional hazards regression analysis. Relative survival was calculated with the Ederer-II method. Treatment with BRAF and MEK inhibitors and immune checkpoint blockade (ICB) was allowed.ResultsMutations in BRAF and NRAS were identified in 40.1 and 24.4% of cases, respectively. Concurrent mutations in both genes were detected in further 2.3%. The remaining 33.2% were wild type for the investigated exons (WT). BRAF mutations were significantly associated with younger age at first diagnosis (p < 0.001) and truncal localization of the culprit primary (p = 0.002). The nodular subtype was most common in the NRAS cohort. In addition, NRAS-mutant melanoma patients showed a higher frequency of nodal relapse (p = 0.013) and development of metastatic disease (p = 0.021). The time to loco-regional nodal relapse was shortest in NRAS-mutant melanoma (p = 0.002). Presence of NRAS mutation was an independent risk factor for disease progression in multivariate analysis (HR 2.01; 95% CI 1.02 – 3.98). BRAF-mutant melanoma patients showed a tendency for better overall and relative survival. Genotype was not a consistent risk factor in multivariate analysis. Instead, positive sentinel lymph node status (HR 2.65; 95% CI 1.15 – 6.10) and treatment with ICB in stage IV disease (HR 0.17; 95% CI 0.06–0.48) were significant multivariate risk factors.ConclusionsNRAS-mutant tumors tended to behave more aggressively particularly in early stages of the disease in this high-risk melanoma population. Treatment with immune checkpoint blockade improved survival in stage IV disease in a real-world setting.

Worse outcome for patients with recurrent melanoma after negative sentinel lymph biopsy as compared to sentinel-positive patients

BackgroundThe long-term outcome of patients with melanoma who had recurrence after negative sentinel lymph node (SLN) biopsy has rarely been evaluated systematically. MethodsWe searched our databases for melanoma patients with SLN biopsy from the end of 1999 and the beginning of 2011. Data was analyzed using uni- and multivariate statistics as well as Kaplan–Meier curves. ResultsData of 651 patients with melanoma was available for statistics. We observed 451 (69.3%) patients with negative SLN who had no evidence of disease recurrence during follow-up. Recurrence in SLN negative patients was found in 50 (7.7%) cases. Tumor subtypes such as invasive lentigo maligna melanoma and acral melanoma (odds ratio 15.2, P = 0.015) and tumor thickness > 2 mm (odds ratio 3.1, P = 0.0017) were independent predictors for recurrence in patients with negative SLN. Patients with negative SLN and subsequent recurrence had a significantly (P = 0.036) reduced 5-year melanoma-specific survival (MSS) when compared with positive SLN patients. Recurrence of disease in positive SLN patients was observed after a median of 39 months when compared to patients with negative SLN and recurrence (28 months, P = 0.0079). Negative SLN with recurrence was an independent predictor for worse recurrence free and melanoma-related survival. ConclusionsPatients with negative SLN and recurrence experience earlier disease relapses and poorer MSS when compared to patients with positive SLN status implicating that more stringent follow-up procedures are warranted in patients with higher tumor thickness and invasive lentigo maligna and acral melanoma, despite a negative SLN.

A retrospective, multicenter analysis of the predictive value of mitotic rate for sentinel lymph node (SLN) positivity in thin melanomas

There is a paucity of studies to substantiate whether the presence of a single mitosis justifies sentinel lymph node (SLN) biopsy (SLNB) in thin melanomas. We sought to determine if mitotic rate is associated with SLNB outcome when taking into account other prognostic factors. All cases of melanoma that underwent SLNB in the province of Alberta, Canada, between 2007 and 2013 were reviewed through a provincial tumor database. A total of 1072 patients fulfilled inclusion criteria. When analyzing all melanomas regardless of thickness, mitotic rate was a good predictor of SLN status. When stratified by Breslow thickness, only intermediate melanomas (1.01-2.0mm) demonstrated a significant relationship between mitotic rate and positive SLN status (P=.010). For melanomas 1mm or smaller, mitotic rate was not associated with SLN status. A statistically significant interaction was identified between Breslow thickness and mitotic rate such that for decreasing Breslow depth, the effect of mitotic rate on SLNB status diminished (P=.028). The study was retrospective in nature. There is underlying variability in mitotic rate reporting methods over time, and between different dermatopathologists. Mitotic rate does not have unequivocal utility in predicting SLNB status in thin melanomas. There is a significant interaction between mitotic rate and Breslow depth, such that the predictive value of mitotic rate on SLN positivity may be dependent on Breslow thickness.

Immune cell profile of sentinel lymph nodes in patients with malignant melanoma – FOXP3+ cell density in cases with positive sentinel node status is associated with unfavorable clinical outcome

BackgroundBesides being a preferential site of early metastasis, the sentinel lymph node (SLN) is also a privileged site of T-cell priming, and may thus be an appropriate target for investigating cell types involved in antitumor immune reactions.MethodsIn this retrospective study we determined the prevalence of OX40+ activated T lymphocytes, FOXP3+ (forkhead box P3) regulatory T cells, DC-LAMP+ (dendritic cell-lysosomal associated membrane protein) mature dendritic cells (DCs) and CD123+ plasmacytoid DCs by immunohistochemistry in 100 SLNs from 60 melanoma patients. Density values of each cell type in SLNs were compared to those in non-sentinel nodes obtained from block dissections (n = 37), and analyzed with regard to associations with clinicopathological parameters and disease outcome.ResultsSentinel nodes showed elevated amount of all cell types studied in comparison to non-sentinel nodes. Metastatic SLNs had higher density of OX40+ lymphocytes compared to tumor-negative nodes, while no significant difference was observed in the case of the other cell types studied. In patients with positive sentinel node status, high amount of FOXP3+ cells in SLNs was associated with shorter progression-free (P = 0.0011) and overall survival (P = 0.0014), while no significant correlation was found in the case of sentinel-negative patients. The density of OX40+, CD123+ or DC-LAMP+ cells did not show significant association with the outcome of the disease.ConclusionsTaken together, our results are compatible with the hypothesis of functional competence of sentinel lymph nodes based on the prevalence of the studied immune cells. The density of FOXP3+ lymphocytes showed association with progression and survival in patients with positive SLN status, while the other immune markers studied did not prove of prognostic importance. These results, together with our previous findings on the prognostic value of activated T cells and mature DCs infiltrating primary melanomas, suggest that immune activation-associated markers in the primary tumor may have a higher impact than those in SLNs on the prognosis of the patients. On the other hand, FOXP3+ cell density in SLNs, but not in the primary tumor, was found predictive of disease outcome in melanoma patients.

Prognostic implications of anatomic location of primary cutaneous melanoma of 1 mm or thicker

Background Breslow thickness, ulceration, and sentinel lymph node (SLN) status are well established as the most important prognostic factors for patients with cutaneous melanoma. Anatomic location of the primary tumor is generally considered to play a minor role in determining prognosis compared with these other factors. This analysis was performed to better define the influence of anatomic location of the primary melanoma on prognosis. Methods In this post hoc analysis of a prospective randomized trial that included patients ages 18 to 70 years with melanomas 1 mm or greater in Breslow thickness, all patients underwent SLN biopsy and completion lymphadenectomy if tumor-positive SLN were found. Kaplan–Meier survival analysis and univariate and multivariate analyses were performed to evaluate factors predictive of disease-free survival (DFS), local and in-transit recurrence-free survival (LITRFS), and overall survival (OS). Results A total of 2,500 patients were included in this analysis with a median follow-up period of 68 months. Anatomic locations included head, neck, trunk, upper extremity, and lower extremity. Age, Breslow thickness, and percentage of patients with a positive SLN were significantly different by anatomic location on univariate analysis, as were positive SLN status, presence of regression, sex, and histologic subtype ( P < .0001). On multivariate analysis, anatomic location was an independent predictor of SLN status ( P < .0001), DFS ( P = .045), LITRFS ( P = .023), and OS ( P < .0001). By Kaplan–Meier analysis, anatomic location was associated significantly with DFS, LITRFS, and OS. Conclusions Anatomic location of the primary melanoma is an important independent predictor of SLN status and prognosis. Patients with primary melanomas of the head/neck and trunk have a worse prognosis than primary melanomas of other anatomic locations.

Prognostic factors in cutaneous desmoplastic melanoma

Desmoplastic melanoma (DM) is a rare subtype of melanoma that is characterized by malignant spindle cells separated by prominent, fibrocollagenous stroma. Primary melanomas either may be entirely desmoplastic or almost entirely desmoplastic (pure DM [pDM]) or may exhibit a desmoplastic component admixed with a nondesmoplastic component (combined DM [cDM]). Patients who were diagnosed between 1993 and 2007 at a single institution with clinically localized, primary cutaneous melanoma (PCM) that contained a desmoplastic component and who underwent sentinel lymph node (SLN) biopsy were identified. Clinical and pathologic features of the primary tumors were correlated with DM type, SLN status, and patient outcome. Two hundred fifty-two patients (167 men, 85 women) were identified (median age, 61 years). The median tumor thickness was 2.0 mm. One hundred twenty-three patients (48.8%) had pDM, and 129 patients (51.2%) had cDM. Overall, 17 patients (6.7%) had positive SLN status, including 12 patients with cDM and 5 patients with pDM. Because of the low SLN-positive rate, a statistically significant difference in SLN status between patients with cDM (8.5%) and patients with pDM (4.9%; P = .25) could not be demonstrated. Older patient age, being a man, positive SLN status, and increasing tumor thickness were associated significantly with poorer disease-free survival (P < .05), although only the latter 2 variables were independently predictive. In addition, cDM type (P = .017) was associated significantly and independently with a shorter time to recurrence. In this largest study to date of patients with DM who underwent SLN biopsy, the SLN-positive rate in patients with DM was lower than that in patients with conventional melanoma. The results indicated that DM type is associated significantly and independently with the time to recurrence and should be evaluated routinely in all patients with PCM. Cancer 2010. (c) 2010 American Cancer Society.

Association of the Presence of Bone Marrow Micrometastases with the Sentinel Lymph Node Status in 410 Early Stage Breast Cancer Patients: Results of the Swiss Multicenter Study

The sentinel lymph node (SLN) status has proven to accurately reflect the remaining axillary lymph nodes and represents the most important prognostic factor. It is unknown whether an association exists between the SLN status and the presence of bone marrow (BM) micrometastases. The objective of the present investigation was to evaluate whether or not such an association exists. In the present investigation 410 patients with early stage breast cancer (pT1 and pT2 <or=3 cm, cN0) were prospectively enrolled between 1/2000 and 12/2003. All patients underwent SLN biopsy and bone marrow aspiration. The histological examination of the SLN consisted of step sectioning, H&E, and immunohistochemistry (Lu-5, CK 22) staining. Cancer cells in the BM were stained with monoclonal antibodies A45-B/B3 against cytokeratin and counted by an automated computerized digital microscope. BM micrometastases were detected in 28.8% (118/410) of all patients. The SLN contained metastases in 32.4% (133/410). Overall 51.2% of the patients (210/410) were SLN negative/BM negative and 12.4% (51/410) SLN positive/BM positive. Of all patients, 16.4% (67/410) were SLN negative/BM positive and 20.0% (82/410) SLN positive/BM negative. There was a statistically significant association between the SLN and BM status, both in unadjusted (Fisher's exact test: P = .004) and multiple logistic regression analysis (P = .007). In the present investigation a significant association was found between a positive SLN status and the presence of BM micrometastases. Nonetheless, the percentage of non-concordance (SLN negative/BM positive and SLN positive/BM negative) was considerable. The prognostic impact of BM micrometastases in our patient sample remains to be evaluated.

Interferon Alfa-2b or Not 2b? Significant Differences Exist in the Decision-Making Process between Melanoma Patients Who Accept or Decline High-Dose Adjuvant Interferon Alfa-2b Treatment

Patients with thick (Breslow>4 mm) primary melanoma and/or regional nodal metastasis have a high risk of tumor recurrence. High-dose adjuvant interferon (IFN) alfa-2b offers<or=10% improvement in relapse-free survival and overall survival with significant toxicity. The objective was to determine which prognostic factors and patient characteristics are significant in the decision to undergo IFN therapy. Of 781 patients who underwent sentinel lymph node (SLN) biopsy, 135 of 781 (17.3%) had positive SLN or thick melanomas and were informed of a >/=50% risk of recurrence/disease-related mortality and offered IFN. Telephone surveys delineated reasons behind patients' decisions to accept IFN. Acceptors, 60 of 135 (45%), decided to take IFN alfa-2b whereas 75 of 135 (55%) declined. Being female (OR, 2.4; 95% CI, 1.17-5.03; p=.017) and positive SLN status (OR, 2.2; 95% CI, 1.01-4.97; p=.048) were strongly associated with patients who chose IFN. Acceptors of IFN were younger, more influenced by physicians, and less affected by depression and side effect profile (p<.05 for all). Decliners were more concerned by strained relationships with family and social life (p<.05). Gender and positive SLN were predictive of high-risk melanoma patients' acceptance of IFN treatment. Physician insight into melanoma patients' therapeutic decision-making process can guide patients through this difficult disease.

The impact of factors beyond Breslow depth on predicting sentinel lymph node positivity in melanoma

In addition to Breslow depth, the authors previously described how increasing mitotic rate and decreasing age predicted sentinel lymph node (SLN) metastases in patients with melanoma. The objectives of the current study were to verify those previous results and to create a prediction model for the better selection of which patients with melanoma should undergo SLN biopsy. The authors reviewed 1130 consecutive patients with melanoma in a prospective database who underwent successful SLN biopsy. After eliminating patients aged <16 years and patients who had melanomas that measured <1 mm, 910 remaining patients were reviewed for clinical and pathologic features and positive SLN status. Univariate association of patient and tumor characteristics with positive SLN status was explored by using standard logistic regression techniques, and the best multivariate model that predicted lymph node metastases was constructed by using a backward stepwise-elimination technique. The characteristics that were associated significantly with lymph node metastasis were angiolymphatic invasion, the absence of regression, increasing mitotic rate, satellitosis, ulceration, increasing Breslow depth, decreasing age, and location (trunk or lower extremity compared with upper extremity or head/neck). Previously reported interactions between mitotic rate and age and between Breslow depth and age were confirmed. The best multivariate model included patient age (linear), angiolymphatic invasion, the number of mitoses (linear), the interaction between patient age and the number of mitoses, Breslow depth (linear), the interaction between patient age and Breslow depth, and primary tumor location. Younger age, increasing mitotic rate (especially in younger patients), increasing Breslow depth (especially in older patients), angiolymphatic invasion, and trunk or lower extremity location of the primary tumor were associated with a greater likelihood of positive SLN status. The current results support the use of factors beyond Breslow depth to determine the risk of positive SLN status in patients with cutaneous melanoma.

Impact of Sentinel Node Status and Other Risk Factors on the Clinical Outcome of Head and Neck Melanoma Patients

To determine the impact of sentinel lymph node (SLN) status and other risk factors on recurrence and overall survival in head and neck melanoma patients. The SLN Working Group, based in San Francisco, Calif, with its 11 member centers, the John Wayne Cancer Institute, and The University of Texas M. D. Anderson Cancer Center pooled data on 629 primary head and neck melanoma patients who had selective sentinel lymphadenectomy. A total of 614 subjects were analyzable. All centers obtained internal review board approval and adhered to the Health Insurance Portability and Accountability Act of 1996 regulations. A Cox proportional hazards model was used to identify factors associated with overall and disease-free survival. Tertiary care medical centers. Clinical outcome of head and neck melanoma patients undergoing selective sentinel lymphadenectomy. Overall, 10.1% (n = 62) of the subjects had at least 1 positive node. Subjects with positive SLN status had significantly thicker tumors (mean thickness, 2.8 vs 2.1 mm; P < .001), and were more likely to have ulcerated tumors (P = .004). During the median follow-up of 3.3 years, the overall mortality from head and neck melanoma was 10%, with more than 20% experiencing at least 1 recurrence. Multivariate analysis showed that tumor site was an independent predictor of mortality; location on the scalp had a more than 3-fold (P < .001) greater mortality than tumors on the face. Tumor thickness was also an independent predictor of overall survival, and SLN status was the most important predictor of disease-free survival in the multivariate model (P < .001). Tumors on the scalp had the highest rate of recurrence, while those on the neck had the lowest. Tumor ulceration was the significant predictor of time to recurrence or disease-free survival (P < .001). In this multicenter study, SLN status and other risk factors have an effect on recurrence and/or overall survival.

Intraoperative cytologic examination of breast sentinel lymph nodes: test utility and patient impact.

The sentinel lymph node (SLN) procedure is a method for ascertaining the axillary lymph node status in patients with breast cancer. Intraoperative examination of the SLN may be important, because a positive result directs surgery to a complete axillary lymph node dissection. Intraoperative cytologic examination (IOCE) is a method of intraoperative evaluation, although little data are available regarding the sensitivity of the method with respect to tumor size and the size of the SLN metastasis. All SLN cases for the years 1997-2002 at Magee-Womens Hospital were tabulated for primary breast carcinoma size, IOCE result, final histologic result, and size of the SLN metastasis. All SLNs had IOCE with touch imprints. Scrape SLN preparations and frozen sections were strongly discouraged. There were 748 SLN cases comprising 1576 SLNs that had IOCE, and there were 247 true positive SLN cases comprising 522 SLNs. Of the 247 true positive SLN cases, 111 had a positive IOCE (111/247; 45% sensitivity overall) and there were 136 false negatives. Of the 247 cases, 164 were SLN micrometastases < or =2.0 mm in size, and 44 (27%) of these were detected by IOCE, while the remaining 120 cases were false negative. Of the 83 SLN macrometastases (>2.0 mm), 66 (80%) were detected by IOCE, with 17 false negatives. In this series, 15 cases (2%) were given the IOCE diagnosis of atypical/defer, and all of these permanent sections were histologically positive. There were five IOCE-positive cases that were histologically negative. Of the 164 SLNs with micrometastases < or =2.0 mm, 17.6% (29/164) were < or =0.5 mm (6/29 [21.4%] were IOCE positive), 5.5% (9/164) were 0.51-1.0 mm (3/9 [33%] were IOCE positive), and 3.6% (6/164) were 1.1-2.0 mm (2/6 [33%] were IOCE positive). There were 83 SLNs with macrometastases larger than 2.0 mm, and 66/83 (80%) were detected by IOCE. In this group, 22% (18/83) were 2.1-5.0 mm (8/18 [44.4%] were IOCE positive) and 57.8% (48/83) were larger than 5.0 mm (41/48 [85%] were IOCE positive). The mean primary breast tumor size was 15.4 mm, with a mean SLN tumor size of 1.4 mm. There was a significant correlation with tumor size and the presence of SLN metastasis, and a significant correlation with tumor size and size of the SLN metastasis. There was a significant t correlation of primary tumor size and positive IOCE, with the group of negative IOCE cases having a mean tumor size of 14 mm and the positive IOCE group having a mean tumor size of 22 mm. The overall sensitivity of the method was 45%, specificity 99%, positive predictive value 0.99, and negative predictive value 0.80. Sensitivity of the IOCE procedure based on SLN tumor size is as follows: < or =0.5 mm, 21.4%; 0.51-1.0 mm, 33%; 1.1-2.0 mm, 33%; 2.1-5.0 mm, 44.4%; and >5.0 mm, 85%. Primary tumor size correlates with a positive SLN status and size of the SLN metastasis. Most false-negative IOCEs are due to micrometastases. Positive IOCE cases had a significantly larger SLN metastasis size (mean 8.0 mm) than the false-negative IOCE group (mean 1.4 mm). The IOCE of SLNs has a high negative predictive value, but this is a poor test for the detection of micrometastases, as this group accounts for the majority of false-negative IOCEs of breast SLNs.

Patterns of recurrence after sentinel lymph node biopsy for cutaneous melanoma

Background Previous sentinel lymph node (SLN) studies for cutaneous melanoma have shown that the SLN accurately reflects the nodal status of the corresponding nodal basin. However, there are few long-term studies that describe recurrence site patterns, predictors for recurrence, and overall survival and disease-free survival after SLN biopsy. Methods A retrospective review of patients over a 6-year period was performed to determine patient outcomes and the patterns of recurrence. In all cases, Tc-99 sulfur colloid along with isosulfan blue dye was injected at the primary melanoma site. After resection, the SLN was serially sectioned and evaluated by hematoxylin and eosin staining and immunohistochemistry. Results One hundred ninety-eight patients were identified who underwent SLN biopsy for cutaneous melanoma including T1 (n = 21), T2 (n = 88), T3 (n = 75), and T4 (n = 14) primary tumors. Of these patients, 38 had a positive SLN. Of the 38 patients with a positive SLN (mean follow-up 38 months), recurrent disease was identified in 10 (26.3%) at a mean interval of 14.2 months. The site of first recurrence was distant (n = 4) and local (n = 6). Regional lymphatic basin recurrence was not identified. Of the 160 patients with a negative SLN (mean follow-up 50 months), recurrent disease was identified in 16 (10.0%) at a mean interval of 31.3 months. The site of first recurrence was systemic (n = 11), local (n = 4), and nodal (n = 1). Overall survival and disease-free survival for patients with a positive SLN at 55 months was 53.3% and 47.7% respectively, while overall survival and disease-free survival for patients with a negative SLN at 53 months was 92.2% and 87.7% respectively ( P <0.01). Univariate and multivariate analysis of the entire cohort (n = 198) identified primary tumor depth and positive SLN status as significant predictors of recurrence. Conclusions The incidence of nodal basin recurrence after SLN biopsy was found to be 0.6%. Primary tumor depth and pathological status of the SLN are significant predictors of local and systemic recurrence. Long-term follow-up indicates that patients with a positive SLN clearly recur sooner and have decreased overall survival than those with a negative SLN.

Sentinel lymph node biopsy in melanoma patients with clinically negative regional lymph nodes--one institution's experience.

The purpose of this prospective study of sentinel lymph node (SLN) biopsy in a large series of melanoma patients with clinically negative regional lymph nodes from one cancer centre was to analyse the reliability of the procedure, the pattern of failures during follow-up and the factors affecting the clinical outcome of patients. Between April 1995 and November 2001, 726 consecutive patients with primary cutaneous malignant melanoma underwent SLN biopsy with preoperative lymphoscintigraphy. The vital blue dye technique was used in 170 patients, and the blue dye technique combined with intraoperative lymphoscintigraphy in 556 patients. The primary melanoma sites were head and neck in nine patients, the extremities in 419 patients, and the trunk in 298 patients. The median Breslow thickness was 3.0 mm. All patients were followed closely, the median follow-up time being 34 months. The sentinel node(s) were successfully identified in 96% of patients. Intraoperative lymphoscintigraphy combined with the blue dye technique improved the SLN identification rate (technical success in 97.3% of cases) compared with the blue dye technique alone (technical success in 91.6%). The rate of failed SLN procedures was significantly (P = 0.007) lower in inguinal basins (3.1%) compared with axillary basins (7.9%). SLN metastases were detected in 147 patients (20.2%). The presence of SLN metastases correlated significantly with primary tumour thickness and ulceration (P < 0.001). The false-negative SLN biopsy rate was 4.66% (27 out of 579 SLN-negative patients). All but two node-positive patients underwent complete lymphadenectomy. Lymph nodes other than SLNs were found to contain metastases in 26.9% of patients (39 out of 145). The 5 year overall survival (OS) rate was 84% for SLN-negative patients and 40% for SLN-positive patients. Five variables showed a strong, statistically significant negative independent prognostic association with OS: positive SLN status (P = 0.000001), primary melanoma thickness > 4 mm (P = 0.0009), male gender (P = 0.001), more than one lymph node involvement (P = 0.02) and lymph node extracapsular extension (P = 0.03). SLN biopsy is currently a valuable and effective diagnostic procedure for the precise staging of patients with clinically N0 cutaneous melanoma. So far SLN biopsy seems to be the only accessible method for consciously oriented detection of nodal micrometastases in melanoma that would otherwise go undetected. SLN status is the most important factor proven to distinguish high and low risk melanoma patients.