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Squamous cell carcinomas are among the most common skin tumors and show a risk of metastasis depending on various factors such as tumor thickness, localization, histological subtype and immune status of the patient. Sentinel lymph node biopsy (SLNB) SLNB represents a possibility for assessing the locoregional lymph node status. In this study, the role of the SLNB in lymph node status and survival was analyzed. Retrospectively, 720 patients with high-risk squamous cell carcinoma (tumor thickness > 5 mm) were examined. 150 patients agreed to SLNB, 570 patients did not undergo histologic confirmation of lymph node status and were included directly in follow-up. In 101 patients, a sentinel lymph node was successfully marked and extirpated, followed by regular follow-up examinations.A total of 11.11% of the patients showed lymph node metastasis in the course of their treatment, with no difference in the proportion of patients in the SLNB group (11.9%) and the observation group (11.4%) (p = 0.873). The proportion of distant metastasis also did not differ between the groups (p = 0.898). In 3.96% of the patients in the SLNB group, a metastasis was found in the sentinel lymph node. Tumor-specific death was observed in 7.14% of the patients in the SLNB group and 4.74% in the observation group (p = 0.269). Although SLNB is a principally suitable method for determining lymph node status, the available data do not provide any benefit regarding further metastasis or tumor-specific survival.

Introduction: Complete lymph node dissection (CLND) after a positive sentinel node (SN) biopsy provides important prognostic information in melanoma patients but has been questioned for therapeutic use recently. We explored whether quantification of the tumour spread to SNs may replace histopathology of non-sentinel nodes (NSNs) for staging purposes., Patients and Methods: We quantified melanoma spread in SNs and NSNs in 128 patients undergoing CLND for a positive SN. In addition to routine histopathology, one-half of each of all 1496 SNs and NSNs was disaggregated into a single cell suspension and stained immunocytochemically to determine the number of melanoma cells per 10 6 lymph node cells, i.e. the disseminated cancer cell density (DCCD)., Results: We uncovered melanoma spread to NSNs in the majority of patients; however, the tumour load and the proportion of positive nodes were significantly lower in NSNs than in SNs. The relation between SN and NSN spread could be described by a mathematical function with DCCD NSN  = DCCD SN c /10 1 - c (c = 0.69; 95% confidence interval [CI]: 0.62-0.76). At a median follow-up of 67 months, multivariable Cox regression analyses revealed that DCCD SN (p = 0.02; HR 1.34, 95% CI: 1.05-1.71) and the total number of pathologically positive nodes (p = 0.02; HR 1.53, 95% CI: 1.07-2.22) were significant risk factors after controlling for age, gender, thickness of melanoma and ulceration status. A prognostic model based on DCCD SN and melanoma thickness predicted outcome as accurately as a model including pathological information of both SNs and NSNs., Conclusion: The assessment of DCCD SN renders CLND for staging purposes unnecessary., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Sentinel lymph node biopsy (SLNB) plays an important role in the prognostic classification of melanoma and is now a standard staging procedure. However, due to the complex drainage pattern and the risk of site associated morbidity, the potential survival benefit of SLNB is controversial in head and neck (H&N) melanoma., Methods: Patients with primary H&N melanoma with a tumor thickness ≥1.00 mm diagnosed in the Department of Dermatology, University of Tuebingen, Germany between 1991 and 2010 were included in this study. Regarding patterns of metastases, disease-free, and overall-survival, 259 patients with SLNB were compared retrospectively to 218 patients without SLNB., Results: The detection of micrometastasis in SLN proved to be a significant prognostic factor in H&N patients [hazard ratio (HR) 3.69, p < 0.0001]. A significant improvement of recurrence-free survival (RFS, p = 0.011), regional lymph node metastasis-free survival (LFS, p = 0.007), and distant metastasis-free survival (DMSF, p = 0.015) was observed for patients with SLNB versus non-SLNB. Furthermore, a trend towards better overall survival (OS) was found (p = 0.053) for the SLNB group., Conclusions: SLNB improved prognostic outcome in H&N melanoma in terms of disease-free and distant metastases survival, reduced subsequent regional lymph node metastases, and showed a trend towards a better OS.

Background: Sentinel lymph node spread is a crucial factor in melanoma outcome. We aimed to define the impact of minimal cancer spread and of increasing numbers of disseminated cancer cells on melanoma-specific survival., Methods and Findings: We analyzed 1,834 sentinel nodes from 1,027 patients with ultrasound node-negative melanoma who underwent sentinel node biopsy between February 8, 2000, and June 19, 2008, by histopathology including immunohistochemistry and quantitative immunocytology. For immunocytology we recorded the number of disseminated cancer cells (DCCs) per million lymph node cells (DCC density [DCCD]) after disaggregation and immunostaining for the melanocytic marker gp100. None of the control lymph nodes from non-melanoma patients (n = 52) harbored gp100-positive cells. We analyzed gp100-positive cells from melanoma patients by comparative genomic hybridization and found, in 45 of 46 patients tested, gp100-positive cells displaying genomic alterations. At a median follow-up of 49 mo (range 3-123 mo), 138 patients (13.4%) had died from melanoma. Increased DCCD was associated with increased risk for death due to melanoma (univariable analysis; p<0.001; hazard ratio 1.81, 95% CI 1.61-2.01, for a 10-fold increase in DCCD + 1). Even patients with a positive DCCD ≤3 had an increased risk of dying from melanoma compared to patients with DCCD = 0 (p = 0.04; hazard ratio 1.63, 95% CI 1.02-2.58). Upon multivariable testing DCCD was a stronger predictor of death than histopathology. The final model included thickness, DCCD, and ulceration (all p<0.001) as the most relevant prognostic factors, was internally validated by bootstrapping, and provided superior survival prediction compared to the current American Joint Committee on Cancer staging categories., Conclusions: Cancer cell dissemination to the sentinel node is a quantitative risk factor for melanoma death. A model based on the combined quantitative effects of DCCD, tumor thickness, and ulceration predicted outcome best, particularly at longer follow-up. If these results are validated in an independent study, establishing quantitative immunocytology in histopathological laboratories may be useful clinically.

Background: This study investigated survival probabilities and prognostic factors in sentinel lymph node biopsy (SLNB) staged patients with cutaneous melanoma (CM) with the aim of defining subgroups of patients who are at higher risk for recurrences and who should be considered for adjuvant clinical trials., Methods: Patients with primary CM who underwent SLNB in the Department of Dermatology, University of Tuebingen, Germany, between 1996 and 2009 were included into this study. Survival probabilities and prognostic factors were evaluated by Kaplan-Meier and multivariate Cox proportional hazard models., Results: 1909 SLNB staged patients were evaluated. Median follow-up time was 44 months. Median tumor thickness was 1.8 mm, ulceration was present in 31.8% of cases. The 5-year Overall Survival (OS) was 90.3% in SLNB negative patients (IB 96.2%, IIA 87.0%, IIB 78.1%, IIC 72.6%). Patients with micrometastases (stage IIIA/B) had a 5-year OS rate of 70.9% which was clearly less favorable than for stages I-II. Multivariate analysis revealed tumor thickness, ulceration, body site, histopathologic subtype and SLNB status as independent significant prognostic factors., Conclusion: Survival rates of patients with primary CM in stages I-II were shown to be much more favorable than previously reported from non sentinel node staged collectives. For future clinical trials, sample size calculations should be adapted using survival probabilities based on sentinel node staging.

In current dermatological practice lymphatic mapping and sentinel lymph node biopsy (SLNB) are frequently used in patients with cutaneous cancers, like malignant melanoma, squamous cell carcinoma and Merkel cell carcinoma. However, those tumors are often located on the head and neck, regions with notoriously variable lymphatic drainage patterns. Consequently, the incidence of successful SLNB in the head and neck is considerably lower compared to the SLNB on the trunk and extremities. Thus, there is a need to improve the hit rate of SLNB in this special area. Therefore, in the current study we analyzed SLNB of 149 patients treated for cutaneous tumors at the Department of Dermatology, University of Tuebingen, Germany. By mapping SLN (sentinel lymph node) locations to their specific tumor sites on the head and neck, we were able to calculate the frequency of SLN distribution to defined tumor locations. Furthermore, our analysis revealed that approximately 7% of tumors on the head and neck drain to contralateral SLN, which is of relevance for the classification in the current cancer TNM system. Thus, our mapping can predict SLN location in patients with cutaneous head and neck tumors and might help to further increase the rate of successful SLNB.

Purpose: Improved detection of early-disseminated melanoma cells may eventually translate into more effective patient care. We present a novel strategy for detection of melanoma cells in sentinel lymph nodes and confirm their malignant descent by genomic characterization., Experimental Design: In sentinel lymph nodes from 358 melanoma patients, we prospectively compared the rates of tumor cell detection between immunocytochemistry using HMB45 and Melan A antibodies on disaggregated lymph node samples and standard histopathology (H&E staining and immunostaining on tissue sections). Immunocytochemical melanoma cell detection was controlled by testing lymph node samples from 59 nonmelanoma patients and by isolation and comparative genomic analysis of 30 antigen-positive cells., Results: Of the 358 patients, 43 (12%) were positive by standard histopathology, whereas HMB45 immunocytochemistry detected 159 of 358 (44%) positive patients. None of the control samples reacted with the HMB45 antibody. Reexamination of samples that were classified as negative by histopathology revealed that extensive serial sectioning would be necessary to achieve sensitivity similar to HMB45 immunocytochemistry. Interestingly, both the number of immunocytochemically positive samples and the number of positive cells in the sentinel node correlated with the thickness of the primary tumor (r = 0.34; P = 0.001 and P < 0.0001, respectively). Twenty-four of 30 isolated immunocytochemically positive cells (80%) displayed chromosomal aberrations, some of which were isolated from histopathologically negative nodes., Conclusion: Immunocytochemical detection of melanoma cells in sentinel lymph nodes is superior to standard histopathology. It remains to be determined whether the detection and genomic characterization of isolated melanoma cells in sentinel lymph nodes will provide relevant prognostic information.

Sentinel node biopsy (SNB) is increasingly being used as a minimally invasive staging procedure in patients with malignant melanoma. For decades elective lymph node dissection (ELND) was performed in many centers on patients at risk for lymph node metastasis but without clinically detectable lymph node involvement. Today, selective lymph node dissection (SLND) is offered only to patients with histologically proven metastasis in a SN (10-29%). A positive SN is one of the most important prognostic parameters. Ten years after the introduction of the technique, the role of SNB in the treatment of cutaneous melanoma still remains controversial. Issues include the usefulness of highly sensitive evaluation of SN using molecular biology or cytology techniques, as well as the therapeutic impact of the SNB per se and the associated combined surgical or medical adjuvant therapies.

Objective: Sentinel lymph node biopsy (SLNB) has been proposed as a minimally invasive procedure for the histopathologic staging of the regional lymph node basin. The aim of this work was to investigate the prognostic value of detection of micrometastasis by SLNB., Methods: In the period from January 1996 to March 2000, a sentinel lymph node (SLN) was identified in 283 patients at the Department Dermatology, University of Tuebingen. In the case of 38 patients (13.4%) histopathologic examination led to the detection of micrometastasis in at least one SLN. The median follow-up period was 29 months., Results: Thirty-one of 245 patients (12.7%) suffered a tumor recurrence following a negative SLNB, and 19 of 38 patients (50%) following positive SLNB. In the case of disease-free survival the remaining significant independent prognostic factors of the multivariate analysis were tumor thickness (p=0.011), ulceration (p=0.026), and the detection of micrometastasis in SLNB (p=0.021). With respect to distant-metastasis-free survival the significant independent prognostic factors of the multivariate analysis were tumor thickness (p=0.0022) and the SLNB results (p=0.0068). For overall survival the tumor thickness (p=0.013) and the SLNB results (p=0.034) were significant independent prognostic parameters in the multivariate analysis., Conclusion: The study examined patients with melanomas of all tumor thicknesses and SLNB for which the prognostic significance of SLNB was tested. Recurrences were more frequent in patients with a micrometastatic SLN. Patients with a negative SNLB are still at risk for tumor recurrence. The histopathologic result of SLNB is, after tumor thickness, the most significant prognostic factor for disease-free survival, distant-metastasis-free survival, and overall survival.

Background: The status of the sentinel lymph node (SLN) is an important prognostic factor in patients with cutaneous melanoma. Reverse transcription-polymerase chain reaction (RT-PCR) has been used as a sensitive means of detecting tumour cells in SLNs., Objectives: To determine whether RT-PCR analysis of the SLN using both the central and the peripheral slices is more sensitive than molecular analysis of the central slice only., Methods: Eighty-three SLNs from 59 patients with primary cutaneous melanoma were identified by SLN mapping. All SLNs were bisected along their longitudinal axis to produce two equal halves. One half was used for histology and immunohistochemistry, and the other was analysed by RT-PCR for tyrosinase and MelanA. Parallel to the longitudinal axis, one central slice (approximately 2 mm in thickness) was cut manually. This central slice was used for our standard RT-PCR protocol. In the current study, up to eight additional peripheral slices (each approximately 2 mm in thickness) were cut parallel to the existing cut surface. These peripheral slices were analysed by additional RT-PCR., Results: Standard RT-PCR of the central slice yielded positive results in 34 of 59 patients (57%). Additional RT-PCR of peripheral slices demonstrated positive findings in six additional patients (10%) who were initially negative by standard RT-PCR of the central slice. In detail, seven of those 34 patients positive by standard RT-PCR of the central slice had positive histological findings. In each of these seven patients, RT-PCR was positive both in the central slice as well as in the peripheral slices. The remaining 27 patients with positive RT-PCR results of the central slice showed negative histological findings. Only nine (33%) of these 27 patients had a positive RT-PCR also in the peripheral slices. Finally, all 25 patients with negative RT-PCR results in the central slice showed negative histological findings. Six of these patients (24%) revealed positive RT-PCR results on the analysis of peripheral slices. However, three of these patients expressed only MelanA but not tyrosinase. Thirty lymph nodes from 24 nonmelanoma patients served as negative controls for RT-PCR. In three of these 24 patients (13%) expression of MelanA but not tyrosinase was detected by RT-PCR., Conclusions: Molecular analysis of peripheral slices yielded six additional patients (10%) positive by RT-PCR who were initially negative by standard RT-PCR of the central slice. However, three of these six patients were found to express only MelanA but not tyrosinase. As MelanA expression was also found in 13% of control lymph nodes, positive MelanA expression alone in SLNs of melanoma patients requires cautious interpretation in order to avoid false-positive findings. Thus, additional molecular processing of peripheral slices did not significantly increase the number of patients with RT-PCR-positive SLNs.

Introduction: It is still unclear whether sentinel lymph node biopsy (SLNB) has an effect on the survival or recurrence-free survival of patients. It would be necessary to compare patients with SLNB (or with selective lymph node dissection in the case of positive SLNB) and patients without SLNB who received only a close clinical and sonographic follow-up. To date, no results from prospective, randomized studies of SLNB are available., Material and Methods: Patients with SLNB (n = 283) and patients in clinical stage I and II with close follow-up examinations only (n = 3,514) were studied retrospectively in this investigation with regard to prognostic factors established in the literature: sex, age, tumor thickness, histological tumor type, ulceration and localization., Results: Multivariate analysis did not show an independent significant advantage with regard to survival when SLNB had been performed (p = 0.37). Compared with patients in clinical stage I and II with close follow-up only (n = 2,617),patients in stage I and II with negative SLNB (n = 238) had no significantly lower melanoma-related mortality (p =0.36) but significantly fewer recurrences in the regional lymph node area (p = 0.0015). With regard to survival without distant metastases and disease-specific survival, patients with positive SLNB (n = 33) did not significantly benefit by comparison with patients who developed lymph node metastasis identified clinically or sonographically later during follow-up examinations (n = 246; p =0.89 and p = 0.38, respectively)., Conclusion: In the relatively short follow-up period after SLNB, patients for whom SLNB had been performed did not have - on the whole - a prognostic advantage over patients who were subject only to close follow-up monitoring. Patients for whom subclinical lymph node metastases had been removed as the result of a positive SLNB did not have a better prognosis than patients without SLNB who had developed lymph node metastases within the follow-up period [corrected], (Copyright 2004 S. Karger AG, Basel)

Background: Tyrosinase reverse transcription-polymerase chain reaction (RT-PCR) has been shown to be highly sensitive in detecting tumour cells in melanoma patients., Objective: To assess whether the detection of minimal residual disease by RT-PCR is improved by concomitant analysis of sentinel lymph nodes (SLNs), bone marrow (BM) and peripheral blood (PB) in patients with primary melanoma., Methods: Thirty-five SLNs, 41 BM samples and 26 PB specimens from 26 patients with primary cutaneous melanoma (tumour thickness > or = 0.75 mm) were examined by nested RT-PCR for tyrosinase and Melan-A. SLNs and BM samples were also analysed by histopathology. RT-PCR findings were related to tumour thickness of the primary melanoma., Results: Overall, melanoma cells were detected by RT-PCR in 13 of 26 patients (50%). Seven patients had positive RT-PCR results in their SLNs (27%), including all patients (n = 4) with histologically positive SLNs, two patients had positive findings in their BM exclusively detected by RT-PCR (8%) and six patients in PB (23%). The presence of tumour cells detected by RT-PCR in SLNs was not related to the presence of melanoma cells in BM and/or PB. The incidence of RT-PCR-positive SLNs was significantly associated with greater tumour thickness (P = 0.004). Both patients with positive RT-PCR findings in their BM had a large tumour thickness (> or = 2 mm). No association between positive RT-PCR findings in PB and greater tumour thickness was observed., Conclusions: RT-PCR-positive SLNs were strongly associated with greater tumour thickness, underlining the prognostic significance of SLN positivity. Similar to certain epithelial malignancies, molecular investigation of the BM might provide complementary prognostic information in the early stages of melanoma. In contrast, no association between positive RT-PCR results in PB and increasing tumour thickness was found, implying that RT-PCR findings in PB are of doubtful clinical relevance in primary melanoma.

Background The ear's specific anatomical and lymphatic characteristics impose special requirements on the treatment of melanoma of the ear. Objectives The aim of this prospective study was to define prognostic factors for melanoma of the ear and to evaluate surgical strategies for excision margins, histological evaluation and sentinel lymph node biopsy (SLNB) in order to achieve better cosmetic and functional results. Patients and methods One-hundred and sixty-one patients with stage I/II melanoma of the external ear were treated in the Department of Dermatology, University of Tuebingen, from March 1976 to March 2004 (median follow-up 62 months). Malignant melanoma of the external ear represented 3% of the stage I/II cutaneous melanomas and 20% of the stage I/II head and neck melanomas recorded in the Melanoma Registry of the Department of Dermatology at the University of Tuebingen. Twenty of 42 lentigo maligna melanomas (LMM) underwent conventional histological evaluation, 22 underwent complete three-dimensional histology of excision margins (3D histology) in a paraffin-technique, i.e. micrographic surgery. SLNB was performed in 28 patients with melanomas thicker than 1.0 mm. Clinical, histological and surgical risk factors were evaluated by univariate and multivariate analysis. Results The median thickness of the tumours in the present study was 1.08 mm (mean 1.51 mm; range 0.18-8.50 mm), and the median excision margins were 11.0 mm (mean 12.61 mm; range 2.0-31.0 mm). The 3-year disease-specific survival rate was 98%, and the 3-year recurrence-free survival rate was 83%. Tumour thickness and invasion level were the only risk factors significant for disease-specific survival. Tumour thickness, location of the tumour and extent of excision margins were independently significant risk factors for recurrence-free survival. LMMs removed surgically with accompanying 3D histology were thicker than those examined by conventional histology (median 0.93 mm vs. 0.83 mm). The use of surgery with 3D histology, i.e. micrographic surgery, made it possible to reduce the excision margins (median 5 mm vs. 10 mm) without an increased risk of recurrence. Two of 29 SLNBs were positive (6.9%). There were six preregional recurrences after negative SLNB and one after positive SLNB. None of the patients who underwent SLNB died of melanoma-related causes during the observation period. Conclusions This is the largest series of ear melanomas reported so far. The overall survival depended only on the tumour thickness and Clark level of invasion. Local recurrence was more frequent with smaller excision margins, but this did not influence the overall survival. Smaller excision margins under 3D-histological control did not carry an increased risk of local recurrence. Our results do not permit conclusions regarding the prognostic impact of SLNB for patients with melanoma of the ear. [ABSTRACT FROM AUTHOR]

Local anaesthetics are an integral part of modern surgery since diluted solutions of cocaine were described nearly 150 years before. Tumescent local anaesthesia (TLA) utilizes a mixture of highly diluted local anaesthetics in a carrier solution and is used for skin biopsies, excision of skin tumours and vein surgery.[1] Also, wide excisions for hidradenitis suppurativa, serial excisions of giant congenital nevi (Fig.), Rhinophyma surgery or lymph node dissections are feasible using TLA.[[2]]. [Extracted from the article]