Complete lymph node dissection or observation in melanoma patients with multiple positive sentinel lymph nodes: A single‐center retrospective analysis

Although the role of sentinel lymph node biopsy (SLNB) as a prognostic factor is well established, its consequences for therapy are controversial. The aim of this study was to analyze if complete lymph node dissection (CLND) in patients with more than one positive sentinel lymph node (SLN) significantly improves melanoma‐specific survival (MSS) and progression‐free survival (PFS). Medical records of patients who underwent SLNB between 2001 and 2016 at the University Hospital of Cologne were reviewed, and patients with positive SLN were identified. Patient and tumor characteristics, patterns of recurrence, progression‐free and melanoma‐specific survival were analyzed. Seventy‐eight patients with multiple positive and 197 patients with one positive SLN were included in this study. Patients with multiple positive SLN had significantly more positive non‐SLN compared with patients with only one positive SLN (26.9% vs 8.6%, P = 0.01). However, in the subgroup of patients with multiple positive SLN, CLND did not significantly improve MSS (mean MSS 95 vs 75 months, P = 0.5) and PFS (mean PFS 59 vs 68 months P = 0.167). CLND did not result in a significant improvement in PFS and MSS in patients with multiple positive SLN.     

Long-Term Survival Analysis and Clinical Follow-Up in Acral Lentiginous Malignant Melanoma Undergoing Sentinel Lymph Node Biopsy in Korean Patients

Background

In cutaneous malignant melanoma (MM) with clinically uninvolved regional lymph nodes, sentinel lymph node (SLN) status is the most powerful indicator of both overall survival (OS) and disease-free survival (DFS). However, no studies on the long-term survival and clinical follow-up of Korean patients with acral lentiginous MM (ALM) undergoing SLN biopsy (SLNB) have been published.

Objective

The purpose of this study was to investigate the clinical prognosis and long-term survival of Korean patients with ALM according to SLN status.

Methods

Thirty-four ALM patients undergoing SLNB were included in this study. We evaluated clinical and histopathological follow-up data such as the stage of disease, treatment, recurrence, and metastasis, and analyzed OS and DFS according to SLN status.

Results

The median follow-up time was 60.5 months (range 3~127 months). Positive SLNs were noted in 14 patients (41.2%). Patients with negative SLNs had better OS and DFS than those with positive SLNs (p<0.05). Increased Breslow thickness was associated with short OS and DFS (p<0.05), and female patients showed better DFS than male patients (p<0.05).

Conclusion

To our knowledge, this is the first study on the long-term survival and clinical follow-up of patients undergoing SLNB for ALM in Korea. Our findings show that SLN status is an important prognostic factor for predicting OS and DFS.     

Disease progression in melanoma patients with negative sentinel lymph node: does false‐negative specimens entirely account for this phenomenon?

Background Sentinel lymph node (SLN) status is the most important prognostic factor for subjects with primary melanoma thicker than 1 mm. Objective We focused our study on patients with disease progression after negative SLN biopsy (SLNB), with the aim of elucidating their clinical and histopathological characteristics, outcome and real incidence of false negative. Methods A total of 688 melanoma patients who underwent SLNB (1 May 1998–31 December 2008) were analysed; all patients had Breslow >1 mm or Breslow <1 mm and at least one of the following features: regression, ulceration and/or Clark level IV–V. Results Progression developed in 114 of 503 negative SLN patients (22.7%); the first metastatic site was regional in 64% and distant in 36% of these cases. Thirty‐nine patients had nodal metastases in the SLN basin as first site of progression. High‐risk melanomas (P = 0.001) and elderly patients (P = 0.0005) had an increased probability of progression. Women with a higher median age and lower limbs primary melanoma developed mainly regional skin metastases, while an increased probability of distant metastases was demonstrated in patients with primary on the trunk and axillary SLN (P = 0.003, P = 0.001 respectively). Age at diagnosis, Breslow thickness and regression showed a prognostic relevance in univariate and multivariate analyses on disease‐free survival and overall survival. Conclusions Even if SLN status remains the most important prognostic factor for melanoma patients, progressive disease after a negative SLNB is a relatively frequent event. However, in our opinion, only a part of negative SLNB patients with metastatic spreading should be considered as false negative (7.75%).     

Acral lentiginous melanoma versus other melanoma: A single‐center analysis in Japan

We summarize herein our 14‐year experience of conventional treatment outcomes before the era of molecular‐targeted therapy and immunotherapy. Specifically, we conducted a retrospective review of our 252 patients with primary cutaneous melanoma (acral lentiginous melanoma [ALM], n = 121; non‐acral lentiginous melanoma [non‐ALM], n = 131), and compared the prognostic factors between ALM and non‐ALM. Melanoma‐specific survival and disease‐free survival were estimated using the Kaplan–Meier method. Regarding the results, all patients were Japanese (106 male and 146 female), with a mean age of 60.1 years. Among ALM patients, age was elder and primary tumor size was larger than non‐ALM. As for tumor thickness, in situ lesions were more frequently observed in ALM. There was no significant difference in the distribution of tumor thickness between the two groups when excluding the in situ lesions. For treatment of the primary melanoma, 248 patients (98.4%) had undergone curative surgical excision and 120 patients with more than 1 mm or ulcerated melanoma had undergone sentinel lymph node biopsy. Patients with systemic metastasis primarily underwent dacarbazine‐based chemotherapy. The Kaplan–Meier survival curves revealed no significant difference in melanoma‐specific survival and disease‐free survival between those with ALM and non‐ALM. The results also showed that both ALM and non‐ALM, when they initially metastasize, first affect the regional lymph nodes. Incisional biopsy was not an adverse prognostic factor. These results suggest that ALM does not differ in its biological behavior from non‐ALM, so we can consider ALM as being equivalent to non‐ALM. The initial treatment for ALM and non‐ALM can involve the same strategy.     

Sentinel lymph node biopsy in patients with thick (= 4 mm) melanoma: a single-centre experience

Background and objective Lymphatic mapping/sentinel lymph node biopsy (LM/SLNB) have become routine techniques for staging the regional lymph nodes in early stage melanoma, yet their role in the management of thick (= 4 mm) melanoma is debated. The aim of the present study is to review our experience with LM/SLNB in a series of patients with thick primary melanoma, to evaluate its utility in this melanoma subset. Patients and methods Thirty patients (18 men and 12 women; mean age 70.6 years; median 75 years) with thick primary melanoma underwent LM/SLNB, using both radioisotope and blue dye. The statistical tests were performed by using SAS software for Windows, version 8.2. Results The primary tumour sites were head/neck (n = 5; 16.6%), trunk (n = 10; 33.3%), and extremities (n = 15; 50%). Tumour thickness ranged from 4 to 17 mm (mean 5.14 mm; median 4.5 mm). Ulceration was observed in 23 (76.6%) tumours. Eleven patients (36.6%) had at least a positive sentinel lymph node (SLN). The mean follow-up was 27.3 months (median 26 months; range 5–63 months). Patients without SLN metastases had a 5-year disease-free survival rate of 78.9%, vs. 18.2% for patients with SLN metastases (P = 0.0121 by log rank test). The 5-year overall survival rate for patients without SLN metastases was 89.5%, whereas patients with SLN metastases had a 5-year overall survival rate of 36.4% (P = 0.0272 by log rank test). Conclusion Our retrospective analysis indicates that the SLN status is predictive of recurrence and survival in patients with thick melanoma, and LM/SLNB should be routinely performed in this subset of melanoma patients.     

Clinical effects of stereotactic radiation surgery in patients with metastatic melanoma

We examined the effectiveness of stereotactic radiation surgery (SRS) in 14 patients with brain metastasis in our hospital. The age of the patients ranged 45–85 years old (mean, 65). Brain metastasis was detected by neurological symptoms in seven patients and by regular imaging examination in the remaining patients. The number of metastatic lesions in the brain before SRS ranged 1–11 (median, 2). The treatment number of SRS was 1–4 times (median, 2). Six of 14 patients had neurological symptoms before SRS. Overall survival (OS) after SRS was 1.7–21.2 months (median, 8.2). The progression‐free survival (PFS) after SRS was 0.9–10.5 months (median, 2.2). The result of univariate analysis showed that the application of two or more courses of SRS was significantly related to OS (P = 0.005). Single metastatic lesion (P = 0.051) and no extracranial lesion (P = 0.055) showed a slight tendency to be related to disease‐free survival (DFS). Neither lactate dehydrogenase nor neurological symptoms were significantly related to OS or DFS. Although OS and DFS after SRS were not very long, the treatment of brain metastases has the potential to prevent neurological events. Repeating SRS may be accepted as a local therapy in the multimodal approach including new molecular targeting drugs for metastatic melanoma.     

Relevance of multiple basin drainage and primary histologic regression in prognosis of trunk melanoma patients with negative sentinel lymph nodes

Background Lymphatic drainage to multiple basins (MLBD) is frequently observed in patients with primary melanoma located in the trunk. Conflicting data regarding the prognostic impact of MLBD are reported. Objective and methods We reviewed our case series of 352 patients with trunk melanoma to evaluate the pattern of basin drainage and to analyse whether different basin drainages may have different significance in negative sentinel lymph node (SLN) patients. The presence of single/multiple basin drainage, the status of SLN, the presence of melanoma regression, Breslow thickness, ulceration and type of melanoma were recorded for each patients and correlated to Disease Free Survival (DFS) and Overall Survival (OS). Results MLBD occurred in 77 patients (21.9%) and single basin lymphatic drainage (SLBD) occurred in 275 patients (79.1%). The presence of metastases in SLN was not significantly different in patients with MLBD compared to those with SLBD (26% vs. 19.6%). No differences in OS and DFS were found in SLBD/MLBD independently from SLN status. However DFS was higher in patients with MLBD and negative SLN (P = 0.0001), in addition, in patients with negative SLN and SLBD disease recurrence was 19% while was only 7% in patients with negative SLN obtained from MLBD (P = 0.03). Multivariate analysis showed that Breslow thickness <2 mm, MLBD pattern and regression of melanoma were favourable variables for DFS of patients with negative SLN. Conclusions An accurate study of the drainage basin and of all the SLNs obtained from MLBD is recommended because of the impact in prognosis of melanoma of the trunk.     

Nodular Melanoma in 62 Japanese Patients: Influence of Initial Surgical Treatment on Local Recurrence and Prognosis

The incidence of malignant melanoma is much lower in Japanese than in Caucasians, and the commonest type of melanoma in Japanese is acral lentiginous melanoma (ALM). In contrast to the improved prognosis noted in ALM, it is now of increasing concern that there is a rise in both the frequency and mortality of nodular melanoma. During the 25 years from 1970 to 1994, we observed 190 patients with melanoma, including 62 nodular melanomas and 96 ALM, at the Department of Dermatology, Tohoku University Hospital, Sendai, Japan. We retrospectively reviewed the recurrence and survival rates of nodular melanoma observed. The proportion of nodular melanoma, once comprising only 24% of all melanomas, showed a sharp increase to 40% after 1982. The anatomical sites of the primary tumor were the hands and feet (29%), extremities excluding hands and feet (27%), head and neck (23%), and trunk (21%). Comparison of the stages of nodular melanoma when diagnosed showed that the proportion of stage III remained highest throughout the whole period, but that of stage II melanomas increased after 1982. After treatment, local recurrence occurred far more frequently in nodular melanoma (19%) than in ALM (1%). The prognosis of nodular melanoma was also less favorable than that of ALM, although it slightly improved after 1982; the 5-year survival rates before and after 1982 were 34 and 50%, respectively. Twenty-eight patients with nodular melanoma had underwent simple excision or incisional biopsy of the primary tumor at another institution and were later referred to us for further intensive care or for the treatment of local recurrence and/or metastases. The rate of local recurrence of melanoma in such referred patients was higher than that in those who underwent an initial excision with wide margins in our hospital. Concurrently, the prognosis in the former group was significantly lower than that in the latter group; the 5-year survival rate for the group of narrow initial margin was 22% in contrast to that of wide margin (56%). Combination therapy including initial surgical excision with wide margins as well as the careful follow-up apparently result in a better outcome for the Japanese patients with nodular melanoma.     

Animal-type melanoma: a clinical and histopathological study of 22 cases from a single institution

Background Animal‐type melanoma is a rare distinct melanoma subtype, characterized by proliferation of heavily pigmented epithelioid and spindled melanocytes that resembles the heavily pigmented melanomas seen in grey horses. While animal‐type melanoma is generally considered to be more indolent than conventional melanoma, only a limited number of cases have been reported and, as such, the clinical characteristics of animal‐type melanoma are incompletely understood. Objectives To characterize the clinical and histopathological features of animal‐type melanoma, and determine any features that may predict outcome. Patients/Methods Data was extracted from a prospectively collected melanoma database (1994–2008), and a retrospective pathology database (1991–2008) for all patients with a diagnosis of both equivocal (8) and unequivocal (14) malignant animal‐type melanoma. We reviewed the clinical and histopathological features, including the sentinel lymph node biopsy (SLNB) status. Results A total of 22 patients were identified, with a median age of 35 years. The median Breslow depth was 2·22 mm. A SLNB was performed in 17 patients, eight (47%) were positive. Younger age was associated with: (i) animal‐type melanoma with features equivocal for malignancy (median age of 7 vs. 48 years, P = 0·01), and (ii) a negative SLNB (median age 12 vs. 53 years, P = 0·03). Four patients with unequivocal animal‐type melanoma developed recurrent metastatic disease, with one patient death. No patient with an equivocal animal‐type melanoma or negative SLNB developed recurrent disease; however, this did not reach statistical significance (P = 0·13 and P = 0·09, respectively). Conclusions Animal‐type melanoma has a propensity for regional lymphatic metastasis and is rarely capable of disseminated metastatic disease and death. Animal‐type melanoma appears to exhibit a spectrum of biological behaviour, with young patient age associated with more indolent disease.     

Indocyanine green fluorescence-guided sentinel lymph node biopsy in dermato-oncology

Background: Sentinel lymph node biopsy (SLNB) for cutaneous malignancies usually carried out with radioactive nanocolloids (Tc‐99m). The SLNE is controversially discussed internationally. This is especially given to the high false‐negative rate up to 44 %. An alternative could be the fluorescent dye indocyanine green (ICG). Material and Methods: We investigated the advantage of intraoperative fluorescence detection of lymphatic vessels and SLN with a Near‐Infrared (NIR) camera in comparison to conventional methods using preoperative lymphoscintigraphy and SPECT/CT in 22 patients with malignant melanoma. Results: A total of 61 SLNs were removed in 22 operative procedures. In 7 SLN (10.3 %; 7/68) the histopathological assessment could demonstrate a metasta‐tic involvement. 11 additional SLN (19.1 %) in 8 patients were only identified using the fluorescent labeling. Two of these additional SLN (9.1 %; 2/22) showed metastatic involvement. Conclusion: The ICG fluorescence‐guided SLNB is an innovative imaging technique for dermato‐oncology, reliable and providing additional information in the detection of SLN. Therefore SLNB with fluorescence‐dye is an attractive option with intraoperative real‐time lymphoscintigraphy to improve the detection of SLN in cutaneous malignancies and potential reduction of the false negative rate in SLN.     

Motor function and survival following radiotherapy alone for metastatic epidural spinal cord compression in melanoma patients

The major goal of this study was the identification of predictors for motor function and survival after irradiation alone for metastatic epidural spinal cord compression (MESCC) from melanoma. Ten variables (age, gender, performance status, number of involved vertebrae, pre‐radiotherapy ambulatory status, further bone metastases, visceral metastases, interval from melanoma diagnosis to MESCC, time developing motor deficits before radiotherapy, fractionation regimen) were investigated for post‐radiotherapy motor function, ambulatory status and survival in 27 patients. On multivariate analysis, motor function was significantly associated with time developing motor deficits (P = 0.006). On univariate analysis, post‐radiotherapy ambulatory rates were associated with pre‐radiotherapy ambulatory status (P < 0.001) and performance status (P = 0.046). Variables having a significant impact on survival in the univariate analysis were performance status (P < 0.001), number of involved vertebrae (P = 0.007), pre‐radiotherapy ambulatory status (P = 0.020), further bone metastases (P = 0.023), visceral metastases (P < 0.001), and time developing motor deficits (P = 0.038). On multivariate analysis of survival, the Eastern Cooperative Oncology Group (ECOG) performance status (risk ratio [RR] = 4.35; 95% confidence interval [CI] = 1.04–16.67; P = 0.044) and visceral metastases (RR = 3.70; 95% CI = 1.10–12.50; P = 0.034) remained significant and were included in a survival score. Scoring points were obtained from 6‐month survival rates divided by 10. Total scores represented the sum scores of both variables and were 3, 9 or 15 points. Six‐month survival rates were 7%, 29% and 100% (P = 0.004). Thus, three predictors for functional outcomes were identified. The newly developed survival score included three prognostic groups. Patients with 3 points may receive 1 × 8 Gy, patients with 9 points 5 × 4 Gy and patients achieving 15 points longer‐course radiotherapy. In the latter two groups, upfront decompressive surgery may be considered.     

The intriguing effect of delay time to sentinel lymph node biopsy on survival: a propensity score matching study on a cohort of melanoma patients

Background

Time between primary melanoma excision and sentinel lymph node biopsy (SLNB) has not been sufficiently studied as an independent predictor of survival in cutaneous melanoma.

Objectives

We used propensity score matching to evaluate whether early SLNB (performed ≤40 days from excisional biopsy) is associated with higher mortality in patients with cutaneous melanoma.

Materials & methods

A retrospective cohort study at a tertiary melanoma referral centre. We included 787 consecutive patients from the melanoma database of the Instituto Valenciano de Oncología who underwent a SLNB between 1^st January 2000 and 31^st December 2015, of whom 350 were matched into pairs using propensity score matching. The variable of interest was the time between primary melanoma excision and SLNB (≤40 days vs >40 days). The study outcomes were disease-free survival (DFS), melanomaspecific survival (MSS), and overall survival (OS).

Results

A delay time of 40 days or less was associated with worse DSF (adjusted hazard ratio [AHR]: 1.68; 95% confidence interval [CI]: 1.07-2.65; p = 0.024), MSS (AHR: 2.06; 95% CI: 1.1-3.53; p = 0.08), and OS (AHR: 1.77; 95% CI: 1.11-2.83; p = 0.017). Other variables associated with shorter MSS were age, tumour location and thickness, mitotic rate, and SLN status.

Conclusion

Early SLNB was associated with worse survival in patients with cutaneous melanoma after adjusting for classic prognostic factors. A delay time of over 40 days was not associated with higher mortality.

     

Improved melanoma outcomes and survival in patients monitored by total body photography: A natural experiment

Total body photography (TBP) facilitates early melanoma detection, but long-term outcomes have not been well studied. Our objectives were to examine melanoma diagnoses, role of TBP-associated follow-up visits, and survival in patients monitored by TBP. A total of 1955 patients meeting inclusion criteria received TBP from 2004–2013 at a single academic center. We compared the melanoma diagnoses and overall survival of 1253 patients with any follow-up visits (median, three visits; range, 1–18) and 702 patients with no follow-up visits. Use of TBP photographs influenced decision to biopsy 66 of 121 (54.5%) melanomas diagnosed after TBP. Lower invasive melanoma Breslow depth was significantly associated with having one or more follow-up visit (median, 0.83 vs 0.33 mm; P = .002) and photographic review (median, 0.31 vs 0.48 mm; P = 0.02). In multivariable analyses, greater overall survival was significantly associated with having one or more follow-up visit after TBP (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.14–0.91; P < 0.032) and having more than 100 nevi (HR, 0.37; 95% CI, 0.22–0.64; P = 0.004). Worse overall survival was significantly associated with increasing age (HR per year, 1.06; 95% CI, 1.04–1.08; P < 0.001) and male sex (HR, 2.65; 95% CI, 1.48–4.73; P = 0.001). Thus, monitoring by TBP was associated with subsequent melanoma diagnoses of lower stage and depth and greater overall survival.     

Adjuvant therapy with nivolumab versus ipilimumab after complete resection of stage III/IV melanoma: Japanese subgroup analysis from the phase 3 CheckMate 238 study

The multinational phase 3 CheckMate 238 trial compared adjuvant therapy with nivolumab versus ipilimumab among patients with resected stage III or IV melanoma (N = 906). In this Japanese subgroup analysis of CheckMate 238 (n = 28; nivolumab, n = 18; ipilimumab, n = 10), both the 12‐ and 18‐month recurrence‐free survival rates were 56% for nivolumab and 30% for ipilimumab (hazard ratio, 0.66; 97.56% confidence interval, 0.19–2.24; P = 0.4390). No new safety signals were reported for Japanese patients. Results were consistent with those from the CheckMate 238 global population, indicating that nivolumab has the potential to be a treatment option for Japanese patients with resected melanoma who are at high risk of recurrence.     

Histological regression in primary melanoma: not a predictor of sentinel lymph node metastasis in a cohort of 397 patients

Background Regression has been proposed as a potential marker of dissemination in thin melanomas. Previous studies have shown conflicting results. Objective To determine if regression in melanoma is associated with an increased risk of sentinel lymph node (SLN) metastasis. Methods A cohort analysis was conducted. Data on all patients were collected on a standardized case report form during 10 years. A total of 397 consecutive patients with melanoma who underwent a SLN biopsy were analysed. All cases of melanoma and SLN biopsies were examined by the same two pathologists. Differences between melanomas with and without SLN metastasis were compared using Fisher’s exact test or the two‐sample t‐test and the χ² test. Multivariable logistic regression was used to adjust for possible confounding factors. Results We analysed 397 patients (411 melanomas) who underwent a SLN biopsy. The median Breslow index was 1·8 mm (interquartile range 1·1–3). Regression was observed in 23% (n = 94). SLN metastases were observed in 26% (n = 106). The frequency of SLN metastasis was 16% in melanomas with regression and 29% without regression (P = 0·012). The adjusted odds ratio (OR) for regressive melanoma was 0·9 [95% confidence interval (CI) 0·4–1·9; P = 0·777]. The risk of SLN metastasis was increased in melanoma cases with a Breslow index from 1·5 to < 2·0 mm (adjusted OR 3·1; 95% CI 1·4–7·1; P = 0·006) and ≥ 2·0 mm (adjusted OR 3·5; 95% CI 1·7–7·4; P = 0·001) and ulceration of the melanoma (adjusted OR 1·8; 95% CI 1·1–3·2; P = 0·03). Conclusion Regression is not an independent predictor of the risk of SLN metastasis in melanoma.     

Sentinel lymph node biopsy for melanoma is becoming a consensus: a national survey of French centres involved in melanoma care in 2008

Background The role of sentinel lymph node (SLN) biopsy in melanoma care remains controversial and is not included in most guidelines for the management of melanoma in Europe. Objective To evaluate the practice of SLN biopsy for melanoma. Methods In 2008, a self‐administered questionnaire was mailed to physicians in 49 hospitals in France. Results Questionnaires were returned by 34 (69.3%). A median number of 90 new cases of melanoma were treated each year per centre. SLN biopsy was performed routinely in 21 (61.7%) centres. The practice of SLN biopsy for melanoma was recommended in the local guidelines in 53% of centres. The proportion of patients reported as undergoing SLN biopsy for melanoma was significantly higher in centres with local guidelines than in centres without local guidelines (33.4 ± 21.4% vs. 13.1 ± 21.8%; P = 0.003). Where the local guidelines recommended SLN biopsy (n = 21), it was advocated in the case of Breslow thickness ≥1.0 mm (76%) and/or ulceration of the primary melanoma (38%) and/or histological regression of the primary melanoma (24%). Conclusion Our study may be considered representative of SLN practice in France. Contrary to current national guidelines for melanoma care in France, SLN biopsy is routinely recommended in the majority of centres. Our study shows that the practice of SLN biopsy for melanoma is increasingly performed in patients with intermediate Breslow melanoma.     

Is the survival rate for acral melanoma actually worse than other cutaneous melanomas?

It is still not clear whether the survival rate for acral melanoma (AM) is better or worse than that of cutaneous melanoma developed at other sites. We sought to evaluate the difference in survival depending on the primary tumor site of cutaneous melanoma. We retrospectively reviewed primary cutaneous melanoma cases diagnosed at Samsung Medical Center, a tertiary institution in Korea, from January 1995 to July 2017. The cohort consisted of 642 patients, with 389 non-acral cutaneous melanoma (NACM) patients and 253 AM patients. The AM patients had a higher percentage of stage 0 diagnoses than the NACM patients (31.6% vs 6.9%, respectively). The factors associated with overall survival were primary tumor site, sex, age, American Joint Committee on Cancer stage, surgery and medical treatment (P < 0.05). Non-acral sites showed worse survival in multivariable analysis (hazard ratio [HR], 1.457; 95% confidence interval [CI], 1.051–2.020; P = 0.0240). Among the NACM, melanomas on the trunk were associated with a higher risk of mortality compared with AM (HR, 1.883; 95% CI, 1.142–3.107; P = 0.0131). Acral melanoma was associated with a better prognosis than non-acral melanoma, specifically when located on the trunk, in Korean patients.     

Sentinel lymph node biopsy in melanoma: Our 8-year clinical experience in a single French institute (2002–2009)

Since the introduction of sentinel lymph node biopsy (SLNB), its use as a standard of care for patients with clinically node-negative cutaneous melanoma remains controversial. We wished to evaluate our experience of SLNB for melanoma. A single center observational cohort of 203 melanoma patients with a primary cutaneous melanoma (tumour thickness > 1 mm) and without clinical evidence of metastasis was investigated from 2002 to 2009. Head and neck melanoma were excluded. SLN was identified following preoperative lymphoscintigraphy and intraoperative gamma probe interrogation. The SLN identification rate was 97%. The SLN was tumor positive in 44 patients (22%). Positive SLN was significantly associated with primary tumor thickness and microscopic ulceration. The median follow-up was 39.5 (5–97) months. Disease progression was significantly more frequent in SLN positive patients (32% vs 13%, p = 0.002). Five-year DFS and OS of the entire cohort were 79.6% and 84.6%, respectively, with a statistical significant difference between SLN positive (58.7% and 69.7%) and SLN negative (85% and 90.3%) patients (p = 0.0006 and p = 0.0096 respectively). Postoperative complications after SLNB were observed in 12% of patients. Our data confirm previous studies and support the clinical usefulness of SLNB as a reliable and accurate staging method in patients with cutaneous melanoma. However, the benefit of additional CLND in patients with positive SLN remains to be demonstrated.     

Acral cutaneous melanoma in caucasians: clinical features, histopathology and prognosis in 112 patients

BACKGROUND: Acral lentiginous melanoma (ALM) is the fourth distinct variant of cutaneous melanoma. The histological diagnosis and prognosis of ALM are still controversial. OBJECTIVES: To review the features of a large series of patients with ALM, and confirm the validity of the histological criteria for this type of melanoma. METHODS: A collection of 2642 patients with cutaneous melanoma was recorded during the period 1986-97, among these 187 were located on acral sites. Histological specimens were reviewed in 112 acral melanomas; the following study is based on this subgroup. RESULTS: Histological examination revealed acral lentiginous melanomas predominantly in palmoplantar and subungual locations (60%), while superficial spreading melanomas (SSM) were found mainly on the dorsal aspects of hands and feet (30%). Nodular melanomas (NM) (9%) occurred in all acral sites. The histological re-examination confirmed the characteristics of ALM as described by Reed in 1976. With increasing tumour thickness nesting of tumour cells and upward migration to the cornified layer was similarly observed. The 5-year survival rate for patients with primary acral melanoma without recognizable metastasis was 82%. ALM differed significantly in survival from SSM (P = 0.001) and lentigo maligna melanoma (P < 0. 001), but survival rates were similar to NM (P = 0.9). CONCLUSIONS: ALM, as diagnosed by current histological criteria, occur on the palms, soles and subungual sites, and have a poor prognosis.     

Aberrant hypermethylation in primary tumours and sentinel lymph node metastases in paediatric patients with cutaneous melanoma

Background Debate on how to manage paediatric patients with cutaneous melanoma continues, particularly in those with sentinel lymph node (SLN) metastases who are at higher risk of poor outcomes. Management is often based on adult algorithms, although differences in clinical outcomes between paediatric and adult patients suggest that melanoma in paediatric patients differs biologically. Yet, there are no molecular prognostic studies identifying these differences. Objectives We investigated the epigenetic (methylation) regulation of several tumour‐related genes (TRGs) known to be significant in adult melanoma progression in histopathology(+) SLN metastases (n = 17) and primary tumours (n = 20) of paediatric patients with melanoma to determine their clinical relevance. Methods Paediatric patients (n = 37; ≤ 21 years at diagnosis) with American Joint Committee on Cancer stage I–III cutaneous melanoma were analysed. Gene promoter methylation of the TRGs RASSF1A, RARβ2, WIF1 and APC was evaluated. Results Hypermethylation of RASSF1A, RARβ2, WIF1 and APC was found in 29% (5/17), 25% (4/16), 25% (4/16) and 19% (3/16) of histopathology(+) SLNs, respectively. When matched to adult cutaneous melanomas by Breslow thickness and ulceration, hypermethylation of all four TRGs in SLN(+) paediatric patients with melanoma was equivalent to or less than in adults. With a median follow‐up of 55 months, SLN(+) paediatric patients with melanoma with hypermethylation of > 1 TRG vs. ≤ 1 TRG had worse disease‐free (P = 0·02) and overall survival (P = 0·02). Conclusions Differences in the methylation status of these TRGs in SLN(+) paediatric and adult patients with melanoma may account for why SLN(+) paediatric patients have different clinical outcomes. SLN biopsy should continue to be performed; within SLN(+) paediatric patients with melanoma, hypermethylation of TRGs can be used to identify a subpopulation at highest risk for poor outcomes who warrant vigilant clinical follow‐up.