Dermoscopy of cutaneous melanoma metastases: A color‐based pattern classification

Dermoscopic studies about cutaneous metastases of malignant melanoma (CMMM) are few. Our objective was to analyze the dermoscopic features of CMMM and propose a new dermoscopic pattern classification based on color pigmentation and some specific dermoscopic features. A retrospective evaluation of 150 dermoscopic images of CMMM taken from 40 patients was performed. One hundred CMMM images were individually evaluated by six dermatologists in order to classify them according to four dermoscopic patterns: (i) blue pattern; (ii) pink pattern; (iii) brown pattern; and (iv) mixed pattern. One hundred and fifty dermoscopic images including 50 CMMM and 100 benign lesions were evaluated by five dermatologists to calculate the accuracy of these patterns in the recognition of CMMM. An intra‐ and interobserver reproducibility agreement study between all different dermoscopic pattern classifications was performed. Seventy‐five percent of our cases of CMMM showed a monochromatic pattern. Light brown pigmented halo, peripheral gray spots and polymorphic atypical vessels were the most significant focal dermoscopic structures. The reproducibility of the color‐based dermoscopic pattern classification was superior to previous dermoscopic pattern classification. In summary, a dermoscopic pattern classification based on color pigmentation and some specific dermoscopic features may be useful in recognizing early cutaneous melanoma metastasis. Multicentric studies are recommended in order to lower the impact of interobserver variability.     

Clinical evaluation of cutaneous malignant melanoma with histologically involved lymph node metastases.

Thirty-six cases of cutaneous malignant melanoma with histologically involved lymph nodes were studied during a 2-10 year study period, and the characteristics of the metastasized nodes and the associated prognosis were compared. The results were as follows: 1) the survival rate in cases with 3 or fewer (n = 16) metastasized nodes was significantly higher than in cases with 4 or more positive nodes (n = 20); 2) the survival rate in cases in which metastasized nodes were limited to one regional lymph node section (n = 12) was significantly higher than in cases where metastasis extended to two or more intra-regional sections of nodes (n = 24); 3) cases which had nodes measuring 3.00 cm or less (n = 25) had significantly higher survival rates than those with nodes of 3.01 cm or more (n = 11). Therefore, the results indicate that the number of metastasized lymph nodes, the extension into regional lymph node sections, and the size of the metastasized lymph node(s) can be considered as important prognostic factors for melanoma patients.     

Short-term morbidity associated with sentinel lymph node biopsy in cutaneous malignant melanoma

Guidelines for the surgical treatment of cutaneous primary malignant melanoma are well established; however, the approach to the treatment of the regional lymph nodes remains more controversial. In many centres, sentinel lymph node biopsy has been adopted as routine in the treatment of malignant melanoma for prognostic purposes, as it is not of proven therapeutic benefit. The Multicentre Selective Lymphadenectomy Trial II aims to determine the comparative benefits of subsequent completion lymphadenectomy versus observation in those found to have a positive sentinel node biopsy. Until results are available, the risks of the procedure must be weighed against the value of prognostic information gained from performing a sentinel node biopsy. In this retrospective analysis of sentinel lymph node biopsies at our institution, we show that in general, short-term morbidity associated with this procedure is low, but that morbidity is higher in a subgroup of people with higher weight or body mass index, and in those whose biopsy is located in the groin.     

Impact of lymph node metastases on serum level of melanoma inhibitory activity in stage III melanoma patients

Melanoma patients in stage III have a considerable recurrence rate. The 10-year survival in this stage depends on the number and size of affected nodes. Currently, there is no optimal serum marker for early detection of relapse available. The goal of the study was to assess the utility of melanoma inhibitory activity (MIA) serum marker in the follow up and primary diagnosis of stage III melanoma patients. One hundred and thirty-eight melanoma patients in stage III at time of primary diagnosis were analyzed at time of primary diagnosis and during periodical routine follow up both for serum MIA using an enzyme-linked immunosorbent assay and for serum lactate dehydrogenase (LDH). Results were correlated with the positivity of the sentinel lymph node (SLN) and the number of lymph node metastases in the completion lymph node dissection at time of primary diagnosis. During follow up, the overall survival time was assessed using the Kaplan-Meier method in terms of elevated MIA (>12 ng/mL) values. Regarding SLN status, significant differences of MIA values (P = 0.024) and LDH (P = 0.007) were found, both within the normal cut-off. Having lymph node metastases in the completion lymph node dissection, significantly higher MIA values (12.55 ng/mL [±0.48], P < 0.0001) were found. In patients with three or more tumor-positive nodes, MIA values were significantly higher when compared to patients with one or two affected nodes (P = 0.024). In the routine follow-up, stage III patients with an MIA value of more than 12 ng/mL had a five times higher risk for developing recurrences (P < 0.0001). Patients with relapsing disease had a significantly (P < 0.0001) higher mean MIA value (13.76 ng/mL) compared to patients without relapse (7.52 ng/mL). The MIA serum marker can be helpful in patients undergoing lymph node dissection. Furthermore, during follow up, patients showing relapsing diseases can have an elevated MIA value.     

Interval sentinel lymph nodes in patients with cutaneous melanoma: A single‐institution study in Japan

Interval sentinel lymph nodes (ISLN) are defined as the lymph nodes located between the primary melanoma and anatomically well‐defined lymph nodal basins. It was reported that the ISLN appeared to be at the same metastatic risk as sentinel lymph nodes (SLN) in the traditional nodal basins. This study aimed to examine the incidence and metastatic risk of the ISLN in melanoma patients. Between June of 1999 and December of 2008, 117 patients enrolled at Nagoya University Hospital underwent SLN biopsy for primary cutaneous melanoma with a Breslow thickness of at least 1.0 mm. Triple techniques with lymphoscintigraphy, blue dye injection and gamma probe were used for the biopsy except for 13 cases that underwent lymphoscintigraphy, ultrasonography and blue dye injection, but without gamma probe. Patients who had melanoma of the head and neck were excluded from this analysis. The SLN were identified in 253 nodal basins from 117 patients, and ISLN were found in six patients (5%). We recognized 41 (17%) SLN metastases in 246 conventional nodal basins and one (14%) in seven ISLN. Although ISLN were identified infrequently, the incidence of metastasis into the ISLN was similar to that into SLN in conventional nodal basins. It is therefore recommended that preoperative lymphoscintigraphy and intraoperative recognition of ISLN should be performed.     

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.     

甲下无色素性黑素瘤远端淋巴结转移

报告1例甲下无色素性黑素瘤远端淋巴结转移.患者女,28岁.左拇指甲下淡红色肿物1年半.结合病史、皮损特点、实验室检查、皮损及肿大淋巴结组织病理改变、免疫组化检查结果,确诊为该病.     

Clinicopathologic and prognostic significance of SATB1 in cutaneous malignant melanoma

Background

Special AT-rich sequence-binding protein-1 (SATB1), a new type of gene regulator, has been reported to be expressed in several human cancers and may have malignant potential. However, no data on SATB1 expression and its relationship to tumor progression in cutaneous malignant melanoma (CMM) has yet been reported.

Objective

We examined the immunohistochemical expression of SATB1 in CMM to determine whether it could serve as a prognostic marker.

Methods

A total of 97 samples of primary CMM and controls were immunostained for SATB1. The following clinicopathologic variables were evaluated: age, gender, subtype, SATB1 expression, Breslow thickness, Clark level, presence of ulceration, lymph node metastasis, distant metastasis, and survival. Statistical analyses were performed to assess for associations. Several parameters were analyzed for survival using the Kaplan-Meier method and Cox proportional-hazards model.

Results

Forty cases (85.1%) of CMM showed positive staining for SATB1 by immunohistochemistry. The intensity of SATB1 staining was significantly higher in CMM than in nevus NV and normal skin (NS) (P < 0.01). High SATB1 expression was significantly correlated with Breslow thickness, Clark level, mortality, presence of ulceration, and lymph node metastasis (P < 0.01). Moreover, Kaplan-Meier analysis revealed that SATB1 overexpression was significantly associated with worse survival (P < 0.01). Further univariate analysis and multivariate regression analysis indicated that SATB1 expression was an independent prognostic marker for CMM (P = 0.03).

Conclusions

The overexpression of SATB1 correlated with metastatic potential of CMM and is a novel independent prognostic marker for predicting outcome.     

Sentinel lymph node biopsy status is not the most powerful predictor of prognosis in cutaneous melanoma

Sentinel lymph node (SLN) status has been advocated in several recently published articles as the single most valuable prognostic marker for melanoma, and of greater prognostic importance than more established parameters such as Breslow thickness. A careful examination of the evidence for these claims, however, indicates that they are not substantiated by the available data, are somewhat misleading and suggest misinterpretation of the statistical analysis of the papers to which they refer. We will examine the basis for these claims and show why they are invalid.     

Sirt5 is dispensable for BrafV600E‐mediated cutaneous melanoma development and growth in vivo

Sirt5 is known to functionally regulate mitochondrial proteins by altering posttranslational modifications, including lysine desuccinylation. While roles for Sirt5 as either a tumor promoter or suppressor, or in chemoresistance, have been implicated in other cancers, the function of Sirt5 in cutaneous melanoma has not been well examined. Therefore, to determine whether Sirt5 is necessary for Braf^V600E‐mediated melanoma formation and/or disease progression, we crossed a genetically engineered murine melanoma model (Tyr^CreERT2/+; Braf^{LSL‐V600E/+}; Pten^flox/flox) to Sirt5^?/? knockout animals. In addition, we tested for synergism with a selective BRAF (V600E) inhibitor in Sirt5^?/? mouse melanoma cells. Taken together, this report demonstrates that, in these models, Sirt5 is dispensable for Braf^V600E‐mediated cutaneous melanoma formation and growth in vivo, and does not improve sensitivity to a selective BRAF inhibitor.     

Variation at HLA‐DPB1 is associated with dermatomyositis in Chinese population

Dermatomyositis (DM) is a polygenic disorder characterized by inflammation of skeletal muscle and skin. To date, the exact etiopathogenesis of DM remains elusive. To explore the genetic basis of DM, we conducted genome‐wide genotyping analysis of 127 patients and 1566 healthy controls by Illumina Human OmniZhongHua‐8 BeadChips in the Chinese Han population. We investigated whether the three SNP ( rs7750458 , rs9501251 and rs9500928 ) at 6p21.32 in the HLA‐DPB1 gene were significantly associated with DM (P < 5 × 10^?8) and identified two susceptibility loci at 7q34 (PIP, rs9986765 , P = 7.45 × 10^?7, odds ratio [OR] = 2.71) and 10q24.2 (CPN1, rs3750716 , P = 9.04 × 10^?7, OR = 4.39) with suggestive evidence. We imputed 6674 classical human leukocyte antigen (HLA) alleles, amino acids and SNP from the discovery dataset, and stepwise analysis revealed that HLA‐DPB1*17 in class II HLA genes were significantly associated with DM susceptibility. This study represents the first genome‐wide association study (GWAS) of DM in the Chinese Han population. For the first time, HLA‐DPB1 was found to be associated with DM in this population. Moreover, we identified two novel suggestive susceptibility loci (PIP and CPN1) and confirmed four previously reported genes (DMB, DQA1, DQB1 and DRB1) having potential associations with DM in the Chinese Han population. Our GWAS results in this population should provide important information regarding the genetic etiopathogenesis of DM and facilitate the development of new therapies for the treatment of DM and the prevention of DM progression.     

Sentinel lymph node biopsy for 102 patients with primary cutaneous melanoma at a single Japanese institute

Sentinel lymph node biopsy (SLNB) is a widely accepted standard procedure for patients with clinically localized melanoma. Melanoma prevalence and Clark's subtype differ between Asians and Caucasians. Here, we evaluated our experience on SLNB for cutaneous melanoma in a Japanese population. SLNB was performed for patients with melanoma between July 2000 and June 2014. We retrospectively analyzed 102 patients regarding association of clinicopathological features with sentinel lymph node (SLN) status, melanoma‐specific survival (MSS) and disease‐free survival (DFS). A positive SLN was significantly associated with primary Breslow thickness. Compared with 43 patients with negative SLN, 59 patients with positive SLN had significantly shorter MSS (5‐year survival rate, 94.3% vs 63.2%; P = 0.0002) and DFS (5‐year survival rate, 92.7% vs 63.4%; P = 0.0004). According to our subgroup analyses, nine patients with positive non‐SLN had significantly shorter MSS compared with 32 patients with negative non‐SLN (5‐year survival rate, 32.4% vs 68.5%; P = 0.0273). The survival of 51 Japanese patients with acral lentiginous melanoma (ALM) was not inferior to the survival of patients with other Clark's subtype. Breslow thickness is an important factor for both MSS and DFS, and the status of SLN is the most predictive prognostic factor in Japanese patients with clinically localized melanomas, as in case of Caucasians. Features of ALM may be different between Asians and Caucasians.     

Oncogenic BRAF signalling increases Mcl‐1 expression in cutaneous metastatic melanoma

The Bcl‐2 family member Mcl‐1 is essential for melanoma survival; however, the influence of oncogenic BRAF signalling remains elusive. In this study, Mcl‐1 splice variant expression was determined in a panel of melanoma cell lines in relation to BRAF mutational status. Mcl‐1L mRNA expression was increased in melanoma cells compared with primary melanocytes with significantly increased mRNA and protein expression observed in BRAF^V600E mutant melanoma cells. Although no change in Mcl‐1S mRNA was observed, Mcl‐1S protein expression also increased in BRAF mutant melanoma cells. Additionally, while over‐expression of mutant BRAF^V600E increased both Mcl‐1L and Mcl‐1S expression, inhibition of hyperactive BRAF signalling resulted in decreased Mcl‐1L expression. These studies suggest that the regulation of Mcl‐1 expression by BRAF signalling is increased by oncogenic activation of BRAF, revealing a mechanism of apoptotic resistance which may be overcome by the use of more specifically targeted Mcl‐1 inhibitors.     

Melanotan‐associated melanoma in situ

Injectable synthetic melanotropic peptides (often called melanotan) to enhance tanning are available over the Internet despite being unlicensed compounds with an unproven safety record. There have been reports of dysplastic naevi and melanoma associated with the use of melanotropic peptides. We report a case of melanotan‐associated melanoma in situ.