Molecular pathology of melanocytic tumors

Genetic and genomic analyses of melanocytic tumors have yielded new opportunities for improvements in diagnostic accuracy for the distinction of nevus from melanoma and better selection of patients affected by melanoma for targeted treatment. Since chromosomal copy number changes are commonly found in malignant melanoma, but rare in melanocytic nevi, cytogenetic assays have emerged as a promising ancillary study for the workup of melanocytic tumors with ambiguous light microscopic features. Comparative genomic hybridization (CGH) permits assessment of the full set of chromosomes, but requires a significant amount of lesional tissue, and may fail to detect aberrations in a minor subpopulation of tumor cells. Fluorescence in situ hybridization (FISH) is the cytogenetic assay of choice for limited amounts of tissue. FISH targets only specific chromosomes, with inherent limitations in test sensitivity and specificity. FISH analysis is also heavily dependent on individual experience. Molecular studies have identified distinct sets of mutations in melanoma and/or nevi. These mutations have become clinically relevant for targeted therapy of patients with advanced disease, especially for the treatment of patients with metastatic melanoma carrying the BRAF^V600 or KIT mutations. However, mutation analysis can on occasion also be used for diagnostic purposes.     

The association of obstructive sleep apnea with melanoma incidence and mortality: a meta-analysis of 5,276,451 patients

BackgroundMelanoma is the most aggressive and lethal form of skin cancer. While emerging in-vivo evidence suggests that intermittent hypoxia, a hallmark feature of obstructive sleep apnea (OSA), may induce melanoma tumorigenesis, the epidemiological association between OSA and melanoma has been inconsistent.MethodsWe performed a literature search of PubMed, Embase, Scopus and Cochrane Library from inception until 6 June 2021. Two reviewers independently selected randomized trials or observational studies that reported the association of OSA with melanoma incidence or mortality in adults, in comparison to participants with no OSA. Two reviewers independently extracted relevant data and assessed the quality of evidence using the GRADE framework and the Newcastle–Ottawa Scale (NOS). We pooled data using an inverse variance-weighted meta-analysis and ran pre-specified subgrourp analyses.ResultsThe meta-analysis included six studies out of 1897 records, comprising a combined cohort of 5,276,451 patients. All studies were adjusted for covariates, with majority of studies adjusting for age (N=5) and sex (N = 4). Compared to those without OSA, patients with OSA had 71% higher pooled hazards of melanoma (HR = 1.71; 95% CI: 1.08–2.69, I² = 99%). Subgroup analyses for studies with (1) median follow-up duration of at least five years, (2) prospective study design, (3) adjustment for obesity yielded HRs of 1.88 (95%CI:1.32–2.67, N = 5), 1.11 (95%CI:0.77–1.60, N = 2) and 1.52 (95%CI:0.75–3.08, N = 3) respectively. One study investigating the relationship between OSA and melanoma mortality detected no association. There were insufficient studies to assess publication bias.ConclusionsMeta-analysis of mainly retrospective observational studies, with significant heterogeneity, suggests increased melanoma incidence in OSA patients. Future studies should prospectively explore the differential risk of melanoma for varying OSA severity, and whether timely OSA treatment may mitigate this risk.     

神经细胞黏附分子通过非Wnt依赖的β-catenin途径促进小鼠黑色素瘤细胞增殖

 目的：研究神经细胞黏附分子（neural cell adhesion molecule, NCAM）对小鼠黑色素瘤B16-F0细胞增殖的影响及其分子机制。方法：采用RNA干扰在B16-F0细胞中基因沉默NCAM,通过MTT和软琼脂克隆形成实验考察细胞增殖能力的变化;通过小鼠皮下肿瘤移植实验考察体内黑色素瘤生长的变化;使用免疫印迹筛选出受NCAM影响的信号分子,在此基础上使用RNA干扰和高表达实验确定介导NCAM调控增殖的主要信号分子。结果：NCAM基因沉默后B16-F0细胞的增殖能力和克隆形成能力明显降低,细胞在小鼠皮下形成的黑色素瘤的生长也明显受到抑制。其中,β-catenin介导了NCAM对于B16-F0细胞增殖的调控,但NCAM对于β-catenin的调控不依赖于经典的Wnt通路。结论：NCAM通过Wnt非依赖性的β-catenin通路促进小鼠黑色素瘤细胞的增殖。     

Cichoric acid attenuates the toxicity of mesotrione. Effect on in vitro skin cell model

There is an important need to increase knowledge regarding the interactions between environmental contaminants and other compounds. Pesticides are an important group of food contaminants. By contrast, cichoric acid (CA) belongs to the category of desirable food ingredients with antioxidant and cytotoxic effects. The aim of the presented study was to test if CA may constitute a food ingredient, which eliminate stimulatory effect of pesticides on skin cancer cells and toxic effect of herbicides on fibroblasts. Therefore, we conducted cytotoxicity studies of environmentally relevant pesticide concentrations and the mixture of both compounds in melanoma and fibroblasts cells. We studied if CA combined with mesotrione change the oxidative stress parameters and apoptotic activity in treated cells. Obtained results indicate that CA exhibits cytotoxic activity against mesotrione-induced skin cancer development by influencing oxidative stress parameters and apoptosis. On the other hand CA inhibits prooxidative and proapoptotic activity of mesotrione in fibroblasts. Presented methods and obtained results could be a useful tool in the analysis of environmental contaminants toxicity and possible preventive activity of antioxidative plant- origin compounds.     

Risk factors associated with lymphedema after lymph node dissection in melanoma patients

Background

Secondary lymphedema is a frequent complication after lymphadenectomy in melanoma patients, although few studies in melanoma adequately characterize risk factors for lymphedema, and of these, sample size is limited. This study aims to identify risk factors associated with the lymphedema after axillary lymph node dissection (ALND) and inguinal lymph node dissection (ILND) in a more robust cohort of melanoma patients.

Methods

We identified 269 ALND or ILND melanoma patients treated between 2008 and 2014. Demographic, clinical, and postoperative data were collected by review of the electronic medical record. Univariate and multivariate analysis were used to determine independent predictors of lymphedema.

Results

Fifty-six (20.8%) of the patients developed lymphedema after lymph node dissection with a median staging group of 3. ILND (odds ratio [OR] = 4.506, P < .001, 95% confidence interval [CI]: 2.289 to 8.869) and peripheral vascular disease (PVD; OR = 3.849, P = .020, 95% CI: 1.237 to 11.975) were significant predictors of lymphedema in multivariate analysis. Obese body mass index approached significance (OR = 1.802, P = .069, 95% CI: .955 to 3.399).

Conclusions

PVD and ILND were the 2 factors associated with the highest risk of lymphedema in melanoma surgery with PVD increasing risk 2-fold in ILND patients and 3-fold in ALND patients. These findings may improve surgeon-patient communication of care goals and surgical risk assessment.     

Primary Intracranial Leptomeningeal Melanomatosis

Primary intracranial malignant melanoma is a very rare and highly aggressive tumor with poor prognosis. A 66-year-old female patient presented a headache that had been slowly progressing for several months. A large benign pigmented skin lesion was found on her back. A brain MRI showed multiple linear signal changes with branching pattern and strong enhancement in the temporal lobe. The cytological and immunohiostochemical cerebrospinal fluid examination confirmed malignant melanoma. A biopsy confirmed that the pigmented skin lesion on the back and the conjunctiva were benign nevi. We report a case of primary intracranial malignant melanoma and review relevant literatures.     

Primary Sinonasal Mucosal Melanoma with Aberrant Diffuse and Strong Desmin Reactivity: A Potential Diagnostic Pitfall!

The broad morphologic spectrum, inherent immunophenotypic heterogeneity of malignant melanoma and its rarity in the sinonasal tract are major challenges in eliciting the correct diagnosis, which may lead to misclassification and inadequate medical management. Herein, we describe a single case of a 70 year-old male with sinonasal mucosal melanoma, exhibiting varying histologic phenotypes including small round blue cell morphology, epithelioid and focal rhabdoid morphology and strong, diffuse desmin immunoreactivity. These constellation of features initially prompted the diagnosis of rhabdomyosarcoma. The differential diagnosis in this anatomic area includes other malignant small round blue cell tumors of the sinonasal mucosa such as rhabdomyosarcoma, olfactory neuroblastoma, sinonasal undifferentiated carcinoma, and lymphoma. We reviewed precedent literature and further discuss the potential pitfalls to which pathologists may be prone.