Case report of a primary subcutaneous melanoma:a surprising entity for a subcutaneous nodule

INTRODUCTION: A melanoma can originate at the subcutis without any visible skin lesion. CASE PRESENTATION: A 73-year old patient came to the outpatient clinic with a subcutaneous nodule on the right thigh without any visible lesion of the skin. It turned out to be a primary subcutaneous melanoma that could be classified as a primary dermal melanoma (PDM). DISCUSSION: A PDM is a very rare subtype of melanoma that stands out for its excellent prognosis in comparison to cutaneous melanomas. No valid reliable staging system or treatment guideline exists for this entity, Breslow depth might overestimate the clinical aggressiveness possibly leading to overtreatment. CONCLUSION: It is of great importance for the clinician to be familiar with a primary dermal melanoma. It deserves an appropriate place in the current AJCC system and a treatment guideline for this unique melanoma subtype with relativity excellent prognosis would be beneficial

Surgical treatment of anorectal melanoma:a systematic review and meta-analysis

BACKGROUND: Anorectal melanoma is a rare neoplasm with a poor prognosis. The surgical approaches for anorectal melanoma can be categorized into local excision (procedures without lymph node removal and preservation of the rectum) and extensive resection (procedures with rectum and pararectal lymph node removal). The aim of this systematic review and meta-analysis was to compare the survival of patients who underwent extensive resection with that of patients who underwent local excision, stratifying patients according to tumour stage. METHODS: A literature review was performed according to PRISMA guidelines by searching MEDLINE/PubMed for manuscripts published until March 2021. Studies comparing survival outcomes in patients with anorectal melanoma who underwent local excision versus extensive resection were screened for eligibility. Meta-analysis was performed for overall survival after the different surgical approaches, stratified by tumour stage. RESULTS: There were 347 studiesidentified of which 34 were included for meta-analysis with a total of 1858 patients. There was no significant difference in overall survival between the surgical approaches in patients per stage (stage I odds ratio 1.30 (95 per cent c.i. 0.62 to 2.72, P = 0.49); stage II odds ratio 1.61 (95 per cent c.i. 0.62 to 4.18, P = 0.33); stage I–III odds ratio 1.19 (95 per cent c.i. 0.83 to 1.70, P = 0.35). Subgroup analyses were conducted for the time intervals (<2000, 2001–2010 and 2011–2021) and for continent of study origin. Subgroup analysis for time interval and continent of origin also showed no statistically significant differences in overall survival. CONCLUSION: No significant survival benefit exists for patients with anorectal melanoma treated with local excision or extensive resection, independent of tumour stage

Screening for germline DND1 mutations in testicular cancer patients

Although several observations suggest that a strong genetic predisposition to developing testicular germ cell tumors (TGCT) exists, no associated, highly penetrant germline mutations have been identified so far. In the 129/Sv mouse strain, a germline mutation in the DND1 gene has been shown to strongly increase the TGCT risk. We screened 272 men with TGCT (89% sporadic cases, 11% familial) for germline mutations in the human homologue of DND1. A single nucleotide substitution c.657C > G (p.Asp219Glu) was observed in a non-familial case of testicular embryonal carcinoma. The variant was also present in the patient’s asymptomatic father and two brothers, but not observed in 210 control chromosomes. The wild type DND1 allele was not lost in the patient’s tumor. In silico analysis of the variant predicts it to be non-pathogenic. We conclude that germline DND1 mutations are unlikely to contribute significantly to human testicular germ cell tumor susceptibility. The role of human DND1 in normal physiology and disease, however, is still virtually unknown and it therefore warrants further research

A physical analysis of the Y chromosome shows no additional deletions, other than Gr/Gr, associated with testicular germ cell tumour

Testicular germ cell tumour (TGCT) is the most common malignancy in men aged 15–45 years. A small deletion on the Y chromosome known as ‘gr/gr' was shown to be associated with a two-fold increased risk of TGCT, increasing to three-fold in cases with a family history of TGCT. Additional deletions of the Y chromosome, known as AZFa, AZFb and AZFc, are described in patients with infertility; however, complete deletions of these regions have not been identified in TGCT patients. We screened the Y chromosome in a series of TGCT cases to evaluate if additional deletions of Y were implicated in TGCT susceptibility. Single copy Y chromosome STS markers with an average inter-marker spacing of 128 kb were examined in constitutional DNA of 271 index TGCT patients. Three markers showed evidence of deletions, sY1291, indicative of ‘gr/gr' (eight out of 271; 2.9%), Y-DAZ3 contained within ‘gr/gr' (21 out of 271; 7.7%) and a single deletion of the marker G66152 was identified in one TGCT case. No other markers demonstrated deletions. While several regions of the Y chromosome are known to be deleted and associated with infertility, our study provides no evidence to suggest regions of Y deletion, other than ‘gr/gr', are associated with susceptibility to TGCT in UK patients

Multi-stage genome-wide association study identifies new susceptibility locus for testicular germ cell tumour on chromosome 3q25

Recent genome-wide association studies (GWAS) and subsequent meta-analyses have identified over 25 SNPs at 18 loci, together accounting for >15% of the genetic susceptibility to testicular germ cell tumour (TGCT). To identify further common SNPs associated with TGCT, here we report a three-stage experiment, involving 4098 cases and 18 972 controls. Stage 1 comprised previously published GWAS analysis of 307 291 SNPs in 986 cases and 4946 controls. In Stage 2, we used previously published customised Illumina iSelect genotyping array (iCOGs) data across 694 SNPs in 1064 cases and 10 082 controls. Here, we report new genotyping of eight SNPs showing some evidence of association in combined analysis of Stage 1 and Stage 2 in an additional 2048 cases of TGCT and 3944 controls (Stage 3). Through fixed-effects meta-analysis across three stages, we identified a novel locus at 3q25.31 (rs1510272) demonstrating association with TGCT [per-allele odds ratio (OR) = 1.16, 95% confidence interval (CI) = 1.06-1.27; P = 1.2 × 10-9]

Oncological outcome of malignant colonic obstruction in the Dutch Stent-In 2 trial

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Genetic predisposition to testicular cancer

Alhoewel zaadbalkanker een zeldzame ziekte is, is het toch de meest voorkomende vorm van kanker bij mannen tussen de 15 en 40 jaar. De ziekte is tegenwoordig goed te behandelen en de 10 jaars overleving is ongeveer 90%. Het hebben van een familielid met zaadbalkanker is de sterkste risicofactor voor het krijgen van zaadbalkanker Dit wijst op een mogelijke erfelijke gevoeligheid voor het krijgen van deze ziekte. Het vinden van deze gevoeligheid, men spreekt ook wel van een gen, zou wetenschappelijk belangrijk zijn omdat het ontstaan van zaadbalkanker dan beter zou kunnen worden begrepen. Omdat het voorkomen van zaadbalkanker bij meerdere leden van een familie zeldzaam is, is onderzoek naar erfelijke zaadbalkanker lastig. In een Nederlandse groep patiënten met zaadbalkanker werd in verschillende regio’s van het DNA gezocht naar een gen voor zaadbalkanker. Er werden daarbij geen aanwijzingen gevonden voor het bestaan van zo’n gen in de zogenaamde HLA klasse II regio op chromosoom 6, die door andere onderzoekers wel in verband was gebracht met zaadbalkanker en ook niet in de AZF regio op het Y-chromosoom. Voor een stukje van het X-chromosoom waren die aanwijzingen er echter wel en dit gebied wordt in de toekomst verder onderzocht. Niet alleen de wetenschap heeft interesse in dit onderwerp. Dit promotie-onderzoek toonde ook aan dat de meeste mannen met zaadbalkanker belangstelling zouden hebben voor een DNA-onderzoek waarbij een gen voor het krijgen van zaadbalkanker zou kunnen worden opgespoord