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Life (Basel, Switzerland) Oct 2023Multiple primary melanoma (MPM) is a diagnostic challenge even with ancillary imaging technologies available to dermatologists. In selected patients' phenotypes, the use...
BACKGROUND
Multiple primary melanoma (MPM) is a diagnostic challenge even with ancillary imaging technologies available to dermatologists. In selected patients' phenotypes, the use of imaging approaches can help better understand lesion characteristics, and aid in early diagnosis and management.
METHODS
Under a 5-year prospective single-center follow-up, 58 s primary melanomas (SPMs) were diagnosed in two first-degree relatives, with fair skin color, red hair, green eyes, and personal history of one previous melanoma each. Patients' behavior and descriptive demographic data were collected from medical records. The information on the first two primary melanomas (PMs) were retrieved from pathology reports. The characteristics of 60 melanomas were collected from medical records, video dermoscopy software, and pathology reports. Reflectance confocal microscopy (RCM) was performed prior to excision of 22 randomly selected melanomas.
RESULTS
From February 2018 to May 2023, two patients underwent a pooled total of 214 excisional biopsies of suspect lesions, resulting in a combined benign versus malignant treatment ratio (NNT) of 2.0:1.0. The number of moles excised for each melanoma diagnosed (NNE) was 1.7:1.0 and 6.9:1.0 for the female and male patient respectively. The in-situ melanoma/invasive melanoma ratio (IIR) demonstrated a higher proportion of in-situ melanomas for both patients. From June 2018 to May 2023, a total of 58 SPMs were detected by the combination of total body skin exam (TBSE), total body skin photography (TBSP), digital dermoscopy (DD), and sequential digital dermoscopy imaging (SDDI) via comparative approach. The younger patient had her PM one month prior to the second and third cutaneous melanomas (CMs), characterizing a case of synchronous primary CM. The male older relative had a total of 7 nonsynchronous melanomas.
CONCLUSIONS
This CM cohort is composed of 83.3% in-situ melanoma and 16.7% invasive melanoma. Both patients had a higher percentage of SPM with clinical nevus-like morphology (84.5%), global dermoscopic pattern of asymmetric multiple component (60.3%) and located on the lower limbs (46.6%). When RCM was performed prior to excision, 81% of SPM had features suggestive of malignancy. As well, invasive melanomas were more frequent in the lower limbs (40%). In the multivariate model, for the two high-risk patients studied, the chance of a not associated with nevus ("de novo") invasive SPM diagnosis is 25 times greater than the chance of a diagnosis of a nevus-associated invasive SPM.
PubMed: 37895483
DOI: 10.3390/life13102102 -
International Journal of Molecular... Sep 20235-Hydroxymethylcytosine (5-hmC) is an important intermediate of DNA demethylation. Hypomethylation of DNA is frequent in cancer, resulting in deregulation of 5-hmC...
5-Hydroxymethylcytosine (5-hmC) is an important intermediate of DNA demethylation. Hypomethylation of DNA is frequent in cancer, resulting in deregulation of 5-hmC levels in melanoma. However, the interpretation of the intensity and distribution of 5-hmC immunoreactivity is not very standardized, which makes its interpretation difficult. In this study, 5-hmC-stained histological slides of superficial spreading melanomas (SSM) and dysplastic compound nevi (DN) were digitized and analyzed using the digital pathology and image platform QuPath. Receiver operating characteristic/area under the curve (ROCAUC) and t-tests were performed. A -value of <0.05 was used for statistical significance, and a ROCAUC score of >0.8 was considered a "good" result. In total, 92 5-hmC-stained specimens were analyzed, including 42 SSM (45.7%) and 50 DN (54.3%). The mean of 5-hmC-positive cells/mm for the epidermis and dermo-epidermal junction and the entire lesion differed significantly between DN and SSM ( = 0.002 and = 0.006, respectively) and showed a trend towards higher immunoreactivity in the dermal component ( = 0.069). The ROCAUC of 5-hmC-positive cells of the epidermis and dermo-epidermal junction was 0.79, for the dermis 0.74, and for the entire lesion 0.76. These results show that the assessment of the epidermal with junctional expression of 5-hmC is slightly superior to dermal immunoreactivity in distinguishing between DN and SSM.
Topics: Humans; Dysplastic Nevus Syndrome; Skin Neoplasms; Melanoma; Computers; Melanoma, Cutaneous Malignant
PubMed: 37834158
DOI: 10.3390/ijms241914711 -
Healthcare (Basel, Switzerland) Sep 2023The excision of lesions that are not oriented along the skin tension lines may cause the surgeon to design extremely broad elliptical preoperative markings, with the...
INTRODUCTION
The excision of lesions that are not oriented along the skin tension lines may cause the surgeon to design extremely broad elliptical preoperative markings, with the intent to follow the tension lines as recommended for the best postoperative course and the best quality scars. The aim of this study is to describe and clinically apply a new surgical technique called the parallelogram excision technique, in which the traditional ellipse with a major axis parallel to the tension lines is converted into a parallelogram whose lesser sides are coincident with the local skin tension lines. This technique was specifically conceived for lesions whose major axis is non-coincident with skin tension lines, and the primary advantage is that it reduces the amount of healthy tissue excised.
METHODS
Preliminarily to this clinical study, a comparative geometrical analysis was conducted between various excision shapes and angles using Geometry Pad version 2.7.10 (Bytes Arithmetic LLC) and verifying the data obtained through AutoCAD 2D 2016 (Autodesk, San Rafael, CA, USA), with the purpose of optimizing the technique from a geometrical point of view. A comparison was performed between the theoretical traditional elliptical excision and the hypothetical parallelogram excision. A pilot proof of concept clinical study was performed to verify the validity of the excisional design proposed. The patients considered for parallelogram excision suffered from skin lesions with a diameter no greater than 4 cm and oriented 45° to 60° with respect to tension lines. In order to limit variability, patients' ages were between 40 and 80, and the selected areas were limbs, sternum and dorsum. Scar quality was assessed with the validated POSAS method at 6 months post-operation.
RESULTS
The geometrical analysis of the parallelogram's design showed that it allows a diminution of the excised healthy skin compared to the traditional ellipse. The clinical series included 16 patients, with a mean age of 63.5. Of these, nine patients were men and seven were women. Diagnoses included basal cell carcinoma in seven cases, dysplastic naevus in five patients, Bowen's disease in three individuals, and one case where a wider excision of a malignant melanoma was performed. Six-month follow up results showed: (1) an uneventful postoperative course; (2) good scar healing with an observer's POSAS median score of 16 and a patient's POSAS median score of 19; and (3) complete excision of lesions.
CONCLUSIONS
When indicated, the parallelogram excision technique appears to be a good option for the excision and primary closure of skin lesions that are not parallel to skin tension lines, since it allows a reproducible and surgeon-friendly method of preoperative marking and implies a favorable use of the local tension, which determines good quality scars. The amount of healthy tissue removed is smaller compared to traditional elliptic excisions.
PubMed: 37830661
DOI: 10.3390/healthcare11192624 -
JAAD Case Reports Oct 2023
PubMed: 37766734
DOI: 10.1016/j.jdcr.2023.08.014 -
Annals of Diagnostic Pathology Dec 2023Pathologists face ongoing challenges distinguishing between benign and malignant melanocytic tumors. PRAME (PReferentially expressed Antigen in Melanoma) has a...
BACKGROUND
Pathologists face ongoing challenges distinguishing between benign and malignant melanocytic tumors. PRAME (PReferentially expressed Antigen in Melanoma) has a demonstrated value distinguishing between these types of lesions. However, the sensitivity of single immunohistochemistry is variable. HMB-45 is another valuable marker, but on its own, has a limited ability in setting of primary melanocytic tumors. This study sought to evaluate the diagnostic potential of a dual panel combining PRAME and HMB-45 in the assessment of primary melanocytic tumors.
METHODS
259 tumors, of which 141 were benign nevi, 31 dysplastic nevi (either low- or high grade dysplasia), and further 87 malignant melanomas, were retrieved from the department's archives and assessed by two experienced dermatopathologists. New sections were stained with PRAME and HMB-45, respectively. For PRAME, a nuclear, and for HMB-45, a cytoplasmic staining, was considered positive and scored as described in the literature on a scale from 0 to 4+. Only dermal component was assessed on HMB-45 stain.
RESULTS
PRAME was diffusely expressed in only 1 benign nevus, with focal expression in further 28 compared to 22 diffusely and 103 focally HMB-45-positive benign nevi. 5 high-grade dysplastic nevi showed diffuse PRAME expression in epidermal component, with varying degree of positivity in adjacent dermal compartment, and further 8 dysplastic nevi showed only focal expression. HMB-45 was diffusely expressed in only 2, with focal expression in 23, and no apparent positivity in remaining 6 dysplastic nevi. In invasive melanoma group, PRAME stained >75 % cells in 64/87 tumors, however, 10/87 melanomas were completely negative. HMB-45 was captured diffusely in 49/87 melanomas, 32 showed patchy expression, and 6 tumors were blank negative. Diffuse 4+ PRAME positivity showed superior sensitivity and specificity of 73,6 % and 96,5 %, respectively, compared to HMB-45, 56,3 % and 86,0 %, respectively. No nevi showed double 4+ positivity, however, the sensitivity for double positivity was only 49,4 %.
CONCLUSION
Our results confirm the superiority of PRAME over HMB-45 in the differential diagnosis of melanocytic tumors. However, combined staining can significantly increase specificity, rendering a benign diagnosis more unlikely in a double 4+ diffuse positivity setting.
Topics: Humans; Dysplastic Nevus Syndrome; Coloring Agents; Melanoma; Skin Neoplasms; Antibodies, Monoclonal; Nevus; Antigens, Neoplasm; Staining and Labeling; Diagnosis, Differential
PubMed: 37717457
DOI: 10.1016/j.anndiagpath.2023.152211 -
BioRxiv : the Preprint Server For... Jul 2023TERT promoter mutations (TPMs) are frequently found in different cancer types, including approximately 70% of sun-exposed skin melanomas. In melanoma, TPMs are among the...
TERT promoter mutations (TPMs) are frequently found in different cancer types, including approximately 70% of sun-exposed skin melanomas. In melanoma, TPMs are among the earliest mutations and can be present during the transition from nevus to melanoma. However, the specific factors that contribute to the selection of TPMs in certain nevi subsets are not well understood. To investigate this, we analyzed a group of dysplastic nevi (DN) by sequencing genes commonly mutated in melanocytic neoplasms. We examined the relationship between the identified mutations, patient age, telomere length, histological features, and the expression of p16. Our findings reveal that TPMs are more prevalent in DN from older patients and are associated with shorter telomeres. Importantly, these TPMs were not found in nevi with BRAF V600E mutations. Conversely, DN with BRAF V600E mutations were observed in younger patients, had longer telomeres, and a higher proportion of p16-positive cells. This suggests that these nevi arrest growth independently of telomere shortening through a mechanism known as oncogene-induced senescence (OIS). These characteristics extend to melanoma sequencing data sets, where melanomas with BRAF V600E mutations were more likely to have inactivation, overriding OIS. In contrast, melanomas without BRAF V600E mutations showed a higher frequency of TPMs. Our data imply that TPMs are selected to bypass replicative senescence (RS) in cells that were not arrested by OIS. Overall, our results indicate that a subset of melanocytic neoplasms face constraints from RS, while others encounter OIS and RS. The order in which these barriers are overcome during progression to melanoma depends on the mutational context.
PubMed: 37503286
DOI: 10.1101/2023.07.14.548818 -
Actas Dermo-sifiliograficas 2023There are no clinical guidelines on the management of dysplastic nevus (DN). The aims of this study were to determine the percentage of dermatologists in the...
BACKGROUND AND OBJECTIVES
There are no clinical guidelines on the management of dysplastic nevus (DN). The aims of this study were to determine the percentage of dermatologists in the center-Spain section of the Spanish Academy of Dermatology and Venereology (AEDV) who would manage a histologically confirmed DN with a watch-and-wait approach or with wider surgical margins and to investigate whether their attitudes would vary depending on whether or not the patient had a personal and/or family history of melanoma.
MATERIAL AND METHODS
We collected data from an anonymous survey sent to 738 dermatologists between June 15 and July 31, 2022. The independent variables were degree of dysplasia (low vs. high), margin status (positive vs. negative), and a personal or family history of melanoma (yes vs. no in both cases). The dependent variables were attitude towards management (watch-and-wait vs. re-excision with a surgical margin of 1 to 4mm or re-excision with a surgical margin of 5 to 10mm).
RESULTS
We obtained 86 responses to the questionnaire. When pathology indicated a low-grade DN, 60.5% of dermatologists stated they would obtain a surgical margin of 1 to 4mm if the first margins were positive, and 97.7% would watch and wait if the report described negative margins. For high-grade DNs, 1.2% of dermatologists would watch and wait to manage DN with positive margins; 68.8% would use this approach for negative margins. A family or personal history of melanoma had no influence on most of the dermatologists' attitudes.
CONCLUSIONS
Management strategies for DN among dermatologists from the center-Spain section of the AEDV varied, particularly when faced with low-grade DN with positive margins and high-grade DN with negative margins. A family or personal history of melanoma did not influence clinical attitudes in most cases.
Topics: Humans; Dysplastic Nevus Syndrome; Margins of Excision; Dermatology; Spain; Venereology; Dermatologists; Melanoma; Surveys and Questionnaires; Skin Neoplasms
PubMed: 37482291
DOI: 10.1016/j.ad.2023.07.015 -
The Journal of Dermatological Treatment Dec 2023
Topics: Humans; Dysplastic Nevus Syndrome; Dermatologists; Follow-Up Studies; Surveys and Questionnaires; Skin Neoplasms
PubMed: 36256525
DOI: 10.1080/09546634.2022.2089324