Multiple Primary Melanomas Research Articles

Multiple primary cutaneous melanoma in the amazon region of Peru

Reportamos el caso de un hombre de 82 años residente de Iquitos, región amazónica del Perú, con una historia de tres meses de lesiones cutáneas dolorosas de leves a moderadas en la extremidad inferior derecha. El examen clínico reveló cuatro tumores en la tibia derecha, que exhibían crecimiento exofítico, apariencia verrugosa y ulceración. Se observaron dos nódulos subcutáneos. Se observó linfadenopatía inguinal agrandada. El examen histopatológico reveló un diagnóstico de melanoma. Este caso enfatiza la necesidad de una vigilancia integral y multidisciplinaria en regiones con datos limitados sobre melanoma que conducen a un subdiagnóstico de esta malignidad. Además, destaca la importancia de la prevención primaria como la protección solar en zonas tropicales para prevenir el melanoma cutáneo, abogando por aumentar la concienciación y las medidas preventivas.

Thin Amelanotic and Hypomelanotic Melanoma: Clinicopathological and Dermoscopic Features.

Background and Objectives: Amelanotic/hypomelanotic melanomas (AHMs) account for 2-8% of all cutaneous melanomas. Due to their clinical appearance and the lack of specific dermoscopic indicators, AHMs are challenging to diagnose, particularly in thinner cutaneous lesions. The aim of our study was to evaluate the clinicopathological and dermoscopic features of thin AHMs. Identifying the baseline clinical-pathological features and dermoscopic aspects of thin AHMs is crucial to better understand this entity. Materials and Methods: We divided the AHM cohort into two groups based on Breslow thickness: thin (≤1.00 mm) and thick (>1.00 mm). This stratification helped identify any significant clinicopathological differences between the groups. For dermoscopic analysis, we employed the "pattern analysis" approach, which involves a simultaneous and subjective assessment of different criteria. Results: Out of the 2.800 melanomas analyzed for Breslow thickness, 153 were identified as AHMs. Among these, 65 patients presented with thin AHMs and 88 with thick AHMs. Red hair color and phototype II were more prevalent in patients with thin AHMs. The trunk was the most common anatomic site for thin AHMs. Patients with thin AHMs showed a higher number of multiple melanomas. Dermoscopic analysis revealed no significant difference between thin AHMs and thick AHMs, except for a more frequent occurrence of residual reticulum in thin AHMs. Conclusions: Thin AHMs typically affect individuals with lower phototypes and red hair color. These aspects can be related to the higher presence of pheomelanin, which provides limited protection against sun damage. This also correlates with the fact that the trunk, a site commonly exposed to intermittent sun exposure, is the primary anatomical location for thin AHMs. Multiple primary melanomas are more common in patients with thin AHMs, likely due to an intrinsic predisposition as well as greater periodic dermatologic follow-ups in this class of patients. Apart from the presence of residual reticulum, no other significant dermoscopic differences were observed, complicating the differential diagnosis between thin and thick AHMs based on dermoscopy alone.

JAAD Game Changers: Multiple primary melanomas among 16,570 patients with melanoma diagnosed at Kaiser Permanente Northern California, 1996 to 2011

JAAD Game Changers: Multiple primary melanomas among 16,570 patients with melanoma diagnosed at Kaiser Permanente Northern California, 1996 to 2011

P16-CD8-Ki67 Triple Algorithm for Prediction of CDKN2A Mutations in Patients with Multiple Primary and Familial Melanoma.

Melanoma, a malignant neuroectodermic tumor originating from the neural crest, presents a growing global public health challenge and is anticipated to become the second most prevalent malignancy in the USA by 2040. The CDKN2A gene, particularly p16INK4a, plays a pivotal role in inhibiting the cell cycle via the cyclin D/CDK2-pRb pathway in certain tumors. In familial melanomas (FM), 40% exhibit CDKN2A mutations affecting p16INK4a, impacting checkpoint G1, and stabilizing p53 expression. This study aims to establish a scoring system using immunohistochemical antibodies, providing a cost-saving approach to classify multiple primary melanomas (MPM) and FM patients based on their mutational status, thus mitigating genetic testing expenses. This retrospective study included 23 patients with MPM and FM, assessing the p16, CD8, and Ki67 immunohistochemical status. Analyses of each parameter and associations between their value intervals and genetic CDKN2A status were conducted. A total score of at least 9 out of 10 points per tumor defined melanomas with homozygous CDKN2A deletions, exhibiting a sensitivity of 100% and specificity of 94.11%. In conclusion, p16, CD8, and Ki67 individually serve as valuable indicators for predicting melanoma evolution. The algorithm, comprising these three immunohistochemical parameters based on their prognostic and evolutionary significance, proves to be a valuable auxiliary diagnostic tool for cost-effective prediction of mutational status in detecting multiple and familial primary melanomas with CDKN2A homozygous deletion.

Abstract 5050: Germline variants in CDKN2A wild-type melanoma prone families

Abstract The presence of germline pathogenic variants in CDKN2A is a well-established underlying cause of familial malignant melanoma. While pathogenic variants in several other genes have also been linked to melanoma development, many familial cases remain unexplained. We analyzed for pathogenic germline variants in a panel of 360 cancer related genes in a set of 56 Norwegian melanoma prone families. The index cases and families were selected based on familial history of melanoma and/or multiple primary melanomas in the same individual, along with previous negative tests for pathogenic CDKN2A variants. We found 6 out of 56 index individuals to carry germline pathogenic or likely pathogenic variants. These variants were found in BRCA2, MRE11, ATM, MSH2, CHEK2 and AR. In addition, one family member with a melanoma diagnosis (not index case) carried a pathogenic variant in MAP3K6. In genes typically linked to xeroderma pigmentosum, we found a high fraction of variants previously considered benign and/or as variants of uncertain significance. In particular the XPCL48F variant was found in 8 out of 56 indexes, thus, the allele fraction (0.07) was significantly higher than in comparable healthy populations (p-values from 0.007 to 0.014). Similarly, we found presumed benign or uncertain variants in MC1R to be significantly enriched or numerically higher in index cases versus comparable healthy populations (p-values from 0.009 to 0.1). The common MC1RArg151Cys variant was highly enriched in our cohort (p=0.001).In conclusion, we found that several melanoma prone families harbored pathogenic variants in genes not usually linked to melanoma. Citation Format: Stian Knappskog, Gjertrud T. Iversen, Marie Loeng, Amalie L. Holth, Per E. Lonning, Jurgen Geisler. Germline variants in CDKN2A wild-type melanoma prone families [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5050.

Simultaneous melanomas in the setting of multiple primary melanomas.

It is estimated that about 1-13% of melanoma patients will develop multiple primary melanomas. Although the occurrence of subsequent tumors has been described during the last few years, the development of simultaneous melanomas has not yet been extensively studied. We reviewed our registries to identify patients with multiple primary melanomas. We studied epidemiological, clinical, and histological characteristics of patients who were diagnosed with simultaneous melanomas and compared them with those of patients who developed non-synchronous multiple primary melanomas. As simultaneous were defined subsequent melanomas that were diagnosed either at the same visit or within a time-period of maximum of 1 month. Between 2000 and 2020, 2500 patients were diagnosed with melanoma at Andreas Syggros Hospital. 86 (3.4%) patients presented multiple primary melanomas and among them, 35 (40.7%) developed simultaneous melanomas. Patients with simultaneous melanomas developed more frequently more than 2 tumors. First tumors of patients with non-synchronous melanomas were significantly thicker than second tumors while those of patients with simultaneous melanomas did not differ significantly. Slight differences in the tumor localization, staging and histologic type were observed between the two groups. However significant differences were ascertained between first and second tumors in both groups. Simultaneous melanomas occupy an important proportion of multiple primary melanomas, affecting a non-negligible number of patients. Slight differences between simultaneous and non-synchronous multiple primary melanomas seem to define a distinct subcategory of multiple primary melanomas.

CD8-Lymphocytic Phenotype Significance in Primary Multiple and Familial Melanoma with Various CDKN2A Mutational Status.

Background and Objectives: In the realm of the rising incidence of cutaneous and mucous melanoma, CDKN2A mutations characterize familial and multiple primary melanoma cases. The involvement of tumor-infiltrating lymphocytes (TILs) is interconnected with survival rates, but may extend even further. The aim of this study is to verify the accuracy of the classical "naked eye" count of CD8-positive T cells comprised within the tumoral population and peritumoral infiltrate versus that obtained via a special software run by the aid of artificial intelligence (AI), used to determine the percentage of CD8-positive TILs. Materials and Methods: The present retrospective cross-sectional study conducted over a period of 5 years (2018-2022) focused on patients diagnosed with mucous and/or cutaneous melanoma, with a positive family history for melanoma, or personal antecedents of primary malignant melanocytic lesions. The 23 selected cases were diagnosed histopathologically, tested for CDKN2A mutations through fluorescent hybridization in situ, and CD8 immunohistochemistry was performed. The included slides were evaluated both manually (naked-eye examination) and automatically (via QuPath platform) for quantifying the CD8-positive TILs. Results: The number of CD8-positive TILs in melanoma samples has been more accurately identified through the use of an AI-mediated software as compared to the human-eye evaluation performed by experimental pathologists. A higher percentage of CD8-positive intratumoral lymphocytes versus stromal lymphocytes was positively associated with more numerous metastatic sites. Conclusions: The CD8 lymphocytic phenotype harbors major significance in the context of familial and multiple primary melanoma and may comprise a cost-effective investigation meant to help in the establishment of melanoma prognosis and response to immunotherapy.

Multiple Primary Melanoma: A Five-Year Prospective Single-Center Follow-Up Study of Two MC1R R/R Genotype Carriers.

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. 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. 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. 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.

Prognosis for people with multiple primary melanomas compared with a single primary melanoma

Prognosis for people with multiple primary melanomas compared with a single primary melanoma

Synchronous Melanoma: Definition, Prognosis, and Implications. A Comprehensive Review of Literature.

Although multiple primary melanomas (MPMs) have been reported in the literature, the subgroup of synchronous melanomas (SMs) remains understudied. We conducted a comprehensive systematic review of the English literature from 1972 to 2023 to characterize SM. Our objective was to clarify the definition, determine incidence and prognosis, and present recommendations. We found 18 case series articles and six case reports that met our criteria. Twelve of eighteen studies defined SM as a second primary melanoma identified within 1 month. The total number of SM patients reported was 1083. The cumulative percentage of MPM in total melanoma patients was 2.9 %, and the cumulative percentage of SM patients in MPM patients was 31.3%. SM patients trended toward higher body anatomical concordance, older age, and male sex. Despite limited data, SMs do not show a worse prognosis for patients compared with single melanomas. Despite a lack of consensus in the past, we recommend that SM be defined as a second primary melanoma detected within 1 month of the initial diagnosis. SMs comprise almost one-third of MPM cases and do not seem to carry any worse prognosis than the patients presenting with single melanoma. We believe older age and male sex may be more prone to SM. We recommend patient education, self-skin evaluations and TSE at initial and follow-up visits. Neither randomized controlled trials nor meta-analyses on SM exist. Ideally, further studies with a large cohort of patients are needed to accurately define SM.

Risk factors for subsequent primary melanoma in patientswith previous melanoma: a systematic review and meta-analysis.

Compared with the general population, people with a previous melanoma are at increased risk of developing another primary melanoma. Understanding the risk factors associated with multiple primary melanomas can inform patient education and tailored surveillance. To examine the risk factors for subsequent primary melanoma in people with a previous melanoma, by conducting a systematic review and meta-analysis of the available data. A systematic literature search was conducted in CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Embase and MEDLINE. Studies that reported a risk estimate or raw frequencies and conducted between 1982 and August 2022 were included. Adjusted risk estimates were prioritized over univariable risk estimates. PRISMA reporting guidelines were followed. Random effects meta-analysis was conducted to derive pooled estimates. Quality assessment was conducted by two researchers using the Newcastle-Ottawa scale. GRADE was used to rate the certainty and quality of the evidence. Data from 27 studies involving 413 181 participants were pooled and analysed. Risk factors assessed included age and sex, environmental, lifestyle, phenotypic, genetic and histopathological factors, and there was wide variation in how they were categorized and analysed. Independent risk factors identified from pooled analyses included male sex [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.40-1.53], increasing age per 10 years (HR 1.19, 95% CI 1.14-1.24), light skin colour (HR 1.44, 95% CI 1.23-1.70), family history [odds ratio (OR) 1.79, 95% CI 1.25-2.56], CDKN2A mutation (OR 5.29, 95% CI 2.70-10.37), a high or moderate naevus count [OR 2.63 (95% CI 1.61-4.30) and OR 1.64 (95% CI 1.07-2.51), respectively], one or more atypical naevi (OR 3.01, 95% CI 1.52-5.97), first lesions occurring on the head or neck, lentigo maligna subtype (HR 1.16, 95% CI 1.15-1.17), other subtype (HR 1.14, 95% CI 1.03-1.27) and inadequate sun protection (HR 1.85, 95% CI 0.98-3.50). Based on the GRADE criteria, there was high to very low confidence in the pooled effect estimates. This meta-analysis identified several consistent, independent risk factors for the development of subsequent primary melanoma. These findings will help stratify the risk of subsequent melanoma, tailor skin-check schedules and inform patient education.

Clinical observation of patients with primary multiple malignant tumors, including primary multiple melanoma

Recently, there has been an increase in the number of patients with primary multiple malignant tumors, which not only affect one or more organs, but also differ in their histological structure. At the same time, melanoma of the skin is a rare localization among primary malignant neoplasms. This nosology accounts for only 3–5 % of all skin tumors. Melanoma is associated with high mortality due to the development of a pronounced metastatic potential, and therefore the study of this malignant formation is of the greatest relevance. Over the past 50 years, the incidence of multiple primary melanoma has increased significantly. At the same time, the number of patients with more than 2 lesions has increased to 18 % of the number of primary multiple melanomas over the past 50 years. This emphasizes the importance of monitoring patients with melanoma and regularly examining patients for new lesions. This article demonstrates a clinical case of a patient with a confirmed diagnosis of a primary multiple disease with melanoma of the skin and rectum. For skin melanoma, the patient underwent a wide excision of the tumor with inguinal-femoral lymph node dissection on the right. Subsequently, radiation therapy and chemotherapy were performed. Further, during a comprehensive examination, the patient was diagnosed with a malignant neoplasm of the lower ampullar rectum with a transition to the anal canal. The patient underwent laparoscopic-assisted abdominoperineal extirpation of the rectum. Histological analysis revealed nodular melanoma. From the anamnesis of the patient, among the comorbidities, breast cancer, uterine myoma, hemangioma of the liver and lung hamartoma were also identified. The clinical course of all malignant tumors was favorable, without the development of relapses and metastases. The greatest interest in this situation is the primary multiple melanoma in connection with successful treatment with the most unfavorable prognosis. The described clinical observation indicates the need for an in-depth study of cases of primary multiple malignant tumors and the search for mechanisms for a favorable course of malignant neoplasms in this case.

Clinical observation of patients with primary multiple malignant tumors, including primary multiple melanoma

Recently, there has been an increase in the number of patients with primary multiple malignant tumors, which not only affect one or more organs, but also differ in their histological structure. At the same time, melanoma of the skin is a rare localization among primary malignant neoplasms. This nosology accounts for only 3–5 % of all skin tumors. Melanoma is associated with high mortality due to the development of a pronounced metastatic potential, and therefore the study of this malignant formation is of the greatest relevance. Over the past 50 years, the incidence of multiple primary melanoma has increased significantly. At the same time, the number of patients with more than 2 lesions has increased to 18 % of the number of primary multiple melanomas over the past 50 years. This emphasizes the importance of monitoring patients with melanoma and regularly examining patients for new lesions. This article demonstrates a clinical case of a patient with a confirmed diagnosis of a primary multiple disease with melanoma of the skin and rectum. For skin melanoma, the patient underwent a wide excision of the tumor with inguinal-femoral lymph node dissection on the right. Subsequently, radiation therapy and chemotherapy were performed. Further, during a comprehensive examination, the patient was diagnosed with a malignant neoplasm of the lower ampullar rectum with a transition to the anal canal. The patient underwent laparoscopic-assisted abdominoperineal extirpation of the rectum. Histological analysis revealed nodular melanoma. From the anamnesis of the patient, among the comorbidities, breast cancer, uterine myoma, hemangioma of the liver and lung hamartoma were also identified. The clinical course of all malignant tumors was favorable, without the development of relapses and metastases. The greatest interest in this situation is the primary multiple melanoma in connection with successful treatment with the most unfavorable prognosis. The described clinical observation indicates the need for an in-depth study of cases of primary multiple malignant tumors and the search for mechanisms for a favorable course of malignant neoplasms in this case.

TINF2 is a major susceptibility gene in Danish patients with multiple primary melanoma

TINF2 encodes the TINF2 protein, which is a subunit in the shelterin complex critical for telomere regulation. Three recent studies have associated six truncating germline variants in TINF2 that have previously been associated with a cancer predisposition syndrome (CPS) caused by elongation of the telomeres. This has added TINF2 to the long telomere syndrome genes, together with other telomere maintenance genes such as ACD, POT1, TERF2IP, and TERT. We report a clinical study of 102 Danish patients with multiple primary melanoma (MPM) in which a germline truncating variant in TINF2 (p.(Arg265Ter)) was identified in four unrelated participants. The telomere lengths of three variant carriers were >90% percentile. In a routine diagnostic setting, the variant was identified in two more families, including an additional MPM patient and monozygotic twins with thyroid cancer and other cancer types. A total of 10 individuals from six independent families were confirmed carriers, all with cancer history, predominantly melanoma. Our findings suggest a major role of TINF2 in Danish patients with MPM. In addition to melanoma, other cancers in the six families include thyroid, renal, breast, and sarcoma, supporting a CPS in which melanoma, thyroid cancer, and sarcoma predominate. Further studies are needed to establish the full spectrum of associated cancer types and characterize lifetime cancer risk in carriers.

CDKN2A/CDK4 status in Brazilian patients meeting clinical criteria for hereditary melanoma: a cross-sectional descriptive trial.

Melanoma is the most lethal skin cancer, and its incidence has increased worldwide. About 10% of cases are classified as hereditary melanoma (HM). CDKN2A and CDK4 are the major high-risk genes. Families are also more prone to develop pancreatic cancer, and different forms of oncological surveillance are recommended. Describe the prevalence of CDKN2A/CDK4 germline mutations in melanoma-prone patients and their phenotypic and histopathological features. A total of 69 patients meeting the clinical criteria for HM were included in this cross-sectional descriptive study. Amplification by PCR and genomic sequencing were used. The variants were classified according to American College of Medical Genetics (ACMG) criteria. The mean age at first diagnosis of melanoma was 44.8 years (SD ± 17.83). Most patients had phototype II (44.9%), more than 50 melanocytic nevi (76.8%), atypical nevus syndrome (72.5%), history of sunburn (76.8%), and multiple primary melanomas without a family history of this tumor (74.3%). Two hundred melanomas were observed. Most tumors had a Breslow index ≤1.0 mm (84.5%), location in the trunk (60.5%), and superficial spreading histological subtype (22.5%). Four variants were found in CDKN2A exons in seven patients (c.305C>A, c.26T>A, c.361G>A e c.442G>A), two variants in the 5'UTR region in five patients (c.-25C>T and c.-33G>C), and two variants in the 3'UTR region in 21 patients (c.*29C>G and c.*69C>T). One likely pathogenic variant (c.305C>A) was identified in one patient (1.4%). No variant was found in CDK4. The prevalence of CDKN2A mutations was 1.4% in Brazilian patients meeting clinical criteria for HM.

Sex-Specific Associations of MDM2 and MDM4 Variants with Risk of Multiple Primary Melanomas and Melanoma Survival in Non-Hispanic Whites.

MDM2-SNP309 (rs2279744), a common genetic modifier of cancer incidence in Li-Fraumeni syndrome, modifies risk, age of onset, or prognosis in a variety of cancers. Melanoma incidence and outcomes vary by sex, and although SNP309 exerts an effect on the estrogen receptor, no consensus exists on its effect on melanoma. MDM2 and MDM4 restrain p53-mediated tumor suppression, independently or together. We investigated SNP309, an a priori MDM4-rs4245739, and two coinherited variants, in a population-based cohort of 3663 primary incident melanomas. Per-allele and per-haplotype (MDM2_SNP309-SNP285; MDM4_rs4245739-rs1563828) odds ratios (OR) for multiple-melanoma were estimated with logistic regression models. Hazard ratios (HR) for melanoma death were estimated with Cox proportional hazards models. In analyses adjusted for covariates, females carrying MDM4-rs4245739*C were more likely to develop multiple melanomas (ORper-allele = 1.25, 95% CI 1.03-1.51, and Ptrend = 0.03), while MDM2-rs2279744*G was inversely associated with melanoma-death (HRper-allele = 0.63, 95% CI 0.42-0.95, and Ptrend = 0.03). We identified 16 coinherited expression quantitative loci that control the expression of MDM2, MDM4, and other genes in the skin, brain, and lungs. Our results suggest that MDM4/MDM2 variants are associated with the development of subsequent primaries and with the death of melanoma in a sex-dependent manner. Further investigations of the complex MDM2/MDM4 motif, and its contribution to the tumor microenvironment and observed associations, are warranted.

Potential risk factors, clinicopathological features and determinants of survival for multiple primary melanoma patients compared to single primary melanoma: a large single-center Italian study.

Melanoma patients have a high risk of developing subsequent primary melanomas, a condition known as multiple primary melanoma (MPM). We aimed to compare risk factors of patients with MPM and single primary melanoma (SPM). Primary MPM and SPM consecutively treated at the National Cancer Institute in Milan, Italy, from 1978 to 2021 were retrospectively investigated. Demographic and clinicopathological characteristics were analyzed. Multivariate hazard ratios and mortality were estimated using Cox proportional hazards regression models. Overall, 9122 patients with SPM and 944 with MPM were included. A total of 1437 and 85 deaths occurred in SPM and MPM group, respectively. Of these, 1315 (14.4%) within SPM patients and 60 (6.4%) in MPM group were melanoma-specific deaths (MSDs). Males had a higher risk for MPM (hazard ratio = 1.29), while age was not associated with MPM (hazard ratio = 0.98). The risk of MPM decreased by about 50% for Breslow thickness >1 mm, and by about 45 and 75% in presence of mitoses and ulceration, respectively. The multivariate hazard ratio of death for MPM compared to SPM patients was 0.85 (95% confidence interval, CI: 0.67-1.06), while considering MSD the corresponding hazard ratio was 0.93 (95% CI: 0.71-1.22). Melanoma patients should receive regular follow-up with complete skin examination to detect early subsequent primary melanoma. Patients with more advanced primary have decreased risk of MPM, while males have higher risk. Our study reported no significant difference in mortality between SPM and MPM, but the issue is still open for discussion and further studies.

Melanocortin 1 receptor variants and their association with phenotypic characteristics and sporadic multiple primary melanomas in a cohort of 402 Spanish subjects.

The melanocortin 1 receptor (MC1R) gene is considered to be a major determinant of the risk of melanoma. The role of MC1R polymorphisms as predisposing factors for the development of a second primary melanoma is not well established. The present study analyses the characteristics from subjects with certain MC1R variants without any other genetic predisposition, as well as the risk of second primary melanoma associated with these variants. We performed a prospective longitudinal single-centre study based on follow-up information of 402 patients diagnosed with cutaneous melanoma. MC1R gene was sequenced in all subjects. High-risk variants were defined as those previously associated with melanoma (V60L, V92M, I155T, R160W, R163Q and D294H). 253 (63%) patients had at least one predisposing variant. These individuals had higher proportion of red/blonde hair, multiple primary melanomas and first melanoma diagnosis under the age of 60. Second primary melanomas were detected in 28 (3.8%) subjects. Having more than 25 melanocytic nevi was associated significantly to the development of second primary melanomas. A higher proportion of individuals carrying at least one predisposing MC1R variant develop a second melanoma, although statistical significance was not reached. Therefore, some MC1R polymorphisms might determine clinical and histological differences between patients with cutaneous melanoma and may represent a risk factor for second primary melanoma, although more studies are needed.

Clinical Features and Survival of Multiple Primary Melanoma: A Belgian Single Center Cohort.

It remains unclear whether multiple primary melanoma (MPM) patients have a worse survival prognosis compared with single primary melanoma (SPM) patients. To investigate the demographics, histological features, and survival of MPM versus SPM patients. Cox regression analyses compared survival between SPM and MPM patients. Furthermore, demographics and histological features of the MPM cohort were compared with the SPM patients retrieved from dermatopathology files between 2000 and 2019. Out of 3853 melanoma patients, 95 MPM patients were retrieved: 81 with two primary melanomas (85.2%) and 14.8% with three or more. Mean Breslow of the first melanoma was 0.84mm [minimum (min): 0mm, maximum (max): 16mm, standard deviation (SD) 1.77] versus 0.37mm (second MPM) (min: 0mm, max: 2.5mm, SD 0.50) and 0.33mm (third MPM) (min: 0mm, max: 0.6mm, SD 0.22). The mean Breslow for the second MPM was significantly higher for men than women (0.59mm versus 0.27mm). First and second melanoma in MPM patients developed on preexisting melanocytic nevi in 13% and 12%, respectively. In contrast with the mean age of primary melanoma in Belgium for women (58.2years) and men (63.3years), MPM patients developed their first melanoma earlier, at 44.8years and 54.6years, respectively. The mean distribution of anatomical localization of primary and secondary melanoma was highly similar in women, whereas in men a shift towards lower extremities was observed (19% versus 28%). The thicker the primary melanoma was, the sooner the second appeared. Follow-up (2-4/year) versus (1/year) yielded a mean Breslow of 0.29mm and 0.55mm, respectively. Cox regression analysis with time-varying covariate revealed a tendency for a worse prognosis in 5-year survival rates, but this was not statistically significant (p = 0.09). Patient phenotypes were not available on the histological reports. A closer follow-up regimen of MPM versus SPM patients is probably justified.

Indoor tanning is associated with an increased risk of multiple primary melanomas: A case-control study

To the Editor: A history of over 10 indoor tanning exposures is associated with an increased risk for melanoma.1,2 Further, our clinical experience is that indoor tanning is the most frequent cause of multiple primary melanomas (MPMs). To investigate this relationship, we performed a case-control study approved by the Northwestern University Institutional Review Board (STU00211546). Cases were defined as patients with 2 or more (2+) primary melanomas and controls as patients with a single primary melanoma (SPM).