Cutaneous melanoma in adolescents and young adults.

BACKGROUND: Cutaneous malignant melanoma (CMM) ranks among the five most common cancers in young people in high-income countries and it features peculiar clinicopathological traits. Very few studies have addressed the quality of care and the costs for adolescents and young adults (AYA) population. OBJECTIVE: To provide a comprehensive epidemiological and clinicopathological profile of CMM in AYA. The study also addresses the cost-of-illness and the diagnostic-therapeutic performance indicators by patient age category. METHODS: This population-based cohort study included 2435 incident CMM (age range 15-65 years; age 15-39 = 394; age 40-65 = 2041), as recorded in 2015, 2017 and 2019 by the Regional Veneto Cancer Registry (Italy). Cramer's-V tested the strength of association between pairs of variables. The Kaplan-Meier method was used to test the association between age and survival rate. The clinical performance indicators were computed using the Clopper-Pearson exact method. RESULTS: In AYA patients (16.2%), CMM incidence rates increased significantly from 1990 to 2019. Low-stage CMM (p = 0.007), radial growth pattern (p = 0.026) and lower Clark levels (p = 0.007) prevailed; males had less advanced malignancies (p = 0.003), with the trunk as the most common primary site (67.5%); the lower limbs (32.6%) were the most common primary site for females (p < 0.001). Overall survival was better in AYA than adults. No significant difference was detected in the clinical management of the two age groups, with the only exception of the margin in wide local excision. The care costs were lower in AYA (€195.99 vs. €258.94, p = 0.004). CONCLUSION: In AYA patients, the CMM clinicopathological presentation shows a distinctive profile. The present results provide critical information for optimizing primary and secondary prevention strategies and for tailoring diagnostic therapeutic procedures to the peculiar profile of AYA CMM patients.

Could the mitotic count improve personalized prognosis in melanoma patients?

A number of studies have indicated that the mitotic rate may be a predictive factor for poor prognosis in melanoma patients. The aim of this study was to investigate whether the mitotic rate is associated with other prognostic clinical and anatomopathological characteristics. After adjusting for other anatomopathological characteristics, we then verified the prognostic value of the number of mitoses, determining in which population subgroup this variable may have greater prognostic significance on 3-year mortality. The Veneto Cancer Registry (Registro Tumori del Veneto-RTV), a high-resolution population-based dataset covering the regional population of approximately 4.9 million residents, served as the clinical data source for the analysis. Inclusion criteria included all incident cases of invasive cutaneous malignant melanoma recorded in the RTV in 2015 (1,050 cases) and 2017 (1,205 cases) for which the number of mitoses was available. Mitotic classes were represented by Kaplan-Meier curves for short-term overall survival. Cox regression calculated hazard ratios in multivariable models to evaluate the independent prognostic role of different mitotic rate cut-offs. The results indicate that the mitotic rate is associated with other survival prognostic factors: the variables comprising the TNM stage (e.g., tumor thickness, ulceration, lymph node status and presence of metastasis) and the characteristics that are not included in the TNM stage (e.g., age, site of tumor, type of morphology, growth pattern and TIL). Moreover, this study demonstrated that, even after adjusting for these prognostic factors, mitoses per mm2 are associated with higher mortality, particularly in T2 patients. In conclusion, these findings revealed the need to include the mitotic rate in the histological diagnosis because it correlates with the prognosis as an independent factor. The mitotic rate can be used to develop a personalized medicine approach in the treatment and follow-up monitoring of melanoma patients.

Cutaneous melanoma in older patients.

BACKGROUND: In industrialized countries, the aging population is steadily rising. The incidence of cutaneous malignant melanoma (CMM) is highest in old people. This study focuses on the clinicopathological profile of CMM and indicators of diagnostic-therapeutic performance in older patients. METHODS: This retrospective population-based cohort study included 1,368 incident CMM, as recorded in 2017 by the Regional Veneto Cancer Registry (Northeast Italy). Older subjects were defined as ≥ 80, old as 65-79, and adults as < 65 years of age. The strength of association between pairs of variables was tested by Cramer's-V. Using age groups as the dependent variable, ordered logistic regression was fitted using the clinicopathological CMM profiles as covariates. In each of the three age-groups, the indicators of clinical performance were computed using the Clopper-Pearson exact method. RESULTS: Compared to patients aged younger than 80 years (1,187), CMM in older patients (181; 13.2%) featured different CMM topography, a higher prevalence of ulcers (43.3% versus 12.7%; p < 0.001), a higher Breslow index (p < 0.001), a lower prevalence of tumor-infiltrating lymphocytes (64.4% versus 76.5%, p < 0.01), and a more advanced pTNM stage at clinical presentation (p < 0.001). Elderly patients with a positive sentinel-lymph node less frequently underwent sentinel- lymph node biopsy and lymphadenectomy (60.0% versus 94.2%, and 44.4% versus 85.5%, respectively; p < 0.001). CONCLUSIONS: In older CMM patients, the clinicopathological presentation of CMM shows a distinctive profile. The present results provide critical information to optimize secondary prevention strategies and refine diagnostic-therapeutic procedures tailored to older patients.

Cost items in melanoma patients by clinical characteristics and time from diagnosis.

Background: Costs related to the care of melanoma patients have been rising over the past few years due to increased disease incidence as well as the introduction of innovative treatments. The aim of this study is to analyse CMM cost items based on stage at diagnosis, together with other diagnostic and prognostic characteristics of the melanoma. Methods: Analyses were performed on 2,647 incident cases of invasive CMM that were registered in 2015 and 2017 in the Veneto Cancer Registry (RTV). Direct melanoma-related costs per patient were calculated for each year ranging from 2 years before diagnosis to 4 years after, and were stratified by cost items such as outpatient services, inpatient drug prescriptions, hospital admissions, hospice admissions, and emergency room treatment. Average yearly costs per patient were compared according to available clinical-pathological characteristics. Lastly, log-linear multivariable analysis was performed to investigate potential cost drivers among these clinical-pathological characteristics. Findings: Overall, the average direct costs related to melanoma are highest in the first year after diagnosis (€2,903) and then decrease over time. Hospitalization costs are 8 to 16 times higher in the first year than in subsequent years, while the costs of outpatient services and inpatient drugs decrease gradually over time. When stratified by stage it is observed that the higher expenditure associated with more advanced stages of CMM is mainly due to inpatient drug use. Conclusion: The results of the present study show that grouping patients according to tumour characteristics can improve our understanding of the different cost items associated with cutaneous malignant melanoma. CMM patients experience higher costs in the first year after diagnosis due to higher hospitalization and outpatient services. Policy makers should consider overall and stage-specific annual costs when allocating resources for the management of CMM patients.

Sex Differences in Soft Tissue Sarcoma: Incidence, Clinicopathological Profile, Survival, and Costs.

Background: There are evident sex differences in the incidence of and mortality rates for several tumors. Soft tissue sarcomas (STSs) account for no more than 1% of all malignancies in adults. This study aimed to provide a comprehensive overview of the sex differences in the epidemiology of STSs and the related costs. Methods: This retrospective population-based study draws on epidemiological data regarding cases of STS collected by the cancer registry of the Italian Veneto region for the years 1990-2018. A joinpoint regression analysis was performed to identify significant changes in the trends of the standardized incidence rates in males and females. Bivariate and survival analyses were conducted to assess differences in clinicopathological characteristics and short-term mortality by sex. Direct health care costs incurred over 2 years after a diagnosis of STS were calculated, stratified by sex. Results: The incidence rates of STS at any age were higher for males; only among males the incidence rates showed a tendency to slightly increase. No significant sex differences came to light in short-term mortality or clinicopathological profile, except for the cancer site. Health care costs in the 2 years after a diagnosis of STS were not sex related. Conclusion: The STS incidence was found to be higher for males and showed a rising trend over the last three decades only for males. These findings could result from the occupational exposure to environmental mutagens mainly involving men. Sex did not affect the survival or the clinicopathological STS profile.

Indicators of clinical performance in monitoring soft tissue sarcoma management: a population-based perspective.

Background: Soft tissue sarcomas (STS) are rare malignancies which prognosis varies significantly by primary site, histological subtype, and tumor stage. Their low incidence, and the complexity of their clinico-pathological characteristics demand standardized, cancer-tailored diagnostics and therapies managed at high-volume, multidisciplinary care centers. This study evaluates the quality of STS management in north-east Italy (Veneto Region) through a list of ad hoc defined clinical indicators. Methods: This population-based study concerns all incident cases of STS in 2018 (214 cases) recorded in the adult population censored by the Veneto's regional Cancer Registry. Based on the international literature, a multidisciplinary working group of experts identified a set of indicators for monitoring the quality of diagnostic, therapeutic, and end-of-life clinical interventions. The quality of care was assessed by comparing the reference thresholds with the indicators' values achieved in clinical practice. Results: Diagnostic procedures showed poor adherence to the thresholds, with a low percentage of histological diagnoses validated by a second opinion. The indicators relating to the surgical treatment of superficial, small, low-grade STS, or of medium, high-grade STS of the head-neck, trunk, or limbs were consistent with the thresholds, while for intermediate, high-grade (large-sized, deep) and retroperitoneal STS they fell significantly below the thresholds. Conclusion: A critical evaluation of the clinical indicators allowed to uncover the procedures needing corrective action. Monitoring clinical care indicators improves cancer care, confirms the importance of managing rare cancers at highly specialized, high-volume centers, and promotes the ethical sustainability of the healthcare system.

Synchronous and metachronous multiple primary cancers in melanoma survivors: a gender perspective.

Background: Long-term survivors of cutaneous malignant melanoma (CMM) risk subsequent malignancies due to both host-related and environmental risk factors. This retrospective population-based study differentially assesses the risk of synchronous and metachronous cancers in a cohort of CMM survivors stratified by sex. Methods: The cohort study (1999-2018) included 9,726 CMM survivors (M = 4,873, F = 4,853) recorded by the cancer registry of all 5,000,000 residents in the Italian Veneto Region. By excluding subsequent CMM and non-CMM skin cancers, the incidence of synchronous and metachronous malignancies was calculated according to sex and tumor site, standardizing for age and calendar year. The Standardized Incidence Ratio (SIR) was calculated as the ratio between the number of subsequent cancers among CMM survivors and the expected number of malignancies among the regional population. Results: Irrespective of the site, the SIR for synchronous cancers increased in both sexes (SIR = 1.90 in males and 1.73 in females). Both sexes also demonstrated an excess risk for synchronous kidney/urinary tract malignancies (SIR = 6.99 in males and 12.11 in females), and women had an increased risk of synchronous breast cancer (SIR = 1.69). CMM male survivors featured a higher risk of metachronous thyroid (SIR = 3.51, 95% CI [1.87, 6.01]), and prostate (SIR = 1.35, 95% CI [1.12, 1.61]) malignancies. Among females, metachronous cancers featured higher SIR values than expected: kidney/urinary tract (SIR = 2.27, 95% CI [1.29, 3.68]), non-Hodgkin's lymphoma (SIR = 2.06, 95% CI [1.24, 3.21]), and breast (SIR = 1.46, 95% CI [1.22, 1.74]). Females had an overall increased risk of metachronous cancers in the first 5 years after CMM diagnosis (SIR = 1.54 at 6-11 months and 1.37 at 1-5 years). Conclusion: Among CMM survivors, the risk of metachronous non-skin cancers is higher than in the general population and differs significantly by sex. These results encourage sex-tailored interventions for metachronous secondary cancer prevention.

Epidemiology, pathological characteristics and survival of retroperitoneal soft­tissue sarcomas compared with non­retroperitoneal soft tissue sarcomas.

Retroperitoneal soft-tissue sarcomas (RPS) are rare forms of mesenchymal tumors that account for ~0.15% of all malignancies. The purpose of the present study was to determine the differences between RPS and non-RPS anatomopathological and clinical features and to analyze whether the hazard ratio for short-term mortality differs between patients with RPS and non-RPS, after adjusting for differences in baseline anatomopathological and clinical features. The Veneto Cancer Registry, a high-resolution population-based dataset spanning the regional population, was used as a data source for the analysis. The current analysis focuses on all incident cases of soft-tissue sarcoma recorded by the Registry from January 1, 2017 to December 31, 2018. A bivariate analysis was carried out to compare demographic and clinical characteristics in RPS and non-RPS. Short-term mortality risk was analyzed by primary tumor site. The significance of variations in survival by site group was determined using Kaplan-Meier curves and the Log-rank test. Finally, Cox regression was used to assess the hazard ratio for survival by sarcoma group. RPS accounted for 22.8% of the total sample (92 out of 404 cases). The mean age at diagnosis was 67.6 years for RPS vs. 63.4 for non-RPS; 41.3% of RPS were >150 mm vs. 5.5% for non-RPS. Stages III and IV were more prevalent in RPS (53.2 vs. 35.6%), despite the fact that, in both groups, advanced stages are the most common onset at diagnosis. Regarding surgical margins, the present study showed that R0 is the most prevalent in non-RPS (48.7%), while R1-R2 is the most frequent in patients with RPS (39.1%). The 3-year mortality rate for retroperitoneum was 42.9 vs. 25.7%. Comparing RPS and non-RPS, the multivariable Cox model showed a hazard ratio of 1.58 after adjusting for all other prognostic factors. RPS clinical and anatomopathological characteristics differ from those of non-RPS. Overall, despite adjusting for other prognostic factors, the retroperitoneum site was an independent prognostic factor associated with a worse overall survival in sarcoma patients compared with other sites.

Uncommon presentation of a giant psoas muscle lipoma: a case report and brief literature review.

Giant retroperitoneal lipomas, particularly within the psoas muscle, are a rare condition. We herein present one such case of a 45-year-old Italian man and a literature review. There are only two case reports published in the literature, thus posing challenges for the appropriate diagnosis and treatment. Our patient was admitted to the emergency department with colicky abdominal pain. Computerized tomography (CT) with contrast enhancement revealed kidney stones and a 19.5×13.6×18 cm mass of adipose tissue with septa located in the right retroperitoneum, in close continuity with the right psoas major muscle. Magnetic resonance imaging showed a voluminous neoformation with predominantly adipose content and a compressive effect on adjacent vascular structures. The CT-guided biopsy indicated spindle cell mesenchymal neoplasm, not otherwise specified. Surgical resection of the retroperitoneal mass with the capsule was performed, and a histopathology examination confirmed the diagnosis of spindle cell lipoma. Despite the fact that CT and MRI are the main diagnostic tools, this case report emphasizes the need for a CT-guided core needle biopsy prior to surgery for appropriate diagnosis.

Per- and polyfluoroalkyl substances (PFAS) exposure in melanoma patients: a retrospective study on prognosis and histological features.

Per- and polyfluoroalkyl substances (PFAS) are endocrine disrupting chemicals which could be associated with cancer development, such as kidney and testicular cancers, pancreatic and hepatocellular carcinoma and thyroid tumor. Available scientific literature offers no information on the role of PFAS in melanoma development/progression. Since 1965, a massive environmental contamination by PFAS has occurred in northeastern Italy. This study compared histopathology and prognosis between melanoma patients exposed (n = 194) and unexposed (n = 488) to PFAS. All patients were diagnosed and/or treated for melanoma at the Veneto Oncological Institute and the University Hospital of Padua (Italy) in 1998-2014. Patients were categorized in exposed or unexposed groups according to their home address and the geographical classification of municipalities affected by PFAS contamination as provided by Veneto Government in 2018. Presence of mitoses was found in 70.5% of exposed patients and 58.7% of unexposed patients (p = 0.005). Median follow-up was 90 months (IQR 59-136). 5-year overall survival was 83.7% in exposed patients and 88.0% in unexposed patients (p = 0.20); 5-year disease-specific survival was 88.0% in exposed patients and 90.9% in unexposed patients (p = 0.50); 5-year disease-free survival was 83.8% in exposed patients and 87.3% in unexposed patients (p = 0.20). Adjusting for imbalanced characteristics at baseline (presence of mitoses), survival was not statistically different between exposed and unexposed patients (overall survival: HR 1.10, 95% CI 0.77 to 1.58, p = 0.57; disease-specific survival: HR 0.99, 95% CI 0.62 to 1.59, p = 0.99; disease-free survival: HR 1.10, 95% CI 0.74 to 1.64, p = 0.62). Although the magnitude of PFAS exposure was not quantifiable, our findings suggested that exposure to PFAS was associated with higher level of mitosis in melanoma patients, but this did not translate into a survival difference. Further studies are required to investigate this relationship and all effects of PFAS on prognosis.

Direct Costs of Care for Adults with Soft Tissue Sarcomas: A Population-Based Study.

The clinical treatment of soft tissue sarcoma (STS) has evolved substantially over the last decade. This population-based cohort study based on real-world data included all incidental STS recorded by the Veneto Cancer Registry in 2017. Data on hospital admissions, emergency department and outpatient visits, drug prescriptions, and use of medical devices within two years from STS diagnosis were obtained from administrative databases. The average per-patient real-world costs over this two-year period, in total and by single expenditure item, were calculated and stratified by stage of disease at diagnosis, tumor histology and tumor site. The mean total cost per patient amounted to EUR 16,793. A higher TNM stage at diagnosis was associated with higher healthcare costs, as follows: compared with stage I, the average total cost per patient was 1.32, 2.18 and 3.36 times greater for stages II, III and IV, respectively. Hospital stays generated the greatest costs (averaging EUR 7950 per patient), followed by outpatient visits (mean EUR 3947 per patient) and drug prescriptions (mean EUR 3664 per patient). Given the paucity of population-based studies, the present results can serve as a reference for further cost-effectiveness analyses on care strategies for patients with STS.

Clinical performance indicators for monitoring the management of cutaneous melanoma: a population-based perspective.

The prognosis of cutaneous malignant melanoma (CMM) is based on disease progression. The highly heterogeneous clinical-pathological characteristics of CMM necessitate standardized diagnostic and therapeutic interventions tailored to cancer's stage. This study utilizes clinical performance indicators to assess the quality of CMM care in Veneto (Northeast Italy). This population-based study focuses on all incidences of CMMs registered by the Veneto Cancer Registry in 2015 (1279 patients) and 2017 (1368 patients). An interdisciplinary panel of experts formulated a set of quality-monitoring indicators for diagnostic, therapeutic, and end-of-life clinical interventions for CMM. The quality of clinical care for patients was assessed by comparing the reference thresholds established by experts to the actual values obtained in clinical practice. The prevalence of stage I-CMM decreased significantly from 2015 to 2017 (from 71.8 to 62.4%; P < 0.001), and almost all the pathology reports mentioned the number of nodes dissected during a lymphadenectomy. More than 90% of advanced CMMs were promptly tested for molecular BRAF status, but the proportion of patients given targeted therapies fell short of the desired threshold (61.1%). The proportion of stage I-IIA CMM patients who inappropriately underwent computerized tomography/MRI/PET dropped from 17.4 to 3.3% ( P < 0.001). Less than 2% of patients received medical or surgical anticancer therapies in the month preceding their death. In the investigated regional context, CMM care exhibited both strengths and weaknesses. The evaluated clinical indicators shed essential insight on the clinical procedures requiring corrective action. It is crucial to monitor clinical care indicators to improve care for cancer patients and promote the sustainability of the healthcare system.

The role of sentinel node tumor burden in modeling the prognosis of melanoma patients with positive sentinel node biopsy: an Italian melanoma intergroup study (N = 2,086).

BACKGROUND: The management of melanoma patients with metastatic melanoma in the sentinel nodes (SN) is evolving based on the results of trials questioning the impact of completion lymph node dissection (CLND) and demonstrating the efficacy of new adjuvant treatments. In this landscape, new prognostic tools for fine risk stratification are eagerly sought to optimize the therapeutic path of these patients. METHODS: A retrospective cohort of 2,086 patients treated with CLND after a positive SN biopsy in thirteen Italian Melanoma Centers was reviewed. Overall survival (OS) was the outcome of interest; included independent variables were the following: age, gender, primary melanoma site, Breslow thickness, ulceration, sentinel node tumor burden (SNTB), number of positive SN, non-sentinel lymph nodes (NSN) status. Univariate and multivariate survival analyses were performed using the Cox proportional hazard regression model. RESULTS: The 3-year, 5-year and 10-year OS rates were 79%, 70% and 54%, respectively. At univariate analysis, all variables, except for primary melanoma body site, were found to be statistically significant prognostic factors. Multivariate Cox regression analysis indicated that older age (P < 0.0001), male gender (P = 0.04), increasing Breslow thickness (P < 0.0001), presence of ulceration (P = 0.004), SNTB size (P < 0.0001) and metastatic NSN (P < 0.0001) were independent negative predictors of OS. CONCLUSION: The above results were utilized to build a nomogram in order to ease the practical implementation of our prognostic model, which might improve treatment personalization.

Altitude Effect on Cutaneous Melanoma Epidemiology in the Veneto Region (Northern Italy): A Pilot Study.

The incidence of cutaneous melanoma has been increasing in the last decades among the fair-skinned population. Despite its complex and multifactorial etiology, the exposure to ultraviolet radiation (UVR) is the most consistent modifiable risk factor for melanoma. Several factors influence the amount of UVR reaching the Earth's surface. Our study aimed to explore the relationship between melanoma and altitude in an area with mixed geographic morphology, such as the Veneto region (Italy). We included 2752 melanoma patients who were referred to our centers between 1998 and 2014. Demographics, histological and clinical data, and survival information were extracted from a prospectively maintained local database. Head/neck and acral melanoma were more common in patients from the hills and the mountains, while limb and trunk melanoma were more common in patients living in plain and coastal areas. Breslow thickness, ulceration and mitotic rate impaired with increased altitude. However, the geographical area of origin was not associated with overall or disease-free survival. The geographical area of origin of melanoma patients and the "coast-plain-hill gradient" could help to estimate the influence of different sun exposure and to explain the importance of vitamin D levels in skin-cancer control.

Malignant Melanoma: Direct Costs by Clinical and Pathological Profile.

INTRODUCTION: A number of studies have examined the impact of tumor stage on direct health care costs of patients with melanoma. This study aimed to investigate the association between the direct costs for melanoma and the patients' clinical and histological characteristics. METHODS: The present analysis included 1368 patients diagnosed with melanoma in 2017 in the Veneto Region (northeast Italy) and recorded in a regional population-based melanoma registry. The costs were assessed taking monthly and total direct costs into account. Log-linear multivariable analysis was used to identify the clinical and histological cost drivers, focusing on monthly and total direct costs per patient incurred during the first 2 years after a patient's diagnosis. RESULTS: On multivariable analysis, besides the stage of melanoma, also the presence of mitoses (> 2) was associated with higher monthly direct costs [odds ratio (OR) 1.55, 95% confidence interval (CI) 1.15-2.08, p = 0.004] in respect to cases with 0-2 mitoses. Vertical growth was associated with higher costs compared with radial growth (OR 1.28, 95% CI 1.00-1.64, p = 0.055). Moreover, the association between the absence of tumor-infiltrating lymphocytes (TILs) and higher monthly direct costs reached statistical significance (OR 1.31, 95% CI 1.05-1.64, p = 0.017). There were no differences in monthly direct costs by patients' sex or age, ulceration, or tumor site. CONCLUSION: This study showed that not only tumor stage but also other clinical and histopathologic characteristics have an impact on the direct monthly and total costs of treating melanoma. Further studies on the cost-effectiveness of the various options for managing this disease should take these variables into account, as well as tumor stage, as cost drivers.

Case Report: Surgical Reconstruction of a Massive Thoracic Wall Defect After the Resection of an Undifferentiated Radiation-Induced Sarcoma of the Breast.

A 54-year-old lady was referred to our institute because of a massive thoracic neoplasm arising from the thoracic wall which infiltrated and dislocated the left breast. Twenty years before, the patient had undergone a quadrantectomy with axillary dissection for an infiltrating ductal carcinoma of the left breast, followed by adjuvant radiotherapy and chemotherapy. A true-cut biopsy of the mass showed a low differentiated malignant neoplasm with spindle-shaped cells. The patient underwent a total-body CT scan which showed a 16 × 15 × 10 cm largely necrotic mass with irregular and undefined margins, with little homolateral round-shaped cervical and mesenteric lymph nodes but no distant metastases. After a multidisciplinary discussion, we proposed surgery as the first therapeutic option. The planned treatment was a wide excision of the mass with the underlying ribs (II-VI) followed by the reconstruction of the thoracic wall using titanium bars covered by the acellular porcine dermis, latissimus dorsi flap, and finally, skin grafts from the thighs.

Corrigendum: Melanoma in Adolescents and Young Adults (AYA): Evaluation of the Characteristics, Treatment Strategies, and Prognostic Factors in a Monocentric Retrospective Study.

[This corrects the article DOI: 10.3389/fonc.2021.725523.].

Melanoma in Adolescents and Young Adults: Evaluation of the Characteristics, Treatment Strategies, and Prognostic Factors in a Monocentric Retrospective Study.

The "Veneto Cancer Registry" records melanoma as the most common cancer diagnosed in males and the third common cancer in females under 50 years of age in the Veneto Region (Italy). While melanoma is rare in children, it has greater incidence in adolescents and young adults (AYA), but literature offers only few studies specifically focused on AYA melanoma. The aim of this study was to describe the characteristics, surgical treatment, and prognosis of a cohort of AYA melanoma in order to contribute to the investigation of this malignancy and provide better patient care. This retrospective cohort study included 2,752 Caucasian patients (702 AYA and 2,050 non-AYA patients) from the Veneto Region who were over 15 years of age at diagnosis, and who received diagnosis and/or treatment from our institutions between 1998 and 2014. Patients were divided in adolescents and youth (15-25 years), young adults (26-39 years) and adults (more than 39 years) for the analysis. We found statistically significant differences in gender, primary site, Breslow thickness, ulceration, pathologic TNM classification (pTNM) stage and tumor subtype among the age groups. Disease-specific survival and disease-free survival were also different among the age groups. Our findings suggest that the biological behavior of melanoma in young people is different to that in adults, but not such as to represent a distinct pathological entity. Additional and larger prospective studies should be performed to better evaluate potential biological and cancer-specific differences between AYAs and the adult melanoma population.

Corrigendum: Melanoma of Unknown Primary: Evaluation of the Characteristics, Treatment Strategies, Prognostic Factors in a Monocentric Retrospective Study.

[This corrects the article DOI: 10.3389/fonc.2021.627527.].

Melanoma of Unknown Primary: Evaluation of the Characteristics, Treatment Strategies, Prognostic Factors in a Monocentric Retrospective Study.

BACKGROUND: Melanoma of unknown primary (MUP), accounts for up to 3% of all melanomas and consists of a histologically confirmed melanoma metastasis to either lymph nodes, (sub)cutaneous tissue, or visceral sites without any evidence of a primary cutaneous, ocular, or mucosal melanoma. This study aimed to investigate the characteristics, treatment strategies, and prognostic factors of MUP patients, in order to shed some light on the clinical behavior of this malignancy. METHODS: All the consecutive patients with a diagnosis of MUP referring to our institutions between 1985 and 2018 were considered in this retrospective cohort study. The records of 173 patients with a suspected diagnosis of MUP were retrospectively evaluated for inclusion in the study. Patient selection was performed according to the Das Gupta criteria, and a total of 127 MUP patients were finally included in the study, representing 2.7% of the patients diagnosed with melanoma skin cancer at our institutions during the same study period. A second cohort of all consecutive 417 MKP patients with AJCC stages IIIB-IV, referring tions in the period considered (1985-2018), was included in the study to compare survival between MUP and MKP patients. All the diagnoses were based on histopathologic, cytologic and immunohistochemical examination of the metastases. All tumors were re-staged according to the 2018 American Joint Committee on Cancer (AJCC) 8th Edition. RESULTS: Median follow-up was 32 months (IQR: 15-84). 3-year progression-free survival (PFS) was 54%, while 3-year overall survival (OS) was 62%. Worse OS and PFS were associated with older age (P = 0.0001 for OS; P = 0.008 for PFS), stage IV (P < 0.0001 for OS; P = 0.0001 for PFS) and higher Charlson Comorbidity Index (P < 0.0001 for OS and P = 0.01 for PFS). Patients with lymph node disease showed longer PFS (P = 0.001) and OS (P = 0.0008) than those with (sub)cutis disease. Complete lymph node dissection (CLND) was the most common surgical treatment; a worse OS in these patients was associated with the number of positive lymph nodes (P = 0.01), without significant association with the number of retrieved lymph nodes (P = 0.79). Survival rates were lower in patients undergoing chemotherapy (CT) and target therapy (TT), and higher in those receiving immunotherapy (IT). 417 patients with AJCC stages IIIB-IV of Melanoma Known Primary (MKP) were included for the survival comparison with MUP. 3-year PFS rates were 54 and 58% in MUP and MKP, respectively (P = 0.30); 3-year OS rates were 62 and 70% in MUP and MKP, respectively (P = 0.40). CONCLUSIONS: The most common clinical scenario of our series was a male patient around 59 years with lymph node disease. We report that CLND associated with IT was the best treatment in terms of survival outcome. In the current era of IT and TT for melanoma, new studies have to clarify the impact of novel drugs on MUP.