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S. Șenilă

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Open access Aug 2026

Risk of Second Primary Cancers in Melanoma Survivors: A Retrospective Hospital-Based Cohort Study from Two Romanian Referral Centres

Background and objectives: Melanoma survivors may develop additional primary malignancies, but data from Eastern European hospital cohorts are scarce. We aimed to estimate the observed incidence of second primary cancers (SPCs) within a Romanian referral-centre cohort, identify associated factors, and explore the association of SPC occurrence with overall survival. Methods: We conducted a retrospective, hospital-based cohort study of 394 patients with histopathologically confirmed cutaneous melanoma followed at two referral centres in Cluj-Napoca. Additional malignancies were counted as new primaries only when clinical and/or histopathological documentation distinguished them from recurrence or metastasis. Incidence density was expressed per 1000 person-years. Multivariable logistic regression assessed age, sex, residence, and Breslow thickness. Fixed-covariate Cox and Kaplan–Meier analyses were considered exploratory because of immortal-time and competing-risk limitations. Results: Over 1848 person-years, 79 patients (20.1%) developed at least one SPC (131 events; observed incidence 70.9/1000 person-years), most frequently cutaneous (53.6/1000 person-years). SPC occurrence increased with age (Cochran–Armitage Z = 5.63, p < 0.001); the Kaplan–Meier complement estimate reached 20.7% at five years. Age independently predicted SPC (OR 1.86 per decade, p < 0.001), whereas greater Breslow thickness was inversely associated (OR 0.86, p = 0.008). Actinic keratosis showed a strong unadjusted association (OR 6.64, p < 0.001) but was not included in the adjusted model. The fixed-status Cox model showed lower mortality among patients with an SPC (HR 0.36, p < 0.001), a finding vulnerable to detection and immortal-time bias. Conclusions: SPCs were frequent in this hospital cohort and predominantly cutaneous. Older age was an independent predictor, while actinic keratosis was a strong unadjusted marker. Prospective, population-based validation is needed before surveillance intensity is individualised.

Salomea-Ruth Halmágyi, L. Ungureanu, A. Vasilovici et al. · 0 citations
Open access Aug 2026

Histopathological Differences Between De Novo and Nevus-Associated Melanoma

Background/Objectives: Cutaneous melanoma arises de novo in the majority of cases; 20–30% develop from pre-existing nevi. Differentiating nevus-associated melanoma (NAM) from de novo melanoma (DNM) is important for understanding melanomagenesis, risk stratification, and prognostic assessment. The objective of this study was to compare the demographic, clinical, and histopathological characteristics of NAM and DNM in a large single-institution retrospective cohort. Methods: A retrospective, longitudinal, observational study was conducted at the Department of Pathological Anatomy, Cluj-Napoca County Emergency Clinical Hospital (2015–2025). Of the 729 initially identified cases, 580 patients with histopathologically confirmed cutaneous melanoma and complete clinical records were included. Analyses comprised Mann–Whitney U and chi-square tests and multivariate logistic regression (p < 0.05). Results: DNM constituted 78.6% (n = 456) and NAM 21.4% (n = 124) of cases. DNM patients were significantly older (median 66 vs. 56 years; p < 0.001). NAM was predominantly located on the trunk (63.7% vs. 45.2%; p = 0.0006), whereas DNM showed greater involvement of the head/neck and upper extremities. Superficial spreading melanoma was more frequent in NAM (79.8% vs. 62.5%; p = 0.004); nodular melanoma was more common in DNM (22.6% vs. 10.5%), and lentigo maligna was exclusive to DNM. DNM demonstrated greater Breslow thickness (median 2.0 vs. 1.25 mm; p = 0.021), more advanced Clark level (p = 0.040), and higher mitotic rate (median 3 vs. 2/mm2; p = 0.049). On multivariate logistic regression, older age (OR = 1.03; 95% CI: 1.02–1.05; p < 0.001) and head/neck localisation (OR = 2.73; 95% CI: 1.39–5.39; p = 0.004) were independent predictors of DNM; histopathological aggressiveness markers did not retain independent significance after adjustment. Conclusions: Although DNM presents with more aggressive histopathological features, these characteristics are driven primarily by patient age and anatomical location rather than an inherent de novo aggressive phenotype, suggesting that observed differences largely reflect cumulative sun-damage pathways and patient demographics.

A. Vasilovici, M. Zaiț, L. Ungureanu et al. · 0 citations

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