Background: Differentiated thyroid cancer (DTC) in children and adolescents is a rare but significant malignancy, often presenting at more advanced stages compared to adults, although it is associated with favorable long-term outcomes. This study aimed to identify prognostic factors and perform risk stratification with the goal of identifying low-risk patients who would benefit from a less radical treatment approach. Methods: This retrospective cohort study included patients aged 21 years and younger with DTC treated at the Institute for Oncology and Radiology of Serbia between 1980 and 2024. Results: The study analyzed 99 patients (39 children, 60 adolescents) with a median follow-up of 15.6 years (range: 0.6–43.6 years). No significant differences in long-term outcomes were observed between children and adolescents. Multivariate regression analysis identified a total number of more than 10.5 positive lymph nodes and extrathyroidal tumor extension as independent predictors of adverse events and event-free interval (EFI). Using these prognostic factors, patients were stratified into three groups: low-risk (no risk factors), intermediate-risk (one of two risk factors), and high-risk (both risk factors). Statistically significant differences in EFI were observed among the three groups. Notably, none of the patients in the low-risk group had evidence of disease after treatment. Patients classified as having no evidence of disease after treatment demonstrated significantly better EFI compared to those with evidence of disease. Conclusions: Our findings highlight the importance of meticulous risk stratification in predicting long-term outcomes and might serve as a basis for developing personalized therapeutic strategies. Identifying low-risk patients who may benefit from a less aggressive treatment approach while ensuring optimal treatment and follow-up for high-risk patients remains a central objective in the modern management of DTC.

Introduction: Radiation-induced breast angiosarcoma (RIBAS) is a rare adverse event associated with postoperative breast irradiation. The data from the literature indicate that RIBAS occurs in less than 0.3% of patients treated with adjuvant radiotherapy for breast cancer. Given the rarity, diverse clinical presentation, poor prognosis, and lack of consensus on the management, this study aimed to present experiences of our specialized cancer center with RIBAS, in terms of the incidence, presentation, management, and outcomes. Methods: We reviewed the medical records of 10,834 breast cancer patients treated at the Institute for Oncology and Radiology of Serbia between January 2013 and June 2024 to detect patients that had breast-conserving surgery, followed by postoperative irradiation, and developed angiosarcoma in the irradiated area at least 3 years after radiotherapy, without distant metastases. The incidence, latency period, management, and treatment outcomes were analyzed. Results: A total of nine female patients with RIBAS were identified and included in this study. The median age at RIBAS diagnosis was 64 years (range: 36–68), with a median latency of 64 months (95% CI > 57) from irradiation to diagnosis. The mean tumor size was 55 mm (SD 32.78). Patients were followed for a median of 30 months (range: 7–40) after initial RIBAS surgery. Local recurrence occurred in seven patients (77.8%), with five undergoing re-do surgery with curative intent. Three patients developed distant metastases during follow-up. The median overall survival (OS) was 31 months (95% CI > 30), with a 3-year survival rate of 15.2% (95% CI 2.5–91.6%). The median local recurrence-free interval was 10 months (95% CI > 3). Median OS after RIBAS local recurrence and after breast cancer treatment was 17 months (95% CI > 15) and 108 months (95% CI > 88), respectively. Conclusions: RIBAS is a rare but increasingly prevalent adverse event associated with BC irradiation, marked by an aggressive disease course and high relapse rates. Awareness, prompt diagnosis, and a radical surgical approach with wide clear margins are critical for improving patients’ outcomes.

Background: Triple-negative breast cancer (TNBC) represents the most aggressive breast cancer subtype, characterized by high genomic instability, metabolic stress, and limited therapeutic options. Ferroptosis, an iron-dependent form of regulated cell death, has emerged as a promising vulnerability in TNBC, yet its subtype-specific regulatory landscape remains insufficiently defined. Methods: Using transcriptomic (METABRIC, TCGA, GEO) and proteomic (CPTAC) datasets, ferroptosis-related genes were profiled across PAM50 breast cancer subtypes. Differential expression, univariate Cox regression, LASSO modeling, survival analyses, GSEA, and dimensionality reduction (PCA, t-SNE) were applied. A Ferroptosis Index (FI) was calculated using β-coefficients from the Cox/LASSO regression model. Single-cell RNA-seq data was used to map ferroptosis-associated signature across tumor and microenvironmental compartments. Results: Basal-like tumors exhibited the strongest ferroptosis-associated transcriptional shift, characterized by upregulation of ACSL4 and EZH2 and downregulation of AR, GPX4, and CIRBP. Sixteen ferroptosis-related genes were associated with overall survival, forming a ferroptosis-associated signature. The FI was significantly higher in Basal-like tumors, indicating elevated ferroptosis-associated transcriptional state. GSEA revealed enrichment of cell cycle, mitotic, cytoskeletal, and metabolic stress pathways. Single-cell analysis demonstrated expression of ferroptosis markers across cancer epithelial, stromal, and myeloid populations. Conclusions: Basal-like tumors harbor a distinct ferroptosis-associated transcriptional state linked to tumor aggressiveness and poor prognosis. These findings provide a biologically grounded framework for ferroptosis-related stratification and support future functional and translational studies targeting ferroptosis vulnerabilities in aggressive breast cancer.

Objective: Papillary thyroid microcarcinoma (PTMC) often presents with multifocality and bilaterality, but the clinical significance of these features and their association with cervical lymph node metastases (LNMs) remain debated. The aim of this study was to investigate the patterns of multifocality and bilaterality in PTMC and their association with central and lateral neck lymph node metastases. Methods: This retrospective study analyzed 254 patients with histologically confirmed PTMC treated at the Institute for Oncology and Radiology of Serbia between 2004 and 2016. All patients underwent total thyroidectomy with central and, when indicated, lateral neck dissection. Associations between multifocality, bilaterality, and cervical LNM were evaluated using appropriate statistical tests. A p-value < 0.05 was considered statistically significant. Results: Multifocal tumors were present in 40.55% of patients, with bilateral involvement in 27.17%. Cervical LNM occurred in 33.07% of patients, with 26.77% showing central and 20.08% lateral metastases. Patients with multifocal tumors were associated with significantly higher proportions of male patients (p = 0.0283), higher rates of capsular invasion (p = 0.0002), larger tumor size (p = 0.0134), and increased incidence of LNM (p = 0.0152). Bilateral tumors were associated with larger tumor size (p = 0.0004) and more frequent capsular invasion (p = 0.0248), but not with a statistically significant increase in LNM. The number of tumor foci was strongly associated with both central and lateral LNM (p < 0.001). Conclusions: Multifocality, particularly with a higher number of tumor foci, is significantly associated with more aggressive tumor features and higher rates of cervical lymph node metastases in PTMC. While bilaterality also reflects a more aggressive phenotype, it was not independently predictive of LNM. These findings underscore the importance of careful risk stratification in PTMC and suggest that multifocality should inform surgical and follow-up strategies.

Introduction: Breast sarcomas (BS) are rare malignant tumors with aggressive behavior and limited evidence guiding outcome assessment. Data on distant metastasis-free interval (DMFI) in this population are scarce. This study aimed to describe oncologic outcomes and clinicopathologic characteristics in patients with BS treated with curative intent. Methods: Patients with primary or secondary breast sarcoma treated at a single tertiary cancer center between 2013 and 2025 were retrospectively analyzed. Patients with metastatic disease at diagnosis were excluded. DMFI was the primary endpoint, and OS was the endpoint. Survival outcomes were estimated using Kaplan-Meier methodology and presented descriptively. Results: Twenty-six patients met the inclusion criteria. Angiosarcoma was the most common histologic subtype, predominantly occurring as secondary disease after prior breast radiotherapy. Median DMFI was not reached during follow-up, with 71.5% of patients remaining metastasis-free at 3 years, whereas median OS was 31 months with a 3-year OS of 46.9%. Patients with higher pathological T stage, larger tumors, tumor necrosis, younger age, and narrower resection margins tended to demonstrate shorter DMFI. Differences in overall survival were most pronounced according to resection margin status. Conclusions: Tumor burden-related factors, tumor necrosis, and surgical margin width showed clinically relevant differences in metastasis-related outcomes and survival in breast sarcoma. Adequate surgical resection remains critical in this rare and heterogeneous disease.

Human placenta-derived amniotic membrane (hAM) and its derivatives have attracted growing interest as bioactive materials for tissue engineering, regenerative medicine, and biomaterial design. This review summarizes the anatomical and cellular characteristics of hAM and examines the interplay between its regenerative and immunomodulatory properties. Key hAM-derived biomolecules are discussed, with an emphasis on their roles in immune regulation, angiogenesis, extracellular matrix remodeling, and tissue repair across diverse regenerative contexts. Current applications of hAM-based materials in tissue engineering and regenerative biomaterials are reviewed, including emerging studies involving soft tissue applications. In addition, recent efforts to integrate hAM derivatives into 3D bioprinting approaches are examined, including their use as bioink components or biofunctional additives to hydrogel-based systems. Although studies involving hAM-based bioprinted constructs remain limited, the available findings suggest promising regenerative, proangiogenic, and bioactive effects. Challenges related to material processing, printability, standardization, and reproducibility are also discussed. Overall, this review highlights the biomaterial potential of hAM derivatives and their emerging relevance to biofabrication strategies aimed at developing biologically instructive constructs for regenerative medicine.