Andrea Vecchione

Background: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a mature T-cell lymphoma linked to textured breast implants. A leading hypothesis suggests that chronic inflammation, combined with immunological and genetic factors, drives its pathogenesis. Two previous studies investigating bacterial biofilms on breast implant capsules have produced conflicting results, particularly regarding the enrichment of Ralstonia spp. Methods: We analyzed the microbiota profiles in seroma samples from 10 BIA-ALCL patients and 12 patients with non-neoplastic effusion, subclassified into acute-, mixed-, and chronic-type based on cellular composition. We used two metagenomic approaches: 16S rRNA gene sequencing and Nanopore sequencing with the “What’s in My Pot?” (WIMP) taxonomic classifier. Our analyses included alpha and beta diversity metrics, as well as comparisons of Gram status and oxygen requirements. Results: Both sequencing methods identified Staphylococcaceae, Propionibacteriaceae, and Bradyrhizobiaceae as the most prevalent bacterial families in both BIA-ALCL and benign seroma samples. Notably, the Burkholderiaceae family was more abundant in some of the benign seromas according to the 16S rRNA sequencing, but Ralstonia spp. were not detected. BIA-ALCL showed higher richness (based on Nanopore data) and higher evenness (based on 16S rRNA data) compared to acute-type seromas, indicating a more homogenous representation of the different taxa identified. BIA-ALCL seromas did not cluster together based on Nanopore data, but they did form a distinct cluster with 16S rRNA data. This cluster was differentiated from the other two clusters by a relatively balanced presence of multiple families without overt dominance. We observed no significant differences in Gram staining between BIA-ALCL and benign samples using either method. However, non-aerobic bacterial families were enriched in BIA-ALCL cases only when analyzed with the Nanopore pipeline. Conclusions: Overall, our findings did not identify a distinctive microbial signature specifically associated with BIA-ALCL.

Background/Objectives: Acute Fibrinous and Organizing Pneumonia (AFOP) is a rare pulmonary condition histologically characterized by intra-alveolar fibrin deposition and organizing pneumonia without hyaline membranes. This study aims to describe the clinicopathologic and radiologic features of isolated AFOP nodules presenting as solitary pulmonary nodules (SPNs) mimicking malignancy in patients with recent COVID-19 infection. Methods: We retrospectively analyzed consecutive cases of histologically confirmed AFOP (n = 20) and organizing pneumonia (OP; n = 119) presenting radiologically as SPNs suspicious for malignancy from January 2021 to December 2023. Clinical data, COVID-19 status, radiologic features (including nodular characteristics, ground-glass opacity [GGO], and consolidation), and histopathological findings were collected and analyzed. Digital image analysis quantified the intra-alveolar fibrin content. Results: AFOP nodules showed a significant association with previous COVID-19 infection compared to OP (55% vs. 0.8%, p < 0.001). Radiologically, AFOP lesions were predominantly located in the upper lobes, frequently exhibiting a mixed pattern of GGO and consolidation within solitary nodules (8–28 mm diameter), distinctly differing from the predominantly lower-lobe homogeneous consolidations in OP. Histologically, AFOP was defined by prominent intra-alveolar fibrin “balls,” correlating significantly with radiological consolidation patterns (r = 0.991, p < 0.05). Regions of consolidation demonstrated higher fibrin contents compared to areas of predominant GGO. Conclusions: Isolated AFOP nodules presenting as SPNs post-COVID-19 infection strongly mimic malignancy radiologically, highlighting the necessity for multidisciplinary diagnostic approaches integrating radiological and histopathological data to avoid unnecessary interventions. Recognition of this rare but distinctive clinical entity is essential for appropriate patient management.

Background: Approximately 25.0% of metastatic prostate cancer patients harbour DNA damage repair mutations, including BRCA1 and BRCA2, which are actionable targets for poly(ADP-ribose) polymerase (PARP) inhibitors. Accurate detection of BRCA1/2 mutations is critical for guiding targeted therapies, but crucial pre-analytical factors, such as tissue storage duration and DNA fragmentation, drastically affect the reliability of next-generation sequencing (NGS) using real-world diagnostic specimens. Methods: This multicentre study analysed 954 formalin-fixed paraffin-embedded tissue samples from 11 centres, including 559 biopsies and 395 surgical specimens. This study examined the impact of storage duration (2 years) and DNA parameters (concentration and fragmentation index) on NGS success rates. Logistic regression and Cox regression analyses were used to assess correlations between these factors and sequencing outcomes. Results: NGS success rates decreased significantly with longer storage, from 87.8% (2 years). Samples with higher DNA concentrations and fragmentation indexes had higher success rates (p < 0.001). Surgical specimens had superior success rates (83.3%) compared with biopsies (72.8%) due to better DNA quality. The DNA degradation rate was more pronounced in older samples, underscoring the negative impact of extended storage. Conclusions: Timely testing of BRCA1/2 mutations is critical for optimizing the identification of prostate cancer patients eligible for PARP inhibitors. Surgical specimens provide more reliable results than biopsies and minimizing the storage duration significantly enhances testing outcomes. Standardizing pre-analytical and laboratory procedures across centres is essential to ensure personalized treatments and improve patient outcomes.

Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized cancer immunotherapy but continues to face significant challenges that limit its broader application, such as antigen targeting, the tumor microenvironment, and cell persistence, especially in solid tumors. Meanwhile, the global implementation of mRNA vaccines during the COVID-19 pandemic has highlighted the transformative potential of mRNA and lipid nanoparticle (LNP) technologies. These innovations, characterized by their swift development timelines, precise antigen design, and efficient delivery mechanisms, provide a promising framework to address some limitations of CAR-T therapy. Recent advancements, including mRNA-based CAR engineering and optimized LNP delivery, have demonstrated the capacity to enhance CAR-T efficacy, particularly in the context of solid tumors. This review explores how mRNA-LNP technology can drive the development of in vivo engineered CAR-T therapies to address current limitations and discusses future directions, including advancements in mRNA design, LNP optimization, and strategies for improving in vivo CAR-T functionality and safety. By bridging these technological insights, CAR-T therapy may evolve into a versatile and accessible treatment paradigm across diverse oncological landscapes.

Breast cancer ranks as the most prevalent form of cancer globally. Currently, advanced screening methods have significantly improved early detection rates. These achievements have led to more non-invasive cancer diagnoses and underscored the clinical relevance of precursor lesions like flat epithelial atypia (FEA), a histological condition characterized by mild atypical changes in the normal epithelium lining the mammary ducts. Despite the increasing detection of FEA in mammary biopsy, our understanding of the biological behavior of this entity remains limited and, as a consequence, the clinical management of patients is still being debated. Evidence from the literature indicates that dysregulation of microRNAs contributes to all stages of breast cancer progression, potentially serving as valuable markers of disease evolution. In this study, through a comparison of the microRNA profiles of normal mammary epithelium, FEA, and non-invasive breast cancer in three cohorts of patients, we identified downregulation of miR-1297 as a common feature in both FEA and non-invasive breast cancer compared to the normal counterpart. Mechanistically, overexpression of miR-1297 inhibits the growth of breast cancer cells by targeting the oncogenic receptor tyrosine kinase EphrinA2. In contrast, downregulation of miR-1297 increases proliferation and alters the morphology of normal mammary epithelial cells in a three-dimensional context. These findings pinpoint the downregulation of miR-1297 as an early event in mammary transformation and suggest its potential role as a driver of progression in FEA, harboring the capacity to evolve into malignancy.

Cancer cells exhibit abnormal behavior compared to normal cells. They ignore growth arrest signals such as contact inhibition, a mechanism that stops their proliferation when they collide with surrounding cells, and proliferate in an uncontrolled manner, destroying tissue. Early detection and treatment of cancer are therefore important for healthy longevity. Cancer cells differ from normal cells in their characteristic gene expression due to their abnormalities. Cancer markers that reflect these characteristics have been searched for and applied to diagnosis. Although analysis of blood antigens has been the main method, further development of a diagnostic system is needed for early detection of cancer. Next-generation sequencers have improved gene expression analysis technology, making it possible to analyze detailed gene expression in cancer cells and nucleic acid molecules in blood or urine. In addition, cancer cells release extracellular vesicles, exosomes, which are known to contain molecules that may serve as cancer markers. This review summarizes the latest findings on exosomal cancer markers.

Cancer is one of the major causes of death, and as it becomes more malignant, it becomes an intractable disease that is difficult to cure completely. Therefore, early detection is important to increase the survival rate. For this reason, testing with blood biomarkers is currently common. However, in order to accurately diagnose early-stage cancer, new biomarkers and diagnostic methods that enable highly accurate diagnosis are needed. This review summarizes recent studies on cancer biomarker detection. In particular, we focus on the analysis of volatile organic compounds (VOCs) in urine and the development of diagnostic methods using olfactory receptors in living organisms. Urinary samples from cancer patients contain a wide variety of VOCs, and the identification of cancer specific compounds is underway. It has also been found that the olfactory sense of organisms can distinguish cancer-specific odors, which may be applicable to cancer diagnosis. We explore the possibility of novel cancer biomarker candidates and novel diagnostic methods.

Malignant pleural effusion (MPE) from patients with advanced non-small-cell lung cancer (NSCLC) has been proven valuable for molecular analysis; however, simultaneous detection of driver fusions in MPE is still challenging. In this study, we investigated the Idylla™ GeneFusion Panel, a stand-alone test in tissue samples, in the evaluation of ALK, ROS1, RET and MET ex14 skipping mutations in MPE and compared its performance with routine reference methods (Real-time-based and Next-generation Sequencing—NGS). The inclusion criteria for sample selection were as follows: advanced NSCLC harboring ALK, ROS1, RET fusions or MET exon-skipping alterations and the availability of MPE collected at diagnosis or disease progression. Molecular alterations have been investigated on tissue by fluorescence in situ hybridization (FISH) or Real-time PCR or NGS. For molecular profiling with the Idylla™ GeneFusion, 200 µL of MPE supernatants combined with 50 µL of RNA Later solution were loaded into the Idylla™ cartridge without cfRNA extraction. The Idylla™ GeneFusion Assay performed on MPEs was able to confirm molecular profile, previously diagnosed with conventional methods, in all cases. Our data confirm that MPE are suitable material for investigating fusion alterations. The Idylla™ GeneFusion, although indicated for investigation of tissue samples, offers the possibility of performing a molecular characterization of supernatants without undertaking the entire cfRNA extraction procedure providing a rapid and reliable strategy for the detection of actionable genetic alterations.

Background. Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) is an autosomal dominant autoinflammatory disorder stemming from mutations in the TNFRSF1A gene affecting the tumor necrosis factor receptor (TNFR)-1. These mutations lead to dysregulated inflammatory responses, primarily mediated by augmented interleukin (IL)-1β release. Case Presentation. We present the case of a 29-year-old woman with a history of recurrent febrile episodes, abdominal pain, and joint manifestations, eventually diagnosed with TRAPS following genetic testing revealing a heterozygous R92Q mutation in TNFRSF1A. Further genetic examinations unveiled additional clinically significant mutations, complicating the clinical picture. Our patient exhibited delayed colonic transit time and right colonic amyloidosis, a rare complication. Surgical intervention was required for overwhelming intestinal obstruction, revealing mucosal atrophy and dense lymphocytic infiltrates on histological examination. Discussion. Gastrointestinal involvement in TRAPS is common but can present diagnostic challenges. Following colon resection, histological examination revealed amyloid deposition, underscoring the importance of a comprehensive evaluation of these patients. Isolated colic amyloidosis has significant diagnostic and prognostic implications, warranting cautious monitoring and tailored management strategies. Treatment of TRAPS typically involves anti-inflammatory agents such as IL-1 inhibitors, with our patient experiencing clinical improvement on anakinra and canakinumab. Conclusion. This case report emphasizes the diverse manifestations of TRAPS and the importance of recognizing gastrointestinal complications, particularly isolated colic amyloidosis. Comprehensive evaluation, including histological examination, is crucial for identifying atypical disease presentations and guiding management decisions. Continued research is needed to elucidate the underlying mechanisms and optimize treatment strategies for TRAPS and its associated complications.