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Human papillomavirus (HPV) plays a crucial role in the pathogenesis of oropharyngeal squamous cell carcinomas (OPSCC). Accurate HPV status classification is essential for therapeutic stratification. While p16 immunohistochemistry (IHC) is the clinical surrogate marker, it has limited specificity. In this study, we implemented a weakly supervised deep learning approach using the Clustering-constrained Attention Multiple-Instance Learning (CLAM) framework to directly predict HPV status from hematoxylin and eosin (H&E)-stained whole-slide images (WSIs) of OPSCC. A total of 123 WSIs from two cohorts (The Cancer Genome Atlas (TCGA) cohort and OPSCC cohort from the University of Naples Federico II (OPSCC-UNINA)) were used. Attention heatmaps revealed that the model predominantly focused on tumor-rich regions. Errors were primarily observed in slides with conflicting p16/in situ hybridization (ISH) status or suboptimal quality. Morphological analysis of high-attention patches confirmed that cellular features extracted from correctly classified slides align with HPV status, with a Random Forest classifier achieving 83% accuracy at the cell level. This work supports the feasibility of deep learning-based HPV prediction from routine H&E slides, with potential clinical implications for streamlined, cost-effective diagnostics.

Background/Objectives: Oral cavity carcinomas (OCCs) represent roughly 50% of all head and neck cancers. The risk of occult neck metastases for early-stage OCCs ranges from 15 to 35%, thus the need to develop tools that can support the diagnosis detecting these neck metastases. Inflammatory biomarkers and perineural and lympho-vascular invasion are emerging as effective in this field. The aim of this study is to demonstrate the effectiveness of these parameters to detect occult neck metastases in early-stage (T1-T2/N0) OCCs. Methods: A retrospective analysis was conducted on 81 patients surgically treated for early-stage OCC. For all patients, data regarding TNM, pN status after the histopathological examination, inflammatory biomarkers, and perineural and lympho-vascular invasion have been obtained. A statistical analysis was performed using the receiver operating characteristic (ROC) curve to calculate the optimal cutoff values for SII, SIRI, PLR, and NLR. Results: Fifty-eight patients confirmed N0 status after surgery, while twenty-three resulted pN+. The best cut-off to detect occult neck metastases were PLR 249.30, NLR 13.10, MLR 0.439, SII 1043.12, and SIRI 1.85. The accuracy to detect occult neck metastases was PLR 75%, NLR 81%, MLR 74%, SII 73%, SIRI 70%, perineural invasion 70%, and lympho-vascular invasion 83%. Conclusions: Our results confirm that inflammatory biomarkers and perineural and lympho-vascular invasion are effective in detecting occult neck metastases in early-stage OCCs. The clinical relevance of this study is that these parameters could be used routinely as preoperative tools to support diagnosis and to help surgeons in the decision-making process, particularly regarding surgical indications for neck lymph nodes treatment.

Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine highly expressed by epithelial cells and several innate and adaptive immune cells. TSLP exerts its biological effects by binding to a heterodimeric complex composed of TSLP receptor (TSLPR) and IL-7Rα. In humans, there are two TSLP isoforms: the short form (sfTSLP), constitutively expressed, and the long form (lfTSLP), which is upregulated in inflammation. TSLP has been implicated in the induction and progression of several experimental and human cancers. Primary human lung macrophages (HLMs), monocyte-derived macrophages (MDMs), and peripheral blood monocytes consitutively expressed sfTSLP mRNA. Incubation of HLMs, MDMs, and monocytes with lipopolysaccharide (LPS) or IL-4, but not with IL-13, induced TSLP release from HLMs. LPS, but not IL-4 or IL-13, induced CXCL8 release from HLMs. LPS, IL-4 alone or in combination with IL-13, induced the expression of lfTSLP, but not of sfTSLP from HLMs. Preincubation of HLMs with IL-4, alone or in combination with IL-13, but not IL-13 alone, synergistically enhanced TSLP release from LPS-activated macrophages. By contrast, IL-4, alone or in combination with IL-13, inhibited LPS-induced CXCL8 release from HLMs. Immunoreactive TSLP was detected in lysates of HLMs, MDMs, and monocytes. Incubation of HLMs with TSLP induced the release of proinflammatory (TNF-α), angiogenic (VEGF-A, angiopoietin 2), and lymphangiogenic (VEGF-C) factors. TSLP, TSLPR, and IL-7Rα were expressed in intratumoral and peritumoral areas of human lung cancer. sfTSLP and lfTSLP mRNAs were differentially expressed in peritumoral and intratumoral lung cancer tissues. The TSLP system, expressed in HLMs, MDMs, and monocytes, could play a role in chronic inflammatory disorders including lung cancer.

Background Medullary thyroid carcinoma is a malignant uncommon and aggressive tumour of the parafollicular C cells. In about 75% of cases it is sporadic while, in case of RET mutation, it is associated to multiple endocrine neoplasia type 2 (25% of cases). The biochemical features of medullary thyroid carcinoma include the production of calcitonin and carcinoembryogenic antigen. The above-mentioned features are useful in the diagnostic process as well as in the follow up and in the prognostication of the disease. Even if calcitonin elevation is strongly associated to MTC, it can also be found increased in many pathological different conditions as pregnancy, lactation, C-cells hyperplasia, autoimmune thyroiditis, end stage renal disease, lung and prostate cancer and several neuroendocrine tumours. Major medullary thyroid tumours are usually connected to high doses of circulating calcitonin, in fact non-secretory variants have hardly been described. Case presentation We herein report the case of a 59 years old male, who had undergone total thyroidectomy for multinodular goiter with negative preoperative calcitonin, showing medullary thyroid carcinoma at definitive pathology. To the best of our knowledge, this is the first case documenting a non-secretory medullary thyroid carcinoma, with double negative markers at the time of diagnosis and at the relapse. Conclusion A Literature review underlining pathological hypothesis, differential diagnosis and alternative and innovative biomarkers to identify non-secretory medullary thyroid carcinoma was carried out.

Background: Despite advances in uveal melanoma (UM) diagnosis and treatment, about 50% of patients develop distant metastases, thereby displaying poor overall survival. Molecular profiling has identified several genetic alterations that can stratify patients with UM into different risk categories. However, these genetic alterations are currently dispersed over multiple studies and several methodologies, emphasizing the need for a defined workflow that will allow standardized and reproducible molecular analyses. Methods: Following the findings published by “The Cancer Genome Atlas–UM” (TCGA-UM) study, we developed an NGS-based gene panel (called the UMpanel) that classifies mutation sets in four categories: initiating alterations (CYSLTR2, GNA11, GNAQ and PLCB4), prognostic alterations (BAP1, EIF1AX, SF3B1 and SRSF2), emergent biomarkers (CDKN2A, CENPE, FOXO1, HIF1A, RPL5 and TP53) and chromosomal abnormalities (imbalances in chromosomes 1, 3 and 8). Results: Employing commercial gene panels, reference mutated DNAs and Sanger sequencing, we performed a comparative analysis and found that our methodological approach successfully predicted survival with great specificity and sensitivity compared to the TCGA-UM cohort that was used as a validation group. Conclusions: Our results demonstrate that a reproducible NGS-based workflow translates into a reliable tool for the clinical stratification of patients with UM.

Background: The COVID-19 outbreak had a massive impact on lung cancer patients with the rise in the incidence and mortality of lung cancer. Methods: We evaluated whether a recent COVID-19 infection affected the outcome of patients undergoing thoracoscopic lobectomy for lung cancer using a retrospective observational mono-centric study conducted between January 2020 and August 2022. Postoperative complications and 90-day mortality were reported. We compared lung cancer patients with a recent history of COVID-19 infection prior to thoracoscopic lobectomy to those without recent COVID-19 infection. Univariable and multivariable analyses were performed. Results: One hundred and fifty-three consecutive lung cancer patients were enrolled. Of these 30 (19%), had a history of recent COVID-19 infection prior to surgery. COVID-19 was not associated with a higher complication rate or 90-day mortality. Patients with recent COVID-19 infection had more frequent pleural adhesions (p = 0.006). There were no differences between groups regarding postoperative complications, conversion, drain removal time, total drainage output, and length of hospital stay. Conclusions: COVID-19 infection did not affect the outcomes of thoracoscopic lobectomy for lung cancer. The treatment of these patients should not be delayed in case of recent COVID-19 infection and should not differ from that of the general population.

Uveal melanoma (UM) is the most frequent primary ocular malignancy of adults; it exhibits an almost invariably poor prognosis with onset of liver metastases within 10–15 years after the diagnosis. Serine and arginine-rich splicing factor 1 (SRSF1) is an RNA-binding protein with proto-oncogene functions, including stimulation of angiogenesis, cell migration and cell growth; regarding the complex regulation of tumor angiogenesis, it has been suggested that SRSF1 regulates the alternative splicing of vascular endothelial growth factor-α, promoting the formation of its pro-angiogenic isoform. The immunohistochemical expression of SRSF1 on a series of 85 primary UMs, including 39 metastasizing and 46 non-metastasizing cases, was investigated; to clarify the potential pathogenetic role of SRSF1 in this tumor and its effect on angiogenesis, we correlated our immunohistochemical findings with the clinico-pathological features, the prognostic data and blood vascular microvessel density (MVD) findings of the cases from our series. Cases with higher immunohistochemical expression of SRSF1 also had higher MVD, higher metastatic potential and shorter metastasis-free survival; conversely, cases with lower SRSF1 immunoexpression showed lower MVD, lower metastatic risk and longer metastasis-free survival times. Our results suggested that SRSF1 has a negative prognostic role and a pro-angiogenic function in UM.

The postoperative follow-up strategies for breast carcinoma (BC) utilize different procedures; the aim of this study was to investigate the role of fine-needle cytology (FNC) in the follow-up of BC patients. Two hundred sixty-six FNC samples from 190 BC patients have been reviewed. The target anatomical sites were 190 breast including 155 ipsilateral and 145 contralateral breast lesions and 76 extra-mammary nodules. Extra-mammary lesions included lymph nodes, thyroidal nodules, soft tissue lesions, (subcutaneous and sub-scars), salivary glands and deep located masses. Diagnostic distribution of the breast lesions was as follows: 51 positive, 15 indeterminate/suspicious, 119 negative and 5 inadequate. Positive cases included 43 ipsilateral and 8 contralateral BC, 9 BC in different quadrants from those of onset of the first BC. Sensitivity, specificity and accuracy have been 90, 91 and 90&, respectively. FNC, in a correct setting, is a reliable and effective method for the follow-up management of BC patients.

Nel 2019 abbiamo ricoverato due pazienti non fumatrici con grave dispnea da invasione della via aerea principale da neoplasia del polmone. Le pazienti avevano 57 e 67 anni; entrambe presentavano stenosi critica infiltrante il bronco principale destro e in entrambi i casi, per la grave insufficienza respiratoria, è stata posta indicazione a disostruzione del bronco principale di destra stenotico con broncoscopio rigido e laser yttrium aluminium perovskite (YAP)-Nd in sala operatoria. Al termine dell’intervento di ricanalizzazione sono state posizionate nel Caso 1 una protesi tracheobronchiale a Y GSS-Y 40x30x30 mm di Novatech e nel Caso 2 una protesi autoespandibile in nitinolo SILMET® 14x40 mm di Novatech. Una volta stabilita la diagnosi istologica di adenocarcinoma EGFR mutato, è stato avviato il trattamento di prima linea con afatinib 40 mg die compresse.