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Simple Summary: Among the pleiotropic functions of vitamin D, its involvement as an anticancer synergistic compound has recently emerged. The active form of VD has been shown to induce cell cycle arrest, cell apoptosis, and autophagy, and to suppress angiogenesis and metastatic progression in the TME via various signal transduction pathways. Interest has focused on the ability of VD to enhance the antitumor activity of some cancer drugs, suggesting its potential role as a chemosensitizer in breast cancer therapy. From our meta-analysis, it emerged that adequate baseline VD levels are associated with a 22% reduction in the risk of a non-response to NACT and a 35% reduction in the risk of disease progression. These results suggest a new potential role of VD as prognostic biomarker of PFS and therapeutic response. Background: Breast cancer remains the leading cause of cancer-related deaths among women despite advances in early detection. Neoadjuvant chemotherapy (NACT) is now standard for early-stage BC, with vitamin D (VD) emerging as a potential prognostic biomarker considering its positive pleiotropic effects. This review and meta-analysis assess the impact of baseline VD levels on outcomes in BC patients undergoing NACT. Methods: Inclusion criteria required patients to be over 18 years of age, have a pathologically confirmed BC diagnosis, and have their VD levels assessed prior to chemotherapy. Studies were included if they reported odds ratios (ORs) for response and/or hazard ratios (HRs) for PFS with 95% confidence intervals (CIs). A comprehensive literature search of PubMed/MEDLINE and Scopus/ELSEVIER (2014–2024) was conducted, and data were analyzed using fixed- and random-effects models, with Forest plots illustrating the results. Study quality and potential biases were assessed using the MINORS, NOS, and RoB2 scales, and statistical heterogeneity was evaluated with I2 statistics and funnel plots. Results: Six studies were included in the analysis. All studies addressed stages II and III, with three also including stage I. The meta-analysis covered data from 722 patients regarding NACT response and 1033 patients for PFS. The results revealed a 22% reduction in the likelihood of non-response to NACT associated with adequate VD levels (low/deficient VD vs. high/sufficient VD; OR: 0.78; 95% CI: 0.30–1.25; p = 0.001) and a 35% reduction in progression risk with sufficient baseline VD levels (low/deficient VD vs. high/sufficient VD; HR: 0.65; 95% CI: 0.33–0.97; p < 0.001). Conclusions: These findings highlight the significance of maintaining adequate vitamin D levels in BC treatment and encourage further studies to unravel the role of VD on cancer biology. [ABSTRACT FROM AUTHOR]

Cancer patients, especially long cancer survivors, are exposed to several cardio-metabolic diseases, including diabetes, heart failure, and atherosclerosis, which increase their risk of cardiovascular mortality. Therapy with glucagon-like peptide 1 (GLP1) receptor agonists demonstrated several beneficial cardiovascular effects, including atherosclerosis and heart failure prevention. Cardiovascular outcome trials (CVOTs) suggest that GLP-1 RA could exert cardiorenal benefits and systemic anti-inflammatory effects in patients with type-2 diabetes through the activation of cAMP and PI3K/AkT pathways and the inhibition of NLRP-3 and MyD88. In this narrative review, we highlight the biochemical properties of GLP-1 RA through a deep analysis of the clinical and preclinical evidence of the primary prevention of cardiomyopathies. The overall picture of this review encourages the study of GLP-1 RA in cancer patients with type-2 diabetes, as a potential primary prevention strategy against heart failure and atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Improving prognosis of BC patients has drawn the attention of health care professionals on disease related long-term side effects and on the multiple treatments BC patients must undergo. Despite advances in procedures, surgery still has multiple detrimental effects, including pain, edema, and limited mobility. For this reason, fostering adapted physical activity (APA) and healthy lifestyle (including a balanced diet and weight management) should become an everyday purpose of healthcare professionals. Fencing may be a well-suited activity to counteract fatigue, pain, and limited arm mobility. Method and analysis: The FENICE study is a mono-center, randomized clinical trial targeting women with BC stages I-III within four weeks from BC surgery. Participants in the control arm will receive the usual recommendations based on the good clinical practice guidelines. In the study arm, participants will be treated with the usual clinical and therapeutic recommendations together with APA and correct lifestyle suggestions. Objective: The primary objective of the study is to compare whether implementation of APA and healthy lifestyle in BC patient after surgery will result in an overall improvement of physical and mental status. Conclusion: Fencing and its early application in postoperative period may represent a feasible strategy to be implemented in the rehabilitation journey of BC patients. Ethics and dissemination: The study protocol FENICE has been approved by an Italian Ethics Committee on May 2023 (R.S 100.23 5th May 2023). [ABSTRACT FROM AUTHOR]

Background: Despite achieving a sustained virological response (SVR) with direct-acting antivirals (DAAs), an unexpected increase in the occurrence rate of hepatocellular carcinoma (HCC) has been observed among HCV-treated patients. This study aims to assess the long-term follow-up of HCV patients treated with DAAs who achieved an SVR to investigate the potential for late-onset HCC. Methods: In this prospective multicenter study, we enrolled consecutive HCV patients treated with DAAs following Italian ministerial guidelines between 2015 and 2018. Exclusion criteria included active HCC on imaging, prior HCC treatment, HBV or HIV co-infection, or liver transplant recipients. Monthly follow-ups occurred during treatment, with subsequent assessments every 3 months for at least 48 months. Abdominal ultrasound (US) was performed within two weeks before starting antiviral therapy, supplemented by contrast-enhanced ultrasonography (CEUS), dynamic computed tomography (CT), or magnetic resonance imaging (MRI) to evaluate incidental liver lesions. Results: Of the 306 patients completing the 48-months follow-up post-treatment (median age 67 years, 55% male), all achieved an SVR. A sofosbuvir-based regimen was administered to 72.5% of patients, while 20% received ribavirin. During follow-up, late-onset HCC developed in 20 patients (cumulative incidence rate of 6.55%). The pattern of HCC occurrence varied (median diameter 24 mm). Multivariate and univariate analyses identified liver stiffness, diabetes, body mass index, and platelet levels before antiviral therapy as associated factors for late HCC occurrence. Conclusions: Our findings suggest that late HCC occurrence may persist despite achieving SVR. Therefore, comprehensive long-term follow-up, including clinical, laboratory, and expert ultrasonography evaluations, is crucial for all HCV patients treated with DAAs. [ABSTRACT FROM AUTHOR]

Cardiovascular disease and cancer are the two leading causes of morbidity and mortality in the world. The emerging field of cardio-oncology described several shared risk factors that predispose patients to both cardiovascular disease and cancer. Post-acute COVID-19 syndrome is a chronic condition that occurs in many patients who have experienced a SARS-CoV-2 infection, mainly based on chronic fatigue, sedentary lifestyle, cramps, breathing difficulties, and reduced lung performance. Post-acute COVID-19 exposes patients to increased visceral adiposity, insulin resistance, myosteatosis, and white adipose tissue content (surrounded by M1 macrophages and characterized by a Th1/Th17 phenotype), which increases the risk of cardiovascular mortality and cancer recurrence. In this review, the main metabolic affections of post-acute COVID-19 syndrome in cancer patients at low and high risk of cardiomyopathies will be summarized. Furthermore, several non-pharmacological strategies aimed at reducing atherosclerotic and cardiac risk will be provided, especially through anti-inflammatory nutrition with a low insulin and glycemic index, appropriate physical activity, and immune-modulating bioactivities able to reduce visceral obesity and myosteatosis, improving insulin-related signaling and myocardial metabolism. [ABSTRACT FROM AUTHOR]

Background: The SOUND study demonstrated that an axillary de-escalation may be sufficient in locoregional and distant disease control in selected early breast cancer (EBC) patients. To establish any preoperative variables that may drive sentinel lymph node biopsy (SLNB) omission, a study named sentinel omission risk factor (SOFT) 1.23 was planned. Methods: A single-center retrospective study from a prospectively maintained database was designed, aiming at underlying preoperative prognostic factors involved in sentinel lymph node (SLN) metastasis (lymph node involvement (LN+) vs. negative lymph node (LN−) group). Secondary outcomes included surgical room occupancy analysis for SLNB in patients fulfilling the SOUND study inclusion criteria. The institutional ethical committee Area Territoriale Lazio 2 approved the study (n° 122/23). Results: Between 1 January 2022 and 30 June 2023, 160 patients were included in the study and 26 (%) were included in the LN+ group. Multifocality, higher cT stage, and larger tumor diameter were reported in the LN+ group (p = 0.020, p = 0.014, and 0.016, respectively). Tumor biology, including estrogen and progesterone receptors, and molecular subtypes showed association with the LN+ group (p < 0.001; p = 0.001; and p = 0.001, respectively). A total of 117 (73.6%) patients were eligible for the SOUND study and the potential operating room time saved was 2696.81 min. Conclusions: De-escalating strategies may rationalize healthcare activities. Multifactorial risk stratification may further refine the selection of patients who could benefit from SLNB omission. [ABSTRACT FROM AUTHOR]

Background: Hormone receptor-positive tumors are unlikely to exhibit a complete pathological tumor response. The association of CDK 4/6 inhibitor plus hormone therapy has changed this perspective. Case presentation: In this study, we retrospectively reviewed the charts of patients with a diagnosis of luminal A/B advanced/metastatic tumors treated with a CDK 4/6 inhibitor-based therapy. In this part of the study, we present clinical and ultrasound evaluation. Eight female patients were considered eligible for the study aims. Three complete and five partial responses were reported, including a clinical tumor response of 50% or more in five out of nine assessed lesions (55%). All patients showed a response on ultrasound. The mean lesion size measured by ultrasound was 27.1 ± 15.02 mm (range, 6-47 mm) at the baseline; 16.08 ± 14.6 mm (range, 0-40 mm) after 4 months (T1); and 11.7 ± 12.9 mm (range, 0-30 mm) at the 6 months follow-up (T2). Two patients underwent surgery. The radiological complete response found confirmation in a pathological complete response, while the partial response matched a moderate residual disease. Conclusion: The evaluation of breast cancer by ultrasound is basically informative of response and may be an easy and practical tool to monitor advanced tumors, especially in advanced/unfit patients who are reluctant to invasive exams. [ABSTRACT FROM AUTHOR]

Simple Summary: Anthracycline-induced cardiomyopathies and sarcopenia are often seen in cancer patients, affecting their quality of life and overall survival. Translational research aimed to find new cardioprotective strategies is strictly needed in cardioncology. Soluble guanylate cyclase activator vericiguat reduces heart failure rates in patients with reduced ejection fraction. In this study, we highlighted the cardioprotective and anti-inflammatory properties of vericiguat during exposure to anthracyclines and demonstrated its preventive properties of sarcopenia induced by doxorubicin (DOXO), which can be exploited for potential cardioprotective strategies in cancer patients. Furthermore, vericiguat reduces chemokines and cytokines involved in cardiomyopathies through NLR family pyrin domain containing 3 (NLRP-3) pathways in human cardiomyocytes and skeletal muscle cells. The findings that emerged from this study could provide the rationale for further preclinical and clinical investigations aimed at reducing anthracycline cardiotoxicity and sarcopenia in cancer patients. Anthracycline-induced cardiomyopathies and sarcopenia are frequently seen in cancer patients, affecting their overall survival and quality of life; therefore, new cardioprotective and anti-sarcopenic strategies are needed. Vericiguat is a new oral guanylate cyclase activator that reduces heart failure hospitalizations or cardiovascular death. This study highlighted the potential cardioprotective and anti-sarcopenic properties of vericiguat during anthracycline therapy. Human cardiomyocytes and primary skeletal muscle cells were exposed to doxorubicin (DOXO) with or without a pre-treatment with vericiguat. Mitochondrial cell viability, LDH, and Cytochrome C release were performed to study cytoprotective properties. Intracellular Ca++ content, TUNEL assay, cGMP, NLRP-3, Myd-88, and cytokine intracellular levels were quantified through colorimetric and selective ELISA methods. Vericiguat exerts significant cytoprotective and anti-apoptotic effects during exposure to doxorubicin. A drastic increase in cGMP expression and reduction in NLRP-3, MyD-88 levels were also seen in Vericiguat-DOXO groups vs. DOXO groups (p < 0.001) in both cardiomyocytes and human muscle cells. GCa vericiguat reduces cytokines and chemokines involved in heart failure and sarcopenia. The findings that emerged from this study could provide the rationale for further preclinical and clinical investigations aimed at reducing anthracycline cardiotoxicity and sarcopenia in cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Ductal carcinoma in situ is a malignant cell proliferation confined to basement membrane. Current consensus guidelines recommend an optimal margin width of 2 mm and re-excision for closer margin is debated and it is sent back to clinical judgment. Our retrospective study evaluating 197 patients aim to investigate the importance of surgical margin and locoregional recurrence in patients with diagnosis of DCIS and treated with conservative breast surgery. We found no correlation between margins and loco-regional recurrence, and re-excision should be avoided in patients with focally positive margin and no evidence of the disease at post-surgical imaging. The current surgical guidelines recommend an optimal margin width of 2 mm for the management of patients diagnosed with ductal carcinoma in situ (DCIS). However, there are still many controversies regarding re-excision when the optimal margin criteria are not met in the first resection. The purpose of this study is to understand the importance of surgical margin width, re-excision, and treatments to avoid additional surgery on locoregional recurrence (LRR). The study is retrospective and analyzed surgical margins, adjuvant treatments, re-excision, and LRR in patients with DCIS who underwent breast-conserving surgery (BCS). A total of 197 patients were enrolled. Re-operation for a close margin rate was 13.5%, and the 3-year recurrence was 7.6%. No difference in the LRR was reported among the patients subjected to BCS regardless of the margin width (p = 0.295). The recurrence rate according to margin status was not significant (p = 0.484). Approximately 36.9% (n: 79) patients had resection margins < 2 mm. A sub-analysis of patients with margins < 2 mm showed no difference in the recurrence between the patients treated with a second surgery and those treated with radiation (p = 0.091). The recurrence rate according to margin status in patients with margins < 2 mm was not significant (p = 0.161). The margin was not a predictive factor of LRR p = 0.999. Surgical re-excision should be avoided in patients with a focally positive margin and no evidence of the disease at post-surgical imaging. [ABSTRACT FROM AUTHOR]

Simple Summary: Vascular Endothelial Growth Factor inhibitors (VEGFi), commonly employed for diverse medical conditions such as advanced neoplasms and ocular diseases, pose potential adverse effects. This review delineates the principal VEGFi utilized in clinical practice and investigates the causes, recognition, management, and prevention of VEGFi toxicities. Its aim is to assist oncologists in both clinical practice and the design of clinical trials. The use of Vascular Endothelial Growth Factor inhibitors (VEGFi) has become prevalent in the field of medicine, given the high incidence of various pathological conditions necessitating VEGF inhibition within the general population. These conditions encompass a range of advanced neoplasms, such as colorectal cancer, non-small cell lung cancer, renal cancer, ovarian cancer, and others, along with ocular diseases. The utilization of VEGFi is not without potential risks and adverse effects, requiring healthcare providers to be well-prepared for identification and management. VEGFi can be broadly categorized into two groups: antibodies or chimeric proteins that specifically target VEGF (bevacizumab, ramucirumab, aflibercept, ranibizumab, and brolucizumab) and non-selective and selective small molecules (sunitinib, sorafenib, cabozantinib, lenvatinib, regorafenib, etc.) designed to impede intracellular signaling of the VEGF receptor (RTKi, receptor tyrosine kinase inhibitors). The presentation and mechanisms of adverse effects resulting from VEGFi depend primarily on this distinction and the route of drug administration (systemic or intra-vitreal). This review provides a thorough examination of the causes, recognition, management, and preventive strategies for VEGFi toxicities with the goal of offering support to oncologists in both clinical practice and the design of clinical trials. [ABSTRACT FROM AUTHOR]

Background: Resection of additional tissue circumferentially around the cavity left by lumpectomy (cavity shave) was suggested to reduce rates of positive margins and re-excision. Methods: A single center retrospective study which analyzed margins status, re-excision, and surgical time in patients who underwent breast conserving surgery and cavity shave or intraoperative evaluation of resection margins. Results: Between 2021 and 2023, 594 patients were enrolled in the study. In patients subjected to cavity shave, a significant reduction in positive, focally positive, or closer margins was reported 8.9% vs. 18.5% (p = 0.003). No difference was reported in terms of surgical re-excision (p < 0.846) (5% vs. 5.5%). Surgical time was lower in patients subjected to cavity shave (<0.001). The multivariate analysis intraoperative evaluation of sentinel lymph node OR 1.816 and cavity shave OR 2.909 were predictive factors for a shorter surgical time. Excluding patients subjected to intraoperative evaluation of sentinel lymph node and patients with ductal carcinoma in situ, patients that underwent the cavity shave presented a reduced surgical time (67.9 + 3.8 min vs. 81.6 + 2.8 min) (p = 0.006). Conclusions: Cavity shaving after lumpectomy reduced the rate of positive margins and it was associated with a significant reduction in surgical time compared to intraoperative evaluation of resection margins. [ABSTRACT FROM AUTHOR]

Oligo-metastatic disease (OMD) in the field of oncology denotes a distinct subset of metastatic tumors characterized by less aggressive biological behavior and extended survival times in comparison to their widely metastatic counterparts. While there is a general consensus regarding the existence of OMD, there remains a lack of widely accepted criteria for its a priori identification at the time of presentation. This review delves into the concept of OMD, placing a particular emphasis on the significance of understanding the limitations and potential of genetic assessments. It explores how these aspects are crucial in advancing our comprehension of this phenomenon. In a rapidly advancing era of precision medicine, understanding the intricacies of OMD opens up exciting possibilities for tailored treatment approaches. By elucidating the genetic underpinnings and dynamic nature of this condition, we stand to improve patient outcomes and potentially shift the paradigm of metastatic cancer management. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is a complex illness marked by aberrant cellular behaviors and genetic variances, resulting in tumor heterogeneity that presents challenges in cancer prognosis and treatment. This review underscores the significance of comprehending tumor heterogeneity, offering perspectives on its attributes and the intricacies involved in its quantification. By emphasizing the need for effective therapies targeting tumor heterogeneity, this work contributes to raising awareness about this elusive characteristic of cancer. Cancer manifests as a multifaceted disease, characterized by aberrant cellular proliferation, survival, migration, and invasion. Tumors exhibit variances across diverse dimensions, encompassing genetic, epigenetic, and transcriptional realms. This heterogeneity poses significant challenges in prognosis and treatment, affording tumors advantages through an increased propensity to accumulate mutations linked to immune system evasion and drug resistance. In this review, we offer insights into tumor heterogeneity as a crucial characteristic of cancer, exploring the difficulties associated with measuring and quantifying such heterogeneity from clinical and biological perspectives. By emphasizing the critical nature of understanding tumor heterogeneity, this work contributes to raising awareness about the importance of developing effective cancer therapies that target this distinct and elusive trait of cancer. [ABSTRACT FROM AUTHOR]

Background: The management of cytological samples can significantly impact diagnostic interpretation. Cell blocks (CB) are a popular method due to their ability to provide additional morphological information and be used for immunocytochemistry and molecular tests. Recently, a new CB technique called the synthetic matrix CytoMatrix (CM) has been introduced, which can gather and hold cytological material within its three‐dimensional structure. Methods: In this study, 40 cytological samples from patients with melanoma metastases were analyzed to evaluate the diagnostic performance of CM compared to another CB method used in the laboratory. The researchers assessed the morphological adequacy of the two techniques, as well as their performance in immunocytochemical analysis and molecular. Results: This study showed that CM was quicker and equally effective compared to the other method, with the laboratory technician having less of an impact on the CM approach across all passages. Additionally, all CMs were adequate, whereas the other method was adequate in 90% of cases. Immunocytochemistry confirmed the diagnosis of melanoma metastases in all cases, and all 40 CMs and 36 of the other method were adequate for fluorescence in situ hybridization analysis. Conclusion: CM is a low‐time‐consuming technology that is unaffected by technicians during all setup phases, making it simpler to standardize the procedure. Moreover, a low loss of diagnostic cells ensures greater benefits for morphological analysis, immunocytochemistry, and molecular testing. Overall, the study highlights the potential of CM as a valuable technique for managing cytological samples. CytoMatrix is a low time‐consuming technique, not subject to the intervention of the technical operator in the various stages of setup, which allows a standardization of the cytological samples process. [ABSTRACT FROM AUTHOR]

In cases of cellular injury, there is an observed increase in the production of reactive oxygen species (ROS). When this production becomes excessive, it can result in various conditions, including cancerogenesis. Glutathione (GSH), the most abundant thiol-containing antioxidant, is fundamental to re-establishing redox homeostasis. In order to evaluate the role of GSH and its antioxi-dant effects in patients affected by cancer, we performed a thorough search on Medline and EMBASE databases for relevant clinical and/or preclinical studies, with particular regard to diet, toxicities, and pharmacological processes. The conjugation of GSH with xenobiotics, including anti-cancer drugs, can result in either of two effects: xenobiotics may lose their harmful effects, or GSH conjugation may enhance their toxicity by inducing bioactivation. While being an interesting weapon against chemotherapy-induced toxicities, GSH may also have a potential protective role for cancer cells. New studies are necessary to better explain the relationship between GSH and cancer. Although self-prescribed glutathione (GSH) implementation is prevalent among cancer patients with the intention of reducing the toxic effects of anticancer treatments and potentially preventing damage to normal tissues, this belief lacks substantial scientific evidence for its efficacy in reducing toxicity, except in the case of cisplatin-related neurotoxicity. Therefore, the use of GSH should only be considered under medical supervision, taking into account the appropriate timing and setting. [ABSTRACT FROM AUTHOR]

Transient elastography by FibroScan® (Echosens, Paris, France) is a non-invasive method that can provide a reliable measurement of liver fibrosis through the evaluation of liver stiffness. Despite its limitations and risks, liver biopsy has thus far been the only procedure able to provide data to quantify fibrosis. Scientific evidence and clinical practice have made it possible to use FibroScan® in the diagnostic work-up of several liver diseases to monitor patients' long-term treatment response and for complication prevention. For these reasons, this procedure is widely used in clinical practice and is still being investigated for further applications. The aim of this narrative review is to provide a comprehensive overview of the main applications of transient elastography in the current clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: In this review, we aim to clarify the prognostic significance of the KRAS p.G12C mutation in metastatic colorectal cancer, emphasizing its potential as a promising therapeutic target. Moreover, our objective is to increase readers' awareness of the factors that can influence diverse clinical, prognostic and therapeutic implications associated with distinct mutations within the same protein. KRAS is frequently mutated in tumors. It is mutated in approximately 30% of all cancer cases and in nearly 50% of cases of metastatic colorectal cancer (CRC), which is the third leading cause of cancer-related deaths worldwide. Recent advancements in understanding CRC biology and genetics have highlighted the significance of KRAS mutations in the progression of CRC. The KRAS gene encodes a small GTPase (Guanosine TriPhosphatases) that plays a key role in signaling pathways associated with important proteins involved in amplifying growth factor and receptor signals. Mutations in KRAS are frequently observed in codons 12 and 13, and these mutations have oncogenic properties. Abnormal activation of KRAS proteins strongly stimulates signals associated with various cancer-related processes in CRC, including cell proliferation, migration and neoangiogenesis. In this review, we explore the distinct prognostic implications of KRAS mutations. Specifically, the KRAS p.G12C mutation is associated with a worse prognosis in metastatic CRC. The correlation between structure, conformation and mutations is visually presented to emphasize how alterations in individual amino acids at the same position in a single protein can unexpectedly exhibit complex involvement in cancer. Last, KRAS p.G12C is discussed as an emerging and promising therapeutic target in metastatic CRC, providing a concise overview of available clinical data regarding the use of new inhibitors. [ABSTRACT FROM AUTHOR]

Most primary cutaneous lymphomas consist of T-cell lymphomas or small cell lymphomas; however, the skin may also be affected by lymphomas with large cell morphology, as a primary or secondary localization. A minority of cases consist of primary cutaneous B-cell lymphomas (PCBCLs). PCBCLs are a heterogeneous group of rare neoplasms with an overlapping morphological and immunohistochemical picture of the different subtypes. Nevertheless, differential diagnosis in the setting of this group of neoplasms is mandatory to identify the correct therapy and prognosis, but it may be challenging since, due to the rarity of these neoplasms, they may not always be familiar to pathologists. Indeed, immunohistochemistry may not be enough to distinguish the different histotypes, which overlap in immunohistochemical features. Furthermore, the ever-increasing knowledge of the molecular features of systemic B-cell lymphomas, such as gene rearrangements with clinical significance, has led in recent years to further investigation into the molecular landscape of PCBCLs with large cell morphology. This work aimed to provide a practical diagnostic guide for pathologists dealing with primary cutaneous large B-cell lymphomas. [ABSTRACT FROM AUTHOR]

Simple Summary: Atherosclerosis is a critical cardiovascular disease associated with the use of immune checkpoint inhibitors (ICIs). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key orchestrator of atherosclerotic process and it is also involved in cancer progression and immune-resistance. In this context, data from recent meta-analysis and cardiovascular outcome trials associate PCSK9 levels to reduced ICIs-related cancer responsiveness and to high risk of atherosclerotic cardiovascular diseases. This review summarizes the pleiotropic effects of PCSK9 in heart failure, atherosclerosis, and cancer immune recognition, and outlines its ability to represent a new pharmacological target in patients who develop ICIs-related atherosclerosis to reduce cardiovascular mortality and to improve overall survival. Cancer patients treated with immune checkpoint inhibitors (ICIs) are exposed to a high risk of atherosclerosis and cardiometabolic diseases due to systemic inflammatory conditions and immune-related atheroma destabilization. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key protein involved in metabolism of low-density lipoprotein (LDL) cholesterol. PCSK9 blocking agents are clinically available and involve monoclonal antibodies, and SiRNA reduces LDL levels in high-risk patients and atherosclerotic cardiovascular disease events in multiple patient cohorts. Moreover, PCSK9 induces peripheral immune tolerance (inhibition of cancer cell- immune recognition), reduces cardiac mitochondrial metabolism, and enhances cancer cell survival. The present review summarizes the potential benefits of PCSK9 inhibition through selective blocking antibodies and siRNA in patients with cancer, especially in those treated with ICIs therapies, in order to reduce atherosclerotic cardiovascular events and potentially improve ICIs-related anticancer functions. [ABSTRACT FROM AUTHOR]