Search Results (116)

Background: Neuroendocrine neoplasms (NENs) represent a heterogeneous group of malignancies arising from neuroendocrine cells and are most commonly localized in the gastroenteropancreatic and pulmonary systems. Overall, most NENs are characterized by a low mutational burden. Consequently, increasing research attention has focused on epigenetic mechanisms and the tumor microenvironment, which may actively contribute to tumor pathogenesis. Moreover, epigenetic modifications represent plausible mediators of communication in the crosstalk between neuroendocrine cancer cells and components of the tumor microenvironment, as observed in other non-neuroendocrine malignancies. Objectives: The aim of this review is to summarize current knowledge on the role of epigenetic regulation and the tumor microenvironment in the pathogenesis of neuroendocrine tumors and to discuss their potential as targets for more effective therapeutic strategies. Methods: We reviewed research articles published over the past decades that investigated the involvement of epigenetic mechanisms and the tumor microenvironment in NENs. Results: Several studies highlight the pivotal role of epigenetic alterations and tumor microenvironment interactions in NEN biology, influencing tumor development, progression, and therapeutic response. Conclusions: Further studies are warranted to deepen understanding in this field, as this may lead to the development of more effective therapies and improved clinical outcomes for patients with neuroendocrine neoplasms. Full article

Mammary gland tumors (MGT) are the most common neoplasms in intact female dogs and represent the third most frequent tumor type in female cats. Imaging plays a central role in the diagnosis, staging, and follow-up of these neoplasms. This review summarizes the diagnostic imaging features of canine and feline MGT and the advantages and limitations of each modality. Radiography and computed tomography (CT) are mainly used to detect pulmonary and abdominal metastases, while ultrasonography provides key information about primary tumor size, margins, echogenicity, vascularization, and elasticity. Advanced ultrasound techniques, such as Doppler, contrast-enhanced ultrasonography (CEUS), and elastography, improve differentiation between benign and malignant lesions. Magnetic resonance imaging (MRI) offers excellent soft-tissue detail and can assist in preoperative planning, whereas nuclear medicine techniques, including scintigraphy and positron emission tomography (PET), allow functional assessment and the early detection of micrometastases. Although histopathology remains the diagnostic gold standard, imaging is indispensable for characterizing primary lesions, evaluating metastatic spread, guiding sampling, and monitoring therapeutic outcomes in small animal oncology. By integrating and comparing the main imaging modalities applied to canine and feline mammary tumors, this review underscores their complementary roles in improving diagnosis, staging, and therapeutic decision-making in small animal oncology. Full article

Background: The prevalence and the prognostic impact of chronic obstructive pulmonary disease (COPD) and asthma in patients with myeloproliferative neoplasms (MPNs) are unknown. Methods: This retrospective multicenter cohort analyzed the prevalence and prognostic implications of COPD and asthma in 246 patients with essential thrombocythemia (ET) and polycythemia vera (PV). Results: A total of 6.5% and 1.6% patients had COPD or asthma, respectively, without statistically significant differences with respect to disease phenotype. The presence of COPD/asthma was more frequently associated with active/prior smoking (p = 0.021) and constitutional symptoms (p = 0.001). After the median follow-up of 47.5 months, the presence of COPD/asthma was univariately associated with an inferior time to thrombosis (TTT; median 135 vs. 190 months, 95% confidence interval (CI) 1.8–29.5, hazard ratio-HR 7.75, p = 0.005), mainly driven by venous (HR 37.3, 95% CI 3.2–43.6, p = 0.003) and not arterial events (HR 1.77, 95% CI 0.40–7.78, p = 0.445, p = 0.445). Statistically significant interactions existed between COPD/asthma, female sex (HR 3.94, 95% CI 1.01–11.02), ET phenotype (HR 7.1, 95% CI 15.3–16.7), JAK2 positive status (HR 4.17, 95% CI 1.04–6.9), hydroxyurea use (HR 4.67, 95% CI 1.10–7.43), and the presence of other cardiovascular risk factors (HR 8.1, 95% CI 1.55–10.72) with overall thrombotic risk (interaction p < 0.050 for all analyses). Finally, the negative effect of COPD/asthma on TTT persisted in the multivariate analysis (HR 6.54, p = 0.010) independently of older (>60 years) age (p = 0.030) when being adjusted for other clinically meaningful variables. There was no effect of COPD/asthma on overall survival. Conclusions: These results provide an important signal regarding the potentially inferior outcomes in ET/PV patients presenting with these common respiratory disorders and may help to further personalize MPN management. Full article

Background and Clinical Significance: Endobronchial leiomyoma is a rare benign tumor of the respiratory tract, accounting for less than 2% of all benign pulmonary neoplasms. Most cases have been treated surgically or with endoscopic modalities such as laser or rigid bronchoscopy-assisted cryotherapy. Flexible bronchoscopic cryoextraction has been rarely reported, typically with 2.2-mm probes. Small-caliber cryoprobes (1.1- and 1.7-mm) have been validated for diagnostic transbronchial cryobiopsy but not for therapeutic removal of leiomyoma. We report a case of complete removal of endobronchial leiomyoma using a 1.7-mm cryoprobe via flexible bronchoscopy, demonstrating full airway and physiologic recovery. Case Presentation: A 25-year-old never-smoking man was referred after an abnormal health-screening chest radiograph demonstrated right middle and lower lobe atelectasis. Chest CT revealed a mass obstructing the proximal bronchus intermedius. Spirometry showed reduced FEV₁ and FVC with preserved FEV₁/FVC ratio, consistent with central airway obstruction. Therapeutic flexible bronchoscopy (Olympus BF-1TQ290) was performed under endotracheal intubation. Initial forceps biopsies were followed by transbronchial cryobiopsy with a 1.7-mm cryoprobe, applied for five freeze–adhesion cycles. The mass detached en bloc and was retrieved without complications, resulting in complete airway recanalization and visualization of the right middle and lower lobe bronchi. Histopathology showed interlacing fascicles of bland spindle cells with cigar-shaped nuclei, positive for SMA and desmin and negative for S-100 and CD34, confirming leiomyoma. The patient was discharged the next day. At one-year follow-up, bronchoscopy and CT demonstrated no recurrence, and spirometry normalized. Conclusions: Reports combining flexible bronchoscopy with a 1.7-mm small-caliber cryoprobe for en bloc removal of endobronchial leiomyoma are rare. This technique may represent a minimally invasive option for selected cases, provided careful hemostatic planning and appropriate case selection. Full article

Canine prostatic carcinoma is a highly aggressive neoplasm with a strong tendency to metastasize, most commonly to regional lymph nodes, lungs, and bones. However, skeletal muscle and myocardial involvement are rarely reported. This report describes an 11-year-old intact male Maltese dog with a two-month history of anorexia and lethargy, referred for further evaluation after failing to respond to piroxicam therapy. Diagnostic imaging revealed a prostatic mass and multiple rim-enhancing lesions in the epaxial musculature and left ventricular wall, without evidence of metastasis to the lymph nodes, lungs, or other visceral organs. Hemostatic analysis indicated a hypercoagulable state. Postmortem examination confirmed metastatic prostatic carcinoma involving the semispinalis, multifidus, and myocardium. Histologically, the neoplastic cells exhibited similar morphology at the primary and metastatic sites. Immunohistochemistry revealed strong cytokeratin expression and absence of uroplakin III, consistent with a non-urothelial epithelial origin. No evidence of lymphatic involvement was observed. To the best of our knowledge, this is the first documented case of canine prostatic carcinoma with exclusive myotropic and myocardial metastases. These findings suggest a possible hematogenous metastatic route and highlight the importance of including muscle and cardiac tissues in staging protocols for canine prostatic carcinoma, even when lymphadenopathy or pulmonary lesions are absent. Full article

Pulmonary neuroendocrine tumors (PULMONARY NETs) are heterogeneous tumors ranging from well-differentiated to highly aggressive neoplasms. The aim of this study is to prospectively test pre-operative circulating free DNA (cfDNA) in PULMONARY NET patients undergoing surgery and evaluate its relationship to clinicopathological features. From February to December 2024, 136 patients with suspected primary lung cancer underwent pre-operative blood sampling, of whom 21 were diagnosed with PULMONARY NETs. Total cell-free nucleic acid extraction was performed using the Genexus Purification System (Thermofisher). cfDNA was quantified using a fluorometric assay with the Qubit dsDNA HS Assay kit (Thermofisher) and a capillary electrophoresis-based assay (cell-free DNA ScreenTape kit) on the Tape Station 4200 systems (Agilent). A cfDNA quality assessment was also obtained (cfDNA sizing and % cfDNA). Most patients had Stage I (18/21.85.7%) typical carcinoids (16/21.76.2%). Nodal involvement was detected in one patient (0.5%). Six months after surgery, all patients were alive without recurrence. Larger tumors presented higher levels of cfDNA. The mean tumor size in patients with cfDNA > 40 ng was 266 mm (±16.7 mm), compared to 13.2 mm (±7.3 mm) for cfDNA < 40 ng (p-value = 0.018). Higher levels of cfDNA were observed in patients with pStages greater than IA (p-value = 0.007). Although limited by a small sample group and biases of a surgical series, we observed that larger/advanced PULMONARY NETs presented higher cfDNA levels pre-operatively. Full article

Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring lung neoplasia in sheep caused by jaagsiekte sheep retrovirus (JSRV). JSRV infects alveolar type II pneumocytes (ATII) and club cells (CC), and the expression of viral oncoproteins induces a lung adenocarcinoma. The gross pathology of OPA exhibits differences in the anatomical patterns known as classical and atypical forms. Thirty natural OPA tumors, divided equally into early OPA tumors (Group A, GA), atypical tumors (Group B, GB), and classical tumors (Group C, GC), were obtained from adult sheep (2–9 years old). Tumor heterogeneity was studied comparing the histopathology (growth patterns, local invasion, mitotic figures, myxoid nodules), together with immunohistochemistry (IHC) using markers of JSRV-ENV, epithelial cells (ATII cells, CC, ki67), progenitor-stem epithelial cells (K5, p63, CD44), and the anterior grade protein 2 (AGR2). Papillary pattern was predominant in all groups. Lepidic pattern was also relevant in GA, and acinar pattern was relevant in GB. Low proliferation indexes and local invasion were observed in all groups. Myxoid nodules were few. IHC showed that all samples were positive for JSRV-ENV. Cell markers demonstrated that GA was different when compared to GB and GC, showing significantly the highest levels of CC, K5, and p63 positive tumor cells. There were no significant differences between GB and GC. The heterogeneity analysis of OPA tumors revealed that in early tumors, repair is important but is not reflected in classical or atypical different anatomical OPA forms. Full article

Fibrotic diseases contribute to nearly half of all deaths in industrialized countries, yet effective early detection strategies remain lacking, particularly in low-resource settings. This study aimed to quantify the global burden of fibrosis-related diseases using updated global burden of disease (GBD) 2021 data across 204 countries and territories and establish a cost-effective diagnostic approach targeting vestigial-like family member 3 (VGLL3), a fibrosis-associated transcriptional co-regulator. Our analysis revealed that from 1990 to 2021, fibrosis-related disability-adjusted life years (DALYs) and mortality increased by 16.71% and 4.83%, respectively, with neoplasms and chronic obstructive pulmonary disease (COPD) being the main contributors. We also found a growing burden disproportionately concentrated in low socio-demographic index (SDI) regions. To address the diagnostic gap, we developed a novel immunoassay targeting VGLL3, an intrinsically disordered transcriptional co-regulator implicated in early fibrotic remodeling. The assay demonstrated a detection range of 27.01–2512.36 nM and a limit of detection of 12.55 nM. Immunohistochemical validation in a mouse myocardial infarction model confirmed the antibody’s specificity in fibrotic tissues. This work highlights widening global health disparities in fibrosis burden and introduces a cost-effective, scalable diagnostic strategy for early fibrosis detection, particularly suitable for resource-limited settings. Full article

Pulmonary carcinoids (PCs) are rare neoplasms involving typical and atypical carcinoids (TCs and ACs), defined histologically by absent or focal necrosis and mitotic counts (<2/mm² vs. 2–10/mm²), respectively. Although uncommon overall, TCs and ACs represent the most frequent non-hematologic malignancies in the pediatric population. However, significantly less is known about PC in AYAs, a population often overlooked or analyzed within pediatric or adult cohorts. In this critical review, we analyzed existing literature on PCs in the AYA population using a question-and-answer format, emphasizing the substantial gap in current knowledge in this field and the urgent unmet clinical need for future scientific proposals. First, we analyzed epidemiology and the data availability about the association between PCs in AYA patients and genetic syndromes that typically reach the maximal diagnostic incidence within this age group. We then reviewed the available literature about the pathologic characteristics, clinical presentation, and treatment strategies for localized and metastatic disease in PC AYA patients. According to our findings, a significant lack of age-specific evidence and the need for international collaboration and prospective, AYA-focused clinical studies were underscored. Advancing research in this area is essential to improve understanding and develop tailored, evidence-based therapeutic approaches for this peculiar population. Full article

Background: Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent worldwide due to ageing and comorbidities. Emerging evidence suggests that Philadelphia-negative chronic myeloproliferative neoplasms (MPNs), particularly those with JAK2 mutations, may contribute to the development of HFpEF, especially by promoting inflammation and increasing thrombotic risk. Methods: This prospective case–control study assessed 58 patients with Philadelphia-negative MPNs and 41 controls, by clinical, paraclinical, and echocardiographic evaluation, to diagnose diastolic dysfunction and HFpEF according to the ESC guideline criteria. Results: Patients with MPNs had a significantly higher prevalence of HFpEF compared to controls (p = 0.008), higher H₂FPEF scores (median 5 vs. 3, p < 0.001), and significant echocardiographic abnormalities, including a higher left ventricular mass index (LVMI) (100.1 vs. 76.6 g/m², p < 0.001), E/e’ (11.00 vs. 7.00, p < 0.001), and pulmonary artery systolic pressure (PASP) (26.0 vs. 7.42 mmHg, p < 0.001). Multivariable logistic regression models identified male sex (OR = 8.993, p = 0.001) and the presence of JAK2 mutation (OR = 5.021, p = 0.002) as independent risk factors for HFpEF in this population. Conclusions: Patients with chronic MPNs, particularly males and those with JAK2 mutations, are at an increased risk of HFpEF, highlighting the importance of routine cardiologic assessment to improve outcomes in this patient population. Full article

Neuroendocrine neoplasms (NENs) of the lung are a biologically and clinically diverse group of tumors that includes well-differentiated typical and atypical carcinoids (LNETs), as well as poorly differentiated large-cell neuroendocrine carcinoma and small-cell lung cancer. Despite their relative rarity, the incidence of LNETs is increasing, primarily due to advancements in diagnostic techniques and heightened clinical awareness. While the current World Health Organization (WHO) classification offers a morphological basis for diagnosis and prognosis, particularly for extrapulmonary neuroendocrine neoplasms (ep-NENs), it has limitations in predicting the clinical behavior of pulmonary carcinoids. Recent evidence highlights the inadequacy of traditional criteria in fully capturing the biological complexity and clinical heterogeneity of these tumors. This review explores the evolving landscape of LNETs, focusing on well-differentiated forms and analyzing current classification systems, clinicopathological features, and the emerging role of novel prognostic and predictive biomarkers. Advances in histopathology and molecular profiling have begun to elucidate distinct molecular subsets within carcinoids, offering potential avenues for improved risk stratification and therapeutic decision-making. Although there are limited treatment options for advanced disease, new insights into tumor biology could facilitate the development of personalized therapeutic strategies and pave the way for future innovations in LNET management. Full article

Background/Objectives: Pulmonary typical carcinoid (TC) is a rare type of primary neuroendocrine neoplasm of the lung with indolent behavior and a good prognosis. The main treatment strategy is surgery, the extent of which is controversial given the nature of the disease. The aim of this study is to assess whether the extent of resection influences survival and recurrence in patients undergoing lung resection and lymphadenectomy for TC and to investigate negative prognostic factors for OS. Methods: A single-centre retrospective study of 15 years’ experience was conducted. Data from all patients who underwent lung resection and lymphadenectomy for TC were collected. Patients were divided into two groups: anatomical and non-anatomical resections. Perioperative and long-term oncological results were analyzed. Results: In total, 115 patients were surgically treated for TC, of whom 83 (72%) underwent anatomical resection and 32 (28%) non-anatomical resection. Univariate analyses showed that age, left lower lobe, and many comorbidities had a detrimental effect on OS, whereas on multivariate analysis, only left lower lobe location and a high Charlson–Deyo comorbidity index (CCI) were confirmed as negative prognostic factors for OS. At a median follow-up of 93 months (IQR 57-129), the OS survival curves show a slightly lower trend for non-anatomical resections (p 0.152), while no differences were found for DFS. Conclusions: The results of this study confirm that in selected patients at risk for major resections, non-anatomical resection can be used to treat TC when R0 is achievable. These data, together with evidence from the literature, highlight the importance of patient-centred care in this rare disease. Full article

Background/Objectives: Lung cancer screening with low-dose computed tomography (LDCT) has reduced lung cancer mortality in high-risk smokers. However, the evidence on LDCT screening in the elderly is limited, with there being few older participants in major trials and ongoing debate about the benefits, risks, and appropriate age limits of LDCT. This study aimed to investigate the prevalence of pulmonary nodules and lung cancer detection rates in men aged 70 and above who underwent a single round of LDCT screening. Methods: We retrospectively analyzed data from elderly male participants aged 70 years or older who underwent a single low-dose CT lung cancer screening at the Veterans Health Service Medical Center between 2010 and 2023. The participants included those who requested screening or were asymptomatic but recommended by physicians. Individuals with prior lung cancer, symptoms suggestive of lung cancer, or suspicious findings on previous imaging were excluded. The nodule prevalence, lung cancer diagnoses, pathological subtypes, and clinical stages were reviewed. Results: A total of 1409 individuals with a mean age of 74.2 years were included. The median follow-up duration was 3.6 years. Among the included individuals, 1304 (92.6%) had a history of smoking. Positive nodules were detected in 179 patients (12.7%, 95% CI: 11.0–14.5%), and lung cancer was diagnosed in 31 patients (2.2%, 95% CI: 1.5–3.1%). Of the diagnosed cases, 14 (45.2%) were adenocarcinomas and 12 (38.7%) were squamous cell carcinomas. Nineteen patients (51.3%) were diagnosed with stage I or II cancer, while seven (22.6%) were diagnosed at stage IV. Conclusions: A single round of LDCT screening in elderly men resulted in a relatively high lung cancer detection rate, with over half of the diagnosed cases being identified at an early stage. This highlights the potential clinical benefit of even one-time screening in enabling timely treatment, which may still be feasible in older adults. However, potential harms such as overdiagnosis should also be considered. Full article

Pulmonary neuroendocrine proliferations and neoplasms represent a broad spectrum of diseases, ranging from neuroendocrine cell hyperplasia and tumorlets to carcinoid tumors. Carcinoid tumorlets are most commonly located in the peripheral airways and are often incidentally detected as pulmonary micronodules on chest CT. We report the radiological, bronchoscopic, and pathological findings of a case of carcinoid tumorlets presenting as endobronchial nodules in the left main bronchus. The patient had previously undergone a left lower lobectomy five years earlier for a typical carcinoid tumor. Follow-up imaging revealed new endobronchial nodules, which were subsequently confirmed as carcinoid tumorlets through histopathologic analysis. This case highlights the rare presentation of carcinoid tumorlets in the central airways, emphasizing the importance of recognizing their potential for late recurrence and atypical localization. It underscores the necessity for physicians to be aware that pulmonary neuroendocrine tumors can recur over the long term and may present in a multicentric fashion within the disease spectrum. Full article

Background/Objectives: Primary pulmonary carcinoma (PC) is a malignant neoplasm that occurs in humans, dogs, and other species. In canine PC, palliative care remains the most practical approach for dogs with inoperable PC. Methods: We investigated the effectiveness of mammalian target of rapamycin (mTOR) inhibitors in canine lung cancer upon PI3K/AKT/mTOR activation. Three canine PC cell lines (AZACL1, AZACL2, and cPAC-1) were treated with three mTOR inhibitors (AZD8055, temsirolimus, and everolimus). In vitro, sensitivity assays were conducted to evaluate proliferation and Western blotting was used to examine pathway activation and phosphorylation of mTOR-related protein. Results: AZD8055 had a stronger inhibitory effect on cell proliferation than temsirolimus and everolimus in all three PC cell lines. The IC₅₀ for AZD8055 in the AZACL1, AZACL2, and cPAC-1 cell lines were 23.8 μM, 95.8 nM, and 237 nM, for temsirolimus they were 34.6 μM, 11.5 μM, and 11.2 μM, and for everolims they were 36.6 μM, 33.4 μM, and 33.0 μM, respectively. Western blotting revealed PI3K/AKT/mTOR pathway activation and differential phosphorylation of mTOR signal-related proteins across the three PC cell lines. In xenograft mice injected with the AZACL1 and AZACL2 cell lines we showed that the AZD8055-treated group exhibited a significant reduction in tumor volume via the inhibition of tumor growth compared to the control group. Conclusions: These findings reveal that the PI3K/AKT/mTOR pathway plays a key role in canine PC and that AZD8055 may be a novel therapeutic agent for PC-bearing dogs. Full article