Transarterial Radioembolization (TARE) currently lacks a defined role in treating neuroendocrine liver metastases (NELM). This systematic review aims to clarify TARE's role based on its prognostic impact. A search identified 138 studies onPubMed/MEDLINE over the past 25 years, focusing on TARE for NELM patients. Of these, 46 studies met eligibility criteria, and 11 were selected for their similar settings, populations, and outcomes. These were grouped into three clusters based on survival outcomes: overall survival (OS), hepatic progression-free survival (HPFS), and imaging response (IR) per RECIST 1.1 criteria. Statistical analyses showed a median OS of 33 months for 809 patients, a median HPFS of 24 months for 414 patients, and an IR of 28.6 % complete or partial response, 57.8 % stable disease, and 13.6 % disease progression in 581 patients. This evidence supports TARE as a viable treatment option, but further studies are needed to optimize its use and dosimetric procedures.

This study aims to evaluate the effectiveness of contrast-enhanced computed tomography (CT) in distinguishing non-hypervascular pancreatic neuroendocrine neoplasms (PNENs) from pancreatic ductal adenocarcinomas (PDACs) with a normal serum level of carbohydrate antigen 19-9 (CA19-9) levels.

This retrospective study included 134 patients with pathologically confirmed non-hypervascular PNENs and 128 patients with CA19-9-negative PDACs, all of whom underwent contrast-enhanced CT prior to surgery between January 2015 and March 2024. Following independent evaluation by two radiologists, qualitative features from both groups were extracted in the arterial and portal venous phase and subsequently compared using univariate and multivariate analysis.

Patients with CA19-9 negative PDACs were significantly older than those with non-hypervascular PNENs (p < 0.001), and the majority of PDACs were located in the head of the pancreas (p < 0.01).Univariate analysis showed that non-hypervascular PNENs exhibited a higher frequency of well-defined tumor margins (p < 0.001) and calcification (p = 0.032) and a lower frequency of local invasion (p < 0.001), peripancreatic vascular invasion (p = 0.001), intra- or extrahepatic bile duct dilatation (p < 0.001), distal main pancreatic duct dilatation (p < 0.001), regional lymphadenopathy (p < 0.001) and tumor homogeneity (p < 0.001) when compared to CA19-9 negative PDACs. Multivariate analysis identified the absence of local invasion (Odds Ratio (OR) = 0.233; 95 % Confidence Internals (95 % CI):0.114-0.476; p < 0.001), absence of peripancreatic vascular invasion (OR = 0.434; 95 % CI:0.217-0.870; p = 0.019), a normal distal main pancreatic duct diameter (OR = 0.398; 95 % CI:0.202-0.785; p = 0.008), absence of regional lymphadenopathy (OR = 0.455; 95 % CI:0.238-0.870; p = 0.017) and tumor heterogeneity (OR = 0.240; 95 % CI:0.126-0.456; p < 0.001) as significant predictors of non-hypervascular PNENs. The area under the receiver operating characteristic curve for the radiological feature model was 0.829 based on logistic regression.

Qualitative features in contrast-enhanced CT images could be beneficial in differentially diagnosing non-hypervascular PNENs and CA19-9 negative PDACs.

Assessing treatment response in neuroendocrine tumors (NET) remains a significant challenge due to their typically indolent growth and heterogenity, the frequent occurrence of disease stabilization rather than tumor shrinkage after therapy, and the inherent limitations of conventional imaging criteria. While molecular imaging-primarily somatostatin receptor (SST) PET/CT-has improved lesion detection, the absence of standardized response criteria limits its clinical utility and prevents its use as full replacement of conventional imaging. Emerging strategies, including revised thresholds for dimensional changes, criteria evaluating different features, such as lesions' density and functional tumor volumes, offer potential improvements in response evaluation but require further validation for routine clinical implementation. This review examines the current challenges in assessing NET treatment response, evaluates the strengths and limitations of available imaging modalities, and discusses emerging approaches and future directions for optimizing therapeutic monitoring in the heterogeneous panorama of NET.

A gastric neuroendocrine tumor (NET) with pancreatic acinar cell differentiation is extremely rare. We report the case of an 87-year-old woman with a submucosal tumor in the gastric body on a background of atrophic gastritis. She also had Sjögren's syndrome. Initially 17.8 × 6.5 mm, the tumor enlarged over 10 years, leading to wedge resection. The resected mass (45 × 40 × 30 mm) was solid with a pale yellow to gray-white cut surface. Histologically, it showed trabecular or solid nests of epithelial cells with round nuclei and eosinophilic cytoplasm. Immunohistochemistry showed positivity for CKAE1/3, VMAT2, neuroendocrine markers, and pancreatic acinar markers. Ki-67 index was 11.2%. The tumor co-expressed PDX1 and ARX and showed loss of menin and ATRX. These findings support a diagnosis of gastric ECL-cell NET G2 arising in autoimmune gastritis, with secondary pancreatic acinar differentiation. This tumor may represent a variant of type 1 gastric NET.

Pancreatic neuroendocrine tumors (PNETs) are comparatively rare pancreatic malignancies that exhibit diverse biologic behavior, ranging from indolent tumors to widely metastatic cancers, with up to 15 % secreting hormones that cause symptoms. As a consequence, the management of PNETs is highly individualized and can include active surveillance of small (1-2 cm) and very small (< 1 cm) nonfunctioning tumors without worrisome features, parenchymal-sparing resection of appropriately located tumors, anatomic pancreatectomy and, in select cases, debulking of metastatic disease, particularly in the liver. This review synthesizes society recommendations and contemporary evidence guiding the surgical management of PNETs. Innovations in molecular profiling and systemic therapies hold promise to refine surgical algorithms for this heterogeneous tumor.

Small bowel tumors are rare gastrointestinal tumors. Neuroendocrine tumors are the most common and demonstrate unique subtypes depending on their location. Adenocarcinomas are most common in the duodenum demonstrating luminal narrowing and irregularity. Gastrointestinal stromal tumors are heterogeneously enhancing lesions with endophytic and/or exophytic growth patterns. Immunotherapy is a unique treatment of these tumors with tumoral response best assessed with both routine computed tomography (CT) and PET/CT. Primary small bowel lymphoma has many imaging patterns, most commonly being aneurysmal dilation and thickening of the small bowel. Metastases are common and may present as polypoid lesions, focal wall thickening, or serosal deposits.

Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare, low-grade malignant tumor, representing 0.9-2.7% of all exocrine pancreatic tumors. SPN patients generally have a favorable prognosis with a 5-year survival rate exceeding 95% following complete surgical resection. Accurate diagnosis is crucial to avoid unnecessary treatments. Currently, SPN diagnosis relies on imaging techniques such as CT and MRI, along with immunohistochemical analysis of biopsy and resection samples. The main challenge in diagnosis is the potential inability to accurately identify recurrent or metastatic SPN, as well as 'malignant' SPN, due to the lack of specific biomarkers. Advances in high-throughput omics technologies, including genomics, transcriptomics, proteomics and metabolomics, have opened new avenues for identifying novel biomarkers for SPN. Additional, liquid biopsy techniques have enabled more comprehensive analysis of biosamples such as pancreatic cyst fluid, offering promising prospects for preoperative diagnosis. This review highlights recent research on SPN diagnosis, focusing on immunohistochemical markers, tissue sampling methods and the potential of omics approaches. It also discusses the challenges and opportunities in improving diagnostic accuracy, particularly for high-grade and metastatic SPNs.

Neuroendocrine tumours (NETs) are rare, heterogeneous neoplasms that often express somatostatin receptors (SSTRs). This allows targeted peptide receptor radionuclide therapy (PRRT) for NETs. PRRT is currently indicated as second- or third-line therapy for metastatic or unresectable, progressive, SSTR-positive NETs of grade (G) 1 or 2. Adequate bone marrow reserves as well as renal and hepatic function are required for PRRT. The most commonly used radiopharmaceutical for PRRT is 177Lu-DOTA-TATE. PRRT prolongs progression-free and overall survival, reduces or stabilises tumour burden, and improves tumour symptoms and quality of life. Adverse events associated with PRRT are mostly mild and transient. Haemato- and nephrotoxicity are the most common toxicities following PRRT. The NETTER‑2 and COMPOSE trials are investigating PRRT with 177Lu-DOTA-TATE/-TOC in G2 and G3 gastroenteropancreatic NETs.

It is challenging to determine the pancreatic neuroendocrine tumors (pNETs) malignancy grade noninvasively. We aim to establish a CT - based diagnostic nomogram to predict the tumor grade of pNETs.

The patients with pathologically confirmed pNETs were recruited in two centers between January 2009 and November 2020. PNETs were subdivided into three grades according to the 2017 World Health Organization classification: low-grade G1 NETs, intermediate-grade G2 NETs, and high-grade G3 NETs. The features on the CT images were carefully evaluated. To build the nomogram, multivariable logistic regression analysis was performed on the imaging features selected by LASSO to generate a combined indicator for estimating the tumor grade.

A total of 162 pNETs (training set n = 114, internal validation set n = 21, external validation set, n = 48) were admitted, including 73 (45.1%) G1 and 89 (54.9%) G2/3. A nomogram comprising the tumor margin, tumor size, neuroendocrine symptoms and the enhanced ratio on portal vein phase images of tumor was established to predict the malignancy grade of pNETs. The mean AUC for the nomogram was 0.848 (95% CI, 0.918-0.953). Application of the developed nomogram in the internal validation dataset still yielded good discrimination (AUC, 0.835; 95% CI, 0.915-0.954). The externally validated nomogram yielded a slightly lower AUC of 0.770 (95% CI, 0.776-0.789).

The nomogram model demonstrated good performance in preoperatively predicting the malignancy grade of pNETs, and can provide clinicians with a simple, practical, and non-invasive tool for personalized management of pNETs patients.

Our study aimed to develop a nomogram to predict overall survival (OS) at 1, 3, and 5 years for patients with primary renal neuroendocrine tumor (PRNET). The Surveillance, Epidemiology, and End Results database (2000-2021) was utilized to gather cases and extract data. We performed a multivariate analysis using a Cox proportional-hazards model to identify prognostic factors independently affecting OS. Based on these predictors, a nomogram was constructed and validated internally via a bootstrap resampling method. Finally, we included 266 PRNET patients. The multivariate analysis demonstrated that age, Fuhrman grade, surgery, summary stage, N stage, and histology were prognostic factors independently affecting OS (all P < 0.05). A nomogram was then constructed using the abovementioned predictors, except for the N stage. The bootstrap-corrected concordance index (C-index) of the nomogram was 0.820 (95% CI 0.805-0.835), surpassing the C-index of the TNM stage (0.571, 95% CI 0.550-0.592, P < 0.001). Based on time-dependent C-index results, the nomogram demonstrated a better discriminative ability compared to the TNM staging system. There was a good consistency between the observed values and predicted probabilities indicated by the calibration curves. The nomogram's clinical utility was supported by the decision curve analysis. Additionally, the nomogram can classify PRNET patients into low-risk and high-risk subgroups, with high-risk patients having poorer OS (P < 0.0001). The prognostic nomogram, based on individualized clinicopathological information, may be helpful in predicting survival outcomes for PRNET patients more accurately. Further external validation is required in future studies to confirm our developed nomogram's prognostic accuracy and clinical applicability.

Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) of the common bile duct (CBD) are extremely rare, with few literature reported. A 68-year-old male was admitted to our hospital with choledocholithiasis with acute cholangitis. Abdominal computed tomography showed that the CBD was occupied and clearly dilated. Consequently, the patient underwent pancreaticoduodenectomy with regional lymph node dissection. The resected tumor at the distal bile duct was 25 × 25 × 13 mm, consisting of 30% adenocarcinoma and 70% neuroendocrine carcinoma microscopically. The patient then received six cycles of adjuvant chemotherapy. Subsequently, regular monitoring of the patient's tumor marker CA19-9 showed progressive elevation. The patient was readmitted to hospital for tumor recurrence and metastasis and received palliative second-line Gemcitabine and cisplatin chemotherapy and three courses of combined immunochemotherapy (Tyvyt [Sintilimab] + Gemcitabine + Cisplatin). Throughout the treatment course, the tumor marker CA19-9 persistently remained elevated. The patient achieved an overall survival (OS) of 29 months. We found that the continuous elevation of the tumor marker CA19-9 during follow-up might suggest tumor recurrence and an unfavorable prognosis. For patients with multiple metastases of cholangiocarcinoma, combined immunotherapy could potentially assist in prolonging survival. Currently, there is no standardized treatment for biliary MiNENs, and larger scale studies are needed to establish diagnosis and treatment protocols to improve the overall survival of patients.

Peptide receptor radionuclide therapy (PRRT) is a well-established treatment option for neuroendocrine tumors (NET), yet randomized controlled trials have not provided data on its impact on overall survival. The real-world efficacy of PRRT and its association with tumor functionality and grading in pancreatic neuroendocrine tumors (PanNET) remains underexplored.

A retrospective analysis of 166 patients with histologically confirmed metastatic PanNET was performed. Subgroup analyses examined progression-free survival (PFS) and overall survival (OS) following PRRT cycles, stratified by tumor grading, tumor functionality and bone metastases.

Of 166 patients, 100 (60.2%) received PRRT with a median of four cycles. In the PRRT cohort, 68% of patients had deceased. PFS after four and eight consecutive cycles was 20 and 18 months, respectively (p=0.4). OS for the entire cohort was 79 months, with patients receiving 4+ cycles of PRRT having an OS of 87 months and those receiving 5+ cycles achieving an OS of 100 months. Patients with grade 1 or 2 tumors had a significantly longer median OS of 97 months compared to 74.5 months for grade 3 tumors (p = 0.0055). There was no significant difference in OS between functioning and non-functioning tumors after PRRT. Patients with bone metastases who received PRRT had a significantly shorter OS than those without (74 vs. 89 months, p = 0.013). In 19% of patients who received PRRT, therapy was discontinued due to progressive disease, toxicity or death.

Patients receiving extended cycles of PRRT showed improved survival outcomes in metastatic PanNET, particularly in patients with lower tumor grades and without bone metastases. No survival difference was seen between functioning and non-functioning PanNET, while patients with grade 3 tumors and bone metastases had significantly shorter survival despite PRRT.

Endoscopic intermuscular dissection (EID) is associated with higher rates of negative margins in treating rectal neuroendocrine tumors (R-NETs), as reported in case studies. However, evidence regarding the safety and effectiveness of EID remains insufficient. This study aimed to evaluate clinical safety and effectiveness of EID in treating 10- to 20-mm R-NETs.

Retrospective clinical data from patients with 10- to 20-mm R-NETs who had undergone EID from 2019 to 2024 were collected from a tertiary hospital. The primary outcome was the histological complete resection rate and secondary outcomes included en bloc resection rate and technical success rate.

Twelve patients who had undergone EID were included, with one patient excluded for pathology indicative of a leiomyoma. Among the 11 patients (mean age, 42.45 years; 72.73% males), median diameter was 11.55 mm (interquartile range 10-13 mm). All patients underwent en bloc resection and postoperative pathology confirmed negative horizontal and vertical margins, achieving a histological complete resection rate of 100%. Mean procedure time was 58.55 minutes (standard deviation [SD] 13.66 minutes) and mean postoperative hospital stay was 5.7 days (SD 1.00). One patient developed fever and another experienced abdominal pain, both of which resolved within 24 hours. There were no cases of bleeding or perforation intraoperatively or postoperatively. During a mean follow-up of 31.73 months, there were no residual tumors, local recurrences, or metastases.

EID is a promising treatment for 10- to 20-mm R-NETs, with high initial cure rates, and a new option for endoscopic resection. More studies of the procedure are needed.

Background: Immunohistochemistry (IHC) provides comprehensive information for morphology and pathologic characteristics and is a valuable tool for establishing the correct cancer diagnosis in clinical diagnostic pathology and determining prognosis. Objectives: The current study analyzes and compares the expression of Immunohistochemistry biomarkers on neuroendocrine and epithelial cell types of appendiceal neoplasms. Design: This systematic review adhered to the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. We performed a meta-analysis employing a random effects model with proportions to gauge the proportion of positive cases. Method: A comprehensive systematic search in PubMed, Web of Science, and Scopus databases was conducted based on the PRISMA statement up to August 2023. Studies reporting the immunohistochemistry biomarkers expression performed in patients with primary appendiceal neuroendocrine and epithelial cell neoplasms according to the most recent World Health Organization classification of malignant tumors were included. Results: Our systematic search included 56 observational articles that meet the eligibility criteria. Meta-analysis revealed an expression rate of 93%, 91%, 87%, 71%, 94%, 99%, 32%, 76%, 25%, and 91% for non-specific enolase (NSE), chromaffin A, synaptophysin, Serotonin, SATB2, Caudal-type homeobox 2 (CDX2), β-catenin, Carcinoembryonic antigen (CEA), Cytokeratin 7, and Cytokeratin 20, respectively. CDX2 and SATB2 were the most expressed markers. The expression rate had a significant association with tumor type. NSE and synaptophysin were the highest in neuroendocrine tumors, whereas CEA was more elevated in gablet cell carcinoids. Cytokeratin 20 is suitable for identifying epithelial cell neoplasms. Conclusion: The study indicates the proportion of positive cases in patients with primary neuroendocrine and epithelial cell appendiceal neoplasms.

The somatostatin analogs (SSA) octreotide and lanreotide are a mainstay in the treatment of neuroendocrine tumors (NET). The two pivotal trials differed considerably in terms of patient characteristics and are not directly comparable. Further comparative data are lacking.

This retrospective chart review study included patients with gastroenteropancreatic NET grade 1 or 2 who were treated with octreotide LAR or lanreotide autogel. The main aim was to compare the two SSA based on progression-free survival (PFS) and overall survival (OS) from treatment start.

In total, 129 patients were analyzed, 60% (n = 77) had a small intestinal NET and 31% (n = 40) a pancreatic NET. Histologically, 34% (n = 44) had NET G1, 55% (n = 71) a NET G2, and 11% (n = 14) a NET G1/G2 unclassified. Lanreotide was used in 90 patients (70%) and octreotide in 39 patients (30%). Overall, the median PFS was 32.2 months (95% CI 23.0-42.9 months). No PFS difference (p = 0.8) was observed between lanreotide (29.8 months, 95% CI 18.7-48.5 months) and octreotide (36.0 months, 95% CI 23.2-68.2 months). Median OS from treatment start was calculated at 93.5 months (95% CI 71.1-132.9 months). Again, the median OS following lanreotide (113.4 months, 95% CI 62.3-NA months) or after octreotide (90.3 months, 95% CI 71.1-NA months) did not differ significantly (p > 0.9).

Our long-term experience with octreotide and lanreotide in NET did not reveal differences in antitumor effectiveness. This is consistent with previous reports and might suggest that both SSA can be used interchangeably if needed.

National Comprehensive Cancer Network guidelines recommend segmental colectomy for appendiceal neuroendocrine neoplasms >2.0 cm given the risk for lymph node involvement. However, additional clinicopathologic factors are associated with nodal metastases, and thus survival. Given dynamic changes of prognosis over time, conditional overall survival, the probability of surviving after a specific interval, has emerged as a novel oncologic outcome, but is scarcely available for appendiceal neuroendocrine neoplasms.

Adults with stage I-III appendiceal neuroendocrine neoplasms who underwent colectomy from 2010-2017 were identified in the National Cancer Database. Tumor histologies included neuroendocrine tumor grade 1, neuroendocrine tumor grades 2 and 3, neuroendocrine carcinoma, mixed neuroendocrine non-neuroendocrine neoplasm, and goblet cell carcinoma.

Of 3,541 patients (median age 51 years, 43% male, 88% White), 16% had positive lymph nodes. Overall, 40% had neuroendocrine tumor grade 1, 4% neuroendocrine tumor grades 2 and 3, 10% neuroendocrine carcinoma, 12% mixed neuroendocrine non-neuroendocrine neoplasm, and 30% goblet cell carcinoma. Increasing depth of invasion, lymphovascular invasion, and increasing size were associated with lymph node metastases. Eighty-seven percent were alive at 2 years. Mortality after 2 years was associated with older age, mixed neuroendocrine non-neuroendocrine neoplasm and goblet cell carcinoma histology, penetration through serosa, nodal involvement, and tumor size.

In a national cohort, 1 in 6 patients had positive lymph nodes, which was associated with depth of invasion, lymphovascular invasion, and size. These findings indicate additional factors should be considered when determining the extent of surgical resection and surveillance to improve survival outcomes. Additionally, patients with penetration through serosa, and mixed neuroendocrine non-neuroendocrine neoplasm or goblet cell carcinoma histology had worse conditional overall survival, potentially reflecting more aggressive tumor biology that warrants closer follow-up.

Pituitary neuroendocrine tumors can sometimes present with leptomeningeal seeding at their initial diagnosis, emphasizing the need for thorough evaluation in cases of leptomeningeal involvement. Additionally, it is crucial for general physicians to inquire about a patient's menstrual status, particularly in low socioeconomic conditions, as this information can provide valuable insights into the hypothalamic-pituitary axis function.

Personalizing care and outcome evaluation are important aims in the field of NEN and nomograms may represent useful tools for clinicians. Of note, gender difference is being progressively more considered in NEN care, as it may also impact on survival. This systematic review aims to describe and analyze the available nomograms on pancreatic NENs (PanNENs) to identify if gender differences are evaluated and if they could impact on patients' management and prognosis.

We performed an electronic-based search using PubMed updated until June 2024, summarizing the available evidence of gender impact on PanNEN survival outcomes as emerges from published nomograms.

34 articles were identified regarding prognostic nomograms in PanNEN fields. The most included variables were age, tumor grade, tumor stage, while only 5 papers (14.7%) included sex as one of the key model variables with a significant impact on patients' prognosis. These 5 studies analyzed a total of 18,920 PanNENs. 3 studies found a significant impact of sex on overall survival (OS), whereas the remaining 2 studies showed no significant impact of sex on OS.

Gender difference is being progressively more considered in PanNEN diagnosis, care and survival. Nomograms represent a potentially useful tool in patients' management and in outcomes prediction in the field of PanNENs. A key role of sex in the prognosis of PanNENs has been found in few models, while definitive conclusions couldn't be drawn. Future studies are needed to finally establish gender impact on PanNEN prognosis.

Cribriform morular thyroid carcinoma is a rare thyroid malignancy with uncertain histogenesis. It predominantly affects young women and is strongly associated with familial adenomatous polyposis. This paper reports a rare case of sporadic cribriform morular thyroid carcinoma in a female patient in her early 50s, with somatic genetic testing revealing a KMT2C mutation. She presented with a solitary lesion confined to the right thyroid lobe and had no family history of familial adenomatous polyposis. Colonoscopy and germline genetic testing revealed no abnormalities. This finding suggests a potential link between KMT2C mutations and sporadic cribriform morular thyroid carcinoma. The clinical and imaging manifestations of this malignancy lack specificity, and the final diagnosis depends on routine pathological examination and immunohistochemical analysis. This report indicates the need for the clinical investigation of family history and genetic testing, thus contributing to the clinical realization of standardized follow-up monitoring and management.

Neuroendocrine neoplasms (NEN) are rare tumors arising from neuroendocrine cells most commonly in the gastrointestinal-tract. In recent years, advancements in therapeutics have increased survival rates in patients with NEN leading to a greater clinical burden compared to the general population.

The aim of this single-center case-control study was to investigate the incidence of low bone mass and changes in body composition in adult patients diagnosed with gastroenteropancreatic neuroendocrine tumors (GEPNET). Enrolled participants underwent measurements of bone mineral density (BMD) at the lumbar spine (LS), femoral neck (FN), and total hip (TH) and body composition analysis with calculation of total fat-mass (TFM) and relative skeletal mass index (RSMI), by dual X-ray absorptiometry.

Ninety GEPNET patients (28 with Pancreatic-NET, 20 with small-intestine-NET, 42 with gastric-NET), and 50 age and sex-matched controls were enrolled. The mean disease duration was 5±4.4 years, the majority of patients (54/90) was classified as stage-1, and were not receiving systemic-treatment (76/90). The incidence of osteoporosis/osteopenia was threefold higher in the patients' cohort, compared to controls (OR: 3.17 95% CI 1.16-7.8, p < 0.001). Among NEN patients, gastric-NET had the lowest bone mass, especially in LS. In addition, GEPNET patients demonstrated significantly lower TFM and RSMI, compared to controls (TFM: 31.6 ± 9.6 kg vs. 38.6 ± 6.4 kg, respectively, p = 0.03; RSMI: 6.4 ± 1.1 vs. 8.2 ± 0.6, respectively, p < 0.001). Within our patients' cohort, RSMI was significantly associated with LS-BMD (rho = 0.49, p < 0.001) and TH-BMD (rho = 0.58, p < 0.001), and TFM was associated with TH-BMD (rho = 0.31, p = 0.004).

Patients with GEPNET even at an early stage exhibit significantly lower bone, muscle and fat mass compared to the non-NET population, highlighting the importance of continuous monitoring of the musculoskeletal system in these patients.

The term "carcinoid tumour" is no longer used and has given up its place to neuroendocrine neoplasms (NENs). Primary hepatic neuroendocrine neoplasms (PHNENs) are as rare as compromising 0.4% of all neuroendocrine neoplasms (NENs). Searching the central medical databases of PubMed/Medline, Web of Science, Scopus, Google Scholar, and the references of the articles, we have collected 10 cases of pediatric PHNENs of children. The inclusion criteria were full-text available literature in English and those under and equal to 19 years old. Diseases found during autopsy, carcinoma, and isolated gall bladder involvement also made the exclusion criteria. The mean age of the patients was 13.86 years, ranging from 8 to 19 years. Six female patients (55%) were in front of 5 males (45%). The right lobe was the most frequent site of involvement and surgery in four cases. Abdominal pain comprised the main symptom, and CT scans of most of them were common which helped in diagnosis. While a hepatic tumour is considered NEN, a detailed systemic evaluation of a primary tumour is mandatory to exclude metastatic HNEN. Secondary hepatic NENs are more common than primary ones. Surgical resection has had the most long-term success.

The structural integrity of the lips is essential for both aesthetic appeal and oral functionality. Defects in this region, which may arise from a variety of causes, can significantly affect a patient's physical and psychological well-being. This case report introduces a novel surgical technique designed for the repair of substantial defects in the lower lip. The procedure utilizes a nasolabial flap in conjunction with the facial artery myomucous flap. This innovative approach addresses considerable lip-related defect challenges effectively. The report delineates the surgical steps implemented and highlights the successful reconstruction of the lower lip. Following the surgery, the patient demonstrated a positive recovery trajectory, marked by significant improvements in both lip symmetry and functionality, with no notable complications. The integration of the nasolabial flap with the mucous membrane has proven effective in the repair of extensive lip defects, particularly in the skin and mucous membrane areas adjacent to the corners of the mouth. This procedure not only facilitates the restoration of appearance and function but also reduces the risk of further surgical trauma. Additionally, the report underscores the necessity of thorough preoperative planning to mitigate complications at the donor site.

There is a general perception that the incidence of neuroendocrine neoplasms (NENs) has been increasing. Nevertheless, reports of actual population-based studies are scarce, and pertinent data from some geographical regions still need to be available. In this systematic literature review of population-based studies, we aimed to evaluate the available data to provide updated figures on the incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Guided by the PRISMA 2020 statement reporting items for systematic reviews, this study conducted a systematic search using Ovid in the bibliographic databases Embase, Medline, and Web of Science Core Collection. Only incidence-reporting studies were included. In total, 847 articles were identified, and through a strict evaluation process using predefined inclusion and exclusion criteria, we found 19 papers that reported the general incidence of GEP-NENs from all sites. In addition, we considered another 15 papers that focused on the epidemiologic aspects of single-organ studies. While the incidence rates of GEP-NEN vary across similar countries, the general incidence of GEP-NEN has been increasing worldwide in recent decades. The incidence of GEP-NENs has increased worldwide over the last two decades, and reliable figures from new regions add to this pattern. Nevertheless, variations in the classification, grading, and reporting of GEP-NENs in various studies make direct comparisons difficult.

A 46-year-old male with no comorbidities was referred to our hospital because of jaundice and elevated LFT markers. After further investigations, he underwent magnetic resonance cholangiopancreatography (MRCP), which revealed a hypo-enhancing periampullary mass measuring 15 mm in size causing common bile duct (CBD) dilatation of 12 mm in cross diameter with intrahepatic biliary obstruction, which explained the patient's symptoms. Side-view endoscopy was performed to obtain a specimen of the mass. Further histopathological workup revealed poorly differentiated neuroendocrine carcinoma (NEC). A multidisciplinary team (MDT) was conducted, and the patient was planned to undergo positron emission tomography-computed tomography (PET-CT) scan to investigate any further organ metastasis. Unfortunately, the patient missed his upcoming appointments and was lost to follow-up. Nevertheless, more research is needed to understand pathogenesis and the best course of management for small periampullary NETs.

Neuroendocrine tumors (NETs) constitute a diverse group of tumors. NETs are often diagnosed late, due to nonspecific symptoms. Second Primary Malignancies (SPMs) have been reported in up to 25% of NETs and their incidence has been described as negative predictor of overall survival. We aimed to assess the prevalence of SPMs in patients with NETs treated at a specialized center.

We conducted a retrospective analysis of patients with metastatic well-differentiated gastro-entero-pancreatic neuroendocrine tumors and lung carcinoids treated with Somatostatin Analogs between 2017 and 2019. Control group patients with hormonally inactive pituitary lesions and microprolactinomas hospitalized between 2016 and 2019 were included.

One hundred thirty-five patients (85 women, 50 men) with NETs were enrolled. SPMs were more common in NETs compared to control group (P = .029). Twenty-six SPMs were diagnosed in 24 patients (17.8%). The control group comprised 94 patients, among whom 7 patients (7.7%) developed SPMs. Mean (standard deviation) age at the end of follow-up was 64.8 (10.2) years, with duration from NETs diagnosis to the end of follow-up of 5.3 (3.8) years.

The risk of SPMs is high in NETs, with multiple neoplasms diagnosed in over one sixth of patients. Active surveillance for SPMs is strongly indicated and should be integral to the follow-up of NETs.

Neuroendocrine tumors (NETs) are a diverse group of neoplasms whose prevalence is increasing globally, primarily due to advancements in diagnostic techniques. NETs arise from cells of the diffuse endocrine system and can occur in various locations, with the gastrointestinal tract being the most common. Their diverse clinical presentations, which range from asymptomatic to severe hormone-induced syndromes, pose significant diagnostic challenges. In emergency care, prompt recognition and management of complications such as bowel obstruction, ischemic events, hormonal crises, and metastases are critical. This review discusses the radiologic spectrum of NETs in emergent care, emphasizing the role of imaging in timely diagnosis and intervention.

The increasing incidence, rapidly evolving classification, rarity and heterogeneity of neuroendocrine neoplasms (NENs) pose challenges to NEN registration including difficulty in distinguishing neuroendocrine carcinoma (NEC) and neuroendocrine tumours (NETs). Thus, in Italy a higher NEC incidence was reported. Focusing on gastroenteropancreatic (GEP) NEN, we aimed to review GEP NEN, and in particular cases of neuroendocrine carcinoma, not otherwise specified (NOS) and estimate the incidence of NEN, NET and NEC of the GEP.MethodsWe launched a pilot study examining cases of neuroendocrine carcinomas NOS (ICD-O3 code 8246) of GEP incidents in the years 2012-2020. Cancer registries (CRs) reviewed information included in the pathology report regarding differentiation and tumour cells proliferation to decide whether to confirm the case as neuroendocrine carcinoma NOS or register it as NET or NEC. After the review, we estimated the GEP NEN, NET and NEC incidence.

Nine CRs contributed to the pilot study. After review, in all CRs, only 31% of GEP NOS neuroendocrine carcinomas were confirmed; 50% were recoded as NETs, and approximately 17% of cases were non-NENs. The IR of GEP NENs was 2.99/100,000, and the incidence of NETs was higher than that of NECs.

After the review, the incidence of GEP NEN, NET and NEC in the eight Italian CRs involved was comparable to that reported in other European countries.

Our results confirmed that heterogeneity of cancer registries in the registration of NEN requires collaborative work to define and promote a standard definition to be extended to all Italian registries.

Neuroendocrine neoplasms (NEN) originate from the secretory cells of the neuroendocrine system, with the majority arising in the gastrointestinal tract and pancreas. Given the heterogeneity in the biological behavior and morphological differentiation of these tumors, advanced imaging techniques are crucial for supporting the suspected diagnosis, accurate staging, and monitoring therapy. As most well-differentiated NEN demonstrate overexpression of somatostatin receptors (SSR) on the cell surface, SSR-directed PET/CT is considered the reference standard for imaging of this particular entity. SSR-PET/CT should be the imaging method of choice in every NEN G1 or G2 and considered for re-staging after both potentially curative and non-curative surgeries. The extent of SSR expression is also crucial for determining a patient's eligibility for peptide receptor radionuclide therapy (PRRT). PRRT utilizes [177Lu]Lu-DOTA-TATE to target the SSR receptor and can significantly prolong progression-free survival in patients with advanced, progressive neuroendocrine tumor of the gastroenteropancreatic system (GEP-NET). PET/CT is a central component of the multidisciplinary management of NEN. Variable follow-up intervals are recommended, considering that tumors with higher proliferation rates or advanced metastatic disease require more frequent assessments. The combination with other imaging modalities, like MRI, complements SSR-PET/CT, further enhancing overall diagnostic accuracy. KEY POINTS: Somatostatin receptor-PET/CT (SSR-PET/CT) is the guideline-recommended reference standard for imaging well-differentiated neuroendocrine tumors (NET). SSR-PET/CT should be the diagnostic imaging of choice for staging and post-therapy re-staging of grade 1 or 2 NET (G1 or G2). Variable follow-up intervals are recommended for NET G1 and G2. Tumors with higher proliferation rates or advanced metastatic disease necessitate more frequent assessments.

Non-functioning paraganglioma of the bladder is extremely rare disease. It is important to know the presence of paraganglioma of the bladder as the early and correct diagnosis affects the management and prognosis of the patient. Pathologists may misinterpret it as part of cystitis cystica/glandularis or nested variant urothelial carcinoma, or secondary bladder involvement by prostatic adenocarcinoma. This report will contribute to the existing literature and provide valuable insights into the clinical characteristics and treatment options for this rare tumor.

35 years old female patient presented after incidental finding of bladder mass on abdominal ultrasound during routine antenatal follow up. Cystoscope showed 2 × 2 cm single solid bladder mass. Microscopic examination was suggestive of neuroendocrine tumor with paragangliom as a differential diagnosis. Imminohistochemical studies showed positive for synaptophysin, S100, GATA-3 and negative for panCK. The patient was managed with partial cystectomy.

Non-functioning paragnaglioma of the urinary bladder is a rare extra-adrenal pheochromocystoma. The diagnosis is usually challenging and it may mimic urothelial carcinoma. Histopathology and immunohistochemistry are almost always confirmatory.

Urinary bladder paraganglioma may mimic nested variant of the bladder tumor. High clinical suspicion is important. Confirmation is with histopathology and immunohistochemistry. Partial cystectomy is treatment of choice.

Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) of the colon is rare with a poor prognosis. Since the first description of a mixed neoplasm 100 years ago, the nomenclature has evolved, most recently with the 2022 World Health Organization (WHO) classification system. We describe our experience of a case of locoregionally advanced MiNEN of the descending colon treated with curative laparoscopic resection and adjuvant chemotherapy. The patient is a 72 year old woman who presented with haematochezia. Initial clinical diagnosis was poorly differentiated adenocarcinoma of the descending colon, cT2N0M0, cStage I. Laparoscopic partial colectomy of the descending colon with D3 lymph node dissection and intracorporeal overlap anastomosis was performed. The pathological diagnosis however, returned mixed adenocarcinoma-neuroendocrine carcinoma (MANEC) of the descending colon, pT4aN1bM0, pStage IIIB, a subgroup of MiNEN: 70% was neuroendocrine carcinoma (NEC), whilst poorly differentiated mucinous carcinoma constituted 30% of the tumour. She completed 4 courses of irinotecan plus cisplatin (IP) adjuvant chemotherapy and is currently recurrence-free at postoperative year 2. The clinical course of MiNEN depends on the biology of the two components, both of which must be pathologically characterised. Even quantitatively discrete components should be carefully subtyped as their prognostic relevance is undetermined.

An 'adenoma' is a benign neoplasm composed of epithelial tissue, and has been standard nomenclature for primary pituitary neoplasms. In 2022, the fifth edition of the WHO Classification of Endocrine Tumours and of Central Nervous System Tumours, renamed pituitary adenomas as neuroendocrine tumours (NETs), assigning an oncology label to pituitary invariably benign neoplasms. Multidisciplinary workshops convened by the Pituitary Society have questioned the process, validity, and merit of this arbitrary change, while addressing the adverse clinical implications of the proposed new nomenclature. Unlike NETs, pituitary adenomas are highly prevalent, indolent and very rarely become malignant, and in general do not affect life expectancy when appropriately managed. A nomenclature change to NET does not advance mechanistic insight, treatment or prognosis but confers a misleading oncology connotation, potentially leading to overtreatment as well as engendering unnecessary patient anxiety. As the majority of pituitary adenomas do not require surgery, exclusion of these disorders is a major shortcoming of the pathology-based WHO classification system which is limited to patients undergoing surgery. Many factors influence prognosis other than histopathology. A new clinical classical classification has been developed for guiding prognosis and therapy of pituitary adenomas by integrating clinical, genetic, biochemical, radiological, pathological, and molecular information for all adenomas arising from anterior pituitary cell lineages. The system uses an evidence-based scoring of risk factors to yield a cumulative grade score that reflects disease severity. It can be used at the bedside to guide pituitary adenoma management. Once validated in prospective studies, this simple classification system could provide a standardised platform for assessing disease severity, prognosis, and effects of therapy on pituitary adenoma outcomes.

In the World Health Organization (WHO) 5th edition, prognosis of gastrointestinal (GI) well-differentiated neuroendocrine tumors (WDNET) depends on proliferation rate, commonly assessed by ki-67 immunohistochemical stain. In daily practice, the gold standard for WHO grade assessment by ki-67 staining, printing a photo of a tumor hotspot, counting the number of ki-67-positive cells out of 500 tumor cells, and calculating a percentage, is time-consuming and many cases are eyeballed. This study investigates the utility of a common tool, the manual cell counter used in hematology smear cell counting, for GI WDNET ki-67 counting. Of 59 resections, the number of cases with a WHO grade difference between gold standard print-and-count and the original report, eyeballing, and hematology counter method, was 23 (39 %), 14 (24 %) and 7 (12 %) cases, respectively. Of 37 biopsies, the number of cases with a WHO grade difference between gold standard print-and-count and the original report, eyeballing, and hematology counter method, was 10 (27 %), 12 (32 %) and 7 (19 %) cases, respectively. For resections, Chi square analysis comparing hematology counter method versus original report, where many cases were likely eyeballed, showed statistically significantly less cases with differing WHO grades from gold standard print-and-count for hematology counter-assessed cases (P = 0.0007), and the same Chi square analysis was marginally not significant (P = 0.09) for hematology counter versus eyeballing. Times taken to perform hematology counter method were statistically significantly lower than times taken for print-and-count. This study suggests the hematology cell counter could strike a reasonable balance between time and accuracy for WDNET resections.

Background: The international medullary thyroid carcinoma (MTC) grading system (IMTCGS) has been proposed as an independent tool to predict disease-specific survival (DSS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS). We aimed to evaluate the performance of IMTCGS in our series of sporadic MTCs and to compare its predictive power with conventional prognostic factors. Methods: In a retrospective cohort study, we evaluated data from 314 patients with sporadic MTC, all managed at the Pisa University Hospital. We divided patients according to the extent of the disease at diagnosis into localized (183/314, 58.3%) (confined to the thyroid), regional (100/314, 31.8%) (limited to the neck, involving surrounding thyroid tissues and/or regional lymph nodes), and distant (31/314, 9.9%) (distant metastases) disease. Data about somatic mutations were available in 212/314 (67.5%) patients. Expert pathologists differentiated high- and low-grade tumors. Results: According to the IMTCGS, 115/314 (36.6%) had high- and 199/314 (63.4%) patients had low-grade tumors. Patients with high-grade tumors showed higher preoperative calcitonin levels compared with low-grade (542 vs. 76 pg/mL, p < 0.01) as well as larger tumor size (2.3 vs. 1.1 cm, p < 0.01) and more frequent multifocality (22.6 vs. 12.1%, p = 0.01), minimal extrathyroidal extension (30.4 vs. 9.5%, p < 0.01), and lymph node metastases (63.5 vs. 27.6%, p < 0.01). Overall, patients with high-grade showed lower DSS, LRFS, and DMFS (p < 0.01). Grouping the whole cohort according to different disease extent at diagnosis, only in the case of localized disease, patients with high-grade tumors had significantly lower LRFS compared with low-grade. Similarly, in the other subgroups, we did not identify any difference in DSS, LRFS, and DMFS. Moreover, in the case of RET aggressive mutations, no differences in DSS, LRFS, and DMFS were observed between high- and low-grade tumors. Conclusions: We confirmed the usefulness of IMTCGS in predicting DSS, LRFS, and DMFS. However, it finds the best utility in patients with a lower risk of recurrence and mortality, identifying those rare cases with more aggressive clinical behavior. Conversely, when laterocervical lymph nodes (N1), distant metastasis (M1), or RET mutations, particularly M918T or indels, are already present at diagnosis, the role of IMTCGS in predicting DSS, DMFS, and LRFS becomes less relevant.

Small cell lung cancer (SCLC) is a high-grade neuroendocrine carcinoma with an incidence of 4.7 cases per 100 000 individuals in 2021 in the US and a 5-year overall survival of 12% to 30%.

Cigarette smoking is the primary risk factor for development of SCLC, as 95% of patients diagnosed with SCLC have a history of tobacco use. Patients with SCLC may present with respiratory symptoms such as cough (40%), shortness of breath (34%), hemoptysis (10%), or metastases with corresponding local symptoms (30%) such as pleuritis or bone pain; approximately 60% of patients with SCLC may be asymptomatic at diagnosis. Chest imaging may demonstrate central hilar (85%) or mediastinal lymphadenopathy (75%). At diagnosis, approximately 15% of patients have brain metastases, which may present as headache or focal weakness. Diagnosis is confirmed by biopsy of a primary lung mass, thoracic lymph node, or metastatic lesion. Small cell lung cancer is classified into limited stage (LS-SCLC; 30%) vs extensive stage (ES-SCLC; 70%) based on whether the disease can be treated within a radiation field that is typically confined to 1 hemithorax but may include contralateral mediastinal and supraclavicular nodes. For patients with LS-SCLC, surgery or concurrent chemotherapy with platinum-etoposide and radiotherapy is potentially curative in 30% of patients. More recently, median survival for LS-SCLC has reached up to 55.9 months with the addition of durvalumab, an immunotherapy. First-line treatment for ES-SCLC is combined treatment with platinum-etoposide chemotherapy and immunotherapy with the programmed cell death 1 ligand 1 (PD-L1) inhibitors durvalumab or atezolizumab followed by maintenance immunotherapy until disease progression or toxicity. Although initial rates of tumor shrinkage are 60% to 70% with platinum-etoposide and immunotherapy treatment, the median overall survival of patients treated for ES-SCLC is approximately 12 to 13 months, with 60% of patients relapsing within 3 months. Second-line therapy for patients with ES-SCLC includes the DNA-alkylating agent lurbinectedin (35% overall response rate; median progression-free survival, 3.7 months) and a bispecific T-cell engager against delta-like ligand 3, tarlatamab (40% overall response rate; median progression-free survival, 4.9 months).

Small cell lung cancer is a smoking-related malignancy that presents at an advanced stage in 70% of patients. Three-year overall survival is approximately 56.5% for LS-SCLC and 17.6% for ES-SCLC. First-line treatment for LS-SCLC is radiation targeting the tumor given concurrently with chemotherapy and followed by consolidation immunotherapy. For ES-SCLC, first-line treatment is chemotherapy and immunotherapy followed by maintenance immunotherapy.

Pancreatic neuroendocrine tumors are a heterogeneous group of rare clinical tumors, which can be classified into functional pancreatic neuroendocrine tumor (insulinoma is the most common) and noninsulinoma. Insulinoma and noninsulinoma have different mutation profiles. In noninsulinoma, ATRX/DAXX mutation is associated with alternative lengthening of telomeres-positive phenotype and positively correlated with poor prognosis. Copy number variation is also a prognostic marker for a high risk of recurrence. Scholars have used epigenetics as well as a multiomics approach (combining epigenetics, metabolomics, proteomics, etc) to molecularly type noninsulinoma, and there are huge differences in molecular expression and patient prognosis between different groups. In this manuscript, we summarize the published studies that utilized genome, epigenome, transcriptome, and proteome data to classify noninsulinoma.

Classical well differentiated neuroendocrine tumors (C-NETs) have plasmacytoid morphology and neuroendocrine differentiation. Oncocytic NETs (O-NETs) have been shown to be more clinically aggressive. Whether O-NETs are more akin to C-NETs or poorly differentiated neuroendocrine carcinomas (PDNECs) is not established.

Clinicopathologic characteristics and immunohistochemical expression of death domain-associated protein (DAXX), α-thalassemia/mental retardation syndrome X-linked genes (ATRX), retinoblastoma 1, p53, and SMAD4 in 30 O-NETs (25 pancreatic and 4 from luminal gastrointestinal tract) was compared to 32 C-NETs (23 pancreatic and 8 from luminal gastrointestinal tract). Whole exome sequencing was performed in a subset of each cohort.

O-NETs were male-predominant (65.6%) and had higher mean Ki-67 index (7.4% versus 2.9% in C-NETs) (P = 0.03), corresponding to more grade 2 or above (53.3%) tumors. O-NET patients had more advanced disease (pT3/pT4, 75% versus 36.8%) (P = 0.024), distant metastasis (50% versus 25%) (P = 0.042), progression (increased size/recurrence/new metastases) (n = 8 versus 3; P = 0.1), and death (n = 3 versus 1; P = 0.32). Forty percent of O-NETs (versus 12.5% of C-NETs; P = 0.041) showed DAXX/ATRX loss, with one showing coexisting retinoblastoma 1 and SMAD4 loss. P53 staining pattern was wild type in all cases. Whole exome sequencing of 10 cases showed DAXX, ATRX, and multiple endocrine neoplasia type 1 alterations in O-NETs and C-NETs, and coexisting DNMT3A and MTOR alterations in one O-NET.

O-NET subtype is associated with advanced disease and unfavorable outcomes compared to C-NETs. O-NETs are cytologically distinct, male-predominant tumors that often present with higher grade and advanced disease. Their aggressive behavior is possibly related to frequent DAXX/ATRX loss and less likely PDNEC-related molecular alterations. Pathologists should be mindful of this aggressive morphologic subtype and clearly convey its presence in pathology reports.

Metabolic flexibility, a key hallmark of cancer, reflects aberrant tumour changes associated with metabolites. The metabolic plasticity of pancreatic neuroendocrine tumours (pNETs) remains largely unexplored. Notably, the heterogeneity of pNETs complicates their diagnosis, prognosis, and therapeutic management.

Here, we compared the plasma metabolomic profiles of patients with pNET and non-cancerous individuals to understand metabolic dysregulation.

Plasma metabolic profiles of 76 patients with pNETs and 38 non-cancerous individuals were analyzed using LC-MS/MS and FIA-MS/MS (Biocrates AbsoluteIDQ p180 kit). Statistical analyses, including univariate and multivariate methods, were performed along with the generation of receiver operating characteristic (ROC) curves for metabolomic signature identification.

Compared with non-cancerous individuals, patients with pNET exhibited elevated levels of phosphoglyceride metabolites and reduced acylcarnitine levels, indicating an upregulation of fatty acid oxidation (FAO), which is crucial for the energy metabolism of pNET cells and one-carbon metabolism metabolites. Elevated glutamate levels and decreased lipid metabolite levels have been observed in patients with metastatic pNETs. Patients with the germline MEN1 mutations showed lower amino acid metabolites and FAO, with increased metabolites related to leucine catabolism and lipid metabolism, compared to non-MEN1 mutated patients. The highest area under the ROC curve was observed in patients with pNET harbouring MEN1 mutations.

This study highlights the distinct plasma metabolic signatures of pNETs, including the critical role of FAO and elevated glutamate levels in metastasis, supporting the energy and biosynthetic needs of rapidly proliferating tumour cells. Mapping of these dysregulated metabolites may facilitate the identification of new therapeutic targets for pNETs management.

Surgery is the primary treatment for pancreatic neuroendocrine carcinoma (PNEC), however, the optimal surgical approach remains undetermined. We aimed to compare long-term survival outcomes between patients who received local resection (LR) and radical resection (RR) for PNEC without distant metastasis. Patients diagnosed with PNEC between 2000 and 2020 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Selection bias was minimized by using propensity score matching (PSM). The Kaplan-Meier method and multivariate Cox proportional hazards models were utilized to evaluate overall survival (OS) and cancer-specific survival (CSS). A total of 1331 patients were enrolled in the study, with 678 receiving LR and 653 undergoing RR. The RR group exhibited a poorer grade, larger tumor size, and TN stage compared to the LR group (P <  0.05). After PSM, 450 matched pairs of patients were compared, with no significant differences in demographic and clinical characteristics observed. No significant differences were observed in long-term OS (P =  0.746) or CSS (P =  0.634) between the two groups. Subgroup analyses also demonstrated comparable OS and CSS between the LR and RR groups (P >  0.05). Multivariate Cox analysis revealed age, AJCC stage, N stage, and chemotherapy as independent prognostic risk factors for OS, while AJCC stage and N stage were identified as independent prognostic risk factors for CSS. Our study demonstrated that in patients with PNEC without distant metastasis, LR and RR exhibit similar prognoses, suggesting that LR may be adequate as a treatment option for these patients.

Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare tumors originating from neuroendocrine cells. Due to lack of neuroendocrine symptoms and specific radiographic characteristics, PHNETs are challenging to differentiate from other liver tumors.

This case involved a 67-year-old male who was admitted with a discovered hepatic mass and a suspicious lung lesion. Primary hepatic carcinoma was initially speculated based on the characteristic magnetic resonance imaging findings. The patient underwent a laparoscopic right partial hepatectomy, and subsequent immunohistochemical examination revealed a HNET. To exclude other potential origins, a positron emission tomography-computed tomography scan and gastrointestinal endoscopy were performed, leading to a final diagnosis of PHNETs. Then we conducted a literature review using the PubMed database, identifying 99 articles and 317 cases related to PHNETs. The characteristics, diagnostic methods, and treatment of PHNETs have been described. Finally, we elaborate on the presumed origins, pathological grades, clinical features, diagnosed methods, and treatments associated with PHNETs.

The diagnosis of PHNETs was primarily an exclusionary process. A definitive diagnosis of PHNETs relied mainly on immunohistochemical markers (chromogranin A, synaptophysin, and cluster of differentiation 56) and exclusion of primary foci in other organs. Radical surgery was the preferred treatment for early-stage tumors.

Mixed neuroendocrine-non-neuroendocrine tumors (MINEN) of the liver are exceptionally rare, with limited data available regarding their clinical behavior, pathogenesis, and optimal management. The coexistence of hepatocellular carcinoma (HCC) and neuroendocrine carcinoma (NEC) within the liver presents diagnostic and therapeutic challenges.

A systematic literature search was conducted on PubMed, identifying cases of primary mixed HCC and NEC in the liver. The search adhered to PRISMA guidelines, and relevant studies were critically analyzed. A total of 45 documented cases were reviewed, focusing on patient demographics, clinical characteristics, treatment strategies, and outcomes.

Most patients (90%) were male, with a median age of 66.5 years. Hepatitis B or C infection was present in 74% of cases, and liver cirrhosis was reported in 38%. The combined type was the most frequently observed histological pattern (65%). Treatment modalities varied, including transarterial chemoembolization (TACE), radiofrequency ablation (RFA), surgery, and systemic therapies. The median overall survival was 10 months, highlighting the aggressive nature of these tumors.

Given the rarity and poor prognosis of hepatic MINEN tumors, multidisciplinary management is essential. Advanced molecular profiling may offer insights into tumor biology and potential therapeutic targets. Future research should explore novel systemic therapies, including immune checkpoint inhibitors, to improve patient outcomes.

Canine neoplasms of the diffuse neuroendocrine system are an enigmatic and heterogeneous group of neoplasms with a wide spectrum of immunohistochemical properties and morphologic features. Through the utilization of tissue microarrays, 82 canine neoplasms of the disseminated neuroendocrine system from 16 different anatomic locations were evaluated. The prototypical canine neoplasm of the disseminated neuroendocrine system was composed of rounded polygonal neoplastic cells arranged in packets supported by delicate fibrovascular stroma. Neoplastic cells typically had moderate quantities of pale eosinophilic cytoplasm stippled by numerous fine argyrophilic granules, round nuclei with finely stippled chromatin, and inconspicuous nucleoli. Immunohistochemical assays utilized in this study included chromogranin A, neuron-specific enolase (NSE), microtubule-associated protein 2 (MAP2), pan-cytokeratin, oligodendrocyte transcription factor 2 (OLIG2), protein gene product 9.5 (PGP9.5), vimentin, synaptophysin, neuronal nuclei (NeuN), S100, SRY-related HMG-box 10 (SOX10), glial fibrillary acidic protein (GFAP), insulinoma-associated protein 1 (INSM1), CD56, and antigen Kiel 67 (Ki67). The 4 immunohistochemical assays that were positive in over 50% of cases included PGP9.5 (77/82, 94%), NSE (68/82, 83%), synaptophysin (59/82, 72%), and chromogranin A (56/82, 69%). In 81/82 (99%) cases, neoplastic cells immunolabeled with at least 1 of these 4 assays, and thus, these 4 immunohistochemical assays are deemed most useful when attempting to substantiate that a neoplasm is of neuroendocrine origin.

Background/Objectives: Neuroendocrine tumors (NETs) can arise in any organ and are most commonly found in the lungs and gastroenteropancreatic (GEP) system. GEP-NETs represent a small percentage of gastrointestinal cancers, and therefore, the standard treatment is not well-defined, especially for advanced disease. Our objective is to review GI NETs among veterans and analyze their therapeutic outcomes. Methods: A total of 61 GI NET cases were identified from our institution from 2019-2024. In total, twenty-seven review papers, ten population-based/multicenter/outcome studies, six case reports, and one case series were reviewed for the literature review. Results: The incidence of GI NETs at our institution was higher than the known epidemiology of GI NETs. Small intestine NETs were one of the most common sites of GEP-NETs at our institution, with only one of nineteen cases being grade 3 poorly differentiated neuroendocrine carcinoma. All cases of colonic and rectal NETs had good clinical outcomes consistent with findings from the literature. Most of the gastric NETs were type 1 and had benign courses of disease, except for one case with an intermediate grade and metastatic liver lesions. One case of esophageal neuroendocrine carcinoma (E-NEC) showed a complete response to chemotherapy despite a significant tumor burden on presentation and high-grade pathology, while another case of ENEC had recurrent disease despite systemic therapy. Conclusions: While the role of surgery or endoscopic resection is limited to localized tumors, combined treatment with chemoradiation can significantly improve patient outcomes, especially in high-grade, poorly differentiated tumors. Further studies are needed to establish systemic (i.e., chemotherapy and radiation) treatment strategies for poorly differentiated GI NETs.