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Neuroendocrine tumors of the small intestine (SI‐NETs) often develop lymph node metastasis (LNM)‐induced mesenteric fibrosis (MF). MF can cause intestinal obstruction as well as ischemia and render surgical resection technically challenging. The underlying pathomechanisms of MF are still not well understood. We examined mesenteric LNM and the surrounding stroma compartment from 24 SI‐NET patients, including 11 with in situ presentation of strong MF (MF+) and 13 without MF (MF−). Differential gene expression was assessed with the HTG EdgeSeq Oncology Biomarker Panel comparing MF+ with MF− within LNM and paired stromal samples, respectively. Most interesting differentially expressed genes were validated by reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) in combination with validation of associated protein levels utilizing immunohistochemistry (IHC) staining of MF+ and MF– formalin‐fixed, paraffin‐embedded (FFPE) patient samples. Overall, 14 genes measured with a 2549‐gene expression panel were differentially expressed in MF+ patients compared to MF−. Of those, nine were differentially expressed genes in LNM and five genes in the stromal tissue (>2‐fold change, p <.05). The top hits included increased COMP and COL11A1 expression in the stroma of MF+ patients compared to MF−, as well as decreased HMGA2, COL6A6, and SLC22A3 expression in LNM of MF+ patients compared to LNM of MF− patients. RT‐qPCR confirmed high levels of COMP and COL11A1 in stroma samples of MF+ compared to MF− patients. IHC staining confirmed the enrichment of α‐smooth muscle actin‐positive fibrosis in MF+ compared to MF− patients with corresponding increase of COMP‐expressing stromal cells in MF+. Since COMP is associated with the known driver for fibrosis development transforming growth factor beta and with a cancer‐associated fibroblasts enriched environment, it seems to be a promising new target for MF research. [ABSTRACT FROM AUTHOR]

Background: The ocular involvement of neuroendocrine neoplasms (NENs) is uncommon and mainly represented by metastases from gastrointestinal and lung neuroendocrine tumors. Primary orbital NENs are even less common and their diagnostic and therapeutic management is a challenge. Methods: A systematic review of the literature was conducted from 1966 to September 2023 on PubMed to identify articles on orbital NENs and to summarize their clinical–pathological features, diagnosis and therapeutic management. Furthermore, we presented a case of a locally advanced retro-orbital primary neuroendocrine tumor that was referred to the certified Center of Excellence of Sant'Andrea Hospital, La Sapienza University of Rome, Italy. Results: The final analysis included 63 records on orbital NENs and 11 records focused on primary orbital NENs. The localization was mostly unilateral and in the right orbit; proptosis or exophthalmos represented the initial symptoms. The diagnostic work-up and therapeutic management was discussed and a diagnostic algorithm for the suspicion of primary orbital NENs was proposed. Conclusions: A multidisciplinary approach is required for the management of primary orbital NENs, emphasizing the importance of early referral to dedicated centers for prompt differential diagnosis, tailored treatment, and an improved quality of life and survival. [ABSTRACT FROM AUTHOR]

Paragangliomas are neuroendocrine tumors that have the potential to secrete catecholamines. They have been linked to genetic mutations in the mitochondrial succinate dehydrogenase (SDH) complex. Patients can experience both physical symptoms and psychiatric symptoms like anxiety, depression, and psychosis. These symptoms can occur as paroxysmal episodes with periods of increased catecholamine secretion. We describe a patient with SDHB gene mutation, who has been diagnosed with a jugular paraganglioma, and was brought to the hospital under Baker Act for threats made online. Since diagnosis this patient has been experiencing both anxiety and post-traumatic stress disorder (PTSD). The patient and a family member report increased emotional lability, and the patient reports multiple daily episodes of anxiousness. This case outlines the connection between paragangliomas and psychiatric symptoms, the impact they can have on patients' daily lives, and the importance of addressing the possibility of these symptoms and establishing a multispecialty healthcare team at the time of diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: In patients with neuroendocrine tumors (NETs) and liver metastases, increased gamma-glutamyltransferase (GGT) is commonly assumed as an indicator for progressive disease. To date, however, empirical data are lacking. This study aimed to investigate associations between GGT and liver tumor burden. In longitudinal analyses, associations of GGT and radiographic responses of liver metastases under therapy were investigated. Methods: The cross-sectional sample consisted of 104 patients who were treated at the University Medical Center Hamburg-Eppendorf from 2008 to 2021 (mean age 62.3 ± 12.6 years, 58.7% male). GGT and liver imaging were identified in a time range of 3 months. Radiologic reassessments were performed to estimate liver tumor burden. In a separate longitudinal sample (n = 15), the course of GGT levels under chemotherapy was analyzed. Data were retrospectively analyzed with a univariate ANOVA, linear regression analyses, and Wilcoxon tests. Results: Of 104 cross-sectionally analyzed patients, 54 (51.9%) showed a GGT elevation. GGT levels and liver tumor burden were positively correlated (p < 0.001), independently from age, gender, primary tumor location, grading, and cholestasis. Notably, GGT increase was associated with a liver tumor burden of >50%. In the longitudinal sample, 10 of 11 patients with progressive disease showed increasing GGT, whereas 4 of 4 patients with regressive disease showed declining GGT. Conclusion: Our findings indicate that GGT is associated with liver tumor burden. Over the course of therapy, GGT appears to change in line with radiographic responses. Further longitudinal studies with larger sample sizes are required to define GGT as a reliable marker for tumor response. [ABSTRACT FROM AUTHOR]

Well-differentiated neuroendocrine tumor, Grade 1 (NET, G1), in the hypopharynx is extremely rare. A 62-year-old woman was referred to our clinic with a tumor in the postcricoid area. The tumor was diagnosed NET on biopsy and there were no metastatic findings on CT, therefore we performed endoscopic resection. Histologic examination revealed well-differentiated neuroendocrine tumor, Grade 1. This case was an extremely rare and valuable case in which endoscopic images can be observed in detail. Endoscopic resection was performed and successful endoscopic and histological resection was achieved. [ABSTRACT FROM AUTHOR]

Background: Young women with NF1 are at a high risk of developing breast cancer. Although they are at risk for abdominal tumors, such as gastrointestinal stromal tumors and neuroendocrine tumors, follow-up strategies for other tumors after breast cancer have not yet been established. Here, we present a case of duodenal neuroendocrine tumor found during follow-up after bilateral mastectomy for breast cancer with type 1 neurofibromatosis (NF1), for which pancreaticoduodenectomy (PD) and lymphadenectomy were performed. Case presentation: A 46-year-old woman with NF1 was referred to our hospital for treatment of a duodenal submucosal tumor. Her previous operative history included bilateral mastectomy for breast cancer: right total mastectomy and left partial mastectomy performed 9 and 5 years ago, respectively. Her daughter was confirmed to have NF1, but her parents were unclear. Although she had no recurrence or symptoms during the follow-up for her breast cancer, she wished to undergo 18-fluorodeoxyglucose–positron emission tomography (FDG–PET) for systemic screening. FDG–PET demonstrated FDG accumulation in the duodenal tumor with a maximum standardized uptake value of 5.78. Endoscopy revealed a 20-mm-diameter tumor in the second duodenal portion, and endoscopic biopsy suggested a NET G1. We performed PD and lymphadenectomy for complete. She was doing well without recurrence and was followed up with PET tomography–computed tomography. Conclusions: Early detection of gastrointestinal tumors is difficult, because most of them are asymptomatic. Gastrointestinal screening is important for patients with NF1, and PD with lymphadenectomy is feasible for managing duodenal neuroendocrine tumors, depending on their size. [ABSTRACT FROM AUTHOR]

Introduction: Neuroendocrine neoplasms (NEN) are a rare and heterogenous group of tumors arising from neuroendocrine cells in multiple organs. Neuroendocrine tumors (NET) G3 encompass a small subgroup accounting for less than 10% of all neuroendocrine neoplasms. In contrast to NET G1 and G2 as well as neuroendocrine carcinomas (NEC), in NET G3 data on treatment and patient outcomes are still limited. Especially in a metastasized tumor stage, the role of surgery, peptide receptor radionucleotide therapy (PRRT), and systemic chemotherapy is not clearly defined. Methods: In this real-life cohort, we consecutively analyzed clinical outcome in NET G3 patients receiving different diagnostic and treatment. Results and discussion: We found that even metastasized NET G3 patients undergoing surgery, or receiving radiation, somatostatin analogues (SSA), and PRRT showed a clear survival benefit. Interestingly, all treatment regimen were superior to classical chemotherapeutic agents. In addition, somatostatin receptor (SSTR) PET-CT, FDG PET-CT, and repetitive biopsies were shown to be useful diagnostic and prognostic tools in NET G3. Our study demonstrates that patients with highly proliferative NET G3 might benefit from less aggressive treatment modalities commonly used in low proliferative NEN. [ABSTRACT FROM AUTHOR]

Introduction: Medullary thyroid carcinoma (MTC) is a rare thyroid malignancy originating from parafollicular C cells. It accounts for 5%-10% of all thyroid malignancies. Methods: An ambispective analysis of pathologically proven MTC presented in a tertiary care hospital in northwest India was performed after considering demography, clinical manifestation, RET mutation status, management, and outcome as denominators. Results: Among 2,735 thyroid malignancy cases who presented to our institute in the last 10 years (2012-2022), 78 (3%) had MTC with a mean age of presentation of 43 ± 11 years; 60% of them were female. The median duration of symptoms was 23 months (IQR 12-36 months). The most common presenting complaint was goiter with lymphadenopathy (80.8%). Among the atypical presentations, one each had ectopic Cushing's syndrome, hypertensive crisis in pregnancy due to pheochromocytoma, synchronous chondrosarcoma, and Von Hippel-Lindau disease spectrum. Median calcitonin and carcinoembryonic antigen (CEA) levels at presentation were 1,274 pg/mL (n = 64) and 149 ng/mL (n = 39), respectively. Twenty-two patients were germline RET mutation-positive, and they presented at a younger age. Majority of the patients presented with stage IV disease. Surgery was the primary modality of therapy. Twenty-nine patients received radiotherapy and 25 patients received tyrosine kinase inhibitors (TKIs). Nine patients received peptide receptor radiotherapy (PRRT) with Lu-177 with neoadjuvant capecitabine. Median progression-free survival (PFS) was 60 months. Patients without structurally and biochemically residual disease and stable disease after the first modality of therapy (Log-rank 11.4; p = 0.004) had a better PFS. Female patients (Log-rank: 9.5; p = 0.002) had a better PFS than male patients. Conclusion: This study showed that MTC comprises 3% of thyroid malignancies with a female preponderance. RET mutation-positive patients had a younger age at presentation. Surgery was the first-line therapy. Radiotherapy, TKI, and PRRT were given as a part of second-line or thirdline therapy due to persistent disease and/or disease recurrence. The median PFS was better in female patients and in patients who had no residual lesions and stable disease after the primary modality of therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Neuroendocrine tumors of the bowel and pancreas are slow-growing cancers that, if identified early, can be treated with surgery. However, even if surgery is successful, many patients must undergo surveillance imaging to check for recurrence; this involves CT or MRI scans every one to two years for up to ten years. CT scans are associated with radiation exposure, which can increase the risk of additional cancers later in life. We sought to assess real life radiation exposure associated with surveillance imaging for patients at our center with surgically removed neuroendocrine tumors. We reviewed patient charts to collect information about the scans they underwent and calculated the total radiation dose they received during follow-up. We found that the average total radiation dose was in the range associated with increased cancer risk. We suggest strategies to minimize radiation risk should be considered in future recommendations for surveillance of neuroendocrine tumors. Background: Neuroendocrine tumors (NET) are neoplasms that secrete peptides and neuroamines. For gastroenteropancreatic (GEP) NET, surgical resection represents the only curative option. Ten-year imaging surveillance programs are recommended due to long time-to-recurrence following resection. We performed retrospective chart review evaluating radiation exposure and practice patterns from surveillance of completely resected GEP NET. Methods: We performed a retrospective cohort study of cases with well-differentiated GEP NET from January 2005 to July 2020. Location of primary, modality of imaging, and duration of follow-up were collected. Dosimetry data was collected to calculate effective dose. Results: 62 cases were included with 422 surveillance scans performed. Cross-sectional imaging was used in 82% and functional imaging was used in 18% of scans. Mean number of scans per year was 1.25 (0.42–3). Mean total effective dose was 56.05 mSv (SD 45.56; 0 to 198 mSv) while mean total effective dose per year was 10.62 mSv (SD 9.35; 0 to 45 mSv). Over the recommended ten years of surveillance the estimated total effective dose was 106 mSv. Conclusions: Surveillance of completely resected GEP NET results in cumulative radiation doses in the range associated with secondary malignancy development. Strategies to minimize radiation exposure in surveillance should be considered in future guideline development. [ABSTRACT FROM AUTHOR]

In the case of neuroendocrine tumors (NETs), additional resection should be considered if the pathological examination shows positive for lymphovascular invasion, but there is not enough evidence on the long-term prognosis. Among patients with a NET G1 < 1 cm in diameter which was confined to the submucosal layer and treated endoscopically at our hospital between January 2005 and December 2021, 44 (27.8%) with vascular invasion were enrolled to investigate the lymph node/distant metastasis rate and the recurrence/mortality rate. Twelve patients were placed in the additional resection group (two with lymph node metastasis), and 32 were placed in the no additional treatment group (five with death from other causes). No distant metastasis, recurrence, or current death was observed in either group. There was also no recurrence of or death due to primary tumor among the patients with positive vascular invasion after endoscopic treatment of a NET G1 tumor < 1 cm in diameter. Colostomy was required in 75% of the patients who underwent an additional resection. Moreover, there were some cases of lymph node metastasis. The decision to perform an additional surgical resection should take into account the patient􀁠s wishes in terms of quality of life and the recurrence rate. How to stratify patients for follow-up remains an issue for future study. [ABSTRACT FROM AUTHOR]

Gastric neuroendocrine neoplasms refer to a group of diseases that are relatively rare. They can be classified into three subtypes based on their clinical and histopathological features, and there are significant differences in diagnosis, treatment, and prognosis among the different subtypes. The incidence of gastric neuroendocrine neoplasms has been increasing globally in recent years with the localized disease being particularly evident. Gastrointestinal endoscopy is of irreplaceable importance for the diagnosis and management of g-NENs. Endoscopy with biopsy is the gold standard for the diagnosis of g-NENs. Ultrasound endoscopy can assess the depth of tumor invasion and the presence of lymphatic metastases, which is important for the development of treatment strategies. Meanwhile, for some small and low-risk lesions, endoscopic surveillance or endoscopic resection has satisfactory therapeutic results and prognosis. This means that even though the incidence has increased, advances in endoscopic techniques have allowed more patients to adopt a relatively conservative treatment strategy. However, the criteria for patients suitable for endoscopic surveillance or endoscopic resection remain controversial. [ABSTRACT FROM AUTHOR]

Introduction: Ampullary neuroendocrine tumors (NETs) are usually diagnosed in the 5th–6th decades of life, and no cases were reported in <20 years of age. We report a rare case, presenting at a very young age, of well-differentiated NET involving the ampulla of Vater with lymph node metastasis. Case Presentation: An 18-year-old man presented with a 3-month history of upper abdominal pain and jaundice. Abdominal ultrasound showed a dilated common bile duct, and endoscopic retrograde cholangiopancreatography revealed two duodenal polypoid lesions, one of them overlying the ampulla of Vater, with an erythematous and ulcerated surface. Histopathological examination confirmed the diagnosis of NET grade 1. Octreotide scan revealed 2 para-aortic lymph nodes with intense radiotracer uptake. The patient had undergone Whipple surgery with para-aortic lymph node dissection. Histopathological examination of the surgical specimens was confirmatory of NET grade 2 and paraganglioma in a few of the dissected lymph nodes. Postoperatively, the patient was kept on monthly intramuscular octreotide. Follow-up gallium-68 DOTATATE is unremarkable apart from an avid left para-aortic lymph node which is showing stability over 12 months of follow-up. Conclusion: This case demonstrates that NETs of the ampulla of Vater can present at a very young age. Radical surgical excision with extended lymph node dissection and postoperative octreotide is associated with better patient outcomes and survival. [ABSTRACT FROM AUTHOR]

Background: The risk‐benefit balance of prophylactic appendectomy in patients undergoing left colorectal cancer resection is unclear. The aim of this report is to assess the proportion of histologically abnormal appendices in patients undergoing colorectal cancer resection in a unit where standard of care is appendectomy, with consent, when left‐sided resection is performed. Methods: A retrospective study on a prospectively collected database was conducted in a single tertiary‐care center. Overall, 717 consecutive patients undergoing colorectal cancer resection between January 2015 and June 2021 were analyzed. The primary outcome was the proportion of histologically abnormal appendix specimens at prophylactic appendectomy. The secondary outcome was complications from prophylactic appendectomy. Results: Overall, 576/717 (80%) patients had appendectomy at colorectal cancer surgery. In total, 234/576 (41%) had a right‐/extended‐right hemicolectomy or subtotal colectomy which incorporates appendectomy, and 342/576 (59%) had left‐sided resection (left‐hemicolectomy, anterior resection or abdominoperineal excision) with prophylactic appendectomy. At definitive histology, 534/576 (92.7%) had a normal appendix. The remaining 42/576 (7.3%) showed abnormal findings, including: 14/576 (2.4%) inflammatory appendix pathology, 2/576 (0.3%) endometriosis, 8/576 (1.4%) hyperplastic polyp, and 18/576 (3.1%) appendix tumors, which encompassed six low‐grade appendiceal mucinous neoplasms (LAMNs), three carcinoids, and nine serrated polyps. In the 342 patients who had prophylactic appendectomy, 10 (2.9%) had a neoplasm (two LAMN, three carcinoids, and five serrated polyps). There were no complications attributable to appendectomy. Conclusion: Occult appendix pathology in patients undergoing colorectal cancer resection is uncommon when prophylactic appendectomy was performed. However, approximately 3% of patients had a synchronous appendix neoplasm. [ABSTRACT FROM AUTHOR]

Simple Summary: 177Lu-DOTATATE is a radioactive drug that can treat advanced neuroendocrine tumors, a type of cancer. However, some patients do not benefit from 177Lu-DOTATATE treatment and there is an unmet need to identify such patients before they receive the treatment. Currently, each patient needs to have a positive result on a scan, such as 68Ga-DOTATATE PET/CT, prior to receiving 177Lu-DOTATATE treatment to verify that the drug can attack the patient's cancer. This study used a semi-automatic analysis of 68Ga-DOTATATE PET/CT to predict the results of 177Lu-DOTATATE treatment. Having a large amount of cancer and/or a tumor with low signal on 68Ga-DOTATATE PET/CT predicted poor results of 177Lu-DOTATATE therapy. The semi-automatic nature of this method allows identification of patients at risk for treatment failure with little time and effort. Background: Treatment of metastatic neuroendocrine tumors (NET) with 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) results in favorable response only in a subset of patients. We investigated the prognostic value of quantitative pre-treatment semi-automatic 68Ga-DOTATATE PET/CT analysis in NET patients treated with PRRT. Methods: The medical records of 94 NET patients who received at least one cycle of PRRT at a single institution were retrospectively reviewed. On each pre-treatment 68Ga-DOTATATE PET/CT, the total tumor volume (TTV), maximum tumor standardized uptake value for the patient (SUVmax), and average uptake in the lesion with the lowest radiotracer uptake (SUVmin) were determined with a semi-automatic tumor delineation method. Progression-free survival (PFS) and overall survival (OS) among the patients were compared based on optimal cutoff values for the imaging parameters. Results: On Kaplan–Meier analysis and univariate Cox regression, significantly shorter PFS was observed in patients with lower SUVmax, lower SUVmin, and higher TTV. On multivariate Cox regression, lower SUVmin and higher TTV remained predictive of shorter PFS. Only higher TTV was found to be predictive of shorter OS on Kaplan–Meier and Cox regression analyses. In a post hoc Kaplan–Meier analysis, patients with at least one high-risk feature (low SUVmin or high TTV) showed shorter PFS and OS, which may be the most convenient parameter to measure in clinical practice. Conclusions: The tumor volume and lowest lesion uptake on 68Ga-DOTATATE PET/CT can predict disease progression following PRRT in NET patients, with the former also predictive of overall survival. NET patients at risk for poor outcomes following PRRT can be identified with semi-automated quantitative analysis of 68Ga-DOTATATE PET/CT. [ABSTRACT FROM AUTHOR]

Research on rare tumors heavily relies on suitable models for basic and translational research. Paragangliomas (PPGL) are rare neuroendocrine tumors (NET), developing from adrenal (pheochromocytoma, PCC) or extra-adrenal (PGL) chromaffin cells, with an annual incidence of 2–8 cases per million. While most PPGL cases exhibit slow growth and are primarily treated with surgery, limited systemic treatment options are available for unresectable or metastatic tumors. Scarcity of appropriate models has hindered PPGL research, preventing the translation of omics knowledge into drug and therapy development. Human PPGL cell lines are not available, and few animal models accurately replicate the disease's genetic and phenotypic characteristics. This review provides an overview of laboratory models for PPGLs, spanning cellular, tissue, organ, and organism levels. We discuss their features, advantages, and potential contributions to diagnostics and therapeutics. Interestingly, it appears that in the PPGL field, disease models already successfully implemented in other cancers have not been fully explored. [ABSTRACT FROM AUTHOR]

Introduction: Paraganglioma of the urinary bladder (PUB) is an extremely rare extra-adrenal catecholamine-secreting neuroendocrine tumor, accounting for only 0.05% of all bladder tumors and 1% of all pheochromocytomas. The clinical presentation of PUB can be diverse and challenging to diagnose. Case Presentation: This case report presents a 37-year-old man with post-micturition palpitation, headache, and sweating, with no history of hematuria or other irritative urinary symptoms. Ultrasound and contrast-enhanced computed tomography revealed a suspicious mass in the right posterolateral wall of the urinary bladder. Despite normal functional hormonal tests, the diagnosis of PUB was confirmed after surgical enucleation and histopathological examination. Conclusion: This report emphasizes the importance of considering PUB as a differential diagnosis in patients with post-micturition symptoms and paroxysmal hypertension, as well as the need for a multidisciplinary approach in the evaluation and management of such rare and complex cases. Early recognition and surgical intervention are crucial for optimal management and favorable clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Early-Onset (EO) pancreatic neuroendocrine tumor (Pan- NET) is a rare disease, but whether it is clinically different from lateonset (LO) PanNET is unknown. Our study aimed to evaluate clinical differences and disease outcomes between EO-PanNET and LOPanNET and to compare sporadic EO-PanNET with those with a hereditary syndrome. Methods: Patients with localized PanNET who underwent pancreatectomy at Memorial Sloan Kettering between 2000 and 2017 were identified. Those with metastatic disease and poorly differentiated tumors were excluded. EO-PanNET was defined as <50 and LO-PanNET >50 years of age at the time of diagnosis. Family history and clinical and pathology characteristics were recorded. Results: Overall 383 patients were included, 107 (27.9%) with EOPanNET. Compared with LO-PanNET, EO-PanNET were more likely to have a hereditary syndrome (2.2% vs. 16%, P<0.001) but had similar pathology features such as tumor grade (P=0.6), size (2.2 Vs. 2.3 cm, P=0.5) and stageof disease (P=0.8). Among patients with EO-PanNET, those with hereditary syndrome had more frequently a multifocal disease (65% vs. 3.3%, P<0.001). With a median follow-up of 70 months (range 0-238), the 5-year cumulative incidence of recurrence after curative surgery was 19% (95% CI 12%-28%) and 17% (95% CI 13%-23%), in EO-PanNET and LO-PanNET (P=0.3). Five-year disease-specific survivalwas 99%(95%CI 98%-100%)with no difference with respect to PanNET onset time (P=0.26). Conclusions: In this surgical cohort, we found that EO-PanNET is associated with hereditary syndromes but has pathologic characteristics and oncological outcomes similar to LO-PanNET. These findings suggest that patients with EO-PanNET can be managed similarly to those with LO-PanNET. [ABSTRACT FROM AUTHOR]

Copyright of Revista Mexicana de Endocrinología, Metabolismo y Nutrición is the property of Publicidad Permanyer SLU and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Case summary This report describes the case of a 7-year-old male neutered domestic mixed-breed cat that was initially referred to the Veterinary Hospital of the State University of Londrina for evaluation of a 2-week history of abdominal distension and a 2-day history of anorexia, infected with feline immunodeficiency virus (FIV). Abdominal ultrasound revealed an expansive mass located around the pancreas and right hepatic lobe. In the transoperative macroscopic observation, multiple white nodules were visualized in the liver, pancreas, mesentery, intestine, stomach and peritoneal wall. Immunohistochemical examination revealed that neoplastic cells demonstrated a strong positivity for AE1/AE3 and CK20. A sparse immunoreactivity to chromogranin A was observed, which demonstrates neuroendocrine cell labeling. The histopathologic changes associated with the immunohistochemical profile confirmed the diagnosis of metastatic carcinoma with neuroendocrine differentiation, originating from the pancreas. Relevance and novel information Neuroendocrine tumors of the pancreas are rare and are associated with a poor prognosis in humans. In humans, approximately 7% of neuroendocrine tumors develop in the pancreas, and the 5-year survival rate for a pancreatic neuroendocrine tumor is 53%, according to the American Cancer Society. To our knowledge, only one case has been described in the feline species so far. Due to the rarity of this type of tumor in cats, there is little information about predisposition related to age, sex or breed, as well as the main clinical signs presented, survival time and treatment options. [ABSTRACT FROM AUTHOR]

Copyright of Tesla Revista Científica is the property of Puerto Madero Editorial Academica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: Capecitabine–Temozolomide (CapTem) is an oral chemotherapy regimen for NETs. Both drugs are radiosensitizers. Integrating CapTem and Y90 transarterial radioembolization (TARE) in patients with grade 2 neuroendocrine tumor (NET) liver metastases achieved an encouraging objective response rate (ORR) and progression-free survival (PFS) in a feasibility study. This study expands that report to a larger cohort with longer follow-up. Methods: Therapy consisted of monthly cycles of capecitabine 600 mg/m2 twice daily for 14 days and temozolomide 150–200 mg/m2 on day 10–14. Simulation angiography was performed during the initial cycle. The dominant lobe was treated with 90Y-resin microspheres using BSA dosimetry on day 7 of the second cycle of CapTem. Patients with bilobar disease had the other lobe treated on day 7 of the third or fourth cycle. CapTem was continued until progression or intolerance. Clinical and laboratory assessment was done monthly and imaging every 3 months. Results: 35/37 patients completed the prescribed regimen. Primary sites of disease were pancreas (16), lung (10), gut (7) and unknown (4). Mean duration of CapTem was 12 months (range, 4–32 months). ORR in the liver was 72% with a disease control rate of 100%. Median PFS was 36 months (95% CI, 25–45 months). Median overall survival was 41 months (95% CI, 24–87 months) from initiation of CapTemY90 therapy and 130 months (95% CI, 56–172 months) from initial diagnosis. Conclusion: Chemoradiation with CapTem and TARE provided durable control of G2 NET liver metastases for substantially longer than expectations for embolotherapy or chemotherapy alone. [ABSTRACT FROM AUTHOR]

Despite the fact that important advances in research on neuroendocrine neoplasms (NENs) have been made, consistent data about their pathogenetic mechanism are still lacking. Furthermore, different primary sites may recognize different pathogenetic mechanisms. This review analyzes the possible biological and molecular mechanisms that may lead to NEN onset and progression in different organs. Through extensive research of the literature, risk factors including hypercholesterolemia, inflammatory bowel disease, chronic atrophic gastritis are evaluated as potential pathogenetic mechanisms. Consistent evidence is available regarding sporadic gastric NENs and MEN1 related duodenopancreatic NENs precursor lesions, and genetic-epigenetic mutations may play a pivotal role in tumor development and bone metastases onset. In lung neuroendocrine tumors (NETs), diffuse proliferation of neuroendocrine cells on the bronchial wall (DIPNECH) has been proposed as a premalignant lesion, while in lung neuroendocrine carcinoma nicotine and smoke could be responsible for carcinogenic processes. Also, rare primary NENs such as thymic (T-NENs) and Merkel cell carcinoma (MCC) have been analyzed, finding different possible pathogenetic mechanisms. New technologies in genomics and epigenomics are bringing new light to the pathogenetic landscape of NENs, but further studies are needed to improve both prevention and treatment in these heterogeneous neoplasms. [ABSTRACT FROM AUTHOR]

Simple Summary: Peptide receptor radionuclide therapy is a well-established therapy for the treatment of neuroendocrine tumors. Therapy typically consists of four cycles administered in 8–10 week intervals, resulting in an average treatment length of 8–10 months. Given the extensive treatment length, early identification of patients with disease progression could help to optimize disease management. Blood-based biomarkers such as chromogranin A, alkaline phosphatase (ALP), or the De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) are continually assessed during treatment and represent a noninvasive and easily accessible source for the intratherapeutic monitoring of patients. Our exploratory analysis indicates that a considerable intratherapeutic increase in ALP may serve as a tool to identify patients who are at a higher risk of early disease progression after PRRT. If our results can be confirmed by other studies, these patients might benefit from intensified follow-up. Background: Pretherapeutic chromogranin A, alkaline phosphatase (ALP), or De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) are prognostic factors in patients with metastatic neuroendocrine tumors (NET) undergoing peptide receptor radionuclide therapy (PRRT). However, their value for intratherapeutic monitoring remains unclear. We evaluated if changes in plasma markers during PRRT can help identify patients with unfavorable outcomes. Methods: A monocentric retrospective analysis of 141 patients with NET undergoing PRRT with [177Lu]Lu-DOTATOC was conducted. Changes in laboratory parameters were calculated by dividing the values determined immediately before each cycle of PRRT by the pretherapeutic value. Patients with low vs. high PFS were compared with the Wilcoxon rank-sum test. Results: Progression, relapse, or death after PRRT was observed in 103/141 patients. Patients with low PFS showed a significant relative ALP increase before the third (p = 0.014) and fourth (p = 0.039) cycles of PRRT. Kaplan–Meier analysis revealed a median PFS of 24.3 months (95% CI, 20.7–27.8 months) in patients with decreasing ALP values (Δ > 10%) during treatment, 12.5 months (95% CI, 9.2–15.8 months) in patients with increasing ALP values (Δ > 10%), and 17.7 months (95% CI, 13.6–21.8 months) with stable ALP values (Δ ± 10%). Conclusions: Based on these exploratory data, a rise in plasma ALP might indicate disease progression and should be interpreted cautiously during therapy. [ABSTRACT FROM AUTHOR]

Determining neuroendocrine tumor (NET) primary sites is pivotal for patient care as pancreatic NETs (pNETs) and small bowel NETs (sbNETs) have distinct treatment approaches. The diagnostic power and prioritization of fluorescence in situ hybridization (FISH) assay biomarkers for establishing primary sites has not been thoroughly investigated using machine learning (ML) techniques. We trained ML models on FISH assay metrics from 85 sbNET and 59 pNET samples for primary site prediction. Exploring multiple methods for imputing missing data, the impute-by-median dataset coupled with a support vector machine model achieved the highest classification accuracy of 93.1% on a held-out test set, with the top importance variables originating from the ERBB2 FISH probe. Due to the greater interpretability of decision tree (DT) models, we fit DT models to ten dataset splits, achieving optimal performance with k-nearest neighbor (KNN) imputed data and a transformation to single categorical biomarker probe variables, with a mean accuracy of 81.4%, on held-out test sets. ERBB2 and MET variables ranked as top-performing features in 9 of 10 DT models and the full dataset model. These findings offer probabilistic guidance for FISH testing, emphasizing the prioritization of the ERBB2, SMAD4, and CDKN2A FISH probes in diagnosing NET primary sites. [ABSTRACT FROM AUTHOR]

Aim: Primary neuroendocrine tumors in the ovary are rare. These tumors arise from the neuroendocrine cell system of ovarian stroma and surface epithelium, and may also arise from teratoma. We present four primary ovarian neuroendocrine tumors and discuss clinical, histomorphological, and immunohistochemical findings. Methods: Four primary ovarian neuroendocrine tumors were identified from our 4-year departmental archives. H and E slides and immunostains were reviewed. Clinical history, imaging studies, and follow-up data were obtained from medical records. Results: Patients' age ranged from 37 to 45 years. All the patients presented with abdominal discomfort, abnormal uterine bleeding, and unilateral or bilateral ovarian masses. Two of the cases were primary ovarian carcinoid tumors, one being the pure primary ovarian carcinoid tumor (PPOCT), and the other being associated with mature cystic teratoma, while the other two cases were neuroendocrine carcinoma. All the cases showed expression of neuroendocrine markers, namely, synaptophysin, chromogranin, and NSE. Conclusions: Primary neuroendocrine tumors in the ovary are rare and consist of a group of heterogeneous tumors that express similar immunohistochemical markers. [ABSTRACT FROM AUTHOR]

We report a rare case mvolving a 52-year-old female diagnosed with an atypical bronchial carcinoid tumor with metastases to the mediastinum, hilar lymph nodes, breast, and pancreas. In additional, the patient had metastases to the iris and ciliary body, resulting in progressive vision loss in her left eye. Treatment was successful by intravitreal injections of anti-vascular endothelial growth factor. [ABSTRACT FROM AUTHOR]

Pancreatic cancers are the third leading cause of cancer-related death in the USA and outcomes remain poor despite improvements in imaging and treatment paradigms. Currently, computed tomography (CT) and magnetic resonance imaging (MRI) are frequently utilized for staging and restaging of these malignancies, but positron emission tomography (PET)/CT can play a role in troubleshooting and improve whole-body staging. PET/MRI is a novel imaging modality that allows for simultaneous acquisition of PET and MRI images, leading to improved image quality and potential increased sensitivity. Early studies suggest that PET/MRI may play a larger role in pancreatic cancer imaging in future. This manuscript will briefly discuss current imaging approaches to pancreatic cancer and outline existing evidence and published data supporting the use of PET/MRI for pancreatic cancers. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumors of the middle ear are rare, comprising of less than 2% of primary tumors of the ear. The clinical and imaging findings of these tumors are nonspecific, and histological and immunohistochemical findings are confirmatory. Herein, we present a case of 48-year-old male, presenting with chief complaints of hearing loss of left ear with foul smelling discharge, with the initial clinical impression of otomastoiditis of the middle ear with cholesteatoma and being operated for the same, the final histopathology report inferred it as well-differentiated neuroendocrine tumor grade 1 with Ki-67 index less than 2%. Immunohistochemical examinations demonstrated positive staining of the tumor cells for cytokeratin, synaptophysin and chromogranin A, and negative for smooth muscle actin, desmin, S-100. The biochemical investigations showed raised serum chromogranin A levels. Based upon the findings on anatomical imaging modalities including high-resolution computed tomography temporal bone and magnetic resonance imaging paranasal sinuses (MRI PNS), the lesion was inferred inoperable due to involvement of dura of petrous apex, and therefore he was referred for consideration of peptide receptor radionuclide therapy (PRRT). MRI PNS also showed involvement of the horizontal part of facial nerve, indicating local aggressiveness of the tumor. 68 Ga-DOTATATE-PET/CT showed high-grade somatostatin receptor expressing soft tissue lesion involving middle ear and external auditory canal (Krenning's score 4), with low-grade metabolic activity on 18 F-FDG-PET/CT. The post-therapy scan following 177 Lu-DOTATATE PRRT, showed abnormal tracer concentration at the described site. Due to extreme rarity of this disease entity, it is important to accrue data for accurate diagnosis, proper management, and follow-up. [ABSTRACT FROM AUTHOR]

Insulinoma is a multifaceted disease that poses several challenges in terms of clinical presentation, diagnostic work‐up, and surgical management. The aim of this study was to describe diagnostic work‐up, surgical management, and postoperative outcomes of patients with insulinoma. All consecutive patients who underwent surgery for insulinoma at San Raffaele Hospital (Milan, Italy) between January 2008 and January 2022 were included. Overall, 98 patients were considered. The median delay between presenting symptoms and insulinoma diagnosis was 10 months (IQR, 4–21). Insulinoma diagnosis was made at our Institution in 45 patients, 20 of whom referred within 6 months from symptoms onset. In this subgroup, the median interval between symptoms presentation and insulinoma diagnosis was 4 months (IQR, 2–6), as compared to 14 months (IQR, 10–26) in patients (n = 25) who referred to our institution after 6 months from symptoms onset (p <.001). The insulinoma was localized preoperatively in all the cases. All patients underwent ≥1 high‐quality imaging: computed tomography (CT: n = 87, sensitivity 84%), magnetic resonance imaging (MRI: n = 55, sensitivity 85%) and endoscopic ultrasound (EUS: n = 79, sensitivity 100%). MRI identified the tumor in eight patients with negative CT. EUS localized the insulinoma in three patients with negative CT and negative MRI. Parenchyma‐sparing resections were performed in 41 patients. Contact with major vessels, lesion close to Wirsung duct and suspect of malignancy were the main reasons to perform a formal resection. An early referral to high‐volume centers is important for reducing diagnostic delay in patients with insulinoma. The diagnostic work‐up of insulinoma frequently requires several imaging modalities to be performed, with EUS being the most sensitive one. Parenchyma‐sparing surgery for insulinoma should be performed whenever technically and oncologically feasible. [ABSTRACT FROM AUTHOR]

Opinion statement: The treatment of neuroendocrine neoplasm (NEN) liver metastases involves a multidisciplinary approach that includes liver-directed therapies (LDT) and systemic treatments, such as peptide receptor radionuclide therapy (PRRT). LDT has demonstrated efficacy in rapidly reducing tumor bulk, improving symptoms, and delaying disease progression. Interventional radiologists should be consulted prior to switching therapy for patients with progressive or symptomatic neuroendocrine tumor liver metastases. Long-term follow-up data on the safety of Yttrium-90 radioembolization before and after PRRT remain limited. Therefore, a more conservative approach may be to preferentially employ transarterial embolization (TAE) or transarterial chemoembolization (TACE) for patients' somatostatin receptor-avid disease who may be future candidates for PRRT. Notable exceptions where radioembolization may be a preferred treatment strategy may be patients with history of biliary tract instrumentation, asymmetric unilobar disease distribution, and rapidly progressive diffuse liver involvement. Selection of local treatment modality, sequencing, and combination of LDT with systemic therapy require further investigation. [ABSTRACT FROM AUTHOR]

Pancreatic neuroendocrine neoplasms (panNENs) are rare pancreatic neoplasms, and descriptions of treatment remain limited. Autotaxin (ATX) is a secreted autocrine motility factor involved in the production of lysophosphatidic acid (LPA), a lipid mediator that promotes the progression of various cancers. The aim of this study was to clarify the importance of the ATX‐LPA axis in panNENs and to confirm its contribution to panNEN progression using clinical data, cell lines, and a mouse model. Serum ATX level was higher in patients with panNEN than in patients with other pancreatic diseases (chronic pancreatitis, pancreatic ductal adenocarcinoma [PDAC], intraductal papillary mucinous neoplasm, autoimmune pancreatitis) and healthy controls, and 61% of clinical specimens stained strongly for ATX. In a case we encountered, serum ATX level fluctuated with disease progression. An in vitro study showed higher ATX mRNA expression in panNEN cell lines than in PDAC cell lines. Cell proliferation and migration in panNEN cell lines were stimulated via the ATX‐LPA axis and suppressed by RNA interference or inhibitors. An in vivo study showed that intraperitoneal injection of GLPG1690, an ATX inhibitor, suppressed tumor progression in a xenograft model. These findings revealed that ATX expression is significantly elevated in panNEN and is related to the progression of panNEN. We showed the potential of ATX as a novel biomarker and therapeutic target. [ABSTRACT FROM AUTHOR]

To pathologically clarify the macroscopic features of endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNA/B) specimens in representative pancreatic diseases and establish tissue-handling standards based on the macroscopic findings. We gathered EUS-FNA/B specimens of cases at our institution with the final diagnoses of pancreatic ductal adenocarcinoma (PDAC, n = 172), neuroendocrine tumor (NET, n = 19), and chronic inflammatory lesion (CIL, n = 24) including autoimmune pancreatitis. We classified the specimens' macroscopic features in five categories (red strings, mixed-red-and-white strings, white cores, gray tissues, gelatinous tissues) and compared the specimens' features on cytological and histological slides. All five macroscopic categories were observed in variable combinations in the PDACs; red strings and white cores predominated in the NETs and CILs. White cores represented neoplastic (PDAC, NET) or lesion (CIL) tissues. Mixed-red-and-white strings were unique to PDACs and contained cancerous cells. Neoplastic cells were numerous in red strings in NETs but not the other groups. Gray and gelatinous tissues represented necrosis and mucin, respectively, and the former were almost exclusively observed in PDACs. Red strings, mixed-red-and-white strings, and white cores were suitable for histological examination, whereas gray and gelatinous tissues were suitable for cytological examination. The white cores, mixed-red-and-white strings, and gelatinous tissues may be composed of non-neoplastic tissues such as contaminated gastrointestinal epithelium. In seven PDACs, although white cores were obtained, a histological diagnosis was not established. Macroscopic evaluations of EUS-FNA/B can enable the identification of specimen components and a possible diagnosis. They also contribute to the selection of the optimal tissue-handling methods. [ABSTRACT FROM AUTHOR]

Purpose: Multiple endocrine neoplasia type 4 (MEN4) is a rare multiglandular endocrine neoplasia syndrome, associated with a wide tumor spectrum but hallmarked by primary hyperparathyroidism, which represents the most common clinical feature, followed by pituitary (functional and non-functional) adenomas, and neuroendocrine tumors. MEN4 clinically overlaps MEN type 1 (MEN1) but differs from it for milder clinical features and an older patient's age at onset. The underlying mutated gene, CDKN1B, encodes the cell cycle regulator p27, implicated in cellular proliferation, motility and apoptosis. Given the paucity of MEN4 cases described in the literature, possible genotype–phenotype correlations have not been thoroughly assessed, and specific clinical recommendations are lacking. The present review provides an extensive overview of molecular genetics and clinical features of MEN4, with the aim of contributing to delineate peculiar strategies for clinical management, screening and follow-up of the last and least known MEN syndrome. Methods: A literature search was performed through online databases like MEDLINE and Scopus. Conclusions: MEN4 is much less common that MEN1, tend to present later in life with a more indolent course, although involving the same primary organs as MEN1. As a consequence, MEN4 patients might need specific diagnostic and therapeutic approaches and a different strategy for screening and follow-up. Further studies are needed to assess the real oncological risk of MEN4 carriers, and to establish a standardized screening protocol. Furthermore, a deeper understanding of molecular genetics of MEN4 is needed in order to explore p27 as a novel therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Neuroendocrine tumors (NETs) are rare tumors that arise from neuroendocrine cells and are the most common tumors of the appendix. NETs of the appendix usually cause no symptoms and often go unnoticed until they cause acute appendicitis or are discovered during an accidental appendectomy. As the trend towards the conservative treatment of acute appendicitis increases in the pediatric population, the question arises as to whether the majority of NETs go undetected and are only discovered at an advanced stage. The purpose of the proposed study is to review the incidence and outcomes of treatment for NETs of the appendix in children and include the data presented in the data pool for further review. Methods: From 1 January 2009 to 1 November 2023, a total of 6285 appendectomies were performed in two large pediatric centers in Croatia. After a retrospective review of the case records and histopathologic findings, a total of 31 children (0.49%) were diagnosed with NET of the appendix and included in the further analysis. The primary outcome of this study was the incidence and treatment outcome of pediatric patients diagnosed with NET of the appendix. Secondary outcomes included the patients' demographic, clinical, and laboratory data and the histopathologic characteristics of tumor species. Results: The overall incidence of NETs of the appendix was stable over the study years, with minor fluctuations. The median age of patients was 14 (interquartile range—IQR: 12, 16) years, with a female predominance (64.5%). The majority of patients (96.8%) presented with acute abdominal pain and underwent appendectomy because acute appendicitis was suspected. Acute appendicitis was confirmed by histopathology in 18 (58%) cases. NETs of the appendix were not detected preoperatively in any of the patients. Among patients with confirmed acute appendicitis, most (n = 14; 77.8%) were found to have non-perforated acute appendicitis. In most children, the tumor was located at the tip of the appendix (n = 18; 58.1%), and the majority of tumors had a diameter of less than 1 cm (n = 21, 67.7%). The mitotic count (n = 25, 80.6%) and Ki-67 proliferation index (n = 23, 74.2%) were low in most patients, so most tumors were classified as NET G1 (n = 25, 80.6%), while NET G2 and NET G3 were found in four (12.9%) and two (6.5%) patients, respectively. All children were treated with appendectomy only. The median follow-up time was 54 (IQR: 24, 95) months. Conclusions: The incidence of appendiceal NET among pediatric patients is very low. NET occurs most frequently in adolescents, with a female predominance. Most tumors are less than 1 cm in diameter, located at the tip, and associated with non-perforated appendicitis. Appendectomy is the treatment of choice, and major surgery was not necessary in our cohort. [ABSTRACT FROM AUTHOR]

Context: Somatic EPAS1 variants account for 5% to 8% of all pheochromocytoma and paragangliomas (PPGL) but are detected in over 90% of PPGL in patients with congenital cyanotic heart disease, where hypoxemia may select for EPAS1 gain-of-function variants. Sickle cell disease (SCD) is an inherited hemoglobinopathy associated with chronic hypoxia and there are isolated reports of PPGL in patients with SCD, but a genetic link between the conditions has yet to be established. Objective: To determine the phenotype and EPAS1 variant status of patients with PPGL and SCD. Methods: Records of 128 patients with PPGL under follow-up at our center from January 2017 to December 2022 were screened for SCD diagnosis. For identified patients, clinical data and biological specimens were obtained, including tumor, adjacent non-tumor tissue and peripheral blood. Sanger sequencing of exons 9 and 12 of EPAS1, followed by amplicon next-generation sequencing of identified variants was performed on all samples. Results: Four patients with both PPGL and SCD were identified. Median age at PPGL diagnosis was 28 years. Three tumors were abdominal paragangliomas and 1 was a pheochromocytoma. No germline pathogenic variants in PPGL-susceptibility genes were identified in the cohort. Genetic testing of tumor tissue detected unique EPAS1 variants in all 4 patients. Variants were not detected in the germline, and 1 variant was detected in lymph node tissue of a patient with metastatic disease. Conclusion: We propose that somatic EPAS1 variants may be acquired through exposure to chronic hypoxia in SCD and drive PPGL development. Future work is needed to further characterize this association. [ABSTRACT FROM AUTHOR]

BackgroundPrimary neuroendocrine neoplasms of the breast (Br-NENs) are rare. The classification has been updated in recent years making interpretation of the data published challenging. It is unclear whether neuroendocrine differentiation is associated with poorer prognosis and what treatment approaches should be applied.MethodsThe database for breast cancer patients treated between 2009 and 2022 at the Maria Sklodowska-Curie National Research Institute of Oncology Branch Krakow was explored to search for Br-NENs. Patients’ medical and pathological data were collected and analyzed.ResultsWe included 22 females with Br-NEN without metastases at the time of diagnosis. The median age was 64 years (range: 28-88), Of the cases, 18 were hormone receptor positive, all were HER-2 negative, the median Ki67 was 27% (10-100%). The median tumor size at the time of diagnosis was 29.5mm (7-75mm), 9 patients were N-positive. DCIS was present in 5 cases. Only one case was negative for chromogranin and synaptophysin staining, but data were missing for 4 cases. Nine patients received adjuvant chemotherapy, mainly based on anthracyclines and taxanes, while 16 received adjuvant hormonal therapy and 15 received postoperative radiotherapy. Radical surgery was performed in all patients, but two underwent suboptimal tumorectomy. One patient had local recurrence, three experienced metastatic disease, all involving the lungs, but these patients are still alive. The median follow-up was 96 months (8–153). Two patients died, with a follow up time of no recurrence >4 years. Our results were compared to twelve case series collecting clinical data on Br-NENs, with median patient number of 10.5 (range: 3-142).ConclusionBr-NENs represent a heterogenous group of diseases, lacking data from prospective studies or clinical trials. There are no established treatment standards tailored for Br-NENs. Our patients’ cohort exhibited a favorable prognosis, potentially attributed to lower tumor stage and Ki67 index compared to other reported case series. We suggest that radical surgery and postoperative radiotherapy be administered akin to standard treatment for breast cancer of no special type. ESMO also advocates for this approach in systemic treatment, although we recommend considering platinum-based chemotherapy for patients with poorly differentiated Br-NENs exhibiting high Ki67.

Circulating tumor cell (CTC) clusters are present in cancer patients with severe metastasis, resulting in poor clinical outcomes. However, CTC clusters have not been studied as extensively as single CTCs, and the clinical utility of CTC clusters remains largely unknown. In this study, we aim sought to explore the feasibility of NanoVelcro Chips to simultaneously detect both single CTCs and CTC clusters with negligible perturbation to their intrinsic properties in neuroendocrine tumors (NETs). We discovered frequent CTC clusters in patients with advanced NETs and examined their potential roles, together with single NET CTCs, as novel biomarkers of patient response following peptide receptor radionuclide therapy (PRRT). We observed dynamic changes in both total NET CTCs and NET CTC cluster counts in NET patients undergoing PRRT which correlated with clinical outcome. These preliminary findings suggest that CTC clusters, along with single CTCs, offer a potential non-invasive option to monitor the treatment response in NET patients undergoing PRRT.

Background/Aims: Although gastric neuroendocrine tumors (NETs) are uncommon neoplasms, their prevalence is increasing. The clinical importance of the World Health Organization (WHO) classification of gastric NETs, compared with NETs in other organs, has been underestimated. This study aimed to systematically evaluate the clinical and pathologic characteristics of gastric NETs based on the 2019 WHO classification and to assess the survival outcomes of patients from a single-center with a long-term follow-up. Methods: The medical records of 427 patients with gastric NETs who underwent endoscopic or surgical resection between January 2000 and March 2020 were retrospectively reviewed. All specimens were reclassified according to the 2019 WHO classification. The clinicopathologic characteristics, treatment, and oncologic outcomes of 139 gastric NETs were analyzed. Results: The patients’ median age was 53.0 years (interquartile range [IQR], 46.0 to 63.0 years). The median follow-up period was 36.0 months (IQR, 15.0 to 63.0 months). Of the patients, 92, 44, and 3 had grades 1, 2, and 3 NETs, respectively. The mean tumor size significantly increased as the tumor grade increased (p=0.025). Patients with grades 2 and 3 gastric NETs more frequently had lymphovascular invasion (29.8% vs 10.9%, p=0.005) and deeper tissue invasion (8.5% vs 0%, p=0.012) than those with grade 1 tumors. The overall disease-specific survival rate was 100%. Two patients with grades 2-3 gastric NETs experienced extragastric recurrence. Conclusions: Although gastric NETs have an excellent prognosis, grade 2 or grade 3 gastric NETs are associated with a larger size, deeper invasion, and extragastric recurrence, which require active treatment.

Introduction: Histologically, endometrial neuroendocrine carcinoma is an extremely rare pathological type of endometrial cancer. In addition, this type is characterized by high invasiveness and poor clinical outcome, which was classified into carcinoid (low grade), and small-cell and large-cell neuroendocrine carcinoma (high grade). Globally, reports on endometrial carcinoid carcinoma are limited. Clinically, it is also rare to see primary squamous cell carcinoma of endometrium. Case Presentation: Here, we report an interesting case of mixed carcinoma of endometrium with both carcinoid and squamous cell carcinoma, which presented with persistent vaginal bleeding and hyponatremia. Conclusion: Careful pathologic review is necessary to diagnose this rare disease. More studies in the future are warranted to demonstrate the primary surgical treatments and the efficacy of adjuvant therapy of this disease.

Neuroendocrine tumor (NET) metastasis to the thyroid is rare, and its presentation as the first manifestation of primary malignancy elsewhere is even more uncommon. We present a case of a 41-year-old female who underwent biopsy of enlarging thyroid nodules with findings suspicious for medullary thyroid cancer (MTC). Subsequent thyroidectomy demonstrated NET of unknown primary in the left lower lobe. Immediate workup with 68Ga-DOTATATE-PET/CT revealed abnormal somatostatin receptor (SR) expressing lesions in the liver, right cervical nodes, thoracic paravertebral soft tissue, precoccygeal soft tissue, and right acetabulum concerning for sites of neuroendocrine malignancy. Due to disease progression while on octreotide injections, a decision was made at the multidisciplinary NET board for the patient to receive peptide receptor radionuclide therapy (PRRT) which includes 4 cycles of 77Lu-DOTATATE (Lutathera). The patient had no side effects nor toxicities during the 8 months of PRRT and achieved a partial treatment response in the early post-treatment scan at 6 weeks. This case illustrates the importance of distinguishing NET metastasis to the thyroid from MTC to ensure appropriate workup and treatment as well as predict the response of neuroendocrine malignancies to PRRT based on the visualized overexpression of SR in the SR-PET scans, despite the organ of origin.

Neuroendocrine tumor of the gall bladder is an extremely rare malignancy, accounting for only 0.2% of all neuroendocrine tumors. Gall Bladder-Neuroendocrine Tumors (GB-NETs) are mainly diagnosed on histological examination of GB samples after cholecystectomy or after any biliary pathology surgery since it is very difficult to diagnose based on imaging. The overall outcome of gallbladder NET is worse than the adenocarcinoma of the gallbladder. No focused approach towards its treatment is available in literature due to its rarity. We share our experience of gall bladder NET in a 37-year-old female who was successfully managed at our institution.

Based on the results of the NETTER-1 trial, peptide receptor radionuclide therapy with Lutetium-177 (177Lu) – DOTATATE is authorized for the treatment of neuroendocrine tumors (NET) grade 1 (G1) and grade 2 (G2) of the intestine. After the failure of 177Lu-DOTATATE therapy, targeted alpha-particle therapy (TAT) may be a possible treatment option. Here, we present a patient with cancer of unknown primary NET G2 later G3. The patient was referred to our hospital with urosepsis due to a second-degree urinary retention. After stent insertion, a contrast-enhanced computed tomography revealed a huge pelvic tumor without metastases. Initially, the patient had undergone surgical treatment. Later the patient developed liver metastasis and was treated by 177Lu-DOTATATE therapy and four lines of systemic therapy. A disease progression was observed and with the knowledge of a germline BRCA1 mutation, the patient was treated with TAT (Actinium-225 [225Ac]-DOTATATE) combined with olaparib. The patient achieved a significant treatment response for 12 months indicating that a combination therapy with an alpha emitter and olaparib demands further investigations in clinical trials.

Appendiceal neoplasms include rare tumor formations, whose treatment ranges from an appendectomy, hemicolectomy, and chemotherapeutic agents for benign or malignant lesions. In this study, we aimed to evaluate appendiceal neoplastic lesions according to the literature on histological subgroups. A review was performed on 2.124 patients who had undergone appendectomy between January 2017 and December 2021. Patients were evaluated retrospectively according to their demographic, clinical, radiological, and histopathological characteristics. In the histopathological evaluation of the 23 (1.06%) patients, who were included in the study upon the detection of the appendiceal neoplastic lesion, sessile serrated adenoma was observed in 7 patients, low-grade appendiceal mucinous neoplasm (LAMN) in 6 patients, mucinous adenocarcinoma in 4 patients, signet ring cell mucinous adenocarcinoma in 1 patient, neuroendocrine tumor (NET) in 4 patients, and tubulovillous adenoma in 1 patient. Appendiceal neoplasms are generally asymptomatic; therefore, pathological examination results should be carefully evaluated after appendectomy, and it should be remembered that appendectomy is not always sufficient alone. [Med-Science 2023; 12(3.000): 955-60]

Abstract Background Non-operative management has been suggested as a therapy for uncomplicated appendicitis. Notwithstanding, the risk of missing an appendiceal tumor must be considered, being the surgical piece crucial to rule out neoplasms. Therefore, we aim to determine the incidence of appendiceal neoplasms in patients with acute appendicitis, tumor types and the importance of the anatomopathological study of the surgical piece. Study design Retrospective study in which we described patients who underwent emergent appendectomy with histopathological findings of appendiceal neoplasms from January 2012 to September 2018. Descriptive analysis included demographic variables, diagnostic methods, and surgical techniques. Results 2993 patients diagnosed with acute appendicitis who underwent an emergency appendectomy. 64 neoplasms of the appendix were found with an incidence of 2,14%. 67.2% were women, the mean age was 46,4 years (± 19.5). The most frequent appendiceal neoplasms were neuroendocrine tumors (42,2%), followed by appendiceal mucinous neoplasms (35,9%), sessile serrated adenomas (18,8%), and adenocarcinomas (3,1%). In 89,1% of the cases, acute appendicitis was determined by imaging, and 14% of cases were suspected intraoperatively. Appendectomy was performed in 78,1% without additional procedures. Conclusions Appendiceal tumors are rare and must be ruled out in patients with suspected acute appendicitis. The incidence of incidental neoplasms is higher in this study than in the previously reported series. This information must be included in decision-making when considering treatment options for acute appendicitis.

Abstract Background Hypercalcemia of malignancy, as a paraneoplastic syndrome, is the most common metabolic disorder that accounts for 30% of malignancies and usually has a poor prognosis. Neuroendocrine tumors are uncommon and arise from neuroendocrine cells throughout the body. Actually, paraneoplastic hypercalcemia in neuroendocrine tumors is unusual and mostly associated with parathyroid hormone-related protein (PTHrP) secretion. Case presentation We report a 51-year-old Iranian man who presented with nausea, vomiting, and significant weight loss for 1 month. Laboratory data revealed calcium of 26 mg/dl, accompanied by low level of PTH. Octreotide scan revealed a large donut-shaped octreotide avid lesion in the epigastric region at the right side of the mid-abdomen, with multiple varying size foci of abnormally increased radiotracer uptake in the epigastric region and both lobes of the liver. Endoscopic ultrasonography demonstrated a large heterogeneous mass lesion with irregular outline and good demarcation in the body of the pancreas with diffuse foci of calcification. Percutaneous biopsy of the liver mass demonstrated a well-differentiated neuroendocrine tumor (low grade) confirmed by immunohistochemistry with strongly positive chromogranin and synaptophysin stain. Hypercalcemia was treated with hydration, few sessions of hemodialysis, calcitonin, and denosumab injection. However, the patient developed symptomatic hypocalcemia. Oncology consultation led to prescription of long-acting octreotide 30 mg monthly and everolimus daily. Conclusion Pancreatic neuroendocrine tumor could lead to malignant hypercalcemia; secretion of PTHrP is the most common cause, and signs and symptoms are usually milder than paraneoplastic syndrome due to hematologic and solid tumor. Generally, survival is better; however, its treatment is challenging, and primary debulking surgery is often required. A team approach to management is important at all points.

We present a rare case of mediastinal capillary hemangioma in a 54-year-old female. She presented with back pain in the left suprascapular region, and the chest radiograph revealed left pleural effusion. On further workup with high-resolution computed tomography (CT) chest, a hypervascular pleural-based neoplastic lesion in the left upper hemithorax with gross left pleural effusion and subtotal collapse of the left lung was identified. 18F-fluorodeoxyglucose positron emission tomography/CT was suggestive of a weakly metabolic well-defined pleural-based soft tissue lesion in the left upper hemithorax along the mediastinal side. Neuroendocrine tumor was suspected. 68Ga-DOTATATE PET/CT was advised, which showed intense uptake in the lesion. The mass was resected completely. Histopathological examination established the final diagnosis as benign vascular tumor consistent with a capillary hemangioma. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumors of the kidney are exceedingly rare. We report the first case of robotic-assisted partial nephrectomy for such tumors in horseshoe kidneys. A 65-year-old woman was incidentally found to have a 27 mm renal mass in the isthmus of her horseshoe kidney during computed tomography. Based on contrast-enhanced computed tomography results, we initially suspected renal cell carcinoma originating from the horseshoe kidney. Subsequently, robotic-assisted partial nephrectomy with isthmus transection was performed. Intraoperatively, we adjusted the port position for camera insertion and the patient's positioning to facilitate better visualization for dorsal isthmus and vessel dissection. Pathological examination and immunohistochemical analysis revealed a well-differentiated neuroendocrine tumor. Therefore, robotic-assisted partial nephrectomy is a safe and effective approach for managing neuroendocrine tumors in the isthmus of horseshoe kidneys. Given the nonspecific clinical presentation of renal neuroendocrine tumors and their rarity, the optimal management of these tumors remains controversial. [ABSTRACT FROM AUTHOR]

A 40-year-old woman presented with dull, boring periumbilical region pain radiating to the back and vomiting for 1 year. Magnetic resonance cholangiopancreatography detected a polypoid growth in the ampullary region. The patient underwent Whipple’s procedure. The specimen revealed a 4.9 × 4.5 × 3.7 cm tumor arising from the pancreas, abutting the posterior pancreatic surface and infiltrating the terminal common bile duct and the ampulla. Microscopic examination showed a pancreatic tumor composed of neuroendocrine cells. In addition, many large foci showing solid sheets of oncocytic cells with abundant granular eosinophilic cytoplasm were observed. Immunohistochemistry studies revealed positivity for synaptophysin, chromogranin, and Ki67 index above 70%. A diagnosis of oncocytic neuroendocrine tumor of Grade 3 was made. In electron microscopy, oncocytic cells showed abundant mitochondria dispersed throughout the cytoplasm. Oncocytic pancreatic neuroendocrine neoplasms are uncommon and can be diagnosed only on histopathological examination. These tumors tend to show a malignant behavior. [ABSTRACT FROM AUTHOR]

Pancreatic cystic lesions (PCLs) pose a diagnostic challenge due to their increasing incidence and the limitations of cross-sectional imaging and endoscopic-ultrasound-guided fine-needle aspiration (EUS-FNA). EUS-guided through the needle biopsy (EUS-TTNB) has emerged as a promising tool for improving the accuracy of cyst type determination and neoplastic risk stratification. EUS-TTNB demonstrates superior diagnostic performance over EUS-FNA, providing critical preoperative information that can significantly influence patient management and reduce unnecessary surgeries. However, the procedure has risks, with an overall adverse event rate of approximately 9%. Preventive measures and further prospective studies are essential to optimize its safety and efficacy. This review highlights the potential of EUS-TTNB to enhance the diagnostic and management approaches for patients with PCLs. It examines the current state of EUS-TTNB, including available devices, indications, procedural techniques, specimen handling, diagnostic yield, clinical impact, and associated adverse events.