Appendiceal Neuroendocrine Tumors Research Articles

Factors Affecting Survival Outcomes in Neuroendocrine Tumor of the Appendix over the Past Two Decades.

Appendiceal neuroendocrine tumors (NETs) rank as the third most frequent neoplasm affecting the appendix, originating from enterochromaffin cells. This study aims to evaluate the influence of various prognostic factors on the mortality rates of patients diagnosed with NETs of the appendix. Conducted retrospectively, the study involved 3346 patients, utilizing data sourced from the Surveillance, Epidemiology, and End Results (SEER) database. Our analysis centered on investigating demographic characteristics, clinical features, overall mortality (OM), and cancer-specific mortality (CSM) among the cohort. Variables showing a p-value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox regression analysis. A Hazard Ratio (HR) > 1 indicated an unfavorable prognosis. In the multivariate analysis, higher OM and CSM were observed in males, older age groups, tumors with distant metastasis, poorly differentiated tumors, and those who underwent chemotherapy. Non-Hispanic Black individuals showed elevated mortality rates. Delayed diagnosis may contribute to the increased mortality in this community. Improved access to healthcare and treatment is crucial for addressing these disparities. Larger prospective studies are needed to pinpoint the underlying causes of elevated mortality in non-Hispanic Black populations, and randomized controlled trials (RCTs) are warranted to evaluate therapies for advanced-stage appendix NETs.

Imaging of pediatric gastrointestinal tumors: A tertiary center experience over 19 years

PurposeGastrointestinal tract (GIT) tumors in children are rare and there is a scarcity of data on their imaging features. The purpose of this study was to determine thefrequency of various GIT tumor types in children and to identify key imaging characteristics. MethodsThis retrospective, single-center study was approved by the local ethics committee. Children with histologically proven GIT tumours (malignantand benign) who had imaging available on the institutional PACS between May 1, 2000 and Dec 31, 2019 were included. Demographic data and available imaging was reviewed by two blinded radiologists. ResultsIn total, 90 children (45 male, mean age 9.3 ± 4.3 years) with GIT tumours were included. The final diagnoses included polyps (n = 28), lymphomas/PTLD (n = 27), neuroendocrine tumours (n = 16), adenocarcinoma (n = 6), adenoma (n = 5), gastrointestinal stromal tumor (GIST) (n = 3), inflammatory myofibroblastic tumours (n = 2) and lastly leiomyoblastoma, leiomyoma and lipoma (1 each). All GIT segments were affected, but overall the small and large bowel had most lesions. Eighty-one percent children had a single lesion while remaining 19 % had multiple lesions. The neoplastic process manifested as intra-luminal lesion (58 %) or wall thickening (42 %) on imaging. Multiple cystic areas and vascular pedicle for polyps; and hypoechogenecity of the mass or wall thickening and aneurysmal dilatation for lymphomas, were the characteristic imaging features. None of the neuroendocrine tumours affecting appendix were seen on pre-resection imaging. ConclusionsVariety of benign and malignant tumors are seen throughout the childhood. Polyps, lymphomas and appendiceal neuroendocrine tumors are common lesions. Characteristic imaging features of juvenile polyps and lymphomas on ultrasound may help narrowing the differentials, and guide further work up.

Lymph node metastases are more frequent in paediatric appendiceal NET ≥1.5 cm but without impact on outcome – Data from the German MET studies

BackgroundPaediatric appendiceal neuroendocrine tumours (appNET) are very rare tumours, mostly detected incidentally by histopathological evaluation after appendectomy. Treatment recommendations are based on adult data considering high-risk NET as defined by European Neuroendocrine Tumour Society (ENETS) guidelines for completion right-sided hemicolectomy (RHC). Recent data suggest that less aggressive therapy may be justified. ProcedureAnalysis of children and adolescents with appNET prospectively registered with the German Malignant Endocrine Tumour (MET) studies between 1997 and 2022. ResultsBy December 2022, 662 patients (64.7% females, 35.3% male) had been reported. Median age was 13.3 years [4.5–17.9], median duration of follow-up 2.2 years [0–10.9]. No distant metastases were reported. Tumour size was <1 cm in 63.5%, 1–2 cm in 33.2%, and >2 cm in 3.2% of patients. WHO grade 1 and 2 tumours were diagnosed in 76.9% and 23.1% of patients, respectively. Lymphovascular invasion and lymph node metastases were associated with tumour size ≥1.5 cm. 27.0% of patients presented with high-risk NET according to ENETS criteria. Of those, only 55.9% underwent secondary oncological right hemicolectomy. Neither distant metastases, nor recurrences or disease-related deaths occurred in patients with appendectomy only as well as in patients with completion RHC. Overall and event-free survival were both 100%. ConclusionsInternationally harmonized consensus recommendations on treatment of children and adolescents with appendiceal NET are urgently needed to avoid completion RHC in high-risk patients.

Appendiceal Neuroendocrine Neoplasms: an Update for 2023.

To summarize the literature from the last 5years on treatment of appendiceal neuroendocrine neoplasms (aNEN). Furthermore, to evaluate the prognostic significance of lymph node metastases, indications for adjuvant treatment, and challenges of the current follow-up regimen. Simple appendectomy is sufficient in tumors < 1cm while extended surgery is indicated in tumors > 2cm. In a multicenter study of aNENs measuring 1-2cm, extended surgery offered no significant prognostic advantage and is now limited to incomplete tumor resection or high-grade G2 or G3 aNEN. Follow-up remains debatable, as the use of imaging and biomarkers lacks validation. While surgical procedure is well established in aNEN tumors < 1cm and > 2cm, the need for extended surgery in aNEN tumors 1-2cm is questionable. Future studies should address the prognostic impact of lymph node metastases and the optimal design and duration of follow-up.

Clinicopathologic features and diagnostic challenges of small cluster pattern appendiceal neuroendocrine tumors

Appendiceal neuroendocrine neoplasms (NENs) can present with various growth patterns including the traditional triad of histologic patterns-insular, trabecular and tubular. A small cluster pattern was also found in this study and the literature on this specific morphology is limited. In this study, we conducted a comprehensive review of appendiceal NENs from our institution over a ten-year period. Clinical and demographic data were obtained from medical records. Immunohistochemical stains were performed with antibodies specific for synaptophysin, chromogranin, INSM1, CD56, serotonin and peptide YY. The small cluster pattern was found in 29.4 % of all cases evaluated. The tumor cells in these cases were predominantly located at the distal tip of the appendix, associated with fibrous obliteration. These tumors were smaller in size and tended towards less advanced tumor stage, with reduced incidence of lymphovascular and/or perineural invasion. Chromogranin expression was identified in 76 % of these cases. There is a heterogeneous hormone profile with 46.7 % serotonin and 33.3 % peptide YY. In conclusion, the small cluster pattern NENs present with unique histological features and hormone expression profile. Among the various neuroendocrine markers, INSM1 showed superior diagnostic performance, with high sensitivity and minimal non-specific staining.

Resistant gastroenteropancreatic neuroendocrine tumors: a definition and guideline to medical and surgical management

Gastroenteropancreatic neuroendocrine tumors (NETs), also historically known as carcinoids, are tumors derived of hormone-secreting enteroendocrine cells. Carcinoids may be found in the esophagus, stomach, small intestine, appendix, colon, rectum, or pancreas. The biologic behavior of carcinoids differs based on their location, with gastric and appendiceal NETs among the least aggressive and small intestinal and pancreatic NETs among the most aggressive. Ultimately, however, biologic behavior is most heavily influenced by tumor grade. The incidence of NETs has increased by 6.4 times over the past 40 years. Surgery remains the mainstay for management of most carcinoids. Medical management, however, is a useful adjunct and/or definitive therapy in patients with symptomatic functional carcinoids, in patients with unresectable or incompletely resected carcinoids, in some cases of recurrent carcinoid, and in postoperative patients to prevent recurrence. Functional tumors with persistent symptoms or progressive metastatic carcinoids despite therapy are called “resistant” tumors. In patients with unresectable disease and/or carcinoid syndrome, an array of medical therapies is available, mainly including somatostatin analogues, molecular-targeted therapy, and peptide receptor radionuclide therapy. Active research is ongoing to identify additional targeted therapies for patients with resistant carcinoids.

Incidence and Management of Appendiceal Neuroendocrine Tumors in Pediatric Population: A Bicentric Experience with 6285 Appendectomies.

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. 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. 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. 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.

Incidence trends and survival analysis of appendiceal tumors in the United States: Primarily changes in appendiceal neuroendocrine tumors.

Appendiceal tumors are considered to be a relatively rare tumor of the gastrointestinal tract and the prognosis is unclear. This study comprehensively investigated trends in the epidemiology and survival of appendiceal tumors in the United States over the past approximately 20 years. Patients with pathologically confirmed appendiceal tumors from 2000 to 2017 were selected from the Surveillance, Epidemiology and End Results (SEER) database. Age-adjusted incidence rates were calculated by SEER*Stat 8.4.0. The Kaplan-Meier method was used to analyze survival and prognostic factors were investigated by a multivariate Cox proportional risk model. Ultimately, 13,546 patients with appendiceal tumors between 2000 and 2017 were included. The annual incidence of colonic adenocarcinoma and mucinous adenocarcinoma remained relatively stable. Interestingly, the annual incidence of appendiceal neuroendocrine tumors (aNETs) increased significantly, from 0.03 to 0.90 per 100,000 person-years, with the most dramatic increase in the number of patients with localized disease. Patients with aNETs showed a significant improvement in survival between 2009-2017, compared to the period 2000-2008. Moreover, this improvement in survival over time was seen at all stages (localized, regional, distant) of aNETs. However, this improved survival over time was not seen in colonic and mucinous adenocarcinoma. The incidence of appendiceal neoplasms has increased significantly over the past nearly two decades, which is mainly due to the increased incidence and significant migration to earlier stages in aNETs. We must note that despite the increased incidence of aNETs, survival rates have improved at different disease stages.

Neuroendocrine Tumor of The Appendix: Retrospective 7266 analysis of Appendectomy Patients in a single center

Objective: We aim to identify appendiceal neuroendocrine tumors (NETs) seen after acute appendicitis and investigate their incidence in patients with laparoscopic or open appendectomy surgery. Here we have shaped the characteristic features of the tumor according to the 2010 classification rating of The World Health Organization (WHO) (surgical margin, invasion, grading, TNM stages) and also explored the disease-free survival in these patients. Material and Methods: This is the medical record of the patient with 7266 appendectomy retrospectively evaluated, and with these examples in histopathological analysis, a total of 43 patients were diagnosed with appendicitis NETs and included in the study. Age, gender, prediction of the surgical team during the operation, location of the tumor, WHO grade, depth of invasion, positive surgical margin, tumor size, TNM stage, and postoperative survival of these patients were analyzed retrospectively. Results: In this study, the incidence of appendiceal (NETs) was found to be 0.59% among 7,266 patients. Out of the 42 patients with appendiceal NETs, 27 were female and 16 were male. The mean age of the patients was 33.65 years (range: 11–78). The diagnosis was aided by clinical examination, ultrasound, and abdominal computerized tomography (CT) imaging. Most patients were initially diagnosed with appendicitis, and surgical interventions, including laparoscopic and conventional appendectomy, were performed. The pathological analysis confirmed appendicitis with NETs, classified according to the WHO 2010 recommendation. The majority of patients had well-differentiated NETs (G1 or G2). Surgical resection achieved negative radial margins, and no pathological signs were detected during follow-up colonoscopies. At a median follow-up of 70.2 months, all patients remained disease-free and alive. Conclusion: Appendiceal neuroendocrine tumors are rare but distinct entities that require a multidisciplinary approach for diagnosis and management. Surgical resection is the primary treatment, with systemic therapies reserved for advanced cases. The prognosis is generally favorable, with better outcomes seen in well-differentiated tumors. Long-term follow-up is crucial. Further research is needed to improve understanding and optimize treatment strategies for these tumors.

THU538 Use Of Multiple Functional And Structural Imaging Modalities Improves Detection Of Ectopic ACTH Tumors

Abstract Disclosure: H. Elenius: None. R. McGlotten: None. A.M. Gharib: None. L.K. Nieman: None. Introduction: In Ectopic ACTH Syndrome (EAS), Cushing's syndrome (CS) is caused by ACTH secretion from a non-pituitary tumor. Tumor resection reduces CS morbidity and mortality, but up to 38% of tumors remain occult despite repeated structural imaging. We prospectively studied whether functional PET imaging with somatostatin receptor ( 111In-pentetreotide Octreoscan [OCT], vs 68Ga DOTA0-Tyr3 octreotate DOTATATE [DOTA]) or amine precursor (18F-DOPA [F-D]) ligands would improve tumor detection. Methods: From 2014-2022, 22 EAS patients underwent imaging with F-D and DOTA PET/CT and/or MRI (1.5 and/or 3 Tesla, T) of chest/abdomen/pelvis (C/A/P), gated cardiac CT (GC-CT) and/or MRI (GC-MRI), and/or OCT before tumor resection. Pre-surgical imaging results were confirmed by pathology or biochemical cure. Results: Tumors included 16 pulmonary (pulm) neuroendocrine tumors (NET), one thymic NET, one appendiceal NET, one pheochromocytoma and one metastatic NET in mediastinal lymph nodes; two patients had tumorlets. Surgery was done if at least CT or MRI was positive; some lesions were seen only after concurrent PET scan review. Shown in decreasing order, the modalities performed as follows (number of patients = N): Sensitivity (S): CT C/A/P 100%, N 22 ; FDG-PET 100%, N 2 ; 3T MRI C/A/P 93%, N 14 ; F-D 91%, N 22 ; DOTA 86%, N 22 ; 1.5T MRI C/A/P 71%, N 21 ; GC-CT 67%, N 6 ; GC-MRI 50%, N 8 ; OCT 31%, N 13. 95% Confidence intervals (CI) overlapped for all except OCT. Positive predictive value (PPV): GC-MRI 100% ; 3T MRI C/A/P 88% ; 1.5T MRI C/A/P 84% ; DOTA 83% ; CT C/A/P 81% ; GC-CT 80% ; F-D 75% ; OCT 67% ; FDG-PET 67%. All CIs overlapped.1.5T MRI, F-D and DOTA missed a 12 mm pulm NET (false negative, FN) only seen on CT. 1.5T MRI missed three other pulm NET (6, 8 and 10 mm) seen on 3T MRI. 1.5T and 3T MRI missed a 13 mm pulm NET that abutted the heart and was seen on both gated studies - this was the only FN lesion in the 3T MRI cohort. F-D missed the 12 mm pulm NET seen on CT and the retrocardiac NET, which was DOTA +. DOTA missed three other pulm NET (6, 8 and 10 mm); all were positive on F-D. OCT detected 4/10 pulm NET, 6-25 mm, all positive on F-D and DOTA, and missed 9 tumors seen on F-D (N=8) or DOPA (N=8). F-D detected false positive (FP) lesions in seven patients while DOTA detected FP lesions in three, mostly infections or thyroid nodules. All but one patient were localized by DOTA (N=19) and/or F-D (N=20). Conclusions: As reported previously, most EAS tumors were intrathoracic. Among structural modalities, CT was the most sensitive (100%) while cardiac MRI and 3T MRI gave the highest PPV (100% and 88%). Dedicated cardiac imaging found pericardiac lesions missed on routine modalities due to motion artefacts. F-D and DOTA were significantly more sensitive (91% and 86%) than OCT (31%). DOTA detected fewer FP lesions, providing a higher PPV (83%) than F-D (75%), but with lower sensitivity. Use of multiple functional and structural scans improved tumor detection. Presentation: Thursday, June 15, 2023

European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for appendiceal neuroendocrine tumours (aNET).

The aim of the present guidance paper is to update the previous ENETS guidelines on well differentiated appendiceal neuroendocrine tumours (NET), providing practical guidance for the diagnosis and management of appendiceal NET (aNET); poorly differentiated neoplasms are dealt with in a separate guidance paper. This paper is structured on a question-answer format in order to also address controversial issues and areas where uncertainty regarding the management and follow-up of aNET exists. All recommendations are offered on the basis of the best available evidence, along with the authors' experiences in managing these neoplasms. Each recommendation for treatment will provide a level of evidence and grade of recommendation as per the GRADE system (adapted in Infectious Disease Society of United States Public Health Service grading system).

Clinical features and outcomes of appendiceal neuroendocrine tumours: 10 year audit from the Irish NET Centre of Excellence.

Appendiceal neuroendocrine tumours (aNETs) are rare neoplasms of the gastrointestinal tract often diagnosed incidentally at the time of appendicectomy. Appendicectomy is considered curative in the majority of cases but guidelines recommend right-sided hemicolectomy (RHC) for those with specific high-risk features despite no data supporting a survival benefit. We performed a retrospective search of multi-disciplinary tumour board and pathology databases from 2012 to 2022 to identify cases of aNET treated at our centre. Follow-up data were obtained from the electronic healthcare records. A total of 142 cases of aNET were included for analysis. Mean age at presentation was 34, of which 76% were female and 92% of aNETs were located in the tip/middle of the appendix; 90% were grade 1, and 93% had R0 resection. Tumour size was <1 cm in 54%, 1-2 cm in 36%, >2 cm in 9%. A total of 43 patients (30%) underwent RHC with lymph node metastases identified in 16 (37%). Lymph node metastases were associated with tumour size >2 cm (p = .008) and higher tumour grade (p = .041) on multivariate analysis. For aNET 1-2 cm, lymph node metastases were identified in 7/22 who had RHC (32%) with tumour grade the only significant risk factor (p = .046). Distant metastases were identified in 2 cases (1%), diagnosed synchronously and associated with grade 2 tumours. Overall survival for those with lymph node metastases was 100% after a median 4 years. Progression-free survival was 93%, with a single case of disease progression associated with synchronous distant metastases at initial diagnosis. Lymph node metastases in aNET are associated with higher tumour grade and tumour size >2 cm. Disease progression in the setting of lymph node metastases is rare. The significance of lymph node metastases and need for completion RHC remains uncertain.

Incidental finding of synchronous neuroendocrine tumor of appendix and rectal adenocarcinoma. A case report and literature review

Abstract Objectives Colorectal cancers represent the predominant malignancies affecting the gastrointestinal tract. In contrast, appendiceal tumors occur less frequently. Among them, appendiceal neuroendocrine tumors (ANETs) account for approximately 50 % of cases and are often detected incidentally during unrelated procedures. Case presentation We present an extremely rare case of an incidental neuroendocrine tumor of the appendix discovered during surgery for rectal adenocarcinoma and provide a review of the relevant literature. A 70-year-old patient with radiologically and endoscopically diagnosed rectal cancer underwent a low anterior resection with total mesorectal excision and a temporary diverting ileostomy following preoperative chemotherapy and radiation therapy. Intraoperatively, a small appendiceal mass was discovered and excised. Histopathological examination confirmed a well-differentiated NET of the appendix measuring 0.4 cm in diameter. Conclusions This case report emphasizes the importance of thorough intraoperative examination during colorectal surgeries and highlights the need for increased awareness of appendiceal NETs among surgeons.

Omitting hemicolectomy for patients with appendiceal neuroendocrine tumours of 1–2 cm

Omitting hemicolectomy for patients with appendiceal neuroendocrine tumours of 1–2 cm

An unusual association between Burkitt's lymphoma and a Carcinoid tumor in a Syrian boy: a rare case report.

The authors report a case of a 15-year-old Syrian adolescent who was admitted to our hospital due to a persistent, severe generalized abdomen pain accompanied by nausea, vomiting, loss of appetite, and inability to pass stool or gas. An abdominal radiograph revealed dilated intestinal loops with air-fluid levels. The patient underwent emergency surgery through which a retroperitoneal mass was removed as well as part of the ileum and the appendix. The final diagnosis was consistent with intestinal BL associated with an appendiceal carcinoid tumor. The correlation between gastrointestinal carcinoids and other types of tumors was frequently reported. However, there have been few reports of carcinoid tumors being associated with lymphoreticular system cancers. BLs were classified into three variants: endemic, sporadic, and acquired immunodeficiency-associated BL while appendiceal neuroendocrine tumors were classified as the following: well-differentiated neuroendocrine tumors with benign or uncertain malignant potential; well-differentiated neuroendocrine carcinoma with low malignant potential; and mixed exocrine-neuroendocrine carcinoma. Our article demonstrates an unusual association between BL and an appendiceal carcinoid tumor that highlights the significant role of histological and immunohistochemical staining in confirming the diagnosis, as well as the role of surgery in treating the complications of intestinal BLs.

37P Survival and prognostic factors in appendiceal neuroendocrine tumours and goblet cell carcinoma

37P Survival and prognostic factors in appendiceal neuroendocrine tumours and goblet cell carcinoma

Incidental diagnosis of appendiceal neuroendocrine (carcinoid) tumors during benign gynecologic surgery: a case series

Incidental diagnosis of appendiceal neuroendocrine (carcinoid) tumors during benign gynecologic surgery: a case series

Well-Differentiated Neuroendocrine Tumors of the Appendix in Children and Adolescents: A Clinicopathologic Study.

Pediatric neuroendocrine tumors (NET) of the GI tract are rare and appendiceal NET are typically incidental. Few studies have been done in the pediatric population and practice guidelines are mainly based on adult data. There are currently no diagnostic studies specific for NET. Our study aimed to identify clinical, radiological, and pathological findings in pediatric appendiceal NET, test criteria for follow up surgical treatment, review potential prognostic pathological findings, and possible pre-operative diagnostic radiological studies. A retrospective data search was conducted for well-differentiated NET of the appendix in patients ≤21 years between 1/1/2003 and 7/1/2022. Available clinical, radiologic, pathological, and follow-up information was recorded. Thirty-seven patients with appendiceal NET were identified. No masses were reported in the patients who underwent presurgical imaging. Appendectomy samples showed NET (0.2->4 cm), most located in the tip. Most cases were WHO G1 (34/37), with negative margins (n = 25). Sixteen cases extended to the subserosa/mesoappendix (pT3). Lymphovascular (6), perineural (2), and both lymphovascular and perineural invasion were also noted (2). The specified tumor stages were pT1 (10/37), pT3 (16/37), and pT4 (4/37). Patients who underwent laboratory testing for chromogranin A (20) and urine 5HIAA (11) had normal limits. Subsequent surgical resection was recommended in 13 cases and performed in 11. To date, all patients have no recurrent or additional metastatic disease. Our study showed that all pediatric well-differentiated appendiceal NET were incidentally found as part of acute appendicitis management. Most NET were localized with low-grade histology. Our small cohort support the previously suggested management guidelines with follow up resection in certain cases. Our radiologic review didn't identify a best modality for NET. Comparing cases with and without metastatic disease, no tumors under 1 cm had metastasis, but serosal and perineural invasion along with G2 status were associated with metastasis in our limited study.

Clinical and pathologic characteristics of appendiceal neuroendocrine neoplasms diagnosed during pregnancy.

Although appendicitis occurs in approximately 1:1000 pregnancies, appendiceal neuroendocrine neoplasm (ANEN) diagnosis during pregnancy is very rare. Data on presentation, treatment and prognosis is scarce. To describe ANEN cases diagnosed during pregnancy. A retrospective appraisal of 7 consecutive ANEN patients diagnosed during pregnancy from four Israeli tertiary medical centers and comparison with 17 cases described in the literature from 1965-2021. Age at ANEN diagnosis was 26.4 ± 3.5 years (range 21-33). Patients were diagnosed between gestational weeks 6-40, most frequently in the third trimester (53%). The most common presenting symptom was abdominal pain. Tumor size was 14.3 ± 8.9mm (range 3-45mm). In patients from our series appendiceal base involvement was reported in 2/7; mesoappendiceal invasion in 5/7; lympho-vascular invasion in 2/7. Ki67 staining was reported in 6/7 cases and ranged from 1-10%. Pathology details were lacking in most of the previously published cases. All 7 pregnancies in our series resulted in term delivery with no complications, whereas in historical cases there were one first trimester abortion, one ectopic pregnancy, and one stillbirth. Right hemicolectomy was performed in 5/7 patients in our series and reported in 2/17 historical cases. All hemicolectomies were performed after delivery, 3-16 months after appendectomy. Local metastases were reported in two cases. Follow-up duration was 7-98 months for our patients and 3-48 months in 5 historical cases. No disease recurrence, distant metastases or mortality were noted. To the best of our knowledge, this is the largest series describing the extremely rare diagnosis of ANEN during pregnancy. Although pathologic characteristics varied, pregnancy outcomes were usually favorable and long-term prognosis was excellent. This data may suggest that a conservative approach to patients with ANEN diagnosis during pregnancy can be considered.

Pathological features associated with lymph node disease in patients with appendiceal neuroendocrine tumors.

238 Background: Appendiceal neuroendocrine tumors (ANETs) are well known for their benign and slow progression; nonetheless, the presence of lymph node metastasis has been described in up to 50% of all cases. The risk of metastasis is mainly associated with tumor size, and the role of other pathological features remains unclear. Hence, this study was designed to assess the pathologic features of ANETs associated with an increased risk of lymph node metastasis. Methods: Patients ≥18yrs of age with ANETs were identified in the National Cancer Database (NCDB) from 2004 to 2017. Groups were defined based on lymph node status as N(-) (all examined nodes were negative) and N(+) (one or more examined nodes were positive). Multivariable models using demographics and oncological features were used to identify factors independently associated with nodal metastasis (N+). Marginal effects, specifically for tumors &lt;2 cm were also calculated. Results: A total of 2,465 cases were identified and included for data analysis. Among these, 23% had lymph node metastases, including 33 of 979 tumors &lt;1 cm (3.4%), and 145 of 696 tumors ≥1 cm but ≤2 cm (20.8%). Tumor size, depth of tumor invasion, and presence of lymphovascular invasion (LVI) were identified as independent predictors of lymph node metastasis (p &lt;0.001). When evaluating marginal effects, both the depth of tumor invasion and the presence of LVI were associated with increased risk of node metastasis in small tumors (&lt;2 cm), comparable to the mere risk of node metastasis in big tumors (≥2cm). In addition, for small ANETs (&lt;2cm), the true positive rates (TPR) of node metastasis vary according to the number of assessed lymph nodes, differing significantly between patients with at least 12 evaluated lymph nodes vs. those with less than 12 (TPR 4.7% vs. 1.6% for &lt;1 cm [p =0.02], and 40.1% vs. 25.7% in ≤2 cm ANETs, [p &lt;0.001]). Conclusions: In ANETs, the presence of high-risk pathological features, including LVI and tumor depth, increases the risk of node metastasis in addition to tumor size, and should be considered when selecting the optimum management and follow-up in these patients. [Table: see text]