Carcinoid Research Articles

Quantitative Analysis of 5-hydroxyindoleacetic Acid in Rat Urine by High-performance Liquid Chromatography Method

ABSTRACT Background: 5-hydroxyindoleacetic acid (5-HIAA) is a metabolite of serotonin, a neurotransmitter primarily associated with regulating mood, appetite, and sleep. When serotonin is broken down in the body, it forms 5-HIAA, which is then excreted in urine. Quantification of 5-HIAA levels in urine is often used as a diagnostic tool for certain conditions, particularly carcinoid tumors, which can produce excess serotonin. Elevated levels of 5-HIAA in urine can indicate increased serotonin production, which may be indicative of carcinoid tumors or other conditions affecting serotonin metabolism. However, there is limited work on employing high-performance liquid chromatography (HPLC)–ultraviolet to estimate monoamines in biological samples. Aim and Objectives: The present study explores the detection of 5-HIAA in rat urine samples, developing an easy, precise validated HPLC method. Materials and Methods: Mobile phase combination acetonitrile and o-phosphoric acid in the ratio of 30:70% v/v and flow rate 0.5 mL/min was able to separate 5-HIAA distinctly. Results: The detection was observed at λmax 277 nm with better sensitivity. According to the parameters indicated in the international council for harmonisation of technical requirements for pharmaceuticals for human use guidelines (Q2A; Q2B), the procedure was verified. The linearity range was selected from 20 to 45 μg/mL, r 2 = 0.992, limit of detection (4.65 μg/mL), limit of quantification (15.52 μg/mL), retention time (6.3 min). Conclusion: The technique has demonstrated that it is repeatable and recoverable within the given range. Thus can be used for routine analysis of 5-HIAA in urine samples.

Imaging with [89Zr]Zr-DFO-SC16.56 anti-DLL3 antibody in patients with high-grade neuroendocrine tumours of the lung and prostate: a phase 1/2, first-in-human trial

Delta-like ligand 3 (DLL3) is aberrantly expressed on the surface of small-cell lung cancer (SCLC) and neuroendocrine prostate cancer cells. We assessed the safety and feasibility of the DLL3-targeted imaging tracer [89Zr]Zr-DFO-SC16.56 (composed of the anti-DLL3 antibody SC16.56 conjugated to p-SCN-Bn-deferoxamine [DFO] serving as a chelator for zirconium-89) in patients with neuroendocrine-derived cancer. We conducted an open-label, first-in-human study of immunoPET-CT imaging with [89Zr]Zr-DFO-SC16.56. The study was done at Memorial Sloan Kettering Cancer Center, New York, NY, USA. Patients aged 18 years or older with a histologically verified neuroendocrine-derived malignancy and an Eastern Cooperative Oncology Group performance status of 0-2 were eligible. An initial cohort of patients with SCLC (cohort 1) received 37-74 MBq [89Zr]Zr-DFO-SC16.56 as a single intravenous infusion at a total mass dose of 2·5 mg and had serial PET-CT scans at 1 h, day 1, day 3, and day 7 post-injection. The primary outcomes of phase 1 of the study (cohort 1) were to estimate terminal clearance half-time, determine whole organ time-integrated activity coefficients, and assess the safety of [89Zr]Zr-DFO-SC16.56. An expansion cohort of additional patients (with SCLC, neuroendocrine prostate cancer, atypical carcinoid tumours, and non-small-cell lung cancer; cohort 2) received a single infusion of [89Zr]Zr-DFO-SC16.56 at the same activity and mass dose as in the initial cohort followed by a single PET-CT scan 3-6 days later. Retrospectively collected tumour biopsy samples were assessed for DLL3 by immunohistochemistry. The primary outcome of phase 2 of the study in cohort 2 was to determine the potential association between tumour uptake of the tracer and intratumoural DLL3 protein expression, as determined by immunohistochemistry. This study is ongoing and is registered with ClinicalTrials.gov, NCT04199741. Between Feb 11, 2020, and Jan 30, 2023, 12 (67%) men and six (33%) women were enrolled, with a median age of 64 years (range 23-81). Cohort 1 included three patients and cohort 2 included 15 additional patients. Imaging of the three patients with SCLC in cohort 1 showed strong tumour-specific uptake of [89Zr]Zr-DFO-SC16.56 at day 3 and day 7 post-injection. Serum clearance was biphasic with an estimated terminal clearance half-time of 119 h (SD 31). The highest mean absorbed dose was observed in the liver (1·83 mGy/MBq [SD 0·36]), and the mean effective dose was 0·49 mSv/MBq (SD 0·10). In cohort 2, a single immunoPET-CT scan on day 3-6 post-administration could delineate DLL3-avid tumours in 12 (80%) of 15 patients. Tumoural uptake varied between and within patients, and across anatomical sites, with a wide range in maximum standardised uptake value (from 3·3 to 66·7). Tumour uptake by [89Zr]Zr-DFO-SC16.56 was congruent with DLL3 immunohistochemistry in 15 (94%) of 16 patients with evaluable tissue. Two patients with non-avid DLL3 SCLC and neuroendocrine prostate cancer by PET scan showed the lowest DLL3 expression by tumour immunohistochemistry. One (6%) of 18 patients had a grade 1 allergic reaction; no grade 2 or worse adverse events were noted in either cohort. DLL3 PET-CT imaging of patients with neuroendocrine cancers is safe and feasible. These results show the potential utility of [89Zr]Zr-DFO-SC16.56 for non-invasive in-vivo detection of DLL3-expressing malignancies. National Institutes of Health, Prostate Cancer Foundation, and Scannell Foundation.

Mucinous cystadenoma and carcinoid tumor arising from an ovarian mature cystic teratoma in a 60 year-old patient: a case report

BackgroundMature cystic teratomas (MCT) of the ovary are benign ovarian germ cell neoplasms. Malignant transformation is possible but rare and ovarian carcinoid tumors in MCT are among the most extremely rare subtypes.Case presentationWe report a case of a 60-year-old Iranian woman suffering from postmenopausal bleeding and hypogastric pain for the last 40 days. An adnexal mass was detected during the physical examination. Ultrasound imaging showed a (55 × 58) mm mass in the left ovary. Total abdominal hysterectomy, bilateral salpingooophorectomy and comprehensive staging surgery were performed for the patient. Intraoperative frozen section of the left ovarian mass was indicative of a malignant tumor. She was diagnosed with a carcinoid tumor with benign mucinous cystadenoma arising on MCT of the ovary, confirmed in the histopathology and immunohistochemistry examination. The tumor was classified as low grade and no chemotherapy cycles were considered. The patient was followed up long-term and no recurrence was observed during 14 months of examinations.ConclusionOvarian carcinoids arising from MCT are rare neuroendocrine neoplasms, and proper diagnosis of these tumors requires careful histopathology evaluation and appropriate examination. Therefore, it is necessary to consider these tumors as a possible differential diagnosis and evaluate them in individuals (especially postmenopausal women) who have abdominal pain or abnormal bleeding and a palpable mass.

Absence of orthopaedia homeobox protein (OTP) expression is associated with disease spread and adverse outcome in pulmonary carcinoid tumour patients.

Pulmonary carcinoid (PC) tumours typically have a good prognosis, although metastases occur, and the disease may progress after a long period of time. Expression of orthopaedia homeobox protein (OTP) has been recognized as a possible independent prognostic marker in PCs. Immunohistochemical (IHC) OTP expression has been associated with better prognosis, but the staining has yet to be implemented in routine clinical diagnostics. In response to this, two new monoclonal OTP antibodies were recently developed.This retrospective study included 164 PC patients operated on at Helsinki University Hospital between 1990 and 2020. Tissue microarray slides, prepared from formalin-fixed and paraffin-embedded primary tumour samples, were stained with OTP IHC using one polyclonal and two novel monoclonal antibodies.Absence of OTP expression was associated with a shorter disease-specific survival (DSS) and disease progression (p < 0.001). Patients without OTP expression had a 5-year DSS of 73-79%, whereas 5-year DSS was 91-94% with OTP expression, depending on the primary antibody. In a univariable Cox regression model, absence of OTP expression was associated with adverse outcome along with atypical histological subtype, metastatic disease, Ki-67 proliferation index > 1%, and larger tumour size. In a multivariable Cox regression model, only absence of OTP expression and lymph node involvement at the time of diagnosis were associated with risk of worse prognosis. All three antibodies showed good concordance with each other.Our findings support the role of OTP as an independent prognostic marker in PCs and applicability of IHC staining in routine clinical use with novel monoclonal antibodies.

Distinguishing Bronchial Carcinoid from Benign Bronchocele using 68Ga-DOTATOC PET/CT Imaging.

Bronchial carcinoids are low-grade neuroendocrine tumors with slow growth rates and the potential to spread to nearby lymph nodes. Here we present a challenging case of bronchial carcinoid visualized alongside an adjacent benign bronchocele. Chest computed tomography (CT) identified the endobronchial mass with unclear morphological and diagnostic insights. A differential diagnosis of several benign and malignant etiologies was made. Subsequently, an endobronchial biopsy confirmed lung carcinoid. For better evaluation, a 68Ga-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe1-Tyr3-octreotide (68Ga-DOTATOC) positron emission tomography/CT scan was performed. The scan revealed a locally confined endobronchial mass with intense 68Ga-DOTATOC expression. Adjacent benign bronchocele was visualized with insignificant 68Ga-DOTATOC expression. Histopathological examination of the resected upper lobe confirmed these findings. This case highlights the importance of somatostatin receptor imaging in accurately identifying the extent of carcinoid tumors in the primary, nodal, and metastatic domains.

A Conjugated Polymer-Based Portable Smartphone Platform for Sensitive and Point-Of-Care Detection of Monoamine Neurotransmitter.

The precise and effective detection of neurotransmitters (NTs) is crucial for clinical investigation of neuronal processes, and timely monitoring of NT-related chronic diseases. However, sensitive detection of specific NT with unprecedented selectivity is highly challenging due to similarities in chemical and electronic structures of various interfering neurochemicals. Herein, an anionic conjugated polyelectrolyte Poly[(9,9-bis(4'-sulfonatobutyl)fluorene-co-alt-1,4-phenylene) sodium], PFPS was rationally designed and synthesized for amplified detection and point-of-care (PoC) determination of monoamine neurotransmitter, serotonin (5-Hydroxy tryptamine or 5-HT, also diagnostic biomarker of carcinoid tumor) in human blood plasma. The PFPS displayed a remarkable sensing response with an exceptionally high fluorescence quenching constant of 1.14×105 M-1 and an ultralow detection limit of 0.67 μM or 0.142 ppm, much below the clinical range. Furthermore, a smartphone-enabled portable platform was constructed for real-time onsite detection of 5-HT by quantification of visual fluorescence response of PFPS into RGB values using a color recognizer android application. The smartphone platform could be readily applied for convenient, non-invasive PoC testing of 5-HT levels in complex biological fluids accurately and is expected to revolutionize clinical diagnosis and personalized health care devices.

Double-snare resection technique: a new approach for treating rectal carcinoid tumors.

Double-snare resection technique: a new approach for treating rectal carcinoid tumors.

Prognosis of unresected versus resected early-stage pulmonary carcinoid tumors ≤3 cm in size: A population-based study.

The observation-based prognosis, rather than resection, for small carcinoid tumors is still unclear. This lack of clarity has important implications for counseling elderly patients or patients for whom surgical resection poses a high risk. This study compared the outcomes of observation and surgical resection in patients with pulmonary carcinoid (PC) tumors ≤3 cm in size without metastasis. Data of patients with PC tumors with ≤3 cm in diameter and without lymph node and distant metastases were retrieved from Surveillance, Epidemiology, and End Results (SEER) registry. To reduce the inherent bias of retrospective studies, propensity score matching analysis was performed. Overall survival (OS) and lung carcinoid-specific survival (LCSS) were analyzed using Kaplan-Meier plots. Multivariate analysis was used to determine predictors of LCSS in different size subgroups. In total, 4552 patients with early-stage PCs ≤3 cm in diameter, including 435 (9.56%) who were observed and 4117 (90.44%) treated by surgery, were recruited. Patients with surgery had significantly better OS and LCSS than those who were observed. However, patients with observation had comparable LCSS to those with surgery for PCs with tumor diameters ≤1 cm. Multivariate analysis indicated that surgical resection was an independent prognostic factor for LCSS in 1 cm < tumors ≤2 cm, and 2 cm < tumors ≤3 cm groups, but not for tumors ≤1 cm in diameter. Surgical resection of small PCs is associated with a survival advantage over observation. However, for early PCs ≤1 cm in diameter, observation may be considered in patients with high risk for surgical resection.

Demographic and socioeconomic factors of enterochromaffin cell carcinoid.

e16288 Background: Gastric carcinoid tumors, previously known as neuroendocrine neoplasms, are derived from enterochromaffin cells and show an increasing incidence globally. Neuroendocrine tumors often result in hormonal syndromes due to the production of exogenous hormonal peptides by the tumor. Current treatment options include surgical resection and somatostatin pharmacotherapy to blunt tumor growth. A gastric carcinoid malignancy that requires more investigation is enterochromaffin cell carcinoid (ECC). Considering the increasing incidence of gastric carcinoids, a retrospective investigation of demographic data involving enterochromaffin cell carcinoids was performed using the National Cancer Database (NCDB). Methods: The 2004-2019 NCDB was explored to perform a retrospective cohort analysis of patients diagnosed with ECC. 200 patients with a histologically confirmed diagnosis (ICD-O-3 code 8241/3) were identified. Descriptive statistics were used to analyze the following demographic data of patients in this study: race, sex, age, income quartile, facility type, Hispanic status, and Chales/Deyo score. Regression analysis was used to interpret incidence trends. Results: The NCDB identified 200 patients diagnosed with ECC from 2004-2019 with incidence rates varying over this time (R² = 0.0001). The mean age at diagnosis was 55 years (SD = 19.7, range = 14-90). Women (62%) were more likely to be diagnosed than men. The majority of patients were White (86%) and non-Hispanic (80%). Most patients (99.9%) received treatment for the remission of the cancer, predominantly through surgical means (86.5%). More patients were treated in an Comprehensive Community Cancer program (34.5%) than in an academic/research program (26.0%). The majority of individuals lived in metropolitan counties with a population greater than 1 million (54%) than in other metropolitan counties (22%). Most patients were in the fourth quartile of income earners (32.1%). The top primary site was the appendix (40.5%), and most individuals (79.5%) had Charles/Deyo comorbidity scores of 0. Conclusions: To the best of our understanding, this is the first NCDB investigation of Enterochromaffin Cell Carcinoid (ECC) and therefore addresses a meaningful educational disparity on the topic. Most ECC patients tend to be White, non-Hispanic individuals with a primary diagnosis site of the appendix, consistent with previous studies. Upon analyzing the socioeconomic factors of ECC patients, it was found that they often fall into the top income quartile, live in densely populated metropolitan counties, and receive treatment from a comprehensive community cancer program. Due to the significance of these demographic and socioeconomic factors, more research is needed to understand their impact on the diagnosis and treatment of ECC.

Open-label, prospective phase 2 study to evaluate the efficacy and safety of camrelizumab combined with etoposide and cisplatin as neoadjuvant therapy in patients with neuroendocrine carcinoma of the cervix.

TPS5624 Background: Camrelizumab, a humanized monoclonal antibody, specifically targets PD-1 to inhibit its interaction with PD-L1, thereby reactivating the T cell immune response against tumors. The NACI study demonstrated that, in the treatment of locally advanced cervical cancer, the combination of camrelizumab and neoadjuvant chemotherapy achieved an overall response rate (ORR) of 100%. Specifically, complete remission was observed in 4 patients (8.33%), while 44 patients (91.67%) experienced partial remission. This regimen significantly outperformed traditional treatments in efficacy, with manageable toxicity levels. Neuroendocrine carcinoma of the cervix (NECC) is a highly rare and aggressive malignancy characterized by its distinctive biological behavior, propensity for early lymph node and hematogenous metastasis, and limited effective treatment options, leading to a dismal prognosis. Although PD-1 inhibitors have shown promise in some NECC case reports, there is a notable absence of comprehensive, prospective clinical trials to substantiate their effectiveness. This study aims to assess the efficacy and safety of neoadjuvant chemo-immunotherapy in patients with NECC. Methods: This open-label, single-arm, prospective phase II study evaluates the antitumor efficacy and safety of camrelizumab in combination with etoposide and cisplatin in roughly 30 patients with NECC. Eligible participants are aged 18-75, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and histologically confirmed NECC, specifically targeting small cell and large cell neuroendocrine cervical carcinoma but excluding atypical and typical carcinoid tumors. Inclusion criteria stipulate that if NECC is present alongside other tumor types, the neuroendocrine carcinoma component must account for more than 60% of the tumor mass. The treatment protocol involves neoadjuvant chemo-immunotherapy, comprising two to three cycles of camrelizumab (200 mg, IV, day 1), cisplatin (75 mg/m², IV, day 1), and etoposide (100 mg/m², IV, days 1-3) administered every three weeks. Following this, patients achieving complete or partial response will proceed to radical surgery and adjuvant therapy, while those with stable or progressive disease, or considered unsuitable for surgery by gynecological oncologists, will transfer to concurrent chemoradiotherapy. The primary objective is to ascertain the objective response rate as per the Response Evaluation Criteria in Solid Tumors version 1.1. Secondary objectives include disease control rate, progression-free survival, overall survival, and evaluations of safety and tolerability. The study began on December 28, 2023, with ongoing enrollment. Clinical trial information: NCT05910177 .

Unveiling inequalities: An analysis of treatment disparities of primary gallbladder neuroendocrine tumors by race, ethnicity, and socioeconomic status from the National Cancer Database.

e16385 Background: Gallbladder neuroendocrine tumors (NETs) are exceedingly rare tumors and carry a poor prognosis. Racial/ethnic disparities and socioeconomic status have been known to influence cancer treatment and outcomes. This study explores racial/ethnic and socioeconomic disparities in treatment patterns of primary gallbladder NETs, focusing on factors affecting receipt of chemotherapy and multimodal therapy. Methods: We analyzed primary gallbladder NETs patients using the National Cancer Database (NCDB) from 2004 to 2020. Racial groups were divided into White and Black categories, and then those groups were further divided into Hispanic White, non-Hispanic White, Hispanic Black, and non-Hispanic Black categories according to ethnicity. We considered socioeconomic factors, tumor histology, and facility type. Logistic regression was used to determine the odds of receiving chemotherapy and multimodality therapy. The significance of disparities was determined using odds ratio (OR) and p-value. Results: Of 1,195 primary gallbladder NET patients, 59% (708 patients) underwent surgery. These patients had a median age of 65 years, with a female majority (64%) and predominantly White ethnicity (73.6%). Insurance coverage varied, with 48.9% having Medicare and 35.6% private insurance, while 3.9% were uninsured and 8.6% were covered by Medicaid. The study highlighted key factors affecting the receipt of surgery. Notably, racial disparities were apparent, with Black patients less likely to receive surgery compared to White patients (OR: 0.52; P &lt; .001). Furthermore, patients with typical carcinoid tumors were markedly more likely to receive surgery than those with other histology (OR: 10.93; P &lt; .001). The type of treatment facility was influential, with patients in Academic/Research Programs more likely to receive surgery (OR: 0.41; P &lt; .001) than those in Community Cancer Programs. Conclusions: This study highlights racial and socioeconomic disparities in chemotherapy and multimodality therapy for gallbladder NETs, with Black, uninsured, and Medicaid-insured patients less likely to receive treatment. These findings call for targeted policy and healthcare reforms to ensure equitable access and outcomes for all patients with this condition. [Table: see text]

240P Contributions of adenocarcinoma and carcinoid tumors to small intestinal cancer incidence rates: An updated SEER analysis 2000-2020

240P Contributions of adenocarcinoma and carcinoid tumors to small intestinal cancer incidence rates: An updated SEER analysis 2000-2020

Pulmonary neuroendocrine tumors : Current review

Neuroendocrine neoplasms of the lung are aheterogenous tumor group. The pathological classification comprises diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, classic neuroendocrine tumors, and neuroendocrine carcinoma. Classic neuroendocrine tumors include typical and atypical carcinoid tumors. Imaging plays an important role in diagnosis and can help in identifying the tumor biology. Overall, this tumor group is rare, comprising less than 2% of all thoracic tumors. In the current review, the various tumors are presented and important aspects regarding pathological classification, imaging modalities, and treatment are described.

Difficult Diagnosis and Management of Concealed Cushing.

Adrenocorticotropic Hormone (ACTH)-secreting tumors account for 5- 10% of Cushing syndrome cases and are often difficult to diagnose and treat. A 44-year-old man presented with arterial hypertension and weight gain. On the physical examination, he exhibited central obesity, abdominal striae rubrae, and facial plethora. Due to the clinical suspicion of Cushing syndrome, the Nugent test and Liddle-1 test were performed, which showed a lack of cortisol suppression. ACTH levels were also high (138 pg/mL), so pituitary MRI and dynamic tests were performed, including the Corticotropin-releasing Hormone (CRH) stimulation test and Liddle-2. MRI showed a 3 mm pituitary microadenoma, but hormonal testing suggested ectopic ACTH production. Chest CT detected a 10-mm nodule in the upper lobe of the right lung, suspicious for a carcinoid tumor. However, the nodule did not exhibit any enhancement on 68-Gallium-DOTATOC PET-CT, and further, 18-FDG PET-CT was inconclusive. In addition, the nodule was deemed non-biopsiable due to its location. Meanwhile, the patient developed osteoporosis, resulting in two vertebral fractures and one rib fracture, which was treated with zoledronate. Furthermore, the patient developed acute aortic insufficiency. During bioprosthetic valve replacement, the thoracic surgeon performed wedge resection of the right upper lung lobe. The histological examination of the lesion revealed a typical lung carcinoid (1.2x0.9 cm, pT1bNXR0, Ki671%, ACTH positive in 95% of neoplastic elements). ACTH levels dropped to 4 pg/mL on the fourth postoperative day. ACTH-secreting tumors are particularly challenging diseases. A comprehensive hormonal and instrumental valuation is often required, necessitating a multidisciplinary approach.

Super-resolution based Nodule Localization in Thyroid Ultrasound Images through Deep Learning.

Currently, it is difficult to find a solution to the inverse inappropriate problem, which involves restoring a high-resolution image from a lowresolution image contained within a single image. In nature photography, one can capture a wide variety of objects and textures, each with its own characteristics, most notably the high-frequency component. These qualities can be distinguished from each other by looking at the pictures. The goal is to develop an automated approach to identify thyroid nodules on ultrasound images. The aim of this research is to accurately differentiate thyroid nodules using Deep Learning Technique and to evaluate the effectiveness of different localization techniques. The method used in this research is to reconstruct a single super-resolution image based on segmentation and classification. The poor-quality ultrasound image is divided into several parts, and the best applicable classification is chosen for each component. Pairs of high- and lowresolution images belonging to the same class are found and used to figure out which image is high-resolution for each segment. Deep learning technology, specifically the Adam classifier, is used to identify carcinoid tumors within thyroid nodules. Measures, such as localization accuracy, sensitivity, specificity, dice loss, ROC, and area under the curve (AUC), are used to evaluate the effectiveness of the techniques. The results of the proposed method are superior, both statistically and qualitatively, compared to other methods that are considered one of the latest and best technologies. The developed automated approach shows promising results in accurately identifying thyroid nodules on ultrasound images. The research demonstrates the development of an automated approach to identify thyroid nodules within ultrasound images using super-resolution single-image reconstruction and deep learning technology. The results indicate that the proposed method is superior to the latest and best techniques in terms of accuracy and quality. This research contributes to the advancement of medical imaging and holds the potential to improve the diagnosis and treatment of thyroid nodules.</p>.

Clinical management of typical and atypical carcinoids/neuroendocrine tumors in ENETS centres of excellence (CoE): Survey from the ENETS lung NET task force.

Lung carcinoid tumours are neuroendocrine neoplasms originating from the bronchopulmonary tract's neuroendocrine cells, accounting for only 1%-3% of all lung cancers but 30% of all neuroendocrine tumours. The incidence of lung carcinoids, both typical and atypical, has been increasing over the years due to improved diagnostic methods and increased awareness among clinicians and pathologists. The most recent WHO classification includes a subgroup of lung carcinoids with atypical morphology and higher mitotic count and/or Ki67 labelling index. Despite appropriate surgery, the 5-year survival rate for atypical carcinoids barely exceeds 50%-70%. The role of adjuvant therapy in lung carcinoids is not well-defined, and clinical decisions are generally based on the presence of high-risk features. Long-term follow-up is essential to monitor for recurrence, although the optimal follow-up protocol remains unclear. To address the lack of consensus in clinical management decisions, the European Neuroendocrine Tumor Society (ENETS) initiated a survey among 20 expert centres. The survey identified varied opinions on approaches to imaging, surgery, use of adjuvant therapy, and follow-up protocols. Notably, the absence of dedicated multidisciplinary lung neuroendocrine tumour boards in some centres was evident. Experts agreed on the need for a prospective adjuvant trial in high-risk patients, emphasizing the feasibility of such a study. In conclusion, the study highlights the need for a more uniform adoption of existing guidelines in the management of lung carcinoid tumours and emphasizes the importance of international collaboration to advance research and patient care. Close collaboration between healthcare providers and patients is vital for effective long-term surveillance and management of these rare tumours.

Atypical thymic carcinoid tumour with ectopic ACTH syndrome: a rare case with a good prognosis

Atypical thymic carcinoid tumour with ectopic ACTH syndrome: a rare case with a good prognosis

Abstract PO2-20-09: Hiding in plain sight: A heterogeneous response in a patient with metastatic HR+/HER2- breast cancer

Abstract INTRODUCTION: Metastatic breast cancer is an infamously heterogeneous disease—characterized by a range of clinical presentations and treatment responses. In light of this heterogeneity, ASCO guidelines recommend patients with new, accessible metastatic tumors undergo a biopsy to inform treatment decisions. Here, we present a patient with HR+/HER2- disease with a long history of unusually heterogeneous responses—and a repeat metastatic biopsy that provided an answer. CASE: A 55-year-old woman presented for consultation of treatment-refractory metastatic breast cancer. She was originally diagnosed with a right-sided Stage III HR+/HER2- invasive ductal carcinoma (IDC) at the age of 33. Upon staging, she was incidentally found to have a right lower-lobe lung carcinoid tumor that was removed by lobectomy. She underwent a partial mastectomy, axillary lymph node dissection, followed by adjuvant chemo- and radiation therapy. She tolerated one week of tamoxifen which was discontinued due to adverse effects. Fifteen years later, screening mammography revealed a suspicious lesion in the right breast—biopsy consistent with a new IDC. She underwent bilateral mastectomies which showed a pT1cNxM0 G2 IDC with associated DCIS (ER+/PR+/HER2 IHC 2+, FISH-negative, Oncotype RS 12). Genetic testing was negative. The patient trialed adjuvant tamoxifen, which was discontinued due to repeat adverse effects. Two years later, rising tumor markers prompted restaging scans that demonstrated an enlarging liver lesion. Liver biopsy was consistent with metastatic adenocarcinoma of the breast (ER+/PR+/HER2 IHC 0), GATA3 positive. Patient was started on letrozole with lupron and palbociclib with disease control for two years until progression in the bone, prompting a switch of letrozole to fulvestrant with continued palbociclib. Her disease was stable for two additional years until progression of multiple liver lesions. She was then started on single-agent paclitaxel. At this point, she was seen in our office for consultation and next-line therapy options. Repeat staging scans showed heterogeneous response in the liver with overall progression. ctDNA testing revealed a mutation in MEN1 (p.Q354*, 2.8% VAF) without other actionable alterations. Patient opted to enroll into a clinical trial of an experimental ER-antagonist but experienced progression of her liver lesions on first staging scans. A second liver biopsy was performed on a progressive lesion which showed ER-/PR-/HER2- disease. She opted to enroll into a Phase 1b/2 trial with sacituzumab govitecan-hziy in combination with a PARPi. Staging scans again showed a mixed response in the liver. Given a history of mixed responses and discordant receptor staining, the differential diagnosis included loss of hormone receptor expression in the breast carcinoma versus metastases from an occult neoplasm. Additional immunohistochemical studies were performed on a subsequent liver biopsy showing positivity for chromogranin, synaptophysin, and INSM1, and negative results for ER, PR, GATA3, and TRPS1. Next-generation sequencing of the progressive lesion revealed a MEN1 SNV (p.Q354*, VAF 82%) as well as loss of 11q (MEN1 locus) suggestive of biallelic loss of MEN1—providing molecular evidence of a metastatic carcinoid tumor. A history of mixed response in the liver was concluded to be two coexisting neoplasms—a metastatic HR+/HER2- breast cancer as well as a late recurrence of a right-lower lobe carcinoid tumor from 22 years prior. DISCUSSION: The unanticipated discovery of an occult, coexisting neoplasm in the setting of a metastatic HR+/HER2- breast cancer illustrates the value of meticulous pathological review, repeat molecular testing and the use of next-generation diagnostic tools such as tumor sequencing in the advanced setting—particularly when a clinical story defies conventional expectations—to personalize care and optimize oncologic management in the face of complex biology. Citation Format: Nolan Priedigkeit, Jane Brock, Olivia Cunningham, Molly Skeffington, Melissa Hughes, Nancy Lin, Susan Lester, Heather Parsons. Hiding in plain sight: A heterogeneous response in a patient with metastatic HR+/HER2- breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-20-09.

Sensitized serotonin-mediated vasodilation in a mouse model of carcinoid disease

Background: Carcinoid tumors secrete vasoactive hormones such as serotonin that impact cardiovascular function. In consequence, patients with metastatic carcinoid disease are at risk for carcinoid syndrome, characterized by profound cutaneous flushing, hypotension, and syncope. Our recent work demonstrates that in patients with carcinoid metastases, higher serotonin levels are associated with lower vascular resistance. However, it is unknown if the vascular sensitivity to serotonin is affected by carcinoid disease. The receptor that mediates the potential vasodilatory effects of serotonin in carcinoid disease is also unknown. Therefore, we hypothesize that serotonin-mediated vasodilation is increased by carcinoid metastases. To test this, we assessed vascular reactivity to serotonin ex vivo in a mouse model of carcinoid disease. Methods: J:Nu nude mice (10 weeks) received intrasplenic injection of 2x107 BON1 neuroendocrine tumor cells (BON1, n=5) or PBS-vehicle (VEH, n=5), and were monitored for 10 weeks to allow the development of liver carcinoid metastases. Animals were then euthanized, and mesentery arteries were harvested. Isolated, pressurized mesentery arteries were pre-constricted with phenylephrine. The dose-response vasodilation to serotonin and acetylcholine was measured. These dose responses were repeated in the presence of 5-HT2B receptor antagonist LY272015 or nitric oxide synthase inhibitor L-NAME. Endothelium-independent vasodilation to sodium nitroprusside was also assessed. Data are mean ± SEM. Results: Mesentery arteries from BON1 mice had a greater vasodilation in response to serotonin compared with arteries from VEH mice (65±6% vs. 44±8%, p=0.04). Incubation with L-NAME partially inhibited the vasodilation to serotonin in the BON1 arteries (42±10%, p=0.04), but not in VEH arteries (30±11%, p=0.17). LY272015 did not affect the serotonin-induced vasodilation in the BON1 or VEH arteries (BON1: 52±10%, p=0.14, VEH: 49±17%, p=0.39). In contrast to serotonin, the vasodilation to acetylcholine did not differ between BON1 and VEH arteries (77±9% vs. 61±16%, p=0.19). There were also no differences in the vasodilation to sodium nitroprusside between groups (p=0.42). Arteries from BON1 mice had a trend for greater vasoconstriction in phenylephrine compared with VEH mice (51±7% vs. 37±9%, p=0.06). Conclusions: These findings demonstrate that serotonin-mediated vasodilation is sensitized in a mouse model of carcinoid disease. This is potentially accompanied by enhanced α-adrenergic-mediated vasoconstriction, which may be a compensatory mechanism in response to sensitized vasodilatory mechanisms. Western University of Health Sciences Intramural Grant (BHM). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A rare case report of a primary lung cancer comprising adenocarcinoma and atypical carcinoid tumor, with the carcinoid component harboring EML4-ALK rearrangement

A rare case report of a primary lung cancer comprising adenocarcinoma and atypical carcinoid tumor, with the carcinoid component harboring EML4-ALK rearrangement