RARE DISEASE
Bronchial neuroendocrine tumor
Bronchial neuroendocrine tumor
Bronchial neuroendocrine tumor
Synonyms: Bronchial NET
Synonyms: Bronchial NET
Synonyms: Bronchial NET
Drug discovery
6
drugs
With orphan designations
Overview
Bronchial Neuroendocrine Tumors (BNETs) are rare, heterogeneous malignancies arising from pulmonary neuroendocrine cells, accounting for ~20% of lung cancers [1][2]. They encompass four subtypes: typical carcinoid (TC), atypical carcinoid (AC), large-cell neuroendocrine carcinoma (LCNEC), and small-cell lung carcinoma (SCLC) [1][16]. Symptoms include cough, hemoptysis, or obstructive pneumonia; <5% present with hormonal syndromes (e.g., carcinoid or Cushing syndrome) [1][7]. Prognosis varies widely, with 5-year survival ranging from >88% (TC) to <5% (SCLC) [1][2].
Therapies
Localized Disease: Surgical resection (lobectomy/pneumonectomy ± lymphadenectomy) [4][13].
Advanced Disease: Somatostatin analogs (symptom/tumor control), CAPTEM chemotherapy (response rate ≥30%), peptide receptor radionuclide therapy (PRRT), and targeted agents (e.g., everolimus) [3][8][18].
High-Grade Tumors: Platinum-based chemotherapy (SCLC/LCNEC); immunotherapy for mismatch repair-deficient cases [3][18].
Categories: rare endocrine diseases, rare neoplastic diseases, rare respiratory diseases
Research Papers
340 drug discovery papers about Bronchial neuroendocrine tumor, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
340 drug discovery papers about Bronchial neuroendocrine tumor, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-06-11 | Alternating Therapy With Osilodrostat and Etomidate in Severe Ectopic Cushing's Syndrome Complicated by Silent Bowel Perforation.
Ectopic adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS), ectopic ACTH secretion (EAS) is a rare condition caused by ACTH-secreting neuroendocrine tumors (NETs), such as bronchial carcinoids. We report a 65-year-old woman with severe EAS complicated by bowel perforation. She presented with hypokalemia (K+ 2.3 mmol/L), metabolic alkalosis, resistant hypertension (180/110 mmHg), worsening diabetes (HbA1c 6.7%-9.1%), proximal muscle weakness, and 14 kg weight gain over 3 months. A silent sigmoid colon perforation required emergency resection and colostomy. Biochemical tests confirmed hypercortisolism (urine free cortisol [UFC], 1256 µg/24 h, plasma ACTH 175 pg/mL, and cortisol >40 µg/dL post-dexamethasone). Imaging identified a 2.3 cm pulmonary nodule with mild uptake on Ga-68 DOTATATE PET/CT. Bronchoscopic biopsy confirmed an ACTH-positive low-grade bronchial carcinoid tumor. Initial treatment with osilodrostat was interrupted due to acute illness and oral medication intolerance. Intravenous etomidate was employed in the ICU for rapid cortisol suppression, followed by resumption of osilodrostat after stabilization. Thoracoscopic lobectomy confirmed a low-grade carcinoid tumor (Ki-67 < 2%). Postoperatively, cortisol normalized, electrolytes stabilized, and HbA1c improved to 6.5%. This case highlights bowel perforation as a severe complication of EAS and underscores the importance of dynamic, alternating therapy with osilodrostat and etomidate, along with individualized surgical and medical management strategies.
2025-08-21 | Preoperative Embolization of a Pulmonary Carcinoid Tumor with Unusual Arterial Supply: A Case Report
Background Pulmonary carcinoid tumors are rare neuroendocrine neoplasms that carry a risk of bleeding. We report a case of a tumor with unusual arterial supply from multiple sources including collateral from the renal artery, successfully managed with preoperative embolization followed by surgical resection. Case presentation: A 39-year-old woman with no significant medical history presented with chronic cough. Chest radiography revealed an opacity in the right hilar region. Computed tomography (CT) showed a mass obstructing the right middle lobe bronchus. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) demonstrated no abnormal uptake in the lesion. However, a Ga-68 DOTATATE somatostatin receptor scan (DOTA-PET) showed intense tracer uptake in the mass. Bronchoscopy identified a reddish endobronchial lesion completely occluding the middle lobe bronchus and causing distal collapse. Biopsy was deferred due to the lesion’s hypervascular appearance. With a presumptive diagnosis of carcinoid tumor, a multidisciplinary team planned for surgical resection. To mitigate intraoperative bleeding, preoperative angiographic evaluation was performed. Digital subtraction angiography (DSA) revealed that the blood supply originated from the right bronchial artery, right internal mammary artery and right renal artery. All identified feeding arteries were selectively catheterized and embolized with coils. The patient underwent a right middle lobectomy. Intraoperative blood loss was minimal, and the tumor was resected completely. Pathology confirmed carcinoid tumor. At two-year follow-up, the patient remains asymptomatic. Conclusions This case highlights a rare arterial supply to a lung tumor and demonstrates that preoperative embolization of multiple feeding vessels can facilitate safe resection of a hypervascular tumor. Awareness of vascular anomalies and multidisciplinary approach were key to successful management.
2025-08-21 | Effects of metabolic inhibition on ion transport by dog bronchial epithelium
Mammalian bronchial epithelium absorbs Na+ under basal conditions, but Cl- secretion can be induced. We studied the effects of several modes of metabolic inhibition on the bioelectric properties and solute permeability of dog bronchial epithelium mounted in Ussing chambers. Net Na+ absorption and short-circuit current were inhibited by ~75% by hypoxia or by 10-3 M NaCN. The reduced net Na+ absorption was characterized by a decrease in absorptive flux and an increase in backflux. The latter change was proportional to an increase in permeability to [14C]mannitol, implying that solute flow through a paracellular shunt was increased. In contrast, the reduction of conductance expected from exposure to amiloride (0.94 ± 0.15 ms/cm2 or 12%) was abolished by NaCN pretreatment. Metabolic inhibition also decreased epithelial conductance and unidirectional Cl- fluxes by ~25%. NaCN rapidly and reversibly inhibited the hyperpolarization on potential difference (PD) induced by low luminal bath [cl-]. This effect was mimicked by the Cl- channel blocker, 5-nitro-2-(3-phenylpropylamino) benzoic acid. Because the transepithelial Cl- diffusion PD reflects, in part, the depolarization of the Cl--conductive apical cell membrane metabolic inhibition appears to affect this path. We conclude that metabolic inhibition not only decreased net ion transport by dog bronchial epithelium but also inhibited cellular Na+- and Cl--conductive pathways and increased paracellular permeability.
2025-04-29 | Expression of YAP1 and TAZ in Melanoma-, Bronchial- and Breast Carcinoma Brain Metastasis: Primary vs. Relapsed Tumors.
Brain metastases from the most common primary sites - lung carcinoma, breast carcinoma, and melanoma - are more frequent than primary brain tumors. YAP1/TAZ are regulators of tissue growth and epithelial-mesenchymal transition (EMT) within the hippo pathway. The aim of the study was the evaluation of the role of YAP1/TAZ in brain metastasis. Expression levels of YAP1 and TAZ were measured in samples of primary and relapsed brain metastases from patients with melanoma, breast carcinoma, and bronchial carcinoma using qPCR and western blot. Expression of YAP1 and TAZ was highest in melanoma followed by bronchial carcinoma and lowest in breast carcinoma. For YAP1, expression in primary metastasis was higher than in relapsed metastasis. Because of the important role of YAP1/TAZ in EMT, targeting these genes could be a promising approach to reduce the risk of metastasis.
2025-04-12 | Bronchial atypical carcinoid in the truncus intermedius persistently controlled by PDT following transbronchial resection instead of surgery: A case report.
Atypical carcinoids (ACs) are rare malignant types of neuroendocrine tumors, accounting for approximately 10-15% of carcinoid neoplasms of the lung. They manifest a higher trend of recurrence and metastasis in comparison with typical carcinoids (TCs). PDT is effective and safe for patients with early-stage central lung cancer, but there are few reports of its application for ACs. The gold standard treatment for bronchial carcinoid is surgery. Endobronchial treatment (EBT) has recently become an option for intraluminal TCs, but EBT for ACs is vague. We report on a45-year-old woman with hemoptysis, diagnosed with AC localized in the truncus intermedius, who underwent photodynamic therapy (PDT) following transbronchial resection instead of surgery, and has survived long-term without recurrence. In our case, PDT induced tumor necrosis and has achieved local control. We avoided a larger surgical procedure and improved the patient's quality of life. PDT may become a treatment options for small intraluminal AC after further clinical trials.
proteins
2025-04-25 | Heterozygous Men1(+/T) Knockout Mice Do Not Develop Bronchopulmonary Neuroendocrine Hyperplasia or Neoplasia but Bronchial Adenocarcinoma.
Bronchopulmonary Neuroendocrine Neoplasms (NEN) occur in 2-7% of patients with multiple endocrine neoplasia type 1 (MEN1). Precursor lesions have been identified for MEN1-related pancreatic, duodenal, and gastric NEN. The aim of the current study using a MEN1 mouse model was to define the precursor lesions of bronchopulmonary NEN and evaluate the potential prophylactic antitumor effects of somatostatin analogues in a transgenic MEN1 mouse model. Fifteen mice, germline heterozygous for Men1(+/T), were treated with subcutaneous injections of lanreotide autogel (Somatuline Autogel®, IPSEN Pharma), while 15 mice were treated with subcutaneous injections of physiologic sodium chloride as the control group. Five mice from each group were euthanized after 12, 15, and 18 months, respectively. The complete lungs were resected and evaluated after hematoxylin and eosin staining and immunohistochemistry for synaptophysin and chromogranin A. In the lungs of the 30 evaluated mice, whether treated or placebo treated, no bronchopulmonary neuroendocrine cell hyperplasia nor neuroendocrine neoplasia was detected through histopathology. However, pulmonary adenocarcinoma developed in 2 (13%) of the 15 untreated mice and in 1 (7%) of the 15 lanreotide-treated mice. Heterozygous Men1(+/T) knockout mice do not develop bronchopulmonary NEN or precursor lesions, but pulmonary adenocarcinoma. This surprising result needs to be investigated in more detail.
2024-10-18 | Evaluation of selected circulating cytokines from the IL-6 family - interleukin 6, oncostatin M, and cardiotrophin-1 - in gastro-entero-pancreatic and bronchial neuroendocrine tumours.
The incidence of neuroendocrine tumours (NETs) increased over the last years. Most of them are non-functioning, and the course of the disease is asymptomatic for a long time. This results in late diagnosis at an advanced stage. The aim of our study was the evaluation of selected circulating cytokines of interleukin-6 family - interleukin 6 (IL-6), oncostatin M (OSM), and cardiotrophin-1 (CT1) - in NETs. The study group comprised 80 patients (56%) in several subgroups, including gastroenteropancreatic (GEPNETs, n = 64, 80%) and bronchopulmonary neuroendocrine tumours (BPNETs, n = 16; 20%). Serum IL-6, OSM, and CT1 concentrations were tested using ELISA. The median concentration of IL-6 was 41.5 pg/ml in the study group and 32.6 pg/ml in the control group, and the difference was statistically significant (p < 0.001). The concentration of OSM was significantly lower in the study group than in the control group (p < 0.001), at 105.6 pg/ml and 115.5 pg/ml, respectively. There was a significant difference (p < 0.01) in concentration of CT1 in the study group (222.0 pg/ml) and controls (267.2 pg/ml). Our investigation into selected IL-6 family cytokines revealed differential modulation of signal transduction pathways. These findings suggest that despite utilising a common signalling transducer, individual IL-6 family cytokines exert distinct biological effects on neuroendocrine tumour development. Notably, IL-6 appears to promote tumourigenesis, while OSM and CT1 exhibit inhibitory effects on gastro-entero-pancreatic and bronchial neuroendocrine tumour development. Further studies are necessary to validate the diagnostic utility of IL-6 family cytokines in NETs.
2022-01-04 | Glucocorticoid Receptor Antagonism Upregulates Somatostatin Receptor Subtype 2 Expression in ACTH-Producing Neuroendocrine Tumors: New Insight Based on the Selective Glucocorticoid Receptor Modulator Relacorilant
Somatostatin exhibits an inhibitory effect on pituitary hormone secretion, including inhibition of growth hormone and adrenocorticotropic hormone (ACTH), and it can have antisecretory and antitumor effects on neuroendocrine tumors (NETs) that express somatostatin receptors. Although the precise mechanism remains unclear, the finding that glucocorticoids downregulate somatostatin receptor subtype 2 (SSTR2) expression has been used to explain the lack of efficacy of traditional SSTR2-targeting analogs in patients with ACTH-secreting NETs. Glucocorticoid receptor (GR) antagonism with mifepristone has been shown to reverse the glucocorticoid-induced downregulation of SSTR2; however, the effects of GR modulation on SSTR2 expression in ACTH-secreting NETs, particularly corticotroph pituitary tumors, are not well known. The current study presents new insight from in vitro data using the highly selective GR modulator relacorilant, showing that GR modulation can overcome dexamethasone-induced suppression of SSTR2 in the murine At-T20 cell line. Additional data presented from clinical case observations in patients with ACTH-secreting NETs suggest that upregulation of SSTR2 via GR modulation may re-sensitize tumors to endogenous somatostatin and/or somatostatin analogs. Clinical, laboratory, and imaging findings from 4 patients [2 ACTH-secreting bronchial tumors and 2 ACTH-secreting pituitary tumors (Cushing disease)] who were treated with relacorilant as part of two clinical studies (NCT02804750 and NCT02762981) are described. In the patients with ectopic ACTH secretion, SSTR2-based imaging (Octreoscan and 68 Ga-DOTATATE positron emission tomography) performed before and after treatment with relacorilant showed increased radiotracer uptake by the tumor following treatment with relacorilant without change in tumor size at computed tomography. In the patients with Cushing disease who received relacorilant prior to scheduled pituitary surgery, magnetic resonance imaging after a 3-month course of relacorilant showed a reduction in tumor size. Based on these findings, we propose that GR modulation in patients with ACTH-secreting NETs upregulates previously suppressed SSTR2s, resulting in tumor-specific antisecretory and anti-proliferative effects. The effect of relacorilant on pituitary corticotroph tumors is being investigated in an ongoing phase 3 study (NCT03697109; EudraCT 2018-003096-35).
2021-11-30 | Pulmonary Neuroendocrine Tumors: Adjuvant and Systemic Treatments.
Bronchial carcinoids are uncommon tumors accounting for 20 to 30% of all neuroendocrine tumors and about 1-2% of all cancers of pulmonary origin. Bronchial carcinoids are well-differentiated neuroendocrine tumors and have a favorable survival outcome when compared with other subtypes of lung cancers. Treatment of bronchial carcinoids is not simple owing to intricacy of symptom presentation and heterogeneity of disease biology. Successful treatment of patients requires a multimodality approach. Resection is curative in the majority of patients with localized tumors and adjuvant treatment is not routinely recommended. Multiple options for systemic therapy exist for patients with advanced disease. To date, very few randomized clinical trials have been done, partly owing to the relative rarity of this malignancy. Somatostatin analogs (SSAs) are reasonable first-line choice for patients with tumors expressing somatostatin receptors. Everolimus is an appropriate first-line choice for somatostatin receptor negative tumors and for any patients with progressive disease. PRRT can also be considered for progressive tumors expressing somatostatin receptors. Based on retrospective series, cytotoxic chemotherapy can be selected in patients with progressive tumors, primarily when cytoreduction is needed. Herein, we will discuss evidence supporting the role of adjuvant and systemic treatment therapies for those with bronchial carcinoid tumors by focusing on various studies.
2019-07-09 | Treatment of Neuroendocrine Tumors (NETs) Using Somatostatin Analogs: Current View, Clinical Achievements and Future Perspectives
Neuroendocrine tumors (NETs), previously known as carcinoid tumors, are a heterogeneous group of neoplasms which originate from cells of the endocrine or nervous system with an overall incidence of 1–5 cases per 100,000 individuals per year. Recent studies showed that their incidence has dramatically increased worldwide over the last few years. The majority of NETs overexpress the somatostatin receptors (SSTRs) in tumor cells which are further being used as the important targets for therapy purposes using somatostatin analogs (SSAs) such as octreotide and lanreotide. Like native somatostatin, SSAs bind to SSTRs and induce a range of cellular effects, including antitumor activity. Antitumor activity of SSAs and their high binding properties for the SSTRs have become valuable tools for developing advanced treatment of NETs. Consequently, SSAs have been used widely in routine clinical practice, especially for treatment of various types of NETs. Despite treatment using SSAs have made a positive contribution, recent development suggests that the used of SSAs in combination with chemotherapy or peptide receptor radionuclide therapy (PRRT) can improve clinical outcome in patients with NETs. This review provides an overview of recent trend in the treatment of NETs using SSAs, their clinical achievements in the last few years and their potential applications in the future.Keywords: neuroendocrine tumors, treatment, somatostatin analogs, chemotherapy, PRRTNeuroendocrine tumors (NETs), previously known as carcinoid tumors, are a heterogeneous group of neoplasms which originate from cells of the endocrine or nervous system with an overall incidence of 1–5 cases per 100,000 individuals per year. Recent studies showed that their incidence has dramatically increased worldwide over the last few years. The majority of NETs overexpress the somatostatin receptors (SSTRs) in tumor cells which are further being used as the important targets for therapy purposes using somatostatin analogs (SSAs) such as octreotide and lanreotide. Like native somatostatin, SSAs bind to SSTRs and induce a range of cellular effects, including antitumor activity. Antitumor activity of SSAs and their high binding properties for the SSTRs have become valuable tools for developing advanced treatment of NETs. Consequently, SSAs have been used widely in routine clinical practice, especially for treatment of various types of NETs. Despite treatment using SSAs have made a positive contribution, recent development suggests that the used of SSAs in combination with chemotherapy or peptide receptor radionuclide therapy (PRRT) can improve clinical outcome in patients with NETs. This review provides an overview of recent trend in the treatment of NETs using SSAs, their clinical achievements in the last few years and their potential applications in the future.Keywords: neuroendocrine tumors, treatment, somatostatin analogs, chemotherapy, PRRT
cell therapies
2026-05-01 | C79-17 Bronchoscopic and Surgical Treatment of Endobronchial Carcinoid Incidentally Diagnosed in a Woman With Abdominal Pain
Abstract Introduction Endobronchial carcinoid is a rare and slow-growing neoplasm of neuroendocrine origin that arises within the bronchus. This case demonstrates the effective use of both bronchoscopic and surgical approaches in the management of endobronchial carcinoid tumors. Case Report A 58-year-old female with no significant past medical history presented with abdominal pain to the emergency department. Computed tomography (CT) of the abdomen and pelvis incidentally revealed an occlusive endobronchial mass in the basilar trunk of the right lower lobe, which was confirmed on CT chest. Upon further questioning, she endorsed a chronic, persistent post-pneumonic cough with occasional production of white sputum. The patient was scheduled for outpatient bronchoscopy. Interventional bronchoscopic recanalization demonstrated an occlusive polypoid mass. Pathology was positive for typical carcinoid cells. A staging positron emission tomography demonstrated a small persistent endobronchial nodule with no functional or anatomical evidence of metastatic disease. A right lower lobectomy is now planned with cardiothoracic surgery. Discussion Endobronchial carcinoid tumors typically originate from bronchial mucosa, particularly from the right bronchial tree. Less commonly arising from tracheobronchial cartilage. Cell types are divided into typical and atypical carcinoids - defined by mutations in genes such as p53, BCL2, or BAX. Atypical carcinoids being associated with poorer outcomes. This slow-growing neoplasm accounts for approximately 1-2% of all lung cancers and, due to its indolent nature, is commonly discovered incidentally. Approximately 25% of patients are asymptomatic at diagnosis. Symptoms include productive cough, chest pain, wheezing, hemoptysis, and recurrent post-obstructive pneumonia. As a consequence of its neuroendocrine origin, some patients may present with new-onset Cushing’s syndrome due to ectopic ACTH secretion. Surgical resection is often first-line treatment. A recent clinical trial by Neuberger et al. (2021) compared outcomes in patients treated with bronchoscopic intervention, surgery, or a combination of both. It was found that the latter resulted in a statistically significant increase in long-term survival. Therefore, as seen in our case, early diagnosis and timely intervention are critical for optimizing positive outcomes in endobronchial carcinoid. This abstract is funded by: none
2026-03-13 | Multidisciplinary management of endobronchial carcinoid tumours through a combined bronchoscopic and surgical approach.
We report the case of a 44-year-old woman with a typical carcinoid tumour of the left mainstem bronchus managed through a multidisciplinary and combined approach. Initial symptoms included haemoptysis and progressive wheezing. A subsequent bronchoscopy revealed a highly vascular, pedunculated mass nearly occluding the airway. En bloc resection using electrocautery and a cryoprobe enabled airway recanalization and diagnosis. Endobronchial ultrasound-guided transbronchial fine needle aspiration ruled out nodal disease. Histopathological examination confirmed a typical carcinoid tumour. Robotic-assisted sleeve resection was subsequently performed, preserving parenchyma and achieving negative margins. Surveillance bronchoscopy showed a well-healed anastomosis with no granulation. This case highlights the importance of bronchoscopic interventions in staging and treatment planning, as well as their role in facilitating lung-sparing surgical strategies.
2023-10-18 | Diagnostics and treatment in bronchial carcinoid tumors
At the start of this thesis there were several unanswered questions with regard to optimal patient selection for different treatments of bronchial carcinoid. Also, there were unanswered questions with regard to classification of bronchial carcinoid on small histological samples and with regard to prognostic value of several new tissue biomarkers. The aim of this thesis was to further optimize patient selection for parenchyma sparing techniques, and to explore the potential value of biomarkers in the treatment of bronchial carcinoid. Part one (chapter 2-5) of this thesis describes the classification of bronchial carcinoid on small histological samples and the use of diagnostic and prognostic biomarkers. In Chapter 2 we analyze patient selection for endobronchial treatment and underscore the importance of radiological assessment of bronchial carcinoids. Differentiation between typical and atypical carcinoid according to the current WHO classification is accomplished by obtaining the mitotic count and the presence of necrosis. As outlined above, TC is defined as a neuroendocrine tumour with less than 2 mitoses per 2 mm2 and absence of necrosis, while AC is defined by 2-10 mitoses per 2 mm2 and/or the presence of (dot-like) necrosis. However, it is known that small biopsies have limited diagnostic value for the distinction between TC and AC. In Chapter 3 and Chapter 4 we analyzed biopsy-resection paired specimens of patients referred for treatment for bronchial carcinoid to measure accuracy of pretreatment biopsies and analyze the value of tumor biopsy size. Furthermore, we describe the reliability of different immunohistochemical markers on different biopsies and resection specimens, and assessed the impact of specimen size on the accuracy of the diagnosis. Because the current classification of TC and AC only partially reflects their metastatic potential, there is a need for more accurate prognostic biomarkers for bronchial carcinoids. In Chapter 5 we investigated a combination of morphological and novel immunohistochemical markers for predicting dissemination. Part two (chapter 6-8) focuses on therapeutic strategies and patient selection for EBT. In Chapter 6 we present the results of a systematic review of the available literature on the feasibility and outcome of endobronchial treatment compared to surgical resection. We studied several endpoints such as overall survival, disease free survival, recurrence rate, complications, quality of life, and healthcare costs. Where EBT can be curative for patients with small intraluminal carcinoid tumors, tumor debulking prior to surgery may potentially result in less lung parenchyma that has to be removed during surgery to achieve complete resection of the tumor. In addition, EBT may reduce the need for sleeve resection to achieve radical margins when bulky tumors are removed. It is in Chapter 7 that we investigated whether endobronchial therapy for bronchial carcinoid, if not curative, can reduce the extent of the surgical resection and whether EBT prior to surgery is associated with increased surgical morbidity. Several letters, in reply to comments from experts in the field of treatment for bronchial carcinoid tumors, regarding published studies by our group, are bundled in Chapter 8.
2022-02-16 | Morbidity and extent of surgical resection of carcinoid tumors after endobronchial treatment.
This study assessed whether endobronchial therapy (EBT) for bronchial carcinoid, if not curative, reduces the extent of the surgical resection and whether EBT is associated with increased surgical morbidity. Analysis was performed in a cohort of patients with bronchial carcinoid who have undergone surgical resection. A group that underwent EBT before the surgery (S + EBT) was compared with a group where no EBT was performed (S-EBT). Postoperative complications were also compared between both groups. A total of 254 patients treated for a bronchial carcinoid tumor between 2003 and 2019 were screened for inclusion. A total of 65 surgically treated patients were included, of whom 41 (63%) underwent EBT prior to surgery. In 5 out of 41 patients (12%) from the S + EBT group, less parenchyma was resected versus 2 out of 24 (8%) from the S-EBT group (OR 1.528, 95% CI 0.273-8.562, p = 1.000). Two patients from the S + EBT group (5%) underwent lobectomy instead of sleeve lobectomy versus 0 from the S-EBT group (OR 1.051, 95% CI 0.981-1.127, p = 0.527). Comparing complications between the S + EBT and S-EBT group did not result in increased postoperative surgical morbidity (15% S + EBT, 24% S-EBT). EBT, if not curative, does not reduce the extent of the subsequent surgical resection. Therefore, if curative EBT is not anticipated, patients should directly be referred for surgery. If curative EBT seems feasible, it should be attempted not only because surgical resection can be prevented, but also because failure of EBT is not associated with excess surgical morbidity.
2022-02-02 | [Observation of Short-term and Long-term Efficacy of Bronchoscopic Interventional Therapy in the Treatment of Typical Carcinoid].
The curative potential of various bronchoscopic treatments such as electric snare, carbon dioxide freezing, argon plasma coagulation (APC), Neudymium-dopted Yttrium Aluminium Garnet (Nd:YAG) laser and photodynamic therapy (PDT) for the treatment of intraluminal tumor has been administered previously, but this regimen is not common in the treatment of typical carcinoid. The aim of this study is to investigate the curative effects both in short-term and long-term of interventional bronchoscopy in the treatment of typical carcinoid. We retrospectively reviewed the clinical data of typical carcinoid patients who were treated with interventional bronchoscopy for tumor suppression and they were hospitalized in the Emergency General Hospital from December 2010 to December 2020, and Wilcoxon rank sum test and chi-square test were used for analysis. A total of 32 patients were included, including 18 cases of preoperative bronchial artery embolization (embolization rate 56%, 95%CI: 31%-79%). The grade score of dyspnea decreased from before treatment to after treatment, and the difference was statistically significant [(1.44±1.03) score vs (0.25±0.58) score, P=0.003]; The degree of bronchial stenosis decreased from pre-treatment to post-treatment, and the difference was statistically significant [(87.50%±13.90%) vs (17.50%±6.83%), P<0.001]; There was significant difference in bronchial diameter before and after treatment [(0.14±0.18) cm vs (0.84±0.29) cm, P<0.001]. Bronchoscopic interventional therapy has significant short-term and long-term effects in the treatment of typical carcinoid. 【中文题目：支气管镜介入技术治疗典型类癌的 近期疗效及远期疗效观察】 【中文摘要：背景与目的 支气管镜下的各种介入治疗技术包括圈套、二氧化碳冷冻、氩等离子体凝固（argon plasma coagulation, APC）、激光（Neodymium-dopted Yttrium Aluminium Garnet, Nd:YAG）、光动力治疗（photodynamic therapy, PDT），以上治疗技术通常用于治疗气管腔内肿瘤，但用于治疗典型类癌（typical carcinoid, TC）的研究并不普遍。本研究拟探讨支气管镜介入技术治疗典型类癌的近期疗效和远期疗效。方法 回顾性分析北京应急总医院2010年12月-2020年12月可消瘤的腔内典型类癌患者的临床资料，采用Wilcoxon秩和检验和卡方检验进行统计分析。结果 共纳入32例患者，术前支气管动脉栓塞18例（栓塞率56%，95%CI: 31%-79%）。呼吸困难分级评分治疗后较治疗前下降，差异有统计学意义［（1.44±1.03）分 vs （0.25±0.58）分，P=0.003］；支气管管腔狭窄程度治疗后较治疗前改善，差异有统计学意义［(87.50%±13.90%) vs (17.50%±6.83%), P<0.001］；支气管内径治疗后较治疗前扩宽，差异有统计学意义［(0.14±0.18) cm vs (0.84±0.29) cm, P<0.001］。近期有效率为100%。32例患者中24例支气管镜介入治疗能够完全消瘤，完全缓解（complete remission, CR）率为75%。结论 支气管镜介入治疗技术治疗典型类癌的近期疗效及远期疗效显著。】 【中文关键词：典型类癌；支气管介入治疗；疗效】.
antibodies
2026-07-23 | Small Cell Lung Cancer: From Histogenesis to a New Therapeutic Paradigm
Pulmonary neuroendocrine neoplasms (NENs) form a histogenetic continuum arising from bronchial Kulchitsky cells, ranging from well-differentiated carcinoids to highly aggressive neuroendocrine carcinomas. The 2021 WHO Classification of Thoracic Tumors maintains a morphology-based, grade-linked framework for typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung cancer (SCLC), defined by mitotic index and necrosis. Genomic data reinforce a fundamental dichotomy: carcinoids harbor low tumor mutational burden with frequent chromatin-remodeling alterations (e.g., MEN1) and wild-type TP53/RB1, whereas high-grade carcinomas are unified by concurrent TP53 and RB1 inactivation. LCNEC occupies a heterogeneous intermediate position, comprising SCLC-like (TP53/RB1 co-inactivated) and NSCLC-like (KRAS, STK11, KEAP1) subsets, explaining therapeutic variability and motivating molecularly stratified management. In SCLC, precise pathological diagnosis is essential given its immediate therapeutic implications. Immunohistochemistry — synaptophysin, chromogranin A, CD56, and INSM1 — remains indispensable, particularly in compromised small-biopsy specimens. Therapeutically, platinum-based chemotherapy combined with immunotherapy yields modest but reproducible survival gains. Molecular subtyping has uncovered lineage-based vulnerabilities, with DLL3-targeted bispecific T-cell engagers achieving the first validated subtype-specific regulatory approval. Nevertheless, clinical translation of biologically rational strategies has broadly underperformed in late-phase trials. Tumor plasticity and phenotypic switching between subtypes remain critical barriers to durable responses. Integrating histology, immunophenotype, and genomics refines diagnosis and risk stratification, yet the transition from biological hypothesis to validated precision oncology in pulmonary NENs remains incomplete.
2024-01-18 | Iridociliary Body Metastasis of Atypical Carcinoid: Case Management with Intravitreal Anti-Vascular Endothelial Growth Factor Injections.
We report a rare case involving 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.
2023-11-06 | Expression of G protein-coupled receptor GPR19 in normal and neoplastic human tissues.
Little is known about the expression of the orphan G protein-coupled receptor GPR19 at the protein level. Therefore, we developed a rabbit antibody, targeting human GPR19. After verification of the antibody specificity using GPR19-expressing cell lines and a GPR19-specific siRNA, the antibody was used for immunohistochemical staining of a variety of formalin-fixed, paraffin-embedded normal and neoplastic human tissue samples. In normal tissues, GPR19 expression was detected in a distinct cell population within the cortex, in single cells of the pancreatic islets, in intestinal ganglia, gastric chief cells, and in endocrine cells of the bronchial tract, the gastrointestinal tract, and the prostate. Among the 30 different tumour entities investigated, strong GPR19 expression was found in adenocarcinomas, typical and atypical carcinoids of the lung, and small cell lung cancer. To a lesser extent, the receptor was also present in large cell neuroendocrine carcinomas of the lung, medullary thyroid carcinomas, parathyroid adenomas, pheochromocytomas, and a subpopulation of pancreatic neuroendocrine neoplasms. In lung tumours, a negative correlation with the expression of the proliferation marker Ki-67 and a positive interrelationship with patient survival was observed. Overall, our results indicate that in adenocarcinomas and neuroendocrine tumours of the lung GPR19 may serve as a suitable diagnostic or therapeutic target.
2021-12-23 | Case Report: Unmasking Hypercalcemia in Patients With Neuroendocrine Neoplasms. Experience From Six Italian Referral Centers.
Hypercalcemia is a common paraneoplastic syndrome which can occur in up to 10% of patients with advanced neoplasms. Paraneoplastic parathyroid hormone-related protein (PTHrP) represents the most frequent cause of this syndrome. In neuroendocrine neoplasms (NENs) paraneoplastic hypercalcemia is rare. The present series includes all patients with NENs and paraneoplastic hypercalcemia from four Italian centres: (I) A 40-year-old man was hospitalized for repeated episodes of falls, hyposthenia and drowsiness. Severe hypercalcemia was found. Metastatic pancreatic G2 NEN and PTHrP-related hypercalcemia were diagnosed. The patient started therapy with somatostatin analogs (SSA) and Denosumab. After disease progression peptide receptor radionuclide therapy (PRRT) was started with an objective response associated with PTHrP reduction and normocalcemia. (II) A 45-year-old man was referred for pancreatic G2 NEN. SSA and subsequently everolimus were administered for metastases occurrence. Hypercalcemia occurred and PRRT and Denosumab were started for disease progression with the onset of bone metastases. Despite disease stability after four cycles of PRRT the patient's performance status worsened until death. (III) A 49-year-old woman was hospitalized for psychic slowdown, confusional state, sensory dullness. A severe hypercalcemia, associated with a pancreatic G1 NEN was diagnosed and treated with haemodialysis, bisphosphonates injections and continuous infusion of calcitonin. 1,25-dihydroxyvitamin D was high, PTHrP was undetectable. After surgery serum calcium levels and 1,25-dihydroxyvitamin D were normalized. (IV) A 69-year-old man was hospitalized after the onset of shortness of breath and dyspnea, asthenia and weight loss. Computed Tomography (CT) and 68Ga DOTATOC Positron Emission Tomography (PET)-CT revealed a left pulmonary nodule. Hypercalcemia and markedly elevated PTHrP levels were detected. The histological examination revealed an atypical carcinoid. After surgery, calcium levels were normalized, PTHrP was significantly reduced with an improvement of general conditions. In our series, paraneoplastic PTHrP-related hypercalcemia occurred in pancreatic NEN and in one bronchial carcinoid representing the third case in the literature. Our case associated with 1,25-dihydroxyvitamin D secretion represents the fourth case in the literature. PTHrP secretion should be considered in NENs' patients with hypercalcemia. Acute treatment should be focused on lowering calcium levels, and long-term control can be achieved by tumor cytoreduction inhibiting PTHrP release.
small molecules
2026-06-11 | Alternating Therapy With Osilodrostat and Etomidate in Severe Ectopic Cushing's Syndrome Complicated by Silent Bowel Perforation.
Ectopic adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS), ectopic ACTH secretion (EAS) is a rare condition caused by ACTH-secreting neuroendocrine tumors (NETs), such as bronchial carcinoids. We report a 65-year-old woman with severe EAS complicated by bowel perforation. She presented with hypokalemia (K+ 2.3 mmol/L), metabolic alkalosis, resistant hypertension (180/110 mmHg), worsening diabetes (HbA1c 6.7%-9.1%), proximal muscle weakness, and 14 kg weight gain over 3 months. A silent sigmoid colon perforation required emergency resection and colostomy. Biochemical tests confirmed hypercortisolism (urine free cortisol [UFC], 1256 µg/24 h, plasma ACTH 175 pg/mL, and cortisol >40 µg/dL post-dexamethasone). Imaging identified a 2.3 cm pulmonary nodule with mild uptake on Ga-68 DOTATATE PET/CT. Bronchoscopic biopsy confirmed an ACTH-positive low-grade bronchial carcinoid tumor. Initial treatment with osilodrostat was interrupted due to acute illness and oral medication intolerance. Intravenous etomidate was employed in the ICU for rapid cortisol suppression, followed by resumption of osilodrostat after stabilization. Thoracoscopic lobectomy confirmed a low-grade carcinoid tumor (Ki-67 < 2%). Postoperatively, cortisol normalized, electrolytes stabilized, and HbA1c improved to 6.5%. This case highlights bowel perforation as a severe complication of EAS and underscores the importance of dynamic, alternating therapy with osilodrostat and etomidate, along with individualized surgical and medical management strategies.
2025-08-21 | Preoperative Embolization of a Pulmonary Carcinoid Tumor with Unusual Arterial Supply: A Case Report
Background Pulmonary carcinoid tumors are rare neuroendocrine neoplasms that carry a risk of bleeding. We report a case of a tumor with unusual arterial supply from multiple sources including collateral from the renal artery, successfully managed with preoperative embolization followed by surgical resection. Case presentation: A 39-year-old woman with no significant medical history presented with chronic cough. Chest radiography revealed an opacity in the right hilar region. Computed tomography (CT) showed a mass obstructing the right middle lobe bronchus. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) demonstrated no abnormal uptake in the lesion. However, a Ga-68 DOTATATE somatostatin receptor scan (DOTA-PET) showed intense tracer uptake in the mass. Bronchoscopy identified a reddish endobronchial lesion completely occluding the middle lobe bronchus and causing distal collapse. Biopsy was deferred due to the lesion’s hypervascular appearance. With a presumptive diagnosis of carcinoid tumor, a multidisciplinary team planned for surgical resection. To mitigate intraoperative bleeding, preoperative angiographic evaluation was performed. Digital subtraction angiography (DSA) revealed that the blood supply originated from the right bronchial artery, right internal mammary artery and right renal artery. All identified feeding arteries were selectively catheterized and embolized with coils. The patient underwent a right middle lobectomy. Intraoperative blood loss was minimal, and the tumor was resected completely. Pathology confirmed carcinoid tumor. At two-year follow-up, the patient remains asymptomatic. Conclusions This case highlights a rare arterial supply to a lung tumor and demonstrates that preoperative embolization of multiple feeding vessels can facilitate safe resection of a hypervascular tumor. Awareness of vascular anomalies and multidisciplinary approach were key to successful management.
2025-08-21 | Effects of metabolic inhibition on ion transport by dog bronchial epithelium
Mammalian bronchial epithelium absorbs Na+ under basal conditions, but Cl- secretion can be induced. We studied the effects of several modes of metabolic inhibition on the bioelectric properties and solute permeability of dog bronchial epithelium mounted in Ussing chambers. Net Na+ absorption and short-circuit current were inhibited by ~75% by hypoxia or by 10-3 M NaCN. The reduced net Na+ absorption was characterized by a decrease in absorptive flux and an increase in backflux. The latter change was proportional to an increase in permeability to [14C]mannitol, implying that solute flow through a paracellular shunt was increased. In contrast, the reduction of conductance expected from exposure to amiloride (0.94 ± 0.15 ms/cm2 or 12%) was abolished by NaCN pretreatment. Metabolic inhibition also decreased epithelial conductance and unidirectional Cl- fluxes by ~25%. NaCN rapidly and reversibly inhibited the hyperpolarization on potential difference (PD) induced by low luminal bath [cl-]. This effect was mimicked by the Cl- channel blocker, 5-nitro-2-(3-phenylpropylamino) benzoic acid. Because the transepithelial Cl- diffusion PD reflects, in part, the depolarization of the Cl--conductive apical cell membrane metabolic inhibition appears to affect this path. We conclude that metabolic inhibition not only decreased net ion transport by dog bronchial epithelium but also inhibited cellular Na+- and Cl--conductive pathways and increased paracellular permeability.
2025-04-29 | Expression of YAP1 and TAZ in Melanoma-, Bronchial- and Breast Carcinoma Brain Metastasis: Primary vs. Relapsed Tumors.
Brain metastases from the most common primary sites - lung carcinoma, breast carcinoma, and melanoma - are more frequent than primary brain tumors. YAP1/TAZ are regulators of tissue growth and epithelial-mesenchymal transition (EMT) within the hippo pathway. The aim of the study was the evaluation of the role of YAP1/TAZ in brain metastasis. Expression levels of YAP1 and TAZ were measured in samples of primary and relapsed brain metastases from patients with melanoma, breast carcinoma, and bronchial carcinoma using qPCR and western blot. Expression of YAP1 and TAZ was highest in melanoma followed by bronchial carcinoma and lowest in breast carcinoma. For YAP1, expression in primary metastasis was higher than in relapsed metastasis. Because of the important role of YAP1/TAZ in EMT, targeting these genes could be a promising approach to reduce the risk of metastasis.
2025-04-12 | Bronchial atypical carcinoid in the truncus intermedius persistently controlled by PDT following transbronchial resection instead of surgery: A case report.
Atypical carcinoids (ACs) are rare malignant types of neuroendocrine tumors, accounting for approximately 10-15% of carcinoid neoplasms of the lung. They manifest a higher trend of recurrence and metastasis in comparison with typical carcinoids (TCs). PDT is effective and safe for patients with early-stage central lung cancer, but there are few reports of its application for ACs. The gold standard treatment for bronchial carcinoid is surgery. Endobronchial treatment (EBT) has recently become an option for intraluminal TCs, but EBT for ACs is vague. We report on a45-year-old woman with hemoptysis, diagnosed with AC localized in the truncus intermedius, who underwent photodynamic therapy (PDT) following transbronchial resection instead of surgery, and has survived long-term without recurrence. In our case, PDT induced tumor necrosis and has achieved local control. We avoided a larger surgical procedure and improved the patient's quality of life. PDT may become a treatment options for small intraluminal AC after further clinical trials.
proteins
2025-04-25 | Heterozygous Men1(+/T) Knockout Mice Do Not Develop Bronchopulmonary Neuroendocrine Hyperplasia or Neoplasia but Bronchial Adenocarcinoma.
Bronchopulmonary Neuroendocrine Neoplasms (NEN) occur in 2-7% of patients with multiple endocrine neoplasia type 1 (MEN1). Precursor lesions have been identified for MEN1-related pancreatic, duodenal, and gastric NEN. The aim of the current study using a MEN1 mouse model was to define the precursor lesions of bronchopulmonary NEN and evaluate the potential prophylactic antitumor effects of somatostatin analogues in a transgenic MEN1 mouse model. Fifteen mice, germline heterozygous for Men1(+/T), were treated with subcutaneous injections of lanreotide autogel (Somatuline Autogel®, IPSEN Pharma), while 15 mice were treated with subcutaneous injections of physiologic sodium chloride as the control group. Five mice from each group were euthanized after 12, 15, and 18 months, respectively. The complete lungs were resected and evaluated after hematoxylin and eosin staining and immunohistochemistry for synaptophysin and chromogranin A. In the lungs of the 30 evaluated mice, whether treated or placebo treated, no bronchopulmonary neuroendocrine cell hyperplasia nor neuroendocrine neoplasia was detected through histopathology. However, pulmonary adenocarcinoma developed in 2 (13%) of the 15 untreated mice and in 1 (7%) of the 15 lanreotide-treated mice. Heterozygous Men1(+/T) knockout mice do not develop bronchopulmonary NEN or precursor lesions, but pulmonary adenocarcinoma. This surprising result needs to be investigated in more detail.
2024-10-18 | Evaluation of selected circulating cytokines from the IL-6 family - interleukin 6, oncostatin M, and cardiotrophin-1 - in gastro-entero-pancreatic and bronchial neuroendocrine tumours.
The incidence of neuroendocrine tumours (NETs) increased over the last years. Most of them are non-functioning, and the course of the disease is asymptomatic for a long time. This results in late diagnosis at an advanced stage. The aim of our study was the evaluation of selected circulating cytokines of interleukin-6 family - interleukin 6 (IL-6), oncostatin M (OSM), and cardiotrophin-1 (CT1) - in NETs. The study group comprised 80 patients (56%) in several subgroups, including gastroenteropancreatic (GEPNETs, n = 64, 80%) and bronchopulmonary neuroendocrine tumours (BPNETs, n = 16; 20%). Serum IL-6, OSM, and CT1 concentrations were tested using ELISA. The median concentration of IL-6 was 41.5 pg/ml in the study group and 32.6 pg/ml in the control group, and the difference was statistically significant (p < 0.001). The concentration of OSM was significantly lower in the study group than in the control group (p < 0.001), at 105.6 pg/ml and 115.5 pg/ml, respectively. There was a significant difference (p < 0.01) in concentration of CT1 in the study group (222.0 pg/ml) and controls (267.2 pg/ml). Our investigation into selected IL-6 family cytokines revealed differential modulation of signal transduction pathways. These findings suggest that despite utilising a common signalling transducer, individual IL-6 family cytokines exert distinct biological effects on neuroendocrine tumour development. Notably, IL-6 appears to promote tumourigenesis, while OSM and CT1 exhibit inhibitory effects on gastro-entero-pancreatic and bronchial neuroendocrine tumour development. Further studies are necessary to validate the diagnostic utility of IL-6 family cytokines in NETs.
2022-01-04 | Glucocorticoid Receptor Antagonism Upregulates Somatostatin Receptor Subtype 2 Expression in ACTH-Producing Neuroendocrine Tumors: New Insight Based on the Selective Glucocorticoid Receptor Modulator Relacorilant
Somatostatin exhibits an inhibitory effect on pituitary hormone secretion, including inhibition of growth hormone and adrenocorticotropic hormone (ACTH), and it can have antisecretory and antitumor effects on neuroendocrine tumors (NETs) that express somatostatin receptors. Although the precise mechanism remains unclear, the finding that glucocorticoids downregulate somatostatin receptor subtype 2 (SSTR2) expression has been used to explain the lack of efficacy of traditional SSTR2-targeting analogs in patients with ACTH-secreting NETs. Glucocorticoid receptor (GR) antagonism with mifepristone has been shown to reverse the glucocorticoid-induced downregulation of SSTR2; however, the effects of GR modulation on SSTR2 expression in ACTH-secreting NETs, particularly corticotroph pituitary tumors, are not well known. The current study presents new insight from in vitro data using the highly selective GR modulator relacorilant, showing that GR modulation can overcome dexamethasone-induced suppression of SSTR2 in the murine At-T20 cell line. Additional data presented from clinical case observations in patients with ACTH-secreting NETs suggest that upregulation of SSTR2 via GR modulation may re-sensitize tumors to endogenous somatostatin and/or somatostatin analogs. Clinical, laboratory, and imaging findings from 4 patients [2 ACTH-secreting bronchial tumors and 2 ACTH-secreting pituitary tumors (Cushing disease)] who were treated with relacorilant as part of two clinical studies (NCT02804750 and NCT02762981) are described. In the patients with ectopic ACTH secretion, SSTR2-based imaging (Octreoscan and 68 Ga-DOTATATE positron emission tomography) performed before and after treatment with relacorilant showed increased radiotracer uptake by the tumor following treatment with relacorilant without change in tumor size at computed tomography. In the patients with Cushing disease who received relacorilant prior to scheduled pituitary surgery, magnetic resonance imaging after a 3-month course of relacorilant showed a reduction in tumor size. Based on these findings, we propose that GR modulation in patients with ACTH-secreting NETs upregulates previously suppressed SSTR2s, resulting in tumor-specific antisecretory and anti-proliferative effects. The effect of relacorilant on pituitary corticotroph tumors is being investigated in an ongoing phase 3 study (NCT03697109; EudraCT 2018-003096-35).
2021-11-30 | Pulmonary Neuroendocrine Tumors: Adjuvant and Systemic Treatments.
Bronchial carcinoids are uncommon tumors accounting for 20 to 30% of all neuroendocrine tumors and about 1-2% of all cancers of pulmonary origin. Bronchial carcinoids are well-differentiated neuroendocrine tumors and have a favorable survival outcome when compared with other subtypes of lung cancers. Treatment of bronchial carcinoids is not simple owing to intricacy of symptom presentation and heterogeneity of disease biology. Successful treatment of patients requires a multimodality approach. Resection is curative in the majority of patients with localized tumors and adjuvant treatment is not routinely recommended. Multiple options for systemic therapy exist for patients with advanced disease. To date, very few randomized clinical trials have been done, partly owing to the relative rarity of this malignancy. Somatostatin analogs (SSAs) are reasonable first-line choice for patients with tumors expressing somatostatin receptors. Everolimus is an appropriate first-line choice for somatostatin receptor negative tumors and for any patients with progressive disease. PRRT can also be considered for progressive tumors expressing somatostatin receptors. Based on retrospective series, cytotoxic chemotherapy can be selected in patients with progressive tumors, primarily when cytoreduction is needed. Herein, we will discuss evidence supporting the role of adjuvant and systemic treatment therapies for those with bronchial carcinoid tumors by focusing on various studies.
2019-07-09 | Treatment of Neuroendocrine Tumors (NETs) Using Somatostatin Analogs: Current View, Clinical Achievements and Future Perspectives
Neuroendocrine tumors (NETs), previously known as carcinoid tumors, are a heterogeneous group of neoplasms which originate from cells of the endocrine or nervous system with an overall incidence of 1–5 cases per 100,000 individuals per year. Recent studies showed that their incidence has dramatically increased worldwide over the last few years. The majority of NETs overexpress the somatostatin receptors (SSTRs) in tumor cells which are further being used as the important targets for therapy purposes using somatostatin analogs (SSAs) such as octreotide and lanreotide. Like native somatostatin, SSAs bind to SSTRs and induce a range of cellular effects, including antitumor activity. Antitumor activity of SSAs and their high binding properties for the SSTRs have become valuable tools for developing advanced treatment of NETs. Consequently, SSAs have been used widely in routine clinical practice, especially for treatment of various types of NETs. Despite treatment using SSAs have made a positive contribution, recent development suggests that the used of SSAs in combination with chemotherapy or peptide receptor radionuclide therapy (PRRT) can improve clinical outcome in patients with NETs. This review provides an overview of recent trend in the treatment of NETs using SSAs, their clinical achievements in the last few years and their potential applications in the future.Keywords: neuroendocrine tumors, treatment, somatostatin analogs, chemotherapy, PRRTNeuroendocrine tumors (NETs), previously known as carcinoid tumors, are a heterogeneous group of neoplasms which originate from cells of the endocrine or nervous system with an overall incidence of 1–5 cases per 100,000 individuals per year. Recent studies showed that their incidence has dramatically increased worldwide over the last few years. The majority of NETs overexpress the somatostatin receptors (SSTRs) in tumor cells which are further being used as the important targets for therapy purposes using somatostatin analogs (SSAs) such as octreotide and lanreotide. Like native somatostatin, SSAs bind to SSTRs and induce a range of cellular effects, including antitumor activity. Antitumor activity of SSAs and their high binding properties for the SSTRs have become valuable tools for developing advanced treatment of NETs. Consequently, SSAs have been used widely in routine clinical practice, especially for treatment of various types of NETs. Despite treatment using SSAs have made a positive contribution, recent development suggests that the used of SSAs in combination with chemotherapy or peptide receptor radionuclide therapy (PRRT) can improve clinical outcome in patients with NETs. This review provides an overview of recent trend in the treatment of NETs using SSAs, their clinical achievements in the last few years and their potential applications in the future.Keywords: neuroendocrine tumors, treatment, somatostatin analogs, chemotherapy, PRRT
cell therapies
2026-05-01 | C79-17 Bronchoscopic and Surgical Treatment of Endobronchial Carcinoid Incidentally Diagnosed in a Woman With Abdominal Pain
Abstract Introduction Endobronchial carcinoid is a rare and slow-growing neoplasm of neuroendocrine origin that arises within the bronchus. This case demonstrates the effective use of both bronchoscopic and surgical approaches in the management of endobronchial carcinoid tumors. Case Report A 58-year-old female with no significant past medical history presented with abdominal pain to the emergency department. Computed tomography (CT) of the abdomen and pelvis incidentally revealed an occlusive endobronchial mass in the basilar trunk of the right lower lobe, which was confirmed on CT chest. Upon further questioning, she endorsed a chronic, persistent post-pneumonic cough with occasional production of white sputum. The patient was scheduled for outpatient bronchoscopy. Interventional bronchoscopic recanalization demonstrated an occlusive polypoid mass. Pathology was positive for typical carcinoid cells. A staging positron emission tomography demonstrated a small persistent endobronchial nodule with no functional or anatomical evidence of metastatic disease. A right lower lobectomy is now planned with cardiothoracic surgery. Discussion Endobronchial carcinoid tumors typically originate from bronchial mucosa, particularly from the right bronchial tree. Less commonly arising from tracheobronchial cartilage. Cell types are divided into typical and atypical carcinoids - defined by mutations in genes such as p53, BCL2, or BAX. Atypical carcinoids being associated with poorer outcomes. This slow-growing neoplasm accounts for approximately 1-2% of all lung cancers and, due to its indolent nature, is commonly discovered incidentally. Approximately 25% of patients are asymptomatic at diagnosis. Symptoms include productive cough, chest pain, wheezing, hemoptysis, and recurrent post-obstructive pneumonia. As a consequence of its neuroendocrine origin, some patients may present with new-onset Cushing’s syndrome due to ectopic ACTH secretion. Surgical resection is often first-line treatment. A recent clinical trial by Neuberger et al. (2021) compared outcomes in patients treated with bronchoscopic intervention, surgery, or a combination of both. It was found that the latter resulted in a statistically significant increase in long-term survival. Therefore, as seen in our case, early diagnosis and timely intervention are critical for optimizing positive outcomes in endobronchial carcinoid. This abstract is funded by: none
2026-03-13 | Multidisciplinary management of endobronchial carcinoid tumours through a combined bronchoscopic and surgical approach.
We report the case of a 44-year-old woman with a typical carcinoid tumour of the left mainstem bronchus managed through a multidisciplinary and combined approach. Initial symptoms included haemoptysis and progressive wheezing. A subsequent bronchoscopy revealed a highly vascular, pedunculated mass nearly occluding the airway. En bloc resection using electrocautery and a cryoprobe enabled airway recanalization and diagnosis. Endobronchial ultrasound-guided transbronchial fine needle aspiration ruled out nodal disease. Histopathological examination confirmed a typical carcinoid tumour. Robotic-assisted sleeve resection was subsequently performed, preserving parenchyma and achieving negative margins. Surveillance bronchoscopy showed a well-healed anastomosis with no granulation. This case highlights the importance of bronchoscopic interventions in staging and treatment planning, as well as their role in facilitating lung-sparing surgical strategies.
2023-10-18 | Diagnostics and treatment in bronchial carcinoid tumors
At the start of this thesis there were several unanswered questions with regard to optimal patient selection for different treatments of bronchial carcinoid. Also, there were unanswered questions with regard to classification of bronchial carcinoid on small histological samples and with regard to prognostic value of several new tissue biomarkers. The aim of this thesis was to further optimize patient selection for parenchyma sparing techniques, and to explore the potential value of biomarkers in the treatment of bronchial carcinoid. Part one (chapter 2-5) of this thesis describes the classification of bronchial carcinoid on small histological samples and the use of diagnostic and prognostic biomarkers. In Chapter 2 we analyze patient selection for endobronchial treatment and underscore the importance of radiological assessment of bronchial carcinoids. Differentiation between typical and atypical carcinoid according to the current WHO classification is accomplished by obtaining the mitotic count and the presence of necrosis. As outlined above, TC is defined as a neuroendocrine tumour with less than 2 mitoses per 2 mm2 and absence of necrosis, while AC is defined by 2-10 mitoses per 2 mm2 and/or the presence of (dot-like) necrosis. However, it is known that small biopsies have limited diagnostic value for the distinction between TC and AC. In Chapter 3 and Chapter 4 we analyzed biopsy-resection paired specimens of patients referred for treatment for bronchial carcinoid to measure accuracy of pretreatment biopsies and analyze the value of tumor biopsy size. Furthermore, we describe the reliability of different immunohistochemical markers on different biopsies and resection specimens, and assessed the impact of specimen size on the accuracy of the diagnosis. Because the current classification of TC and AC only partially reflects their metastatic potential, there is a need for more accurate prognostic biomarkers for bronchial carcinoids. In Chapter 5 we investigated a combination of morphological and novel immunohistochemical markers for predicting dissemination. Part two (chapter 6-8) focuses on therapeutic strategies and patient selection for EBT. In Chapter 6 we present the results of a systematic review of the available literature on the feasibility and outcome of endobronchial treatment compared to surgical resection. We studied several endpoints such as overall survival, disease free survival, recurrence rate, complications, quality of life, and healthcare costs. Where EBT can be curative for patients with small intraluminal carcinoid tumors, tumor debulking prior to surgery may potentially result in less lung parenchyma that has to be removed during surgery to achieve complete resection of the tumor. In addition, EBT may reduce the need for sleeve resection to achieve radical margins when bulky tumors are removed. It is in Chapter 7 that we investigated whether endobronchial therapy for bronchial carcinoid, if not curative, can reduce the extent of the surgical resection and whether EBT prior to surgery is associated with increased surgical morbidity. Several letters, in reply to comments from experts in the field of treatment for bronchial carcinoid tumors, regarding published studies by our group, are bundled in Chapter 8.
2022-02-16 | Morbidity and extent of surgical resection of carcinoid tumors after endobronchial treatment.
This study assessed whether endobronchial therapy (EBT) for bronchial carcinoid, if not curative, reduces the extent of the surgical resection and whether EBT is associated with increased surgical morbidity. Analysis was performed in a cohort of patients with bronchial carcinoid who have undergone surgical resection. A group that underwent EBT before the surgery (S + EBT) was compared with a group where no EBT was performed (S-EBT). Postoperative complications were also compared between both groups. A total of 254 patients treated for a bronchial carcinoid tumor between 2003 and 2019 were screened for inclusion. A total of 65 surgically treated patients were included, of whom 41 (63%) underwent EBT prior to surgery. In 5 out of 41 patients (12%) from the S + EBT group, less parenchyma was resected versus 2 out of 24 (8%) from the S-EBT group (OR 1.528, 95% CI 0.273-8.562, p = 1.000). Two patients from the S + EBT group (5%) underwent lobectomy instead of sleeve lobectomy versus 0 from the S-EBT group (OR 1.051, 95% CI 0.981-1.127, p = 0.527). Comparing complications between the S + EBT and S-EBT group did not result in increased postoperative surgical morbidity (15% S + EBT, 24% S-EBT). EBT, if not curative, does not reduce the extent of the subsequent surgical resection. Therefore, if curative EBT is not anticipated, patients should directly be referred for surgery. If curative EBT seems feasible, it should be attempted not only because surgical resection can be prevented, but also because failure of EBT is not associated with excess surgical morbidity.
2022-02-02 | [Observation of Short-term and Long-term Efficacy of Bronchoscopic Interventional Therapy in the Treatment of Typical Carcinoid].
The curative potential of various bronchoscopic treatments such as electric snare, carbon dioxide freezing, argon plasma coagulation (APC), Neudymium-dopted Yttrium Aluminium Garnet (Nd:YAG) laser and photodynamic therapy (PDT) for the treatment of intraluminal tumor has been administered previously, but this regimen is not common in the treatment of typical carcinoid. The aim of this study is to investigate the curative effects both in short-term and long-term of interventional bronchoscopy in the treatment of typical carcinoid. We retrospectively reviewed the clinical data of typical carcinoid patients who were treated with interventional bronchoscopy for tumor suppression and they were hospitalized in the Emergency General Hospital from December 2010 to December 2020, and Wilcoxon rank sum test and chi-square test were used for analysis. A total of 32 patients were included, including 18 cases of preoperative bronchial artery embolization (embolization rate 56%, 95%CI: 31%-79%). The grade score of dyspnea decreased from before treatment to after treatment, and the difference was statistically significant [(1.44±1.03) score vs (0.25±0.58) score, P=0.003]; The degree of bronchial stenosis decreased from pre-treatment to post-treatment, and the difference was statistically significant [(87.50%±13.90%) vs (17.50%±6.83%), P<0.001]; There was significant difference in bronchial diameter before and after treatment [(0.14±0.18) cm vs (0.84±0.29) cm, P<0.001]. Bronchoscopic interventional therapy has significant short-term and long-term effects in the treatment of typical carcinoid. 【中文题目：支气管镜介入技术治疗典型类癌的 近期疗效及远期疗效观察】 【中文摘要：背景与目的 支气管镜下的各种介入治疗技术包括圈套、二氧化碳冷冻、氩等离子体凝固（argon plasma coagulation, APC）、激光（Neodymium-dopted Yttrium Aluminium Garnet, Nd:YAG）、光动力治疗（photodynamic therapy, PDT），以上治疗技术通常用于治疗气管腔内肿瘤，但用于治疗典型类癌（typical carcinoid, TC）的研究并不普遍。本研究拟探讨支气管镜介入技术治疗典型类癌的近期疗效和远期疗效。方法 回顾性分析北京应急总医院2010年12月-2020年12月可消瘤的腔内典型类癌患者的临床资料，采用Wilcoxon秩和检验和卡方检验进行统计分析。结果 共纳入32例患者，术前支气管动脉栓塞18例（栓塞率56%，95%CI: 31%-79%）。呼吸困难分级评分治疗后较治疗前下降，差异有统计学意义［（1.44±1.03）分 vs （0.25±0.58）分，P=0.003］；支气管管腔狭窄程度治疗后较治疗前改善，差异有统计学意义［(87.50%±13.90%) vs (17.50%±6.83%), P<0.001］；支气管内径治疗后较治疗前扩宽，差异有统计学意义［(0.14±0.18) cm vs (0.84±0.29) cm, P<0.001］。近期有效率为100%。32例患者中24例支气管镜介入治疗能够完全消瘤，完全缓解（complete remission, CR）率为75%。结论 支气管镜介入治疗技术治疗典型类癌的近期疗效及远期疗效显著。】 【中文关键词：典型类癌；支气管介入治疗；疗效】.
antibodies
2026-07-23 | Small Cell Lung Cancer: From Histogenesis to a New Therapeutic Paradigm
Pulmonary neuroendocrine neoplasms (NENs) form a histogenetic continuum arising from bronchial Kulchitsky cells, ranging from well-differentiated carcinoids to highly aggressive neuroendocrine carcinomas. The 2021 WHO Classification of Thoracic Tumors maintains a morphology-based, grade-linked framework for typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung cancer (SCLC), defined by mitotic index and necrosis. Genomic data reinforce a fundamental dichotomy: carcinoids harbor low tumor mutational burden with frequent chromatin-remodeling alterations (e.g., MEN1) and wild-type TP53/RB1, whereas high-grade carcinomas are unified by concurrent TP53 and RB1 inactivation. LCNEC occupies a heterogeneous intermediate position, comprising SCLC-like (TP53/RB1 co-inactivated) and NSCLC-like (KRAS, STK11, KEAP1) subsets, explaining therapeutic variability and motivating molecularly stratified management. In SCLC, precise pathological diagnosis is essential given its immediate therapeutic implications. Immunohistochemistry — synaptophysin, chromogranin A, CD56, and INSM1 — remains indispensable, particularly in compromised small-biopsy specimens. Therapeutically, platinum-based chemotherapy combined with immunotherapy yields modest but reproducible survival gains. Molecular subtyping has uncovered lineage-based vulnerabilities, with DLL3-targeted bispecific T-cell engagers achieving the first validated subtype-specific regulatory approval. Nevertheless, clinical translation of biologically rational strategies has broadly underperformed in late-phase trials. Tumor plasticity and phenotypic switching between subtypes remain critical barriers to durable responses. Integrating histology, immunophenotype, and genomics refines diagnosis and risk stratification, yet the transition from biological hypothesis to validated precision oncology in pulmonary NENs remains incomplete.
2024-01-18 | Iridociliary Body Metastasis of Atypical Carcinoid: Case Management with Intravitreal Anti-Vascular Endothelial Growth Factor Injections.
We report a rare case involving 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.
2023-11-06 | Expression of G protein-coupled receptor GPR19 in normal and neoplastic human tissues.
Little is known about the expression of the orphan G protein-coupled receptor GPR19 at the protein level. Therefore, we developed a rabbit antibody, targeting human GPR19. After verification of the antibody specificity using GPR19-expressing cell lines and a GPR19-specific siRNA, the antibody was used for immunohistochemical staining of a variety of formalin-fixed, paraffin-embedded normal and neoplastic human tissue samples. In normal tissues, GPR19 expression was detected in a distinct cell population within the cortex, in single cells of the pancreatic islets, in intestinal ganglia, gastric chief cells, and in endocrine cells of the bronchial tract, the gastrointestinal tract, and the prostate. Among the 30 different tumour entities investigated, strong GPR19 expression was found in adenocarcinomas, typical and atypical carcinoids of the lung, and small cell lung cancer. To a lesser extent, the receptor was also present in large cell neuroendocrine carcinomas of the lung, medullary thyroid carcinomas, parathyroid adenomas, pheochromocytomas, and a subpopulation of pancreatic neuroendocrine neoplasms. In lung tumours, a negative correlation with the expression of the proliferation marker Ki-67 and a positive interrelationship with patient survival was observed. Overall, our results indicate that in adenocarcinomas and neuroendocrine tumours of the lung GPR19 may serve as a suitable diagnostic or therapeutic target.
2021-12-23 | Case Report: Unmasking Hypercalcemia in Patients With Neuroendocrine Neoplasms. Experience From Six Italian Referral Centers.
Hypercalcemia is a common paraneoplastic syndrome which can occur in up to 10% of patients with advanced neoplasms. Paraneoplastic parathyroid hormone-related protein (PTHrP) represents the most frequent cause of this syndrome. In neuroendocrine neoplasms (NENs) paraneoplastic hypercalcemia is rare. The present series includes all patients with NENs and paraneoplastic hypercalcemia from four Italian centres: (I) A 40-year-old man was hospitalized for repeated episodes of falls, hyposthenia and drowsiness. Severe hypercalcemia was found. Metastatic pancreatic G2 NEN and PTHrP-related hypercalcemia were diagnosed. The patient started therapy with somatostatin analogs (SSA) and Denosumab. After disease progression peptide receptor radionuclide therapy (PRRT) was started with an objective response associated with PTHrP reduction and normocalcemia. (II) A 45-year-old man was referred for pancreatic G2 NEN. SSA and subsequently everolimus were administered for metastases occurrence. Hypercalcemia occurred and PRRT and Denosumab were started for disease progression with the onset of bone metastases. Despite disease stability after four cycles of PRRT the patient's performance status worsened until death. (III) A 49-year-old woman was hospitalized for psychic slowdown, confusional state, sensory dullness. A severe hypercalcemia, associated with a pancreatic G1 NEN was diagnosed and treated with haemodialysis, bisphosphonates injections and continuous infusion of calcitonin. 1,25-dihydroxyvitamin D was high, PTHrP was undetectable. After surgery serum calcium levels and 1,25-dihydroxyvitamin D were normalized. (IV) A 69-year-old man was hospitalized after the onset of shortness of breath and dyspnea, asthenia and weight loss. Computed Tomography (CT) and 68Ga DOTATOC Positron Emission Tomography (PET)-CT revealed a left pulmonary nodule. Hypercalcemia and markedly elevated PTHrP levels were detected. The histological examination revealed an atypical carcinoid. After surgery, calcium levels were normalized, PTHrP was significantly reduced with an improvement of general conditions. In our series, paraneoplastic PTHrP-related hypercalcemia occurred in pancreatic NEN and in one bronchial carcinoid representing the third case in the literature. Our case associated with 1,25-dihydroxyvitamin D secretion represents the fourth case in the literature. PTHrP secretion should be considered in NENs' patients with hypercalcemia. Acute treatment should be focused on lowering calcium levels, and long-term control can be achieved by tumor cytoreduction inhibiting PTHrP release.
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Drug Discovery Landscape
6 orphan drug designations for Bronchial neuroendocrine tumor.
6 orphan drug designations for Bronchial neuroendocrine tumor.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Humanised IgG1 monoclonal antibody against delta-like ligand 3, octakis(thioether) with N-[6-(2-mercapto-5-pyrimidinyl)-1-oxo-5-hexyn-1-yl]-L-valyl-N6,N6-dipropyl-L-lysyl-N-[[3-[(7S)-7-ethyl-7,8,11,13-tetrahydro-7-hydroxy-8,11-dioxo-10H-1,3-dioxolo[4,5-g]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-14-yl]propoxy]methyl]glycinamide | antibodies | EMA | 2026-05-20 | — | PPD Bulgaria EOOD |
Atigotatug, nivolumab | antibodies | EMA | 2026-03-25 | — | Bristol-Myers Squibb Pharma EEIG |
Humanised IgG1 monoclonal antibody against SEZ6, conjugated to (2S)-2-(2-bromoacetamido)-N-[(2S)-1-({3-[(7S)-7-ethyl-7-hydroxy-8,11-dioxo-7,8,11,13-tetrahydro-2H,10H-[1,3]dioxolo[4,5-g]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-14-yl]bicyclo[1.1.1]pentan-1-yl}amino)-1-oxopropan-2-yl]-3-methylbutanamide | antibodies | EMA | 2026-03-25 | — | AbbVie Deutschland GmbH & Co. KG |
Humanised bispecific monoclonal antibody against programmed cell death 1 ligand 1 and tumor necrosis factor receptor superfamily member 9 | — | EMA | 2026-01-09 | — | Voisin Consulting Life Sciences |
Human IgG1 monoclonal antibody against B7-H3, conjugated to N-((2R,10S)-10-Benzyl-2-cyclopropyl-1-(((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-1,6,9,12,15-pentaoxo-3-oxa-5,8,11,14-tetraazahexadecan-16-yl)-6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamide | antibodies | EMA | 2025-10-22 | — | GlaxoSmithKline Trading Services Limited |
IgG-like T-cell engager binding to DLL3 and CD3 | antibodies | EMA | 2024-08-21 | — | Boehringer Ingelheim International GmbH |
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