Immune checkpoint inhibitors (ICIs) have become the cornerstone of treatment for driver gene-negative advanced non-small cell lung cancer (NSCLC). However, resistance is inevitable, and the underlying mechanisms remain incompletely understood. Histological transformation is a rare but emerging cause of acquired resistance to immunotherapy, with only sporadic case reports documented to date. Here, we report the first case of lung adenocarcinoma that underwent histological transformation to atypical carcinoid following first-line therapy with ICIs combined with chemotherapy, highlighting the critical role of histological lineage switching in mediating NSCLC resistance to ICIs. Notably, the patient harbored a rearranged during transfection (RET) fusion mutation. Subsequent targeted therapy with Selpercatinib after histological transformation demonstrated favorable efficacy, suggesting a potential therapeutic strategy for atypical carcinoid patients with co-occurring rare driver mutations. This case provides a potential therapeutic option for atypical carcinoid patients with rare mutations.
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Humans ; Carcinoid Tumor/drug therapy* ; Carcinoma, Non-Small-Cell Lung/immunology* ; Drug Resistance, Neoplasm ; Immune Checkpoint Inhibitors/therapeutic use* ; Immunotherapy ; Lung Neoplasms/immunology* ; Oncogene Proteins, Fusion/genetics* ; Proto-Oncogene Proteins c-ret/genetics*

To standardize the prevention and clinical management of lung cancer, improve patients' survival outcomes, and offer professional insight for clinicians, the Oncology Society of Chinese Medical Association has summoned experts from departments of pulmonary medicine, oncology, thoracic surgery, radiotherapy, imaging, and pathology to formulate the Oncology Society of Chinese Medical Association guideline for clinical diagnosis and treatment of lung cancer in China (2023 edition) through consensus meetings. Updates in this edition include 1) cancer screening: deletion of high-risk traits of lung cancer based on epidemiological investigations in the Caucasian population, while preserving features confirmed by research on the Chinese population. Advice on screening institutions is also added to raise awareness of the merits and demerits of lung cancer screening through detailed illustrations. 2) Principles of histopathologic evaluation: characteristics of four types of neuroendocrine tumors (typical carcinoid, atypical carcinoid, large cell carcinoma, and small cell carcinoma) are reviewed. 3) Surgical intervention: more options of resection are available for certain peripheral lesions based on several clinical studies (CALGB140503, JCOG0802, JCOG1211). 4) neoadjuvant/adjuvant therapy: marked improvement in the prognosis of non-small cell lung cancer (NSCLC) patients receiving neoadjuvant immunotherapy are reviewed; more options for consolidation immunotherapy after radiochemotherapy have also emerged. 5) Targeted and immune therapy: tyrosine kinase inhibitors of sensitive driver mutations such as EGFR and ALK as well as rare targets such as MET exon 14 skipping, RET fusion, ROS1 fusion, and NTRK fusion have been approved, offering more treatment options for clinicians and patients. Furthermore, multiple immune checkpoint inhibitors have been granted for the treatment of NSCLC and SCLC, resulting in prolonged survival of late-stage lung cancer patients. This guideline is established based on the current availability of domestically approved medications, recommendations of international guidelines, and present clinical practice in China as well as integration of the latest medical evidence of pathology, genetic testing, immune molecular biomarker detection, and treatment methods of lung cancer in recent years, to provide recommendations for professionals in clinical oncology, radiology, laboratory, and rehabilitation.
Humans ; Lung Neoplasms/therapy* ; Carcinoma, Non-Small-Cell Lung/therapy* ; Protein-Tyrosine Kinases/therapeutic use* ; Early Detection of Cancer ; Proto-Oncogene Proteins ; Small Cell Lung Carcinoma ; Carcinoid Tumor

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.
Humans ; Female ; Middle Aged ; Endothelial Growth Factors ; Intravitreal Injections ; Case Management ; Carcinoid Tumor/pathology*

Objective: To investigate the clinical features, morphological characteristics, immunophenotype, and differential diagnosis of goblet cell adenocarcinoma (GCA) in the digestive system. Methods: The clinicopathological data, morphological characteristics, immunophenotypes of 22 cases of GCA in the digestive system diagnosed from January 2010 to January 2021 were collected. Meanwhile, 25 cases of neuroendocrine neoplasm (NEN) and 24 cases of adenocarcinoma were used as controls. Relevant literature was also reviewed. Results: There were 16 males and 6 females, aged from 36 to 79 years with an average of 56 years. The anatomical sites of the 22 GCA were mostly appendix (17 cases) and occasionally extra-appendix (5 cases), including 3 cases in stomach, 1 case in duodenum and 1 case in anal. All 17 cases of appendiceal GCA were pure GCA. Among the 5 cases of extra-appendiceal GCA, One case of gastric GCA was pure, two cases of gastric GCA with NEN or adenocarcinoma, duodenal GCA with NEN and adenocarcinoma, anal GCA with NEN.Low-grade GCAs were composed of goblet, Paneth and neuroendocrine cells, which were arranged in intestinal crypt tubular or cluster structures and distributed in the wall of digestive system. The tubular and cluster structures lacked adhesion. Goblet cells were columnar, located in the base, with clear cytoplasm, small nuclei, inconspicuous atypia, and uncommon mitoses. Extracellular mucus and signet-ring cells with nuclear variations could be seen in some cases. Nerve fiber bundle invasion and tumor thrombus in vessels were often present. High-grade GCAs lacked tubular and cluster structures, and their histological structures were more complex. Tumor cells expressed mixed neuroendocrine and glandular epithelial markers. Similar to the expression patterns of synaptophysin and chromogranin A, CD200 and INSM1 were also dot-like or patch-positive in GCA. Conclusions: GCA is an infrequent tumor of the digestive system and shows the bi-directional differentiation characteristics of neuroendocrine and glandular epithelium. Accurate diagnosis and staging are related to its prognosis.
Adenocarcinoma/pathology* ; Appendiceal Neoplasms/surgery* ; Carcinoid Tumor/surgery* ; Chromogranin A ; Female ; Goblet Cells/pathology* ; Humans ; Male ; Neuroendocrine Tumors/pathology* ; Repressor Proteins ; Synaptophysin

Objective: To investigate the clinical and pathological features, treatments and prognosis of laryngeal neuroendocrine carcinoma (LNEC). Methods: We conducted the retrospective analysis of the clinical data of 12 patients with LNEC admitted to the Department of Otorhinolaryngology Head and Neck Surgery, Second Hospital of Shanxi Medical University from May 2014 to December 2021, including 9 males and 3 females, aged 50-77 years. There were 4 cases of typical carcinoid tumour (highly differentiated), 5 cases of atypical carcinoid tumour (moderately differentiated) and 3 cases of neuroendocrine small cell carcinoma (hypofractionated). The clinical features, diagnosis, treatment and prognosis of LNEC were analysed. Results: The clinical manifestations of LNEC varied according to the tumour type but did not correlate with the pathological types. The supraglottic type was characterized by sore throat, foreign body sensation in the pharynx, coughing, obstructive sensation when eating and choking on water. The treatments were determined according to the pathological types, lesion location and invasion scope. Of 12 patients 4 underwent horizontal partial laryngectomy plus elective lymphatic dissection plus postoperative radiotherapy/chemotherapy, 4 underwent vertical partial laryngectomy (3 of them with cervical lymphatic dissection), 3 underwent supported laryngoscopic plasma laryngectomy for laryngeal cancer, and 1 abandoned for treatment. With the follow-up of 8 -78 months, 5 patients were alive, 1 died from chemotherapy reactions, 3 died from other diseases, 1 died from lung metastasis, 1 died from lung infection and 1 was lost to follow-up. Conclusion: LNEC is clinically rare, the clinical manifestations are less specificity, diagnosis relies on pathological and immunohistochemical examinations, and treatment modalities and prognoses are closely related to the pathological subtypes of LNEC.
Humans ; Male ; Female ; Laryngeal Neoplasms/pathology* ; Retrospective Studies ; Carcinoma, Neuroendocrine/pathology* ; Laryngectomy ; Carcinoid Tumor/pathology*

Carcinoid Tumor/pathology* ; Carcinoma, Neuroendocrine/pathology* ; Humans ; Lung Neoplasms/pathology* ; Neuroendocrine Tumors/pathology*

Lung and thymus neuroendocrine neoplasms (NENs) are rare tumors. According to the fifth edition of the World Health Organization classification of thoracic tumors published in 2021, lung and thymus NENs include typical carcinoids, atypical carcinoids, large cell neuroendocrine carcinomas, and small cell carcinomas. Although the incidence of lung and thymus NENs has gradually increased in recent years, there is a lack of randomized controlled clinical study results to guide clinical practice. The treatment of early-stage lung and thymus NENs is complete surgical resection, and the treatment methods for unresectable advanced diseases include different medical treatments, peptide receptor radionuclide therapy, and local therapy. To improve the standardization of diagnosis and treatment of lung and thymus NENs in China, the Expert Committee of Neuroendocrine Neoplasms, Chinese Society of Clinical Oncology developed the expert consensus after multidisciplinary expert discussions based on existing clinical study evidences and guidelines from different neuroendocrine tumor societies. The contents of the consensus cover the epidemiology, diagnosis, pathological classification, staging, treatment and follow-up of lung and thymus NENs (except small cell lung cancer).
Carcinoid Tumor ; China ; Consensus ; Humans ; Lung ; Neuroendocrine Tumors/therapy*

BACKGROUND: 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. METHODS: 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. RESULTS: 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]. CONCLUSIONS Bronchoscopic interventional therapy has significant short-term and long-term effects in the treatment of typical carcinoid.
Bronchial Neoplasms/surgery* ; Bronchoscopy ; Carcinoid Tumor/surgery* ; Humans ; Neuroendocrine Tumors ; Retrospective Studies

Pulmonary neuroendocrine tumors (PNETs) are a kind of epithelial tumors originating from pulmonary neuroendocrine cells, accounting for about 20% of primary lung tumors, including typical carcinoid, atypical carcinoid, small cell carcinoma, and large cell neuroendocrine carcinoma. The morphologic and clinical characteristics of these four types of PNETs are relatively highly heterogeneous. Immune checkpoint inhibitors (ICIs) have been shown robust antitumor activity in a variety of solid tumors. Treatment regimens of advanced PNETs have developed greatly in the past decade, but ICIs are still in their infancy in the field of PNETs. This review focuses on the landscape of current clinical trials and research as well as the situation of ICIs-related biomarkers in PNETs.
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Carcinoid Tumor ; Carcinoma, Neuroendocrine ; Humans ; Immune Checkpoint Inhibitors ; Lung Neoplasms/drug therapy* ; Neuroectodermal Tumors, Primitive ; Neuroendocrine Tumors/drug therapy*

Goblet cell carcinoid (GCC) is a rare neoplasm of the vermiform appendix and can be mistaken as a typical neuroendocrine tumour (TNET). The natural history of this disease is more aggressive compared to TNETs and requires a more aggressive approach. We report a case of a 37-year-old male who was initially diagnosed with TNET, but subsequently revised as Tang's A GCC. He underwent appendectomy and right hemicolectomy. Aside from a persistently elevated carcinoembyrogenic antigen (CEA) result, his 18F-fluorodeoxyglucose (FDG) PET/CT and a 68-Gallium DOTATATE PET/CT scan showed no FDG or DOTATATE avid lesions.