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*

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*

Neuroendocrine carcinoma (NEC) has been reported to comprise 25% of lung cancer cases. NEC is classified as typical carcinoid, atypical carcinoid, large-cell neuroendocrine carcinoma, and small-cell lung cancer. Carcinoid tumors are less aggressive and surgery is the mainstay of treatment; however, patients with metastatic or inoperable disease need systemic therapy to control carcinoid symptoms and improve survival. Somatostain analogues, targeted agents including everolimus, sunitinib, bevacizumab, and conventional chemotherapy have emerged as treatment options for such patients. Large-cell neuroendocrine carcinoma exhibits more aggressive behavior and has a poorer prognosis than carcinoid tumors. No standard adjuvant and palliative chemotherapeutic agents have yet been established. This review sets out the treatment options for neuroendocrine tumors.
Adenocarcinoma* ; Carcinoid Tumor ; Carcinoma, Neuroendocrine* ; Drug Therapy* ; Humans ; Lung Neoplasms ; Lung* ; Neuroendocrine Tumors ; Prognosis ; Bevacizumab ; Everolimus

PURPOSE: To report the first case of pigmented choroidal metastases without enucleation diagnosed with fine-needle aspiration biopsy. CASE SUMMARY: A 47-year-old male was referred to our clinic with a suspected diagnosis of choroidal melanoma in his left eye. Positron emission tomography-computer tomography used to evaluate systemic metastases revealed lung cancer. Pathology of the detected lung mass was primary lung neuroendocrine tumor. To differentiate choroidal metastasis and primary choroidal melanoma, we performed a fine-needle aspiration biopsy for choroidal tumors. The cytology showed results favoring metastatic atypical carcinoid and the patient was started on systemic chemotherapy. CONCLUSIONS: All pigmented choroidal tumors are not choroidal melanomas and choroidal metastases may be pigmented. The present case suggests that proper systemic evaluation and biopsy for suspected choroidal tumor could be helpful in diagnosis.
Biopsy ; Biopsy, Fine-Needle ; Carcinoid Tumor ; Choroid* ; Diagnosis ; Drug Therapy ; Electrons ; Humans ; Lung ; Lung Neoplasms ; Male ; Melanoma* ; Middle Aged ; Neoplasm Metastasis* ; Neuroendocrine Tumors ; Pathology

We report a case of a goblet-cell carcinoid tumor of the appendix which metastasized to the peritoneum and was treated by using cytoreductive surgery (CRS) with intraperitoneal chemotherapy. A 47-year-old male presented with chronic constipation and was diagnosed as having a rectal adenocarcinoma with a signet-ring-cell component under colonoscopy. Computed tomography suggested peritoneal metastases with diffuse nodular parietal peritoneal thickening of the entire abdomen and focal invasion of the upper rectum by a seeding mass. CRS with intraperitoneal chemotherapy was done under the diagnosis of a rectal adenocarcinoma with peritoneal metastases. The pathologic diagnosis was a goblet-cell carcinoid tumor of the appendix with peritoneal metastasis. The histological discrepancy between a peritoneal metastatic mass and a rectal mass was due to the mixed histological pattern of a goblet-cell carcinoid tumor. A metastatic mass may not share identical immunohistochemical characteristics from its origin. This histologic discrepancy necessitates caution in diagnosing a distant metastasis of a goblet-cell carcinoid tumor.
Abdomen ; Adenocarcinoma ; Appendix ; Carcinoid Tumor* ; Colonoscopy ; Constipation ; Diagnosis ; Drug Therapy* ; Goblet Cells ; Humans ; Infusions, Parenteral ; Male ; Middle Aged ; Neoplasm Metastasis ; Peritoneal Neoplasms ; Peritoneum ; Rabeprazole ; Rectum

OBJECTIVETo investigate the epidemiology, diagnosis, and treatment status of neuroendocrine tumors (NETs) in our hospital.

METHODSMedical records of 252 patients with neuroendocrine tumors diagnosed and treated in our hospital from January 1, 2004 to December 31, 2009 were collected and retrospectively reviewed in this study. The clinicopathological data including age of onset, initial symptoms, primary site, pathological conditions (Sny, CgA, Ki-67), disease stage at diagnosis, treatment, and follow up were analyzed.

RESULTSThe gender ratio M/F of the 252 cases was 1.9:1, with mean age of 55.2 years, and the high incidence was in age of 60-69 years. The tumors were located in the gastrointestinal tract (117 cases, 46.4%), broncho-pulmonary system (74 cases, 29.4%), other sites (61 cases, 24.2%) and unknown primary site (2 cases, 0.8%). Their first clinical symptoms vary, depending on the primary site. The common symptoms of primary rectal NETs were changes in bowel habits (29.3%) and diarrhea or constipation (17.5%), and most gastric NETs presented epigastric discomfort (86.4%). Most patients (71.4%) were diagnosed with stage I, II, III disease. Among the 252 cases, there were 110 carcinoids (43.7%), 108 neuroendocrine carcinomas (42.9%), 23 atypical carcinoids (9.1%), five neuroendocrine tumors (2.0%), four Merkel cell tumors (1.6%), and two composite carcinoids (0.8%). 206 patients (81.7%) received surgery, 39 (15.5%) received chemotherapy, and 31 cases (12.3%) were treated by palliative radiotherapy.

CONCLUSIONSThis single-center retrospective analysis of data demonstrated that males have a higher incidence rate than females. The most common primary sites of NETs are the digestive tract and lungs. The initial symptoms of NETs are different depending on their primary sites. Good prognosis can be achieved in the majority of patients after surgery, chemotherapy and palliative radiotherapy.

Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoid Tumor ; drug therapy ; pathology ; radiotherapy ; surgery ; Carcinoma, Merkel Cell ; drug therapy ; pathology ; radiotherapy ; surgery ; Carcinoma, Neuroendocrine ; drug therapy ; pathology ; radiotherapy ; surgery ; Cisplatin ; administration & dosage ; Digestive System Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery ; Etoposide ; administration & dosage ; Female ; Fluorouracil ; administration & dosage ; Follow-Up Studies ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery ; Male ; Middle Aged ; Neoplasm Staging ; Neuroendocrine Tumors ; drug therapy ; pathology ; radiotherapy ; surgery ; Organoplatinum Compounds ; administration & dosage ; Paclitaxel ; administration & dosage ; Palliative Care ; Retrospective Studies ; Sex Factors ; Survival Rate ; Young Adult

BACKGROUND: Metastases to the pancreas are uncommon, and are usually a part of widespread disease. However, isolated metastatic lesions can be resected, which can lead to prolonged survival of the patient. The aim of this study was to evaluate the characteristics of metastatic tumors of the pancreas in a Korean poulation. METHODS: We evaluated clinical features and treatment results in patients with a pathological confirmation of metastasis to the pancreas from January 1997 to June 2005. RESULTS: Twenty-five patients were included in the study. Nineteen patients were male. The mean age at the diagnosis of the metastasis was 58.2 years. Renal cell carcinoma was the most frequent primary malignancy (n=8), followed by gastric carcinoma (n=5), colorectal carcinoma (n=2), hepatocellular carcinoma (n=1), lymphoma (n=1), thymic carcinoid (n=1), gastrointestinal stromal tumor (n=1), liposarcoma (n=1), cholangiocarcinoma (n=1), osteosarcoma (n=1), small cell lung cancer (n=1), and non-small cell lung cancer (n=1). Eleven patients were asymptomatic upon diagnosis. The mean interval between the primary diagnosis and diagnosis of the metastases was 4.9 years. Fourteen patients underwent surgery with or without chemotherapy, five patients received chemotherapy, one patient received radiation therapy, and five received palliative care. The mean survival after the diagnosis of metastasis was 44.3 months. Renal cell carcinoma as the primary tumor, asymptomatic upon diagnosis of the metastasis, the interval between primary diagnosis and diagnosis of the metastases of more than 43 months, and surgery with or without chemotherapy were associated with a prolonged survival. CONCLUSIONS: Metastasis to the pancreas can occur after a prolonged period from an initial diagnosis. In selected patients (e.g., renal cell carcinoma), aggressive treatment can prolong survival.
Carcinoid Tumor ; Carcinoma, Hepatocellular ; Carcinoma, Non-Small-Cell Lung ; Carcinoma, Renal Cell ; Cholangiocarcinoma ; Colorectal Neoplasms ; Diagnosis ; Drug Therapy ; Gastrointestinal Stromal Tumors ; Humans ; Liposarcoma ; Lymphoma ; Male ; Neoplasm Metastasis ; Osteosarcoma ; Palliative Care ; Pancreas* ; Small Cell Lung Carcinoma

Primary lung cancer is unusual in children; the squamous cell variant is extremely rare. Lung cancer is classified by histologic types into small-cell lung cancer, non-small cell lung caner, carcinoid, mucoepidermoid carcinoma, and adenoid cystic carcinoma. Furthermore, non-small cell lung cancer is subclassified into adenocarcinoma, large-cell carcinoma, and squamous cell carcinoma. The incidence of lung cancer is influenced by smoking, especially in squamous cell carcinoma, and large cell carcinoma. The present treatments for these tumors are chemotherapy, radiation therapy, and surgical resection depending on their histologic types or stages, but yield very poor survival rates. In this article, we report a case of basaloid squamous cell lung carcinoma in an 11-year-old boy who had symptoms of both leg weakness and back pain radiating to both legs. We confirmed the primary lung carcinoma cells by percutaneous transthoracic needle biopsy. The metastatic carcinoma cells were identified at the bone marrow and lumbar spine. We treated with a combination chemotherapy and radiation therapy. However, he expired 4 months after the onset of disease.
Adenocarcinoma ; Back Pain ; Biopsy, Needle ; Bone Marrow ; Carcinoid Tumor ; Carcinoma, Adenoid Cystic ; Carcinoma, Large Cell ; Carcinoma, Mucoepidermoid ; Carcinoma, Non-Small-Cell Lung ; Carcinoma, Squamous Cell ; Child* ; Drug Therapy ; Drug Therapy, Combination ; Humans ; Incidence ; Leg ; Lung Neoplasms ; Lung* ; Male* ; Smoke ; Smoking ; Spine ; Survival Rate

An adenocarcinoma of the appendix is a rare tumor, and so far only 130 cases have been reported worldwide. We report one patient with peritoneal seeding of an adenocarcinoma. A 51-year-old man was admitted to our hospital with the impression of intestinal obstruction. He had undergone an appendectomy 5 years ago due to acute appendicitis. At that time, postoperative histopathological analysis had revealed an adenocarcinoid tumor in the appendix. The patient had been told to visit our hospital for follow-up but he hadn't visited. When he finally visited our hospital diagnostic laparoscopy revealed the peritoneal seeding of a recurrent adenocarcinoma. A palliative right hemicolectomy was done to relieve the bowel obstruction. After recovering from operation, the patient was treated with the 5-fluoruracil, leucovorin, and oxaloplatin (FOLFOX). The patient was discharged in improved general condition with a future plan for regular cyclic chemotherapy.
Adenocarcinoma ; Appendectomy ; Appendicitis ; Appendix* ; Carcinoid Tumor ; Drug Therapy ; Follow-Up Studies ; Humans ; Intestinal Obstruction ; Laparoscopy ; Leucovorin ; Middle Aged ; Neoplasm Metastasis*

Carcinoid tumor is the most commen tumor of appendix. Metastases from the appendecial carcinoid tumor is rare, and the prognosis of metastatic appendecial carcinoid tumors are closely related to the histologic findings. Atypical, aggressive metastatic carcinoid tumors shows poor prognosis. We experienced a case of atypical aggressive carcinoid tumor of appendix with metastasis. We treated her with combination chemotherapy, etoposide and cisplatin, and achieved partial remission. The duration of remission was 5 months, and survival duration was 19 months. To the best of our knowledge, this is the first case of atypical appendiceal carcinoid tumor with distant metastasis in Korea, so we report this case and the result of chemotherapy.
Appendix* ; Carcinoid Tumor* ; Cisplatin ; Drug Therapy ; Drug Therapy, Combination* ; Etoposide ; Korea ; Neoplasm Metastasis ; Prognosis