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 carcinoids are infrequent neoplasms of the lung that normally display a less aggressive biological behavior compared to small cell and non-small cell lung cancers. Approximately 15-25% of carcinoids, in particular atypical carcinoids, show lymph node metastasis and have a worse prognosis than their non-metastasized counterparts. To date, there is no morphological or molecular marker that may help to differentiate between carcinoids that metastasize and carcinoids of identical differentiation that show only local tumor growth. In this study, we analyzed 7 metastasized and 10 non-metastasized pulmonary carcinoids for chromosomal and microsatellite instability in order to determine whether microsatellite instability or chromosomal imbalances are associated with metastasis. Due to the rare occurrence of metastasized carcinoids we compared our results of chromosomal instability with the hitherto published comparative genomic hybridization (CGH) profiles of pulmonary carcinoids, for which information about the absence or presence of metastasis was available. While microsatellite instability was not detected we found chromosomal instability as a common event in pulmonary carcinoids with an increase of frequency and extent of chromosomal alterations in atypical and metastasized carcinoids. These findings are in accordance with the collected and herein compiled data of previous studies and indicate increasing numbers of chromosomal imbalances to play a role in the sequential process of tumor development and metastasis.
Carcinoid Tumor/*genetics/pathology/*secondary ; Chromosomal Instability/*genetics ; Comparative Genomic Hybridization ; Humans ; Lung Neoplasms/*genetics/pathology ; Lymphatic Metastasis ; Prognosis

Pulmonary carcinoids are infrequent neoplasms of the lung that normally display a less aggressive biological behavior compared to small cell and non-small cell lung cancers. Approximately 15-25% of carcinoids, in particular atypical carcinoids, show lymph node metastasis and have a worse prognosis than their non-metastasized counterparts. To date, there is no morphological or molecular marker that may help to differentiate between carcinoids that metastasize and carcinoids of identical differentiation that show only local tumor growth. In this study, we analyzed 7 metastasized and 10 non-metastasized pulmonary carcinoids for chromosomal and microsatellite instability in order to determine whether microsatellite instability or chromosomal imbalances are associated with metastasis. Due to the rare occurrence of metastasized carcinoids we compared our results of chromosomal instability with the hitherto published comparative genomic hybridization (CGH) profiles of pulmonary carcinoids, for which information about the absence or presence of metastasis was available. While microsatellite instability was not detected we found chromosomal instability as a common event in pulmonary carcinoids with an increase of frequency and extent of chromosomal alterations in atypical and metastasized carcinoids. These findings are in accordance with the collected and herein compiled data of previous studies and indicate increasing numbers of chromosomal imbalances to play a role in the sequential process of tumor development and metastasis.
Carcinoid Tumor/*genetics/pathology/*secondary ; Chromosomal Instability/*genetics ; Comparative Genomic Hybridization ; Humans ; Lung Neoplasms/*genetics/pathology ; Lymphatic Metastasis ; Prognosis

ACTH Syndrome, Ectopic ; etiology ; Adult ; Carcinoid Tumor ; pathology ; secretion ; Cushing Syndrome ; etiology ; Humans ; Male ; Pro-Opiomelanocortin ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Thymus Neoplasms ; pathology ; secretion

Primary testicular carcinoid tumor, occupying 0.23% of testicular neoplasm, is a rare and indolent neoplasm with the potential for distant metastasis. We present two cases of primary pure carcinoid tumor of the testis. Both patients were 36 years old. Physical examination revealed testicular mass with and without tenderness. The preoperative serum levels of beta-human chorionic gonadotropin and alpha-fetoprotein were normal and neither patient had carcinoid syndrome. The tumors measured 7.5x6x4 cm and 5.5x5x4 cm in size. Histologically, immunohistochemically and ultrastructurally, the tumors showed typical features of the carcinoid tumor. Case 1 showed extensive tumor necrosis and vascular invasion. DNA flow cytometric analysis showed aneuploidy with DNA index of 1.47 and S+G2M of 14.0% in case 1 and tetraploidy with DNA index of 1.96 and S+G2M of 22.1% in case 2. Both patients have been well without any signs of metastasis after operation for 24 months in case 1 and for 16 months in case 2.
Adult ; Carcinoid Tumor/pathology ; Carcinoid Tumor/metabolism ; Carcinoid Tumor/genetics* ; Case Report ; DNA, Neoplasm/analysis* ; Flow Cytometry/methods* ; Human ; Immunohistochemistry ; Male ; Testicular Neoplasms/pathology ; Testicular Neoplasms/metabolism ; Testicular Neoplasms/genetics*