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Neoadjuvant and adjuvant treatment in lung neuroendocrine tumors (NETs) is a field that has not been explored in-depth, with little information on the impact on disease-free survival. This case study highlights the effectiveness of neoadjuvant treatment with capecitabine plus temozolomide (CAPTEM) in a woman with well-differentiated atypical carcinoid. The patient was asymptomatic at diagnosis and was referred to the outpatient NET clinic at Sotiria Hospital in Athens, following an incidental finding on a chest x-ray. 18F-fluorodeoxyglucose (FDG) PET/CT and 68Ga-Dotatoc PET/CT revealed another mass in the pancreas, with avidity in both imaging studies. The patient underwent treatment for 6 months with CAPTEM with a response in the lung NET and mediastinal lymph nodes. However, the mass in the pancreas slightly increased and was removed with a central pancreatectomy. The patient continued treatment with CAPTEM for 6 more months. There was further response according to RECIST 1.1 criteria (partial response in the mediastinal lymph nodes and a 21% regression in the primary tumor size). Pathology report after lobectomy with lymph node dissection showed a pathologic complete response in the mediastinal lymph nodes. Twenty-four months after surgery, the patient remains disease-free and has a good quality of life. Although large clinical trials are needed, this case study underlines the value of preoperative chemotherapy in atypical carcinoids.
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Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Neoplasias Pulmonares , Terapia Neoadjuvante , Temozolomida , Humanos , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , Feminino , Temozolomida/uso terapêutico , Temozolomida/administração & dosagem , Terapia Neoadjuvante/métodos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pessoa de Meia-Idade , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodosRESUMO
BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) presents significant treatment challenges due to its rarity and limited therapeutic options. The LANCE study was designed to explore the survival benefits of incorporating atezolizumab in chemotherapy for metastatic LCNEC. METHODS: In this non-randomized study, patients with metastatic LCNEC were prospectively enrolled and assigned to receive either standard chemotherapy plus atezolizumab followed by maintenance with atezolizumab or standard chemotherapy alone. The primary outcomes measured were 12- and 24-month survival rates, progression-free survival (PFS), and overall survival (OS) between the two groups. RESULTS: Of the 22 patients screened, 17 met the inclusion criteria and received either atezolizumab plus platinum-based chemotherapy (n = 10) or chemotherapy alone (n = 7). After a median follow-up of 23.3 months, the 12-month survival rate was 57.1% (95% CI: 32.6-100%) and 14.3% (95% CI: 2.33-87.7%) for the atezolizumab and the chemotherapy-only groups, respectively. The survival benefit for the atezolizumab group was sustained at 24 months (45.7% vs. 14.3%). Overall survival was significantly higher for the atezolizumab group, and PFS was non-significantly associated with the addition of atezolizumab (log-rank p = 0.04 and 0.05, respectively). CONCLUSIONS: This pilot study suggests that the addition of atezolizumab to standard platinum-based chemotherapy may provide a substantial survival benefit compared with chemotherapy alone in the first-line treatment of metastatic LCNEC.
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Lung neuroendocrine tumors (LNETs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are two distinct types of neuroendocrine tumors (NETs) that have traditionally been treated as a single entity despite originating from different sources. Although they share certain phenotypic characteristics and the expression of neuroendocrine markers, they exhibit differences in their microenvironment, molecular mutations, and responses to various therapeutic regimens. Recent research has explored the genetic alterations in these tumors, revealing dissimilarities in the frequently mutated genes, the role of EGFR in carcinogenesis, the presence of transcription factors, and the immunogenicity of the tumor and its microenvironment. Spread Through Air Spaces (STAS), a phenomenon unique to lung carcinomas, appears to play a crucial role in LNET prognosis. These distinctions are also evident in the cascade response of lung and GI tract neuroendocrine tumors to somatostatin analogs, Peptide Receptor Radionuclide Therapy (PRRT), chemotherapy, and immunotherapy. Identifying similarities and differences between the two groups may improve our understanding of the underlying mechanisms and facilitate the development of more effective treatment strategies.
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BACKGROUND: Lung cancer is associated with a high incidence of mortality worldwide. Molecular mechanisms governing the disease have been explored by genomic studies; however, several aspects remain elusive. The integration of genomic profiling with in-depth proteomic profiling has introduced a new dimension to lung cancer research, termed proteogenomics. The aim of this review article was to investigate proteogenomic approaches in lung cancer, focusing on how elucidation of proteogenomic features can evoke tangible clinical outcomes. METHODS: A strict methodological approach was adopted for study selection and key article features included molecular attributes, tumor biomarkers, and major hallmarks involved in oncogenesis. RESULTS: As a consensus, in all studies it becomes evident that proteogenomics is anticipated to fill significant knowledge gaps and assist in the discovery of novel treatment options. Genomic profiling unravels patient driver mutations, and exploration of downstream effects uncovers great variability in transcript and protein correlation. Also, emphasis is placed on defining proteogenomic traits of tumors of major histological classes, generating a diverse portrait of predictive markers and druggable targets. CONCLUSIONS: An up-to-date synthesis of landmark lung cancer proteogenomic studies is herein provided, underpinning the importance of proteogenomics in the landscape of personalized medicine for combating lung cancer.
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BACKGROUND: Mediastinal lymph node enlargement is prevalent in patients with idiopathic pulmonary fibrosis (IPF). Studies investigating whether this phenomenon reflects specific immunologic activation are lacking. METHODS: Programmed cell death-1 (PD-1)/ programmed cell death ligand-1 (PD-L1) expression in mediastinal lymph nodes and lung tissues was analyzed. PD-1, PD-L1 mRNA expression was measured in tracheobronchial lymph nodes of mice following bleomycin-induced injury on day 14. Finally, the effect of the PD-1 inhibitor, pembrolizumab, in bleomycin-induced pulmonary fibrosis was investigated. RESULTS: We analyzed mediastinal lymph nodes of thirty-three patients (n = 33, IPF: n = 14, lung cancer: n = 10, concomitant IPF and lung cancer: n = 9) and lung tissues of two hundred nineteen patients (n = 219, IPF: 123, controls: 96). PD-1 expression was increased, while PD-L1 expression was decreased, in mediastinal lymph nodes of patients with IPF compared to lung cancer and in IPF lungs compared to control lungs. Tracheobronchial lymph nodes isolated on day 14 from bleomycin-treated mice exhibited increased size and higher PD-1, PD-L1 mRNA levels compared to saline-treated animals. Pembrolizumab blunted bleomycin-induced lung fibrosis, as indicated by reduction in Ashcroft score and improvement in respiratory mechanics. CONCLUSIONS: Mediastinal lymph nodes of patients with IPF exhibit differential expression profiles than those of patients with lung cancer indicating distinct immune-mediated pathways regulating fibrogenesis and carcinogenesis. PD-1 expression in mediastinal lymph nodes is in line with lung tissue expression. Lower doses of pembrolizumab might exert antifibrotic effects. Clinical trials aiming to endotype patients based on mediastinal lymph node profiling and accordingly implement targeted therapies such as PD-1 inhibitors are greatly anticipated.
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Fibrose Pulmonar Idiopática , Neoplasias Pulmonares , Humanos , Camundongos , Animais , Receptor de Morte Celular Programada 1/genética , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Pulmão/metabolismo , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/metabolismo , Bleomicina/toxicidade , Neoplasias Pulmonares/metabolismo , Linfonodos/patologia , RNA Mensageiro/genéticaRESUMO
Benign metastasizing leiomyoma is a metastasizing form of leiomyoma, which is a benign uterine tumor that typically affects women of reproductive age. A hysterectomy is typically performed 10-15 years before the disease's metastatic progression. We present a case of a postmenopausal woman who presented to the emergency department with worsening dyspnea and a history of hysterectomy due to leiomyoma. A computed tomography scan of the chest revealed diffuse bilateral lesions. An open-lung biopsy was performed, and the lung lesions were found to have leiomyoma cells. The patient began letrozole treatment and showed clinical improvement without any serious adverse events.
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Leiomioma , Neoplasias Pulmonares , Neoplasias Uterinas , Feminino , Humanos , Neoplasias Pulmonares/patologia , Leiomioma/patologia , Neoplasias Uterinas/patologia , Pulmão/patologia , Tomografia Computadorizada por Raios XRESUMO
A large number of alveolar type I and II cells from the lungs of both smokers and non-smokers was collected using 40x magnification histological images from our digital archive. These images underwent a transformation into binary images of nuclear contours, followed by the application of the box-counting method. Statistical analysis revealed a significant difference in the mean box-counting dimension values between type I cells of smokers and non-smokers. However, no significant difference was observed in the mean fractal dimensions of alveolar type II cells. This study provides preliminary evidence of the impact of cigarette smoking on the nuclear shape of alveolar type I cells. Given the high toxicity of cigarette smoke to lung cells and the interconnection between morphology and function, further study is needed to understand its impact on the nuclear shape of these cells. Future research should also explore the effects of second-hand smoke on cell shape.
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BACKGROUND: Accurate predictions of tumor dissemination risks and medical treatment outcomes are critical to personalize therapy. Patient-derived xenograft (PDX) models in mice have demonstrated high accuracy in predicting therapeutic outcomes, but methods for predicting tumor invasiveness and early stages of vascular/lymphatic dissemination are still lacking. Here we show that a zebrafish tumor xenograft (ZTX) platform based on implantation of PDX tissue fragments recapitulate both treatment outcome and tumor invasiveness/dissemination in patients, within an assay time of only 3 days. METHODS: Using a panel of 39 non-small cell lung cancer PDX models, we developed a combined mouse-zebrafish PDX platform based on direct implantation of cryopreserved PDX tissue fragments into zebrafish embryos, without the need for pre-culturing or expansion. Clinical proof-of-principle was established by direct implantation of tumor samples from four patients. RESULTS: The resulting ZTX models responded to Erlotinib and Paclitaxel, with similar potency as in mouse-PDX models and the patients themselves, and resistant tumors similarly failed to respond to these drugs in the ZTX system. Drug response was coupled to elevated expression of EGFR, Mdm2, Ptch1 and Tsc1 (Erlotinib), or Nras and Ptch1 (Paclitaxel) and reduced expression of Egfr, Erbb2 and Foxa (Paclitaxel). Importantly, ZTX models retained the invasive phenotypes of the tumors and predicted lymph node involvement of the patients with 91% sensitivity and 62% specificity, which was superior to clinically used tests. The biopsies from all four patient tested implanted successfully, and treatment outcome and dissemination were quantified for all patients in only 3 days. CONCLUSIONS: We conclude that the ZTX platform provide a fast, accurate, and clinically relevant system for evaluation of treatment outcome and invasion/dissemination of PDX models, providing an attractive platform for combined mouse-zebrafish PDX trials and personalized medicine.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Linfonodos/patologia , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Modelos Animais de Doenças , Humanos , Neoplasias Pulmonares/patologia , Metástase Neoplásica , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-ZebraRESUMO
A key unknown of the functional space in tumor immunity is whether CD4 T cells depend on intratumoral MHCII cancer antigen recognition. MHCII-expressing, antigen-presenting cancer-associated fibroblasts (apCAFs) have been found in breast and pancreatic tumors and are considered to be immunosuppressive. This analysis shows that antigen-presenting fibroblasts are frequent in human lung non-small cell carcinomas, where they seem to actively promote rather than suppress MHCII immunity. Lung apCAFs directly activated the TCRs of effector CD4 T cells and at the same time produced C1q, which acted on T cell C1qbp to rescue them from apoptosis. Fibroblast-specific MHCII or C1q deletion impaired CD4 T cell immunity and accelerated tumor growth, while inducing C1qbp in adoptively transferred CD4 T cells expanded their numbers and reduced tumors. Collectively, we have characterized in the lungs a subset of antigen-presenting fibroblasts with tumor-suppressive properties and propose that cancer immunotherapies might be strongly dependent on in situ MHCII antigen presentation.
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Apresentação de Antígeno/imunologia , Antígenos de Neoplasias/imunologia , Fibroblastos Associados a Câncer/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Neoplasias Pulmonares/imunologia , Animais , Apoptose , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Proteínas de Transporte/metabolismo , Modelos Animais de Doenças , Humanos , Interferon gama/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Ativação Linfocitária , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Camundongos , Proteínas Mitocondriais/metabolismo , Análise de Célula Única , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Transcriptoma , Microambiente Tumoral/imunologiaAssuntos
Miastenia Gravis , Radiologia , Timoma , Neoplasias do Timo , Glucocorticoides/uso terapêutico , Humanos , Miastenia Gravis/complicações , Miastenia Gravis/diagnóstico por imagem , Miastenia Gravis/tratamento farmacológico , Timectomia , Timoma/complicações , Timoma/diagnóstico por imagem , Timoma/patologia , Neoplasias do Timo/complicações , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/patologiaRESUMO
INTRODUCTION: Pulmonary blastoma is a rare malignancy, accounting for less than 0.5% of primary lung tumors. It belongs to the group of pulmonary sarcomatoid carcinomas, and it is typically characterized by a biphasic pattern of an epithelial and a mesenchymal component. Only a few hundred cases have been reported worldwide. The aim of this study is to review and critically assess the literature regarding pulmonary blastoma. MATERIAL AND METHODS: A narrative literature review of PubMed database from the inception of the database up to January 2021, limited to the English language, was conducted, using combinations of the following keywords: "pulmonary blastoma", "biphasic pulmonary blastoma", "sarcomatoid carcinoma". RESULTS: Pulmonary blastoma is composed of an epithelial and a mesenchymal malignant component. Regarding pathogenesis, the origin of the biphasic cell population remains elusive. Characteristic immunohistochemical stains are supportive of diagnosis.Clinically, the symptomatology is non-specific, while 40% of the cases are asymptomatic. It is diagnosed at a younger agecompared to other types of lung cancer, and it is often non-metastatic at diagnosis allowing for surgical treatment. Data on management and survival are scarce and mainly come from isolated cases. Advances on targeted therapy may provide novel treatment options. Given the rarity of the cases, multicenter collaboration is needed in order to establish therapeutic guidelines.
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Neoplasias Pulmonares/diagnóstico , Blastoma Pulmonar/diagnóstico , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Estadiamento de Neoplasias , Blastoma Pulmonar/patologia , Blastoma Pulmonar/terapiaRESUMO
Recent advances in sequencing technologies have allowed the in-depth molecular study of tumors, even at the single cell level. Sequencing efforts have uncovered a previously unappreciated heterogeneity among tumor cells, which has been postulated to be the driving force of tumor evolution and to facilitate recurrence, metastasis, and drug resistance. In the current study, focused on early-stage operable non-small cell lung cancer, we used tumor growth in patient-derived xenograft (PDX) models in mice as a fast-forward tumor evolution process to investigate the molecular characteristics of tumor cells that grow in mice, as well as the parameters that affect the grafting efficiency. We found that squamous cell carcinomas grafted significantly more efficiently compared with adenocarcinomas. Advanced stage, patient age and primary tumor size were positively correlated with grafting. Additionally, we isolated and characterized circulating tumor cells (CTC) from patients' peripheral blood and found that the presence of CTCs expressing epithelial-to-mesenchymal (EMT) markers correlated with the grafting potential. Interestingly, exome sequencing of the PDX tumor identified genetic alterations in DNA repair and genome integrity genes that were under-represented in the human primary counterpart. In conclusion, through the generation of a PDX biobank of NSCLC, we identified the clinical and molecular properties of tumors that affected growth in mice.
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Thymic neoplasms are rare and may run an indolent course. Among them, thymic epithelial carcinoma is exceptional as it may be presented with extensive local invasion and distant metastases. There is a wide spectrum of autoimmune/paraneoplastic syndromes associated with thymic tumors including autoimmune diseases, some of which may precede the diagnosis of thymoma. This article describes a 37-year-old woman with metastatic malignant thymoma and a combination of manifestations from different organs. Vitiligo, Raynaud's phenomenon and anti-centromere antibodies were preceded while eosinophilia, interstitial lung disease, rash, thickening of the skin and asymptomatic cryoglobulinemia were diagnosed concomitantly with the neoplasm. We have reviewed the literature and found only twenty case reports with a cluster of three or more autoimmune/paraneoplastic syndromes in the same patient but none with this unique constellation of disorders. The diversity of thymoma's clinical presentation and laboratory/histological features may cause diagnostic dilemmas and therapeutic challenges.
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Síndromes Paraneoplásicas/diagnóstico por imagem , Timoma/diagnóstico por imagem , Neoplasias do Timo/diagnóstico por imagem , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Feminino , Humanos , Síndromes Paraneoplásicas/complicações , Síndromes Paraneoplásicas/tratamento farmacológico , Timoma/complicações , Timoma/tratamento farmacológico , Neoplasias do Timo/complicações , Neoplasias do Timo/tratamento farmacológicoRESUMO
Primary mediastinal neuroendocrine tumor (PMNET) is an extremely rare clinical entity and few cases have been described in the literature. Here, we report a histologically confirmed rare PMNET case of a 66-year-old male patient with a mass detected in the anterior upper mediastinum by chest high-resolution computed tomography (HRCT). Early detection and surgical intervention of this neoplasm are critical for long term survival, though the tumor is associated with a dismal outcome.
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Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Broncoscopia/métodos , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
CASE PRESENTATION: A 52-year-old man, current smoker with a 50 pack-year history, presented to our department with cough, yellow sputum, and localized right chest pain. Chest radiograph revealed a large mass in the right upper lobe. He denied the presence of fever, night sweats, or weight loss. He has a medical history of COPD and anxiety disorder. He was receiving long-acting beta agonists/long-acting muscarinic antagonists as a treatment for COPD and quetiapine 100 mg for anxiety disorder.
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Dor no Peito , Tosse , Granuloma do Sistema Respiratório , Pulmão , Pneumonectomia/métodos , Toracotomia/métodos , Biópsia/métodos , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Tosse/diagnóstico , Tosse/etiologia , Diagnóstico Diferencial , Granuloma do Sistema Respiratório/diagnóstico por imagem , Granuloma do Sistema Respiratório/fisiopatologia , Granuloma do Sistema Respiratório/cirurgia , Humanos , Inflamação , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Necrose , Radiografia Torácica/métodos , Nódulo Pulmonar Solitário/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
BACKGROUND/AIM: Primary sarcomas of the lung (PSL) represent a rare, largely unknown entity. We herein present a retrospective study of 26 patients diagnosed with PSL. PATIENTS AND METHODS: For a period of 10 years, the records of patients from 5 centers were gathered and analyzed. RESULTS: Median age at diagnosis was 61.96 years (range=31-75 years). Eight patients (33.33%) had mediastinal node invasion (MNI). From 17 patients (70.83%) with localized disease, 11 patients (64.70%) underwent surgery. Recurrence rate was 72.72%. Median disease-free interval was 15 months. The median overall survival (OS) of patients with metastatic disease was 4 months and 10 months for the whole population. Only surgery had an impact on survival. CONCLUSION: Prognosis of PSL is somber. The high proportion of patients with MNI at diagnosis may serve as an indication for surgical evaluation of mediastinum and raises the question whether patients with locoregional PSL should be treated with a more aggressive approach.
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Neoplasias Pulmonares/diagnóstico , Sarcoma/diagnóstico , Adulto , Idoso , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Sarcoma/mortalidade , Sarcoma/patologia , Taxa de SobrevidaRESUMO
Primary gastric malignant melanoma (PGMM) is an extremely rare clinical entity, and few cases have been described in the literature. Here, we report a histologically confirmed PGMM case of a 74-year-old man with a mass in the stomach found by gastroscopy. The patient had no history of melanoma. This rare disease may be misdiagnosed for another gastric malignant tumor type when there is no known primary lesion. Early detection and surgical intervention are critical for long term survival or cure, though the tumor is often advanced at the time of diagnosis and is associated with a dismal outcome.