Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine tumor with unique characteristics, and its treatment regimens are primarily derived from those for small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). In recent years, the incidence rate has been on the rise, and the prognosis are affected by the interaction of multiple factors such as individual, clinical stage and treatment mode, and the heterogeneity is significant. In the study of molecular subtypes, multiple subgroups were divided according to key gene mutations such as RB1 and TP53, and genomic subtypes were associated with survival, chemotherapy response, and efficacy of precision therapy. Targeted therapy excavates multiple targets, and the efficacy of drugs is different. Immunotherapy has made remarkable progress, and immune checkpoint inhibitors (ICIs) have been effective in all stages of chemotherapy alone or in combination with chemotherapy or radiation therapy, but there is a risk of hyperprogressive diseases, and accurate prognostic markers need to be explored urgently. This review reviews the latest research progress in the study of molecular subtypes and precision therapies such as targeted therapy and immunotherapy of pulmonary LCNEC, and points out that pulmonary LCNEC treatment will develop in the direction of precision and individualization in the future.
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Humans ; Lung Neoplasms/drug therapy* ; Carcinoma, Neuroendocrine/drug therapy* ; Precision Medicine ; Immunotherapy ; Carcinoma, Large Cell/drug therapy*

No abstract available.
Adenocarcinoma/chemistry/*drug therapy/secondary ; Adult ; Antineoplastic Agents/*therapeutic use ; Biopsy ; Carcinoma, Large Cell/chemistry/*pathology ; Carcinoma, Neuroendocrine/chemistry/*pathology ; Carcinoma, Non-Small-Cell Lung/chemistry/*drug therapy/secondary ; *Drug Resistance, Neoplasm ; Humans ; Lung Neoplasms/chemistry/*drug therapy/pathology ; Magnetic Resonance Imaging ; Male ; Protein Kinase Inhibitors/*therapeutic use ; Quinazolines/*therapeutic use ; Tomography, X-Ray Computed ; Treatment Outcome ; Tumor Markers, Biological/analysis

Primary mediastinal choriocarcinoma is an extremely rare extragonadal germ cell malignancy. A 58-year-old male presented with a lung mass, which was incidentally discovered during a periodic medical checkup. Percutaneous needle biopsy showed poorly differentiated carcinoma with large pleomorphic morphology. After the patient underwent right upper lobectomy and lymphadenectomy, the final diagnosis was choriocarcinoma. The patient received four sequential cycles of BEP chemotherapy (bleomycin, etoposide, cisplatin). After completion of BEP chemotherapy, follow-up positron emission tomography (PET) showed a complete metabolic response. Although the mediastinum is one of the most common primary sites of extragonadal germ cell tumors, primary mediastinal choriocarcinoma is liable to be misdiagnosed as lung cancer or Hodgkin lymphoma. Notably, large cell carcinoma of the lung can be confused with choriocarcinoma even after percutaneous needle biopsy. We report a case of primary mediastinal choriocarcinoma mimicking large cell carcinoma of the lung in a male patient in his 50s.
Biopsy, Needle ; Carcinoma, Large Cell* ; Choriocarcinoma* ; Diagnosis ; Drug Therapy ; Etoposide ; Female ; Follow-Up Studies ; Germ Cells ; Hodgkin Disease ; Humans ; Lung Neoplasms ; Lung* ; Lymph Node Excision ; Male ; Mediastinum ; Middle Aged ; Neoplasms, Germ Cell and Embryonal ; Positron-Emission Tomography ; Pregnancy

Platinum-based chemotherapy remains the main treatment of advanced lung cancer. However, platinum resistance has become a major treatment obstacle. Novel therapies, particularly tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKI) and agents that target vascular endothelial growth factor (VEGF), have improved the treatment. Both chemotherapy and targeted therapy have their molecular mechanisms. This study aimed to determine the mutation, amplification, or expression status and interrelationships of the epidermal growth factor receptor (EGFR), K-Ras proto-oncogene, excision repair cross-complementation group 1 (ERCC1), and VEGF genes as well as their correlations to prognosis of large cell lung carcinoma (LCLC) after EGFR-targeted therapy, chemotherapy, and anti-VEGF therapy. EGFR and K-Ras mutations in 60 specimens of LCLC were detected by direct DNA sequencing. EGFR, ERCC1, and VEGF protein expression was detected by immunohistochemistry (IHC). EGFR gene copy number was detected by fluorescence in situ hybridization (FISH). One (1.7%) patient had an EGFR L858M point mutation in exon 21, 3 (5.0%) had K-Ras mutations, and 10 (19.6%) had EGFR amplification (FISH positive). Positive rates of EGFR, ERCC1, and VEGF proteins were 38.3%, 56.7%, and 70.0%, respectively. EGFR amplification was positively correlated to EGFR protein expression (r = 0.390, P = 0.005). The positive rate of VEGF protein was significantly higher in patients with lymph node metastasis than in those without (84.6% vs. 58.8%, P = 0.046). No significant correlations were observed among the EGFR, K-Ras, ERCC1, and VEGF genes. EGFR gene amplification and the low rate of EGFR mutation suggest that patients with LCLC are likely to obtain little benefit from anti-EGFR therapies.
Adult ; Aged ; Carcinoma, Large Cell ; drug therapy ; genetics ; metabolism ; pathology ; DNA-Binding Proteins ; metabolism ; Endonucleases ; metabolism ; Female ; Gene Amplification ; Genes, ras ; genetics ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Mutation ; Neoplasm Staging ; Receptor, Epidermal Growth Factor ; genetics ; metabolism ; Survival Rate ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVEThe aim of this study was to explore the clinical characteristics and analyze the prognostic factors of large cell lung cancer (LCLC).

METHODSThe clinical data of 111 LCLC cases were collected and retrospectively analyzed. The prognostic factors were evaluated by univariate and multivariate analyses.

RESULTSAmong the 111 cases, the lesions were in the right lung of 53 patients and 26 of them were located in the superior lobe. The lesions were in the left lung of 58 cases, and 35 of them were in the superior lobe. The lesions were presented as central in 36 cases and peripheral in 75 cases, with a mean diameter of 5.3 cm. All the 111 patients were diagnosed as stage I in 38 cases, stage II in 11 cases, stage III in 45 and stage IV in 17 cases. 60 patients had lymph node metastasis and 17 cases had distant metastasis. The overall 1-, 3- and 5-year survival rates of the LCLC were 54.7%, 30.9% and 20.6%, respectively. Cox univariate analysis revealed that TNM stage (P = 0.000), lymph node metastasis (P = 0.000) and M stage (P = 0.000) are prognostic factors. Cox multivariate analysis indicated that TNM stage (P = 0.000) is an independent prognostic factor.

CONCLUSIONThe prognosis of LCLC is worse than other types of non-small cell lung cancer. Complete surgical resection remains the main therapeutic approach. TNM stage is an independent prognostic factor.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Large Cell ; drug therapy ; pathology ; surgery ; Cisplatin ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; analogs & derivatives ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Paclitaxel ; Pneumonectomy ; methods ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate ; Taxoids ; therapeutic use ; Tumor Burden ; Young Adult

OBJECTIVETo study the morphologic features, immunophenotypes, differential diagnoses and prognosis of histiocytic sarcoma (HS).

METHODSThe clinical and pathologic findings of 6 cases of HS were reviewed. Immunohistochemical assay (Elivision staining) was also performed. Follow-up information was available in 4 patients.

RESULTSThere were altogether 3 males and 3 females. The age of patients ranged from 12 to 81 years old (median = 54.6 years). The sites of involvement included lymph node (number = 2 cases) and skin or soft tissue (number = 4 cases). The tumor was composed of sheets of large epithelioid cells with abundant eosinophilic cytoplasm, oval to irregular nuclei, vesicular chromatin and large nucleoli. Binucleated form was not uncommon. Two of the cases showed increased pleomorphism with multinucleated tumor giant cell formation. Focal cytoplasmic with foamy appearance was identified in 3 cases. One case demonstrated foci of spindly sarcomatoid appearance. Hemophagocytosis was identified in 2 cases. Mitotic figures were readily identified. The tumor cells were often accompanied by various numbers of inflammatory cells. Immunohistochemical study showed that all cases were diffusely positive for leukocyte common antigen, CD4, CD68 and CD163. Four of the 5 cases studied also expressed lysozyme. Amongst the 4 patients with follow-up information available, 3 died of the disease at 6 to 11 months interval after diagnosis. One patient, whose lesion was localized at the skin and soft tissue, survived for 3 years, with no evidence of tumor recurrence.

CONCLUSIONSAccurate diagnosis of the HS is based on the combination of morphologic examination and immunohistochemical assay. HS often presents with clinically advanced disease and pursues an aggressive clinical course, with a poor response to therapy. However, a subset of cases presenting with clinically localized lesion may carry a relatively favorable long-term outcome.

Adult ; Aged ; Aged, 80 and over ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Carcinoma, Renal Cell ; metabolism ; pathology ; Child ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Histiocytic Sarcoma ; drug therapy ; metabolism ; pathology ; surgery ; Humans ; Lymphoma, Large B-Cell, Diffuse ; metabolism ; pathology ; Lymphoma, Large-Cell, Anaplastic ; metabolism ; pathology ; Male ; Melanoma ; metabolism ; pathology ; Muramidase ; metabolism ; Prognosis ; Receptors, Cell Surface ; metabolism ; Skin Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Soft Tissue Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Young Adult

PURPOSE : Lung Cancer has been the leading cause of cancer deaths in South Korea since the year 2000, and its incidence continues to rise. Here we report the result of national survey of lung cancer conducted by Korean association for the study of lung cancer (KASLC). MATERIALS AND METHODS : A total of 8,788 lung cancer patients diagnosed in 2005 were registered using a web based case report form issued to hospitals equipped with more than 400 beds. RESULTS : The age distribution ranged from 11 to 105 years (64.7+/-0.7 years), 75.8% (6,664) of the patients were male and 28.9% of patients were never smokers. Subjective symptoms at the time of diagnosis included coughing (3,350 patients), dyspnea (2,105), chest pain (1,067), hemoptysis (805), weight loss (789), general weakness (498) and hoarseness (190), while 12% (1,015) of patients had no subjective symptoms. Of the carcinomas grouped into non-small cell lung carcinoma (NSCLC), adenocarcinoma including bronchoalveolar cell carcinoma (1.3%) was the most frequent (36.1%) histopathologic type, followed by squamous cell lung carcinoma (32.1%), large cell carcinoma (1.5%), unclassified non-small cell carcinoma (13.2%) and others (3.7%). In addition, 13.5% of all of the patients were afflicted with small cell lung carcinoma (SCLC). The stage at diagnosis was IA (7.3%), IB (10.2%), IIA (1.3%), IIB (6.1%), IIIA (12.8%), IIIB (21.6%), and IV (40.6%) in the NSCLC group. In SCLC group, 44.6% of the patients were in the limited stage, while 55.4% of the patients were in the extensive stage. The initial treatments included surgery (22.1%), radiation therapy (7.8%), chemo-radiation therapy (5.4%) and chemotherapy (38%), however, 26.6% of the patients were transferred or recorded to have supportive care only. Therefore we compared the outcomes of the Treatment Group (TG, 73.4%) and the Supportive Group (SG, 26.6%). The median survival time (MST) in months (m) was 28 (95% confidence interval 26.5~29.5 m). Multivariate analysis indicated that the independent prognostic factors for NSCLC were age, gender, ECOG PS score, stage, histopathologic type, and treatment or supportive care. In the SCLC group, age, PS score, stage, treatment or supportive care were significant prognostic factors. The TG group showed significantly superior survival when compared to the SG group, even in patients with stage IV disease and in patients that were >75 years old. CONCLUSION : Adenocarcinoma was found to be the most frequent histopathologic type, and active treatments were found to improve the survival of patients with lung cancer, even when they were in advanced stages or elderly
Adenocarcinoma ; Age Distribution ; Aged ; Carcinoma, Large Cell ; Chest Pain ; Cough ; Diagnosis ; Drug Therapy ; Dyspnea ; Hemoptysis ; Hoarseness ; Humans ; Incidence ; Korea* ; Lung Neoplasms* ; Lung* ; Male ; Multivariate Analysis ; Small Cell Lung Carcinoma ; Weight Loss

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

BACKGROUND: To evaluate the efficacy and safety of gemcitabine and cisplatin chemotherapy in advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Forty patients (21 men, 19 women ; age range, 37 to 73 years; median, 63 years) with unresectable stage IIIB to IV NSCLC were evaluated. Patients received cisplatin 60mg/m2 (Day 1), gemcitabine 1200mg/m2 (Day 1 and 8) every 21 days. Eighteen patients had stage IIIB disease and 22 had stage IV. There were 28 patients of adenocarcinoma (70.0%), 11 of squamous cell carcinoma (27.5%), and one of large cell carcinoma (2.5%). RESULTS: Of 40 patients, no patients showed complete response while 15(37.5%) showed partial response, 7(17.5%) had stable diseases, 18(45%) had progressive diseases. During a total of 195 courses of chemotherapy, grade 3 or more granulocytopenia and thrombocytopenia occured in 12.5% and 2.5% of patients respectively. Non-hematologic toxicity was mild and easily controlled. There was one case of treatment-related death by pneumomia. The median survival was 55 weeks (95% CI, 34~75weeks), and the time to progression was 19 weeks (95% CI, 16~23weeks). One year survival rate was 55% and 2 year survival rate was 10%. CONCLUSION: The efficacy of cisplatin and gemcitabine combination chemotherapy was acceptable in the treatment of advanced NSCLC.
Adenocarcinoma ; Agranulocytosis ; Carcinoma, Large Cell ; Carcinoma, Non-Small-Cell Lung* ; Carcinoma, Squamous Cell ; Cisplatin ; Drug Therapy ; Drug Therapy, Combination* ; Female ; Humans ; Male ; Survival Rate ; Thrombocytopenia

PURPOSE: To evaluate the efficacy and toxicity of combination chemotherapy with low-dose paclitaxel and cisplatin in patients with advanced non-small cell lung cancer. MATERIALS AND METHODS: Chemotherapy-naive patients with unresectable, pathologically proven non-small cell lung cancer were eligible for inclusion in the study. Patients received paclitaxel (145 mg/m2 iv 3 hour D1) and cisplatin (60 mg/m2 iv D1) every 3 weeks. RESULTS: Forty-two patients were enrolled between February 2000 and February 2001. The median age was 53.5 years. Patients with adenocarcinoma numbered 29, squamous cell carcinoma 7, large cell carcinoma 3, and undifferentiated carcinoma 3. Seventeen patients had stage IIIB, 19 had stage IV disease and the remaining 6 displayed recurred disease after previous surgical resection. Four patients terminated treatment early because of hypersensitivity (1) and severe emesis (3). Of the 38 evaluable patients, 14 had PR and the response rate was 36.8%. Among partial responders, 6 patients received additional chest radiation. The median duration of response was 47.9 weeks and the median overall survival was 54.0 weeks. Of the total 176 courses, 14 were delayed, 22 required dose reduction, and grade 3~4 neutropenia occurred in 5.6% of courses. Only one episode of neutropenic fever developed and there were no treatment- related mortalities. Other toxicities were generally mild. CONCLUSION: The combination chemotherapy with low-dose paclitaxel and cisplatin was effective and tolerable in patients with advanced non-small cell lung cancer.
Adenocarcinoma ; Carcinoma ; Carcinoma, Large Cell ; Carcinoma, Non-Small-Cell Lung* ; Carcinoma, Squamous Cell ; Cisplatin* ; Drug Therapy ; Drug Therapy, Combination ; Fever ; Humans ; Hypersensitivity ; Mortality ; Neutropenia ; Paclitaxel* ; Thorax ; Vomiting