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Large Cell Carcinoma (LCC) observed in low-dose computed tomography (LDCT) screening trials typically presented as a single solid peripheral nodule or mass, often with lobulated margins (panels A-D), and exhibited a fast growth (panels E-F and G-H). The 5-year survival (panel I) reflected the stage at diagnosis and was fair (15/20 alive) for stages I-II (dashed line) and poor (1/10 alive) (continuous line) for stages III-IV. [Display omitted] • LDCT screening enables the definition of early radiological features of LCC. • LCC was diagnosed in 30 (4%) of 750 subjects with LDCT screen-detected lung cancers. • LCC appeared as a peripheral solid nodule/mass often (43%) with lobulated margins. • 5 years after diagnosis, 5/20 stages I-II and 9/10 stages III-IV subjects had died of LCC. • Survival of screen-detected LCC depends on the stage at diagnosis. To investigate the early radiological features and survival of Large Cell Carcinoma (LCC) cases diagnosed in low-dose computed tomography (LDCT) screening trials. Two radiologists jointly reviewed the radiological features of screen-detected LCCs observed in NLST, ITALUNG, and LUSI trials between 2002 and 2016, comprising a total of 29,744 subjects who underwent 3–5 annual screening LDCT examinations. Survival or causes of death were established according to the mortality registries extending more than 12 years since randomization. LCC was diagnosed in 30 (4 %) of 750 subjects with screen-detected lung cancer (LC), including 15 prevalent and 15 incident cases. Three additional LCCs occurred as interval cancers during the screening period. LDCT images were available for 29 cases of screen-detected LCCs, and 28 showed a single, peripheral, and well-defined solid nodule or mass with regularly smooth (39 %), lobulated (43 %), or spiculated (18 %) margins. One case presented as hilar mass. In 9 incident LCCs, smaller solid nodules were identified in prior LDCT examinations, allowing us to calculate a mean Volume Doubling Time (VDT) of 98.7 ± 47.8 days. The overall five-year survival rate was 50 %, with a significant (p = 0.0001) difference between stages I-II (75 % alive) and stages III-IV (10 % alive). LCC is a fast-growing neoplasm that can escape detection by annual LDCT screening. LCC typically presents as a single solid peripheral nodule or mass, often with lobulated margins, and exhibits a short VDT. The 5-year survival reflects the stage at diagnosis. [ABSTRACT FROM AUTHOR]

This paper presents a novel approach that merges a lightweight parallel depth-wise separable convolutional neural network (LPDCNN) with a ridge regression extreme learning machine (Ridge-ELM) for precise classification of three lung cancer types alongside normal lung tissue (adenocarcinoma, large cell carcinoma, normal, and squamous cell carcinoma) using CT images. The proposed methodology combines contrast-limited adaptive histogram equalization (CLAHE) and Gaussian blur to enhance image quality, reduce noise, and improve visual clarity. The LPDCNN extracts discriminant features while minimizing computational complexity (0.53 million parameters and 9 layers). The Ridge-ELM model was developed to enhance classification performance, replacing the traditional pseudoinverse in the ELM approach. Through comprehensive evaluation against state-of-the-art models, the framework achieves remarkable average recall and accuracy values of 98.25 ± 1.031 % and 98.40 ± 0.822 %, respectively, through rigorous five-fold cross-validation for four-class classifications. In binary classifications, outstanding results are obtained with recall and accuracy values of 99.70 ± 0.671 % and 99.70 ± 0.447 %%, respectively. Notably, the framework exhibits exceptional efficiency, with a testing time of only 0.003 s. Additionally, integrating the SHAP (Shapley Additive Explanations) in the proposed framework enhances Explain-ability, providing insights into decision-making and boosting confidence in real-world lung cancer diagnoses. [ABSTRACT FROM AUTHOR]

Large cell carcinoma (LCC) is a merely descriptive term indicating a subtype of lung cancer with no specific features of small-cell lung cancer (SCLC), adenocarcinoma (ADC) or squamous cell carcinoma (SQC). This diagnosis is allowed on surgical specimens only, whereas its counterpart in biopsy/cytology samples is non-small-cell lung carcinoma (NSCLC), not otherwise specified (NOS). Although these two terms do not fulfill the same concept, they can be interchangeable synonyms at the clinical level, reflecting, in different ways, the inability to define a specific subtype. Immunohistochemistry (IHC), next generation sequencing (NGS) analysis and, historically, electron microscopy have been unveiling diverse cell differentiation lineages in LCC, resulting in LCC-favor ADC, LCC-favor SQC and LCC-favor large-cell neuroendocrine carcinoma (LCNEC), the latter hopefully to be included into the neuroendocrine tumor (NET) group in the future. Paradoxically, however, the interpretation issues of LCC/NSCLC-NOS are not diminishing, but even increasing albeight an accurate diagnosis is oncologically required and crucial. Also, rare LCC/NSCLC-NOS cases exhibiting null/unclear phenotype, are difficult to classify, and this terminology could be maintained for the sake of classification (basically these tumors are serendipitous ADC, as also confirmed by the lack of p40). In this review article, seven relevant issues to LCC have been addressed by using a question–answer methodology, with final key points discussing major interpretation issues. In conclusion, most LCC/NSCLC-NOS may be eventually re-classified and addressed by exploiting IHC and/or molecular testing to satisfy the criteria of precision medicine (the right drug, to the right patient, at the right time). [ABSTRACT FROM AUTHOR]

Abstract: Background: Heparanase is the only known mammalian glycosidase capable of cleaving heparan sulfate chains. The expression of this enzyme has been associated with tumor development because of its ability to degrade extracellular matrix and promote cell invasion. Methods: We analyzed heparanase expression in lung cancer samples to understand lung tumor progression and malignancy. Of the samples from 37 patients, there were 14 adenocarcinomas, 13 squamous cell carcinomas, 5 large cell carcinomas, and 5 small cell carcinomas. Immunohistochemistry was performed to ascertain the expression and localization of heparanase. Results: All of the tumor types expressed heparanase, which was predominantly localized within the cytoplasm and nucleus. Significant enzyme expression was also observed in cells within the tumor microenvironment, such as fibroblasts, epithelial cells, and inflammatory cells. Adenocarcinomas exhibited the strongest heparanase staining intensity and the most widespread heparanase distribution. Squamous cell carcinomas, large cell carcinomas, and small cell carcinomas had a similar subcellular distribution of heparanase to adenocarcinomas but the distribution was less widespread. Heparanase expression tended to correlate with tumor node metastasis (TNM) staging in non-small cell lung carcinoma. Conclusion: In this study, we showed that heparanase was localized to the cytoplasm and nucleus of tumor cells and to cells within the microenvironment in different types of lung cancer. This enzyme exhibited a differential distribution based on the type of lung tumor. General significance Elucidating the heparanase expression patterns in different types of lung cancer increased our understanding of the crucial role of heparanase in lung cancer biology. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. [Copyright &y& Elsevier]

Summary: Lung cancer that presents with secretion of beta HCG is rare. We report a case of a young female patient who presented with symptoms of pneumonia and was found to have a positive pregnancy test. With non-resolution of the consolidation and progression of her symptoms she subsequently was found to have large cell lung cancer with ectopic beta HCG secretion. Ectopic production of a variety of hormones such as ADH, parathyroid hormone, ACTH, insulin-like growth factor thus leading to presentation as endocrine syndromes in patients with lung cancer is well known. The presentation of lung cancer mimicking as pregnancy has not been previously reported. This case illustrates the importance of considering the possibility of paraneoplastic secretion of beta HCG in female patients who have a positive pregnancy test in an appropriate clinical setting. This may prevent a delay in the diagnosis and treatment of malignancy in young women. [Copyright &y& Elsevier]

Abstract: Lung cancer is the second most common cancer and the leading cause of cancer death in both men and women. The purpose of the study is to explore the distribution of the 4 major histologic types of lung carcinoma and the incidence of lung cancer with reference to all other sites of cancer. The clinical and histopathologic data of 4,439 patients with lung carcinoma between January 1980 and December 2003 were reviewed. Adenocarcinoma has become the most frequent histologic type in men and women (36.8% and 46.5%, respectively), followed by squamous cell carcinoma (31.6% and 25.4%, respectively). The incidence of large cell (undifferentiated) carcinoma in men and women is 18.0% and 9.9%, respectively. The incidence of small cell carcinoma in men and women is 13.7% and 18.3%, respectively. In addition, analysis of our data indicates that lung cancer rate is decreasing, relative to all other primary cancer sites. The results of this study suggest that the incidence of lung cancer has decreased in comparison with other sources of cancer in southern Texas. This observation is consistent with the current national trends. In addition, there are significant changes in the distribution of the major histologic types of lung cancer. The results of this study may portend important changes in the selection of targeted therapy and patient management. [Copyright &y& Elsevier]

Abstract: The aim of this study was to evaluate gastrointestinal metastases from primary lung cancer confirmed by autopsy. We identified and examined patients with a diagnosis of primary lung cancer over 33 years. We also reviewed patients with gastrointestinal metastases including the stomach, small bowel, and large bowel. This study comprised 470 patients with lung cancer. We detected 56 (11.9%) cases with gastrointestinal metastases. There were 12 (30%) cases with gastrointestinal metastases among 40 cases with large cell carcinoma. The histological type of large cell carcinoma led to a significantly higher rate of gastrointestinal metastases compared with that of non-large cell carcinoma (P =0.004, odds ratio 3.524). Life threatening gastrointestinal metastases occurred in 12 cases and five occurred in large cell carcinoma. Gastrointestinal metastases from primary lung cancer may occur in the clinical course and result in life threatening gastrointestinal metastases, particularly if patients have the histological type of large cell carcinoma. [Copyright &y& Elsevier]

Abstract: Large cell carcinoma of the lung with a rhabdoid phenotype is very rare. We present a 55-year-old man with multiple nodules in his lung. He had an emergency operation because of abundant hemoptysis. The microscopic appearance was a large cell carcinoma with a pure rhabdoid phenotype. There were no foci of any other carcinomatous components. Tumor cells had abundant eosinophilic cytoplasmic globules and eccentric nuclei and did not adhere to each other. Histochemically, these cells were periodic acid-Schiff–negative. Immunohistochemically, vimentin and neuron-specific enolase were positive. Epithelial membrane antigen was focally and weakly positive, p53 was positive in 60% of tumoral cells, and Ki-67 (MIB-1 labeling index) was 50%. The patient died of disseminated disease 2 months after the operation. [Copyright &y& Elsevier]

Abstract: In the UK, the incidence of lung cancer is falling slowly. In 1999, there were 39,000 new registrations of lung cancer, second only to breast cancer. Because of its poor prognosis, it is the number one killer among cancers in the UK, and kills more females than breast cancer (about 13,000 per annum). The incidence is about 80 per 100,000 males and about 40 per 100,000 females. It is estimated that a male has a 1 in 13 chance of lung cancer in his lifetime. The highest incidence is in those over 75 years of age, with a peak incidence at age 80; among males over 75 years, the incidence is about 800 per 100,000. [Copyright &y& Elsevier]

Summary: A 67-year-old man with lung cancer developed an isolated metastasis to the thyroid gland. The patient had undergone a right upper lobectomy, followed by chemotherapy consisting of cisplatin and etoposide based on post-surgical diagnosis of small cell lung cancer. Four years later, he had an isolated metastasis to the thyroid gland. The patient underwent a metastasectomy and adjuvant chemotherapy including cisplatin and irinotecan. The cancer cells in resected thyroid tumor had large nuclei and cytoplasm, and expressed the neuroendocrine markers, CD56 and chromogranin A. Retrospectively, the primary lung cancer consisted of both small cell and large cell cancer, and the latter was consistent with the pathological finding of the thyroid tumor. This is the first report to document an isolated recurrence of the lung cancer to the thyroid. [Copyright &y& Elsevier]

Large-cell carcinoma (LCC) of the lung is defined as an undifferentiated non-small cell lung cancer (NSCLC) and accounts for approximately 7.5% of lung cancers. Immune checkpoint inhibitors (ICIs) may be effective for LCC, but there has been no firm evidence due to its low frequency. We herein report an 80-year-old woman with LCC of the lung who was successfully treated with pembrolizumab but developed sclerosing cholangitis as an immune-related adverse event. This case highlights the efficacy of ICIs for LCC as well as the importance of the immediate and detailed management of ICI-related sclerosing cholangitis. [ABSTRACT FROM AUTHOR]

Abstract: Lung cancer is the leading cause of cancer death in the industrialised world and is becoming a significant cause of mortality in developing countries. The vast majority of cases are a result of cigarette smoking. A number of genetic alterations are found in lung cancer, especially those effecting p53, a tumour suppressor gene that appears particularly sensitive to damage by tobacco carcinogens. Not all smokers develop lung cancer, suggesting that some individuals have greater genetic susceptibility. Lung cancers are usually subdivided according to the 1999 World Health Organisation (WHO) classification. Adenocarcinoma, squamous cell carcinoma, small cell carcinoma and large cell carcinoma are the commonest subtypes. Adenocarcinoma is now the commonest primary lung tumour. Pathological diagnosis is usually made by examination of cytological preparations from sputum or bronchial lavage fluid, or by histological examination of small biopsies. The most useful pathological distinction to make is between small cell and non-small cell carcinoma as this has implications for patient management. Once the diagnosis of lung cancer is made, clinical, thoracoscopic and radiological findings are used to produce a clinical stage of the disease. This enables the most appropriate treatment to be planned and gives prognostic information. Surgical resection of the tumour offers the best chance of a cure but, sadly, the majority of patients present with clinically advanced disease and are unsuitable for such treatment. Radiotherapy and chemotherapy may be effective in selected patients. Effective palliative therapy is the goal for the majority of patients. [Copyright &y& Elsevier]