Search Results (9)

We report a 26-year-old male presenting with a chronic cough and hemoptysis. Imaging revealed a large hypermetabolic mass in the left lower lung with the invasion of adjacent great vessels. A biopsy confirmed sarcomatoid carcinoma, a rare and aggressive form of primary pulmonary sarcoma. Due to vascular involvement, the patient underwent preoperative bronchial artery embolization followed by left pneumonectomy with pulmonary arterioplasty via median sternotomy. Postoperative recovery was uneventful. A two-year follow-up CT showed no recurrence. Primary pulmonary sarcomas are extremely rare, accounting for only 0.013–0.4% of lung malignancies, and are often diagnosed late due to nonspecific symptoms. This case highlights the importance of timely imaging, multidisciplinary planning, and aggressive surgical management in achieving long-term disease control, even in cases with extensive vascular invasion. Full article

Immunotherapy has transformed lung cancer management, but PSC remains an aggressive subtype with a poor prognosis. This study investigates the differential expression of PD-L1 and alternative immune checkpoints (ICs; B7x, B7-H3, and HHLA2), and genetic alterations in PSCs. Tumor specimens of 41 PSC patients were evaluated. PD-L1, B7x, B7-H3, and HHLA2 were positive in 75.0%, 67.6%, 73.0%, and 91.9% of tumors, respectively. PD-L1 expression was significantly higher in the epithelial compared to the sarcomatoid component (median TPS: 50% vs. 0%, p = 0.010). Expression of PD-L1 in both components was only seen in 32.1% of patients. However, at least one IC was expressed in 92.9% of epithelial and 100% of sarcomatoid components. Furthermore, METex14 was detected in 19.5% of patients and was associated with a higher sarcomatoid percentage. Our preclinical studies revealed that METex14 induced PD-L1 expression via MAPK or PI3K/Akt pathways, and MET inhibitors decreased PD-L1 expression. Our findings demonstrate distinct expressions of ICs in PSC subcomponents. Thus, combination IC inhibition as a therapeutic strategy in PSC warrants further exploration. A high percentage of METex14 in PSC and its role in regulating PD-L1 expression reveal different therapeutic targets in this aggressive NSCLC subtype. Full article

Pulmonary sarcomatoid carcinoma (PSC) has highly aggressive biological behaviour and poor clinical outcomes, raising expectations for new therapeutic strategies. We characterized 179 PSC by immunohistochemistry, next-generation sequencing and in silico analysis using a deep learning algorithm with respect to clinical, immunological and molecular features. PSC was more common in men, older ages and smokers. Surgery was an independent factor (p < 0.01) of overall survival (OS). PD-L1 expression was detected in 82.1% of all patients. PSC patients displaying altered epitopes due to processing mutations showed another PD-L1-independent immune escape mechanism, which also significantly influenced OS (p < 0.02). The effect was also maintained when only advanced tumour stages were considered (p < 0.01). These patients also showed improved survival with a significant correlation for immunotherapy (p < 0.05) when few or no processing mutations were detected, although this should be interpreted with caution due to the small number of patients studied. Genomic alterations for which there are already approved drugs were present in 35.4% of patients. Met exon 14 skipping was found more frequently (13.7%) and EGFR mutations less frequently (1.7%) than in other NSCLC. In summary, in addition to the divergent genomic landscape of PSC, the specific immunological features of this prognostically poor subtype should be considered in therapy stratification. Full article

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung cancer (NSCLC) with an aggressive clinical nature and poor prognosis. With novel targeted therapeutics being developed, new ways to effectively treat PSC are emerging. In this study, we analyze demographics, tumor characteristics, treatment modalities, and outcomes of PSC and genetic mutations in PSC. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) database were reviewed to analyze cases of pulmonary sarcomatoid carcinoma from 2000 to 2018. The molecular data with the most common mutations in PSC were extracted from the Catalogue Of Somatic Mutations in Cancer (COSMIC) database. Results: A total of 5259 patients with PSC were identified. Most patients were between 70 and 79 years of age (32.2%), male (59.1%), and Caucasian (83.7%). The male-to-female ratio was 1.45:1. Most tumors were between 1 and 7 cm in size (69.4%) and poorly differentiated (grade III) (72.9%). The overall 5-year survival was 15.6% (95% confidence interval (95% CI) = 14.4–16.9)), and the cause-specific 5-year survival was 19.7% (95% CI = 18.3–21.1). The five-year survival for those treated with each modality were as follows: chemotherapy, 19.9% (95% CI = 17.7–22.2); surgery, 41.7% (95% CI = 38.9–44.6); radiation, 19.1% (95% CI = 15.1–23.5); and multimodality therapy (surgery and chemoradiation), 24.8% (95% CI = 17.6–32.7). On multivariable analysis, age, male gender, distant stage, tumor size, bone metastasis, brain metastasis, and liver metastasis were associated with increased mortality, and chemotherapy and surgery were associated with reduced mortality (p < 0.001). The best survival outcomes were achieved with surgery. The most common mutations identified in COSMIC data were TP53 31%, ARID1A 23%, NF1 17%, SMARCA4 16%, and KMT2D 9%. Conclusions: PSC is a rare and aggressive subtype of NSCLC, usually affecting Caucasian males between 70 and 79. Male gender, older age, and distant spread were associated with poor clinical outcomes. Treatment with surgery was associated with better survival outcomes. Full article

Non-small cell lung cancer (NSCLC) is increasingly being treated with targeted therapies. Savolitinib (Orpathys^®) is highly selective mesenchymal epithelial transition (MET)–tyrosine kinase inhibitor (TKI), which is conditionally approved in China for advanced NSCLC with MET exon 14 skipping mutations (METex14). This article summarizes the clinical development of savolitinib, as a monotherapy in NSCLC with METex14 mutation and in combination with epidermal growth factor receptor (EGFR) inhibitor in post EGFR–TKI resistance NSCLC due to MET-based acquired resistance. Preclinical models demonstrated anti-tumor activities in MET-driven cancer cell line and xenograft tumor models. The Phase Ia/Ib study established an optimized, recommended phase II dose in Chinese NSCLC patients, while TATTON study of savolitinib plus osimertinib in patients with EGFR mutant, MET-amplified and TKI-progressed NSCLC showed beneficial efficacy with acceptable safety profile. In a pivotal phase II study, Chinese patients with pulmonary sarcomatoid carcinoma, brain metastasis and other NSCLC subtype positive for METex14 mutation showed notable responses and acceptable safety profile with savolitinib. Currently, results from ongoing clinical trials are eagerly anticipated to confirm the efficacious and safety benefits of savolitinib as monotherapy and in combination with EGFR–TKI in acquired resistance setting in advanced NSCLC and its subtypes with MET alterations. Full article

Lung cancer remains the leading cause of cancer deaths worldwide. Among the Non-Small Cell Carcinoma (NSCLC) category, Adenocarcinoma (ADC) represents the most common type, with different reported driver mutations, a bunch of models described and therapeutic options. Meanwhile, Pulmonary Sarcomatoid Carcinoma (PSC) is one of the rarest, with very poor outcomes, scarce availability of patient material, no effective therapies and no models available for preclinical research. Here, we describe that the combined deletion of Pten and Trp53 in the lungs of adult conditional mice leads to the development of both ADC and PSC irrespective of the lung targeted cell type after naphthalene induced airway epithelial regeneration. Although this model shows long latency periods and incomplete penetrance for tumor development, it is the first PSC mouse model reported so far, and sheds light on the relationships between ADC and PSC and their cells of origin. Moreover, human ADC show strong transcriptomic similarities to the mouse PSC, providing a link between both tumor types and the human ADC. Full article

Congenital pulmonary airway malformations (CPAM) are rare conditions generally diagnosed in childhood and possibly harboring malignant tumor growths. We describe a unique case of pleomorphic carcinoma in a longstanding type 1 CPAM diagnosed by wedge resection. The patient underwent completion left lower lobectomy and lymphadenectomy, but cancer recurred in nodal station #7 six months later. Clinicians should keep in mind that CPAM may hide radiologically undetectable malignancy in a relevant rate of cases, then requiring surgery in all patients. While MIA is the most common histology in type 1 CPAM, sarcomatoid change has herein been demonstrated. Full article

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 Guideliness. Full article

Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small-cell lung carcinoma with a poor prognosis and poor response to chemotherapy and radiotherapy. A previous study reported that psc expresses high levels of PD-L1, suggesting the potential efficacy of immune checkpoint inhibitors in these tumours. We report 2 cases of patients with a lung sarcomatoid carcinoma. Both patients initially underwent curative lung resection, but developed early recurrent disease. Because PD-L1 was highly expressed in the tumour cells, we initiated therapy with nivolumab, which showed good efficacy, almost complete radiologic tumour remission, and a remarkable improvement in the condition of those patients. Immune checkpoint inhibitors targeting PD-1 might be a valuable therapy option for PSCS. Full article