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RICTOR gene, which encodes the scaffold protein of mTORC2, can be amplified in various tumor types, including squamous cell carcinoma (SCC) of the lung. RICTOR amplification can lead to hyperactivation of mTORC2 and may serve as a targetable genetic alteration, including in lung SCC patients with no PD-L1 expression who are not expected to benefit from immune checkpoint inhibitor therapy. This study aimed to compare RICTOR amplification detected by fluorescence in situ hybridization (FISH) with Rictor and PD-L1 protein expression detected by immunohistochemistry (IHC) in SCC of the lung. The study was complemented by analysis of the publicly available Lung Squamous Cell Carcinoma (TCGA, Firehose legacy) dataset. RICTOR amplification was observed in 20% of our cases and 16% of the lung SCC cases of the TCGA dataset. Rictor and PD-L1 expression was seen in 74% and 44% of the cases, respectively. Rictor IHC showed two staining patterns: membrane staining (16% of the cases) and cytoplasmic staining (58% of the cases). Rictor membrane staining predicted RICTOR amplification as detected by FISH with high specificity (95%) and sensitivity (70%). We did not find any correlation between RICTOR amplification and PD-L1 expression; RICTOR amplification was detected in 18% and 26% of PD-L1 positive and negative cases, respectively. The TCGA dataset analysis showed similar results; RICTOR copy number correlated with Rictor mRNA and protein expression but showed no association with PD-L1 mRNA and protein expression. In conclusion, the correlation between RICTOR amplification and Rictor membrane staining suggests that the latter can potentially be used as a surrogate marker to identify lung SCC cases with RICTOR amplification. Since a significant proportion of PD-L1 negative SCC cases harbor RICTOR amplification, analyzing PD-L1 negative tumors by RICTOR FISH or Rictor IHC can help select patients who may benefit from mTORC2 inhibitor therapy.

Lung cancer is one of the most common cancers and has the highest risk of mortality in both genders. This devastating cancer is also a significant financial and emotional burden to patients and the healthcare system. Chemotherapy and immunotherapy have become the cornerstone for the treatment of lung cancer. However, treatment may come with severe and sometimes fatal side effects. In this report, we present the case of a 52-year-old Caucasian male who suffered two episodes of prolonged cardiac arrest after the infusion of paclitaxel and pembrolizumab.

Context.--Studies of lungs in patients with COVID-19 have focused on early findings. Objective.--To systematically study histopathologic and imaging features and presence of SARS-CoV-2 RNA in lung tissue from patients in later stages of COVID-19. Design.--Autopsies, explants, surgical lung biopsies, transbronchial biopsies, cryobiopsies, and needle biopsies from patients with COVID-19 whose onset of symptoms/ confirmed diagnosis was more than 28 days before the procedure were studied. Available images were reviewed. Reverse transcription droplet digital polymerase chain reaction for SARS-CoV-2 RNA was performed on lung tissue. Results.--Of 44 specimens (43 patients; median age, 59.3 years; 26 [60.5%] male) features of acute lung injury (ALI) were seen in 39 (88.6%), predominantly organizing pneumonia and diffuse alveolar damage, up to 298 days after onset of COVID-19. Fibrotic changes were found in 33 specimens (75%), most commonly fibrotic diffuse alveolar damage (n = 22) and cicatricial organizing pneumonia (n = 12). Time between acquiring COVID-19 and specimen was shorter in patients with diffuse ALI (median, 61.5 days) compared with patients with focal (140 days) or no AlI (130 days) (P =.009). Sixteen (of 20; 80%) SARS-CoV-2 reverse transcription droplet digital polymerase chain reaction tests were positive, up to 174 days after COVID-19 onset. Time between COVID-19 onset and most recent computed tomography in patients with consolidation on imaging was shorter (median, 43.0 days) versus in patients without consolidation (87.5 days; P =.02). Reticulations were associated with longer time to computed tomography after COVID-19 onset (median, 82 versus 23.5 days; P =.006). Conclusions.--ALI and SARS-CoV-2 RNA can be detected in patients with COVID-19 for many months. ALI may evolve into fibrotic interstitial lung disease., Coronavirus disease 2019 (COVID-19) is a viral infection caused by SARS-CoV-2. More than 235 million people have been infected globally, with a death burden in excess of 4.8 million since [...]

Key message Diffuse pulmonary meningotheliomatosis (DPM) is an ultra‐rare pulmonary disease characterized by innumerable bilateral minute meningothelial‐like nodules, sometimes presenting a characteristic ‘cheerio‐sign’ on imaging. Most patients with DPM are asymptomatic and experience no disease progression. Although little is known about its nature, DPM may be associated with pulmonary malignancies, mostly lung adenocarcinoma.

Abstract Robotic‐assisted bronchoscopy (RAB) improves endoscopic diagnostic yield of solitary pulmonary nodules (SPN). Needle‐based confocal laser endomicroscopy (nCLE) is an emerging technology that allows high‐resolution, in‐vivo, real‐time assessment of living tissues at a cellular and subcellular level. Their combined use has been scarcely reported. We used them simultaneously in three patients with SPNs. For each, the nodule was evaluated with nCLE and sampled for pathology, followed by mediastinal staging. Median age was 77 years (67% male). Median nodule minimum size was 1.8 cm and maximum was 2.1 cm. nCLE detected abnormal patterns suggestive of malignancy for all nodules and pathology confirmed primary lung adenocarcinomas in two patients and lung primary squamous cell carcinoma in the other. The combined use of RAB with nCLE may potentially enhance the differentiation of malignant cells in real‐time and increase sample adequacy, accuracy, and diagnostic yield when biopsying a suspicious pulmonary lesion.

Simple Summary: Despite recent advances in targeted therapy and immunotherapy, the treatment of lung cancer remains challenging due to its high metastatic potential, which adversely affects both the prognosis and the quality of life of these patients. Rictor, the scaffold protein of the mTORC2 complex, plays an important role in regulating essential cellular functions and promoting metastases through epithelial–mesenchymal transition. Amplification of the RICTOR gene and subsequent overexpression of the Rictor protein can activate mTORC2 and promote cell survival and migration. Recent studies suggest that RICTOR amplification and Rictor overexpression may serve as markers of mTORC2 activation. Potentially, they can also provide druggable targets for advanced therapy. Although these drugs are still in a preclinical phase, selective mTORC2 inhibitors are a promising approach to inhibit tumor cell migration and metastasis formation. This review highlights the importance of Rictor and mTORC2 as predictive markers and promising therapeutic targets in the treatment of lung cancer. Lung carcinoma is one of the most common cancer types for both men and women. Despite recent breakthroughs in targeted therapy and immunotherapy, it is characterized by a high metastatic rate, which can significantly affect quality of life and prognosis. Rictor (encoded by the RICTOR gene) is known as a scaffold protein for the multiprotein complex mTORC2. Among its diverse roles in regulating essential cellular functions, mTORC2 also facilitates epithelial–mesenchymal transition and metastasis formation. Amplification of the RICTOR gene and subsequent overexpression of the Rictor protein can result in the activation of mTORC2, which promotes cell survival and migration. Based on recent studies, RICTOR amplification or Rictor overexpression can serve as a marker for mTORC2 activation, which in turn provides a promising druggable target. Although selective inhibitors of Rictor and the Rictor-mTOR association are only in a preclinical phase, they seem to be potent novel approaches to reduce tumor cell migration and metastasis formation. Here, we summarize recent advances that support an important role for Rictor and mTORC2 as potential therapeutic targets in the treatment of lung cancer. This is a traditional (narrative) review based on Pubmed and Google Scholar searches for the following keywords: Rictor, RICTOR amplification, mTORC2, Rictor complexes, lung cancer, metastasis, progression, mTOR inhibitors. [ABSTRACT FROM AUTHOR]

COPA syndrome is a newly discovered, rare genetic autoimmune disorder, which can affect the lungs, joints, and kidneys. It is difficult to recognize, and the survival benefit of lung transplantation for these patients is not yet known. We present a case of a 24-year-old woman who received bilateral lung transplant for COPA syndrome. At 15 months posttransplant, her pulmonary function is stable with no episodes of acute cellular- or antibody-mediated rejection and no evidence of disease recurrence.

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare inflammatory condition that mostly affects lungs in smokers. On imaging, it usually presents as multiple, upper lobe predominant, solid, and cavitary nodules, but presentation as solitary pulmonary nodule (SPN) is rare. We describe a case of SPN seen on low-dose lung cancer screening CT (LDCT) that was FDG avid on PET/CT. Given concern for malignancy, lobectomy was planned if intraoperative frozen section was consistent with malignancy. Lobectomy was performed based on frozen section; however, on formal pathology review, the nodule was ultimately found to be PLCH. This case illustrates an atypical presentation of PLCH as a solitary nodule. Furthermore, it helps demonstrate how rare etiologies (like PLCH) may be more frequently encountered and should be considered in the differential diagnosis for solitary lung nodules, especially in the era of lung cancer screening.

Summary: Lung squamous cell carcinoma (LSCC) is a prevalent form of lung cancer exhibiting distinctive histological and genetic characteristics. Chromosome 3q26 copy number gain (CNG) is a genetic hallmark of LSCC present in >90% of tumors. We report that 3q26 CNGs occur early in LSCC tumorigenesis, persist during tumor progression, and drive coordinate overexpression of PRKCI, SOX2, and ECT2. Overexpression of PRKCI, SOX2, and ECT2 in the context of Trp53 loss is sufficient to transform mouse lung basal stem cells into tumors with histological and genomic features of LSCC. Functionally, PRKCI and SOX2 collaborate to activate an extensive transcriptional program that enforces a lineage-restricted LSCC phenotype, whereas PRKCI and ECT2 collaborate to promote oncogenic growth. Gene signatures indicative of PKCι-SOX2 and PKCι-ECT2 signaling activity are enriched in the classical subtype of human LSCC and predict distinct therapeutic vulnerabilities. Thus, the PRKCI, SOX2, and ECT2 oncogenes represent a multigenic driver of LSCC. : Liu et al. report that three oncogenes, PRKCI, SOX2, and ECT2, which are coordinately amplified and overexpressed in lung squamous cell carcinoma (LSCC), can transform Trp53−/− mouse lung basal stem cells into tumors with histological and genomic features of LSCC and drive oncogenic signaling necessary to maintain a LSCC phenotype. Keywords: lung squamous cell carcinoma, LSCC, 3q26 copy number gain, CNG, PRKCI, SOX2, ECT2, lung basal stem cells, oncogenic transformation

Context.--Hypersensitivity pneumonitis (HP) is a lung disease that develops in susceptible individuals after inhalational exposure to an organic antigen or chemical compound. Pathogenesis is attributed to a combination of type III (immune complex-mediated) and type IV (delayed) hypersensitivity reactions to the inciting agent.Objective.--To provide an overview of the current status of the medical literature regarding hypersensitivity pneumonitis.Data Sources.--A literature search was performed using PubMed and Google search engines. The terms 'hypersensitivity pneumonitis' and 'extrinsic allergic alveolitis' were used, with the search starting on January 9, 2017, and concluding March 8, 2017.Conclusions.--As a pathologist, it is important to consider hypersensitivity pneumonitis when examining lung specimens because it is often clinically and pathologically overlooked. Recognizing the often subtle findings and correlating them with the patient's history or suggesting a thorough clinical investigation of potential exposures can be of help in identifying the underlying condition so that the patient can be appropriately managed.(Arch Pathol Lab Med. 2018;142:120-126; doi: 10.5858/arpa.2017-0138-SA), Hypersensitivity pneumonitis (HP, also referred to as extrinsic allergic alveolitis in the medical literature) can develop after inhalational exposure to a particular antigen or chemical in a susceptible individual. Hypersensitivity [...]