Clinical and Bronchoscopy Assessment in Diagnosing the Histopathology Type of Primary Central Lung Tumors.

Background: The location and type of a tumor influence the prognosis of lung cancer. Primary Central Lung Tumors (PCLTs) are correlated with poor prognoses and certain histologic types. This study aimed to present a comprehensive exploration of clinical and bronchoscopic assessments for diagnosing the histopathology types of PCLTs and identified the factors associated with certain histologic types. Methods: This was an observational cross-sectional study of PCLTs, defined as tumors in direct contact with hilar structures or located within the inner two-thirds of the hemithorax. We gathered demographic and clinical data, as well as data on bronchoscopy assessment and histopathology type. Tumor stage, symptoms of superior vena cava syndrome, and enlargement of lymph nodes in the paratracheal and subcarinal regions were also documented. Results: Of the 895 patients, 37.87% had primary lung tumors, with 17.76% classified as PCLTs. Notably, PCLT cases exhibited a higher proportion of stage III (28.9% vs. 18.3%; p = 0.03) and Squamous Cell Carcinoma (SCC) histopathology (37.1% vs. 17.2%; p = 0.00) compared with non-PCLT cases. Bronchoscopic findings in PCLTs revealed a predilection for central airway masses (25.2%) and compressive distal airway stenosis (25.2%). Subgroup analysis of 159 PCLT cases identified 37.10% as SCC. Multivariate analysis underscored that intraluminal masses predict central SCC (odds ratio 2.075, 95% confidence interval 1.07-3.99; p = 0.028). Conclusion: The proportion of stage III, SCC histopathological type, and intraluminal lesions was higher in patients with PCLT than in non-PCLT cases. The presence of intraluminal lesions can predict the histopathological type of SCC in patients with PCLTs.

The application of Raman spectroscopy for the diagnosis and monitoring of lung tumors.

Raman spectroscopy is an optical technique that uses inelastic light scattering in response to vibrating molecules to produce chemical fingerprints of tissues, cells, and biofluids. Raman spectroscopy strategies produce high levels of chemical specificity without requiring extensive sample preparation, allowing for the use of advanced optical tools such as microscopes, fiber optics, and lasers that operate in the visible and near-infrared spectral range, making them increasingly suitable for a wide range of medical diagnostic applications. Metal nanoparticles and nonlinear optical effects can improve Raman signals, and optimized fiber optic Raman probes can make real-time, in vivo, single-point observations. Furthermore, diagnostic speed and spatial accuracy can be improved through the multimodal integration of Raman measurements and other technologies. Recent studies have significantly contributed to the improvement of diagnostic speed and accuracy, making them suitable for clinical application. Lung cancer is a prevalent type of respiratory malignancy. However, the use of computed tomography for detection and screening frequently reveals numerous smaller lung nodules, which makes the diagnostic process more challenging from a clinical perspective. While the majority of small nodules detected are benign, there are currently no direct methods for identifying which nodules represent very early-stage lung cancer. Positron emission tomography and other auxiliary diagnostic methods for non-surgical biopsy samples from these small nodules yield low detection rates, which might result in significant expenses and the possibility of complications for patients. While certain subsets of patients can undergo curative treatment, other individuals have a less favorable prognosis and need alternative therapeutic interventions. With the emergence of new methods for treating cancer, such as immunotherapies, which can potentially extend patient survival and even lead to a complete cure in certain instances, it is crucial to determine the most suitable biomarkers and metrics for assessing the effectiveness of these novel compounds. This will ensure that significant treatment outcomes are accurately measured. This review provides a comprehensive overview of the prospects of Raman spectroscopy and its applications in the diagnosis and analysis of lung tumors.

Dose Optimization of Intravenous Indocyanine Green for Malignant Lung Tumor Localization.

Background: Intravenously administered indocyanine green (ICG) accumulates in lung tumors, facilitating their detection via a fluorescence spectrum measurement. This method aids in identifying tumor locations that are invisible to the naked eye. We aim to determine the optimal ICG dose and administration method for accurate tumor identification during lung resection surgeries, utilizing a novel ICG fluorescence spectroscopy system for precise tumor localization. Materials and Methods: ICG should be dissolved in the provided solution or distilled water and administered intravenously approximately 24 h before surgery, beginning with an initial dose of 0.5 mg/kg. If the tumor detection rate is insufficient, the dose may be gradually increased to a maximum of 5.0 mg/kg to determine the optimal dosage for effective tumor detection. This fluorescence spectroscopy during surgery may reveal additional lesions that remain undetected in preoperative assessments. The primary endpoint includes the correct diagnostic rate of tumor localization. The secondary endpoints include the measurement of the intraoperative ICG fluorescence spectral intensity in lung tumors, the assessment of the operability and safety of intraperitoneal ICG administrations, the measurement of the ICG fluorescence spectral intensity in surgical specimens, the comparison of the spectral intensity in lung tissues during collapse and expansion, the correlation between ICG camera images and fluorescence spectral intensity, and the comparison of fluorescence analysis results with histopathological findings. The trial has been registered in the jRCT Clinical Trials Registry under the code jRCTs011230037. Results and Conclusions: This trial aims to establish an effective methodology for localizing and diagnosing malignant lung tumors, thereby potentially improving surgical outcomes and refining treatment protocols.

A Case Report of Inflammatory Myofibroblastic Tumor: A Rare Benign Lung Tumor.

Inflammatory myofibroblastic tumors (IMTs) of the lung are a rare type of mesenchymal tumors that tend to occur more in the lungs of children. They are extremely rare in adults. IMTs require extensive pulmonary resection because they are commonly locally invasive. The key to preventing recurrence is complete resection, and the prognosis is excellent after surgery. We report a case of a patient with an inflammatory pseudotumor of the lung. The patient is a 27-year-old female who presented with a dry cough. A chest radiograph and computed tomography showed a lesion in the left main bronchus and near-total left lung collapse. As surgery was necessary to establish the diagnosis, left pneumonectomy was performed followed by a histological examination of the surgical specimen which confirmed inflammatory pseudotumor.

Identifying symptom clusters and temporal interconnections in patients with lung tumors after CT-guided microwave ablation: A network analysis.

PURPOSE: To explore symptom clusters and interrelationships using a network analysis approach among symptoms in patients with lung tumors who underwent computed tomography (CT)-guided microwave ablation (MWA). METHODS: A longitudinal study was conducted, and 196 lung tumor patients undergoing MWA were recruited and were measured at 24 h, 48 h, and 72 h after MWA. The Chinese version of the MD Anderson Symptom Inventory and the Revised Lung Cancer Module were used to evaluate symptoms. Network analyses were performed to explore the symptom clusters and interrelationships among symptoms. RESULTS: Four stable symptom communities were identified within the networks. Distress, weight loss, and chest tightness were the central symptoms. Distress, and weight loss were also the most key bridge symptoms, followed by cough. Three symptom networks were temporally stable in terms of symptom centrality, global connectivity, and network structure. CONCLUSION: Our findings identified the central symptoms, bridge symptoms, and the stability of symptom networks of patients with lung tumors after MWA. These network results will have important implications for future targeted symptom management intervention development. Future research should focus on developing precise interventions for targeting central symptoms and bridge symptoms to promote patients' health.

Impact of COVID-19 pandemic among patients with lung and head and neck cancer assisted in a public cancer center in Brazil.

BACKGROUND: There is no updated national data regarding the real impact of the COVID-19 pandemic on delaying diagnosis and treatment among patients with lung, and head, and neck cancers in Brazil. This study aimed to analyze the COVID-19 pandemic impact on cancer diagnosis and clinical outcomes among lung, head, and neck cancer patients assisted in a tertiary cancer center in Southeastern Brazil, as well as to analyze these patients' pretreatment clinical features. METHODS: Retrospective cohort of patients with lung or head and neck cancer assisted in a tertiary cancer center in southeastern Brazil between January/2019 and December/2021. To assess statistical differences among groups [i.e., cohort 2019 versus (vs.) 2020 and 2019 vs. 2021] chi-square test was used with a 5% significance level and 90% power for sample size calculation. Differences among baseline clinical features and sociodemographic characteristics were evaluated either by T-test for two samples or Fisher's or Pearson's chi-square test (for quantitative or qualitative variables). All utilized tests had a 5% significance level. RESULTS: Six hundred fifty-two patients were included, 332 with lung and 320 with head and neck cancer; it was observed a significant decrease in oncologic treatment recommendations and increase in palliative care recommendation for patients with lung cancer, despite similar stages at diagnosis. During the COVID-19 pandemic, more pain symptoms were reported at the first Oncology assessment for patients with head and neck cancer (p < 0.05). Compared to 2019, head and neck cancer patients diagnosed in 2021 presented a worse initial performance status (p = 0.008). There was a statistically significant increase in survival for patients diagnosed with head and neck cancer in 2021 when compared to 2019 (p = 0.003). CONCLUSIONS: This research highlights low survival rates for patients with lung and head and neck cancer in Brazil, even before the pandemic started, as consequence of advanced diseases at diagnosis at the public health system and clinical degrading features. Additionally, there was an increase incidence in both lung cancer and head and neck cancer despite no differences in clinical stage. This reflects how fragile is the public healthcare system even before facing an acute public health crisis such as the COVID-19 pandemic. Yet, the total impact on public health may follow for many years.

Primary pulmonary monophasic synovial sarcoma initially presenting with bloody pleural effusion: A case report and literature review.

Key Clinical Message: Primary pulmonary synovial sarcoma (PPSS) can originate from blood vessels of the bronchial wall, lung interstitium, and interstitial components, and accounts for 0.1%-0.5% of all primary lung malignancies, the most common symptoms are chest pain, cough, dyspnea, and hemoptysis. Abstract: Synovial sarcoma (SS) is a rare malignant tumor of stromal origin, which accounts for approximately 8%-10% of all soft tissue sarcomas. Primary pulmonary synovial sarcoma (PPSS) can originate from blood vessels of the bronchial wall, lung interstitium, and interstitial components, and accounts for 0.1%-0.5% of all primary lung malignancies. Patient concerns: We report the first case of a 57-year-old man with bloody pleural effusion as an initial manifestation of PPSS in the middle lobe of the right lung diagnosed after surgery. Diagnosis: Chest computed tomography (CT) revealed a mass in the middle lobe of the right lung, which was pathologically diagnosed as a monophasic SS after surgical resection. Interventions: Ten days after preoperative closed chest drainage, a right thoracotomy was performed to remove the right middle lobe of the lung. Outcomes: The patient recovered smoothly and was discharged from the hospital without any other postoperative treatment. A follow-up chest CT scan 7 months postoperatively revealed intrapulmonary recurrence with multiple metastases. Lessons: Monophasic PPSS of the lung may present with bloody pleural effusion as its first manifestation.

Potential of Thermal Ablation Combined with Immunotherapy in Peripheral Lung Tumors: A Review and Prospect.

BACKGROUND: Lung tumors are prevalent malignancies associated with a high mortality rate, imposing significant medical and societal burdens. Although immunotherapy shows promise in improving survival, response rates are relatively modest. Thermal ablation can not only eliminate tumor cells directly but also enhance antitumor immunity response, thus manifesting a remarkable propensity to synergize with immunotherapy. SUMMARY: In this review, we provided a brief overview of the application of thermal ablation in peripheral lung tumors. We summarized the patient selection of thermal ablation. We highlighted the potential of thermal ablation to augment the antitumor immune response, offering a promising avenue for combined therapies. We summarized studies assessing the synergistic effects of thermal ablation and immunotherapy in preclinical and clinical settings. Lastly, we underscored the urgent issues that warrant in-depth exploration when applying thermal ablation and immunotherapy to lung tumor patients. KEY MESSAGES: This review emphasized the prospects of using thermal ablation combined with immunotherapy in patients with peripheral lung tumors. However, further research is needed to enhance and optimize this treatment strategy.

Blockade of CD93 in pleural mesothelial cells fuels anti-lung tumor immune responses.

Background: CD93 reportedly facilitates tumor angiogenesis. However, whether CD93 regulates antitumor immunity remains undeciphered. Methods: Lung tumor tissues, malignant pleural effusions (MPEs) were obtained from lung cancer patients. Blood was obtained from healthy volunteers and lung cancer patients with anti-PD-1 therapy. Furthermore, p53fl/flLSL-KrasG12D, Ccr7-/-, Cd93-/- mice and CD11c-DTR mice were generated. Specifically, EM, NTA and western blotting were utilized to identify Tumor extracellular vesicles (TEVs). EV labeling, detection of EV uptake in vitro and in vivo, degradation of EV proteins and RNAs were performed to detect the role of TEVs in tumor progression. Pleural mesothelial cells (pMCs) were isolated to investigate related signaling pathways. Recombinant proteins and antibodies were generated to test which antibody was the most effective one to increase CCL21a in p-pMCs. RNA-Seq, MiRNA array, luciferase reporter assay, endothelial tube formation assay, protein labeling and detection, transfection of siRNAs and the miRNA mimic and inhibitor, chemotaxis assay, immunohistochemical staining, flow cytometry, Real-time PCR, and ELISA experiments were performed. Results: We show that CD93 of pMCs reduced lung tumor migration of dendritic cells by preventing pMCs from secreting CCL21, thereby suppressing systemic anti-lung tumor T-cell responses. TEV-derived miR-5110 promotes CCL21 secretion by downregulating pMC CD93, whereas C1q, increasing in tumor individuals, suppresses CD93-mediated CCL21 secretion. CD93-blocking antibodies (anti-CD93) inhibit lung tumor growth better than VEGF receptor-blocking antibodies because anti-CD93 inhibit tumor angiogenesis and promote CCL21 secretion from pMCs. Anti-CD93 also overcome lung tumor resistance to anti-PD-1 therapy. Furthermore, lung cancer patients with higher serum EV-derived miR-5193 (human miR-5110 homolog) are more sensitive to anti-PD-1 therapy, while patients with higher serum C1q are less sensitive, consistent with their regulatory functions on CD93. Conclusions: Our study identifies a crucial role of CD93 in controlling anti-lung tumor immunity and suggests a promising approach for lung tumor therapy.

Contributions of Dr. Wick to the pathology of diseases of the lung and pleura.

The curriculum vitae of Dr. Mark R. Wick contains 57 peer-reviewed publications, 3 editorials, 6 book chapters and a whole book dedicated to diseases of the lung and pleura. It is remarkable that such productivity should represent only a small portion of the overall output of Dr. Wick, which includes (at last count) 341 original peer-review publications, 119 invited review articles, 93 book chapters, 42 editorials, 3 society-related position papers, 18 books and 2 interactive video disks. Yet, his contributions to the literature in pulmonary and pleural pathology have been significant and influential and have established for him a national and international reputation as one of the leading experts in pulmonary pathology. Herein, it is my privilege to recount the various publications contributed by Dr. Wick to this topic, which span the gamut from transplant pathology to neoplastic diseases of the lung and pleura.

Fusion of laser-induced breakdown spectroscopy technology and deep learning: a new method to identify malignant and benign lung tumors with high accuracy.

Precisely distinguishing between malignant and benign lung tumors is pivotal for suggesting therapeutic strategies and enhancing prognosis, yet this differentiation remains a daunting task. The growth rates, metastatic potentials, and prognoses of benign and malignant tumors differ significantly. Developing specialized treatment protocols tailored to various tumor types is essential for enhancing patient survival outcomes. Employing laser-induced breakdown spectroscopy (LIBS) in conjunction with a deep learning methodology, we attained a high-precision differential diagnosis of malignant and benign lung tumors. First, LIBS spectra of malignant tumors, benign tumors, and normal tissues were collected. The spectra were preprocessed and Z score normalized. Then, the intensities of the Mg II 279.6, Mg I 285.2, Ca II 393.4, Cu II 518.3, and Na I 589.6 nm lines were analyzed in the spectra of the three tissues. The analytical results show that the elemental lines have different contents in the three tissues and can be used as a basis for distinguishing between the three tissues. Finally, the RF-1D ResNet model was constructed by combining the feature importance assessment method of random forest (RF) and one-dimensional residual network (1D ResNet). The classification accuracy, precision, sensitivity, and specificity of the RF-1D ResNet model were 91.1%, 91.6%, 91.3%, and 91.3%, respectively. And the model demonstrates superior performance with an area under the curve (AUC) value of 0.99. The above results show that combining LIBS with deep learning is an effective way to diagnose malignant and benign tumors.

[Synchronous association of two primary lung tumors: a case report]. / Association synchrone de deux tumeurs pulmonaires primitives: à propos d'un cas.

Synchronous multiple primary lung tumors are a relatively rare entity with an increasing incidence in recent years due to the development of thoracic imaging and immunohistochemical techniques. The second lesion is considered in most cases as a secondary location, which partly explains the decrease in the incidence of this entity. We report the observation of a 74-year-old patient with two synchronous primary lung tumors, an adenocarcinoma and an epidermoid carcinoma. Through this clinical observation, we highlight the difficulty of diagnosing synchronous tumors and the major interest of new imaging modalities and immunohistochemical techniques for the optimal management of these tumors.

Dosimetric analysis of 17 cardiac Sub-structures, Toxicity, and survival in ultra central lung tumor patients treated with SBRT.

•Data on cardiac toxicity after SBRT for ultra-central lung tumors remains limited.•We analyzed the dose to 18 cardiac sub-structures and cardiovascular toxicity.•A SBRT regimen of 45 Gy in 8-10 fractions yields good local control and low toxicity.•The highest cardiac doses were observed in the pulmonary artery and left atrium.•Higher doses to the base of the heart seem to be associated with non-cancer deaths.

Predicting successful clinical candidates for fiducial-free lung tumor tracking with a deep learning binary classification model.

OBJECTIVES: The CyberKnife system is a robotic radiosurgery platform that allows the delivery of lung SBRT treatments using fiducial-free soft-tissue tracking. However, not all lung cancer patients are eligible for lung tumor tracking. Tumor size, density, and location impact the ability to successfully detect and track a lung lesion in 2D orthogonal X-ray images. The standard workflow to identify successful candidates for lung tumor tracking is called Lung Optimized Treatment (LOT) simulation, and involves multiple steps from CT acquisition to the execution of the simulation plan on CyberKnife. The aim of the study is to develop a deep learning classification model to predict which patients can be successfully treated with lung tumor tracking, thus circumventing the LOT simulation process. METHODS: Target tracking is achieved by matching orthogonal X-ray images with a library of digital radiographs reconstructed from the simulation CT scan (DRRs). We developed a deep learning model to create a binary classification of lung lesions as being trackable or untrackable based on tumor template DRR extracted from the CyberKnife system, and tested five different network architectures. The study included a total of 271 images (230 trackable, 41 untrackable) from 129 patients with one or multiple lung lesions. Eighty percent of the images were used for training, 10% for validation, and the remaining 10% for testing. RESULTS: For all five convolutional neural networks, the binary classification accuracy reached 100% after training, both in the validation and the test set, without any false classifications. CONCLUSIONS: A deep learning model can distinguish features of trackable and untrackable lesions in DRR images, and can predict successful candidates for fiducial-free lung tumor tracking.

Multiple Primary Lung Cancers: Treatment Outcomes After Stereotactic Body Radiotherapy (SBRT).

PURPOSE/OBJECTIVES: Patients with lung cancer sometimes present with multiple primary lung cancers (MPLCs), either simultaneously (synchronous) or after treatment of an initial lesion (metachronous). Although open surgery remains a treatment mainstay for patients with stage I-II non-small-cell lung cancer (NSCLC), stereotactic body radiation therapy (SBRT) is an acceptable alternative for patients who are medically unfit for or who refuse surgery. In this study, we retrospectively examine the outcome among patients with early-stage MPLCs treated at our institution with SBRT. MATERIALS/METHODS: Patients at our institution receiving SBRT for MPLC between June 2011 and March 2020 were reviewed retrospectively. Prior to undergoing definitive SBRT, the imaging, and pathology for every patient were reviewed in a multi-disciplinary thoracic/pulmonary tumor board. Dose and fractionation varied with the most common prescriptions being 50 Gy/5 fractions, 56 Gy/4 fractions, and 55 Gy/5 fractions. RESULTS: A total of 38 patients with a total of 80 MPLCs were treated, among which 68 were T1 lesions and 12 were T2 lesions. Median follow-up was 25.9 months, with local control (LC) rates calculated per lesion to be 98.6%, 93.3%, and 88.2% at one, two, and three years. Median overall survival (OS) was 43.5 months; 83.6%, 67.8%, and 52.3% at one, two, and three years, respectively. Sixty-two of the 80 (77.5%) treated lesions were not associated with any subsequent acute or late toxicity. The 18 (22.5%) lesions associated with toxicity included nine acute and nine late events. All toxicity was either grade 1 (13 of 18) or grade 2 (five of 18). CONCLUSIONS: SBRT for early-stage MPLC achieves high control rates with limited toxicity. MPLC patients deemed unfit for open surgical management should be considered for definitive SBRT.

A rare case of Pleuropulmonary blastoma type III with Immunohistochemical Study.

Here we intend to document a rare case of PPB type III in a 2-year male presenting with an extensive tumor occupying the right hemithorax with immunohistochemical (IHC) study. Pleuropulmonary blastoma (PPB) is a rare variably aggressive, dysodontogenetic, childhood primary intrathoracic malignancy which in up to 25% of cases can be extrapulmonary with attachment to the parietal pleura. It is found in pediatric population under 5 years of age. It was initially proposed as a distinct entity by Manivel et al. in 1988. PPB is a proliferation of primitive mesenchymal cells that initially form air-filled cysts lined by benign-appearing epithelium (type I, cystic). Later on, the mesenchymal cells outgrow the cysts with formation of focal solid areas (type II, solid and cystic) and finally, mainly solid mass (type III, solid PPB).

Claudin expression in pulmonary adenoid cystic carcinoma and mucoepidermoid carcinoma.

Background: Although the expression of tight junction protein claudins (CLDNs) is well known in common histological subtypes of lung cancer, it has not been investigated in rare lung cancers. The aim of our study was to examine the expression of different CLDNs in pulmonary salivary gland tumors. Methods: 35 rare lung cancers including pathologically confirmed 12 adenoid cystic carcinomas (ACCs) and 23 mucoepidermoid carcinomas (MECs) were collected retrospectively. Immunohistochemical (IHC) staining was performed on formalin fixed paraffin embedded (FFPE) tumor tissues, and CLDN1, -2, -3, -4, -5, -7, and -18 protein expressions were analyzed. The levels of immunopositivity were determined with H-score. Certain pathological characteristics of ACC and MEC samples (tumor grade, presence of necrosis, presence of blood vessel infiltration, and degree of lymphoid infiltration) were also analyzed. Results: CLDN overexpression was observed in both tumor types, especially in CLDN2, -7, and -18 IHC. Markedly different patterns of CLDN expression were found for ACC and MEC tumors, especially for CLDN1, -2, -4, and -7, although none of these trends remained significant after correction for multiple testing. Positive correlations between expressions of CLDN2 and -5, CLDN3 and -4, and CLDN5 and -18 were also demonstrated. Tumors of never-smokers presented lower levels of CLDN18 than tumors of current smokers (p-value: 0.003). Conclusion: This is the first study to comprehensively describe the expression of different CLDNs in lung ACC and MEC. Overexpression of certain CLDNs may pave the way for targeted anti-claudin therapy in these rare histological subtypes of lung cancer.

Does the dose matter? Antiproliferative efficacy and toxicity of everolimus in patients with neuroendocrine tumors - Experiences from a tertiary referral center.

The mTOR-inhibitor everolimus has been approved for the treatment of advanced neuroendocrine tumors (NETs) but is associated with relevant toxicities in clinical practice. Hence, optimal treatment sequencing and the impact of dose reductions have yet to be clarified. This retrospective analysis assessed patients with advanced, well-differentiated NET treated with everolimus at the Medical University of Vienna. The primary objective was to evaluate the efficacy of everolimus in a real-world cohort. A total of 52 patients treated with everolimus for advanced NET grade 1 (G1) or G2 (or typical or atypical carcinoid) 2010-2021 were included in this analysis. The most common sites of origin were pancreas (44%) and lung (29%). The initial dose was decided by the treating physician based on clinical assessment and 25 patients (48%) each were started at 10 mg/day and 5 mg/day. Median progression-free survival (PFS) following everolimus in the overall cohort was 9.8 months (95% CI: 4.3-15.3), with a statistically significant PFS difference (p = .03) between NET G1/typical carcinoids (42.9 months) and NET G2/atypical carcinoids (8.9 months). PFS was numerically but not significantly shorter in patients treated with a reduced dose (7.5 months vs. 12.4 months, p = .359). Even in this mixed full/half dose cohort, 93% developed treatment-related side effects (mostly grade I, no grade IV), 63% had dose reductions or interruptions, and five stopped due to toxicity. Median survival following treatment was 40.9 months (95% CI: 21.5-60.3) and no difference with regard to dosing was observed (p = .517). These data from an unselected patient cohort show long-term outcomes similar to those reported in the pivotal studies. Comparing everolimus starting dose, median PFS did not significantly differ for patients treated at a lower dose. While this finding is limited by the sample size and warrants prospective verification, initiating therapy at a reduced dose might be practicable and safe in a distinct subset of patients.

PD-1 and PD-L1 expression in rare lung tumors.

Background: Our knowledge is still limited about the characteristics and treatment of rare lung tumors. The aim of our study was to determine programmed cell death ligand-1 (PD-L1) and programmed cell death-1 (PD-1) expression in rare pulmonary tumors to assess the potential role of immunotherapy. Methods: 66 pathologically confirmed rare lung tumors including 26 mucoepidermoid carcinomas (MECs), 27 adenoid cystic carcinomas (ACCs), and 13 tracheobronchial papillomas (TBPs) were collected retrospectively. Immunohistochemical (IHC) staining was performed on formalin fixed paraffin embedded (FFPE) tumor tissues, and PD-L1 expression on tumor cells (TCs) and immune cells (ICs), and PD-1 expression on ICs were determined. The cut off value for positive immunostaining was set at 1% for all markers. Results: PD-L1 expression on TCs was observed in two cases of MEC (7.7%), one case of ACC (3.7%), and was absent in TBP samples. PD-L1 expression on ICs could be demonstrated in nine cases of MEC (34.6%), four cases of ACC (14.8%), and was absent in TBPs. All PD-L1 TC positive tumors were also PD-L1 IC positive. Higher expression level than 5% of PD-L1 TC and/or IC was observed only in one ACC and in two MEC patients. Among them, strong PD-L1 immunopositivity of >50% on TCs and of >10% on ICs could be demonstrated in one MEC sample. PD-L1 expression of ≥1% on ICs was significantly more common in MEC, than in TBP (p < 0.001). In MEC ≥1% PD-L1 TC or IC expressions were significantly more common in patients aged 55 or older, than in younger patients (p = 0.046, and p = 0.01, respectively). PD-1 expression on ICs was found in five cases of MEC (19.2%), four cases of ACC (14.8%), and in two cases of TBP (15.4%). Only one MEC case showed a higher than 5% expression level of PD-1 on ICs. Conclusion: This retrospective study comprehensively demonstrated the rare expression of PD-L1 and PD-1 in pulmonary MEC, ACC, and TBP. However, we found very strong PD-L1 immunopositivity on both TCs and ICs in one MEC sample, which warrants further investigations in a larger cohort.

Giant inflammatory pseudotumor of the lung: a case report.

The inflammatory myofibroblastic tumor, which was first described in 1939, is a rare neoplasm that accounts for 0.04%-0.7% of all lung neoplasms. These neoplasms occur most often in children, as they are the most common primary lung tumors in children. Preoperative diagnosis of such patients using bronchoscopy with endoluminal biopsy and transthoracic biopsy is not always informative and often the diagnosis can only be established during surgery. The presented case shows that on rare occasions, a giant myofibroblastic tumor of the lung may be encountered in adults, and radical intervention with subsequent rehabilitation can lead to full recovery.