Impacts of 18F-FDG PET/CT Parameters on Differential Diagnosis and Outcome of Patients with Primary Invasive Mucinous and Lepidic Predominant Adenocarcinoma of the Lung.

Objectives: The purpose of this study was to investigate whether 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) parameters have a role in differentiating invasive mucinous lung adenocarcinoma (IMA) from lepidic predominant lung adenocarcinoma (LPA). Additionally, we compared the 18F-FDG-PET/CT features between survivors and non-survivors. Methods: Tumors were divided into 2 groups according to CT appearance: Group 1: nodular-type tumor; group 2: mass- or pneumonic-type tumor. Unilateral and bilateral multifocal diseases were detected. Clinicopathological characteristics and PET/CT findings were compared between IMAs and LPAs, as well as between survivors and non-survivors. Results: We included 43 patients with IMA and 14 with LPA. Tumor size (p=0.003), incidence of mass/pneumonic type (p=0.011), and bilateral lung involvement (p=0.049) were higher in IMAs than in LPAs. IMAs had more advanced T, M, and Tumor, Node, and Metastasis stages than in LPAs (p=0.048, p=0.049, and p=0.022, respectively). There was no statistically significant difference in maximum standardized uptake value (SUVmax) between the IMA and LPA (p=0.078). The SUV was significantly lower in the nodular group than in the mass/pneumonic-type group (p=0.0001). A total of 11 patients died, of whom SUVmax values were significantly higher in these patients (p=0.031). Male gender (p=0.0001), rate of stage III-IV (p=0.0001), T3-T4 (p=0.021), M1 stages (p=0.0001), multifocality (p=0.0001), and bilateral lung involvement (p=0.0001) were higher in non-survivor. Conclusions: Although CT images were useful for the differential diagnosis of LPAs and IMAs, SUVmax was not helpful for differentiation of these 2 groups. However, both 18F-FDG uptake and CT findings may play an important role in predicting prognosis in these patients.

Extremely Rare Coexistence of Peripherally Located Mucous Gland Adenoma and Pulmonary Chondroid Hamartoma.

Pulmonary mucous gland adenomas (MGAs) originating in mucous-secreting cells in the bronchi are extremely rare benign tumours. Pulmonary chondroid hamartomas (PCHs) are the most common benign neoplasms of mesenchymal origin of the lung. This study reports an unusual case where MGA and PCH coexisted in a peripheral intra-parenchymal location. A patient with a 1-cm non-specific nodule in the left lung on a computed tomography scan underwent wedge resection. Microscopically, mesenchymal elements consisting of fat and cartilage tissue were observed. Mucous glands were present around these mesenchymal elements. No cellular atypia or mitosis was observed. This allowed for complete treatment without the need for a segmentectomy.

Role of orthopedia homebox protein in subclassification of pulmonary carcinoid tumors: Retrospective analysis of 110 cases.

Background: Orthopedia homeobox protein (OTP), highlighted as a sensitive and specific marker for pulmonary carcinoids, may provide a more objective criterion for subclassification. Materials and Methods: A total of 110 patients who underwent surgery for pulmonary carcinoids (2009-2019) were included. Gender, age, application complaint, tumor diameter and location, typical and atypical tumor type, lymph node involvement, stage, recurrence, and survival data were evaluated retrospectively with OTP nuclear staining. Results: The sensitivity of OTP was 66.4%. OTP in subclassifying pulmonary carcinoids was not significant. There was no significant relationship between OTP and lymph node involvement, recurrence, and survival. Conclusion: OTP does not provide significant results in the subclassification of typical and atypical carcinoid tumors and the evaluation of recurrence and survival of carcinoid tumor cases.

High grade tumor budding is associated with poor survival in pathologic stage I lung adenocarcinoma.

AIM: Tumor budding is a significant prognostic parameter that has been related to aggressive behavior in early-stage tumors of various origins. The aim of this study was to evaluate the clinicopathological significance of tumor budding in pathologic stage (pStage) I lung adenocarcinomas. METHODS: This study comprised 107 patients who underwent curative resection for pStage I lung adenocarcinomas at our hospital between December 2010 and January 2016. We examined tumor budding on routine hematoxylin and eosin (H&E) slides from resected specimens. Tumors were categorized into two groups based on the degree of tumor budding: low grade (grade 0-1) and high grade (grade 2-3). We evaluated the relationship between tumor budding and overall survival (OS), disease-free survival (DFS) and clinicopathological parameters. RESULTS: There is a significant difference (p = 0.002) between the 5-year DFS rates of the high-grade and the low-grade tumor budding group, which were 70 % and 90 %, respectively. High-grade tumor budding positive patients from the same pathological stage (p < 0.001; HR = 2.93 [1.51-5.68]) and clinical stage (p = 0.002) had poorer cumulative survival rates than low grade tumor budding positive patients. High grade tumor budding was positively associated with spread through air spaces (STAS) (p < 0 0.001), lymphovascular invasion (LVI) (p < 0.001), tumor necrosis (p < 0.001), high SUVmax value (SUVmax>3.0) (p < 0.001), and tumor size >20 mm (p = 0.024). High-grade tumor budding was significant prognostic factor of OS (p < 0.006) and DFS (p < 0.001) on univariate Cox regression hazard model analysis. However, it did not show significance in the multivariate analysis (p > 0.05). CONCLUSIONS: High-grade tumor budding is an independent prognostic factor and associated with adverse clinicopathological features and poor survival rates. We proposed that high-grade tumor budding should be recognized as a new prognostic parameter and will be beneficial in predicting the clinical course in pStage I lung adenocarcinomas.

Does cryptogenic organizing pneumonia change seasonal?

BACKGROUND AND AIM: Meteorological factors affect the respiratory system, and the most important factor is the change in ambient temperature and humidity. We aimed to investigate the seasonal characteristics of patients diagnosed with cryptogenic organizing pneumonia. METHODS: The study included 84 cryptogenic organizing pneumonia, 55 chronic obstructive pulmonary disease, and 42 asthma patients. To determine the characteristics of the disease according to the seasons, the number of attacks and admissions was grouped according to the seasonal characteristics and analyzed for three groups. RESULTS: Among cryptogenic organizing pneumonia and chronic obstructive pulmonary disease patients, males significantly predominated (p<0.001). The hospitalization rate was highest in chronic obstructive pulmonary disease patients but similar to cryptogenic organizing pneumonia and asthma patients (p<0.001). The highest admission rate in cryptogenic organizing pneumonia patients was observed in spring (39.3% in spring, 26.2% in fall, 22.6% in winter, and 11.9% in summer). In winter, cryptogenic organizing pneumonia patients were admitted less frequently than chronic obstructive pulmonary disease and asthma patients. The neutrophil-to-lymphocyte ratio was higher in cryptogenic organizing pneumonia patients than in asthma patients and similar to chronic obstructive pulmonary disease patients. CONCLUSION: As a result of our study, the high rate of diagnosis and admission in the spring in cryptogenic organizing pneumonia suggested that the effect of allergens on the formation of cryptogenic organizing pneumonia should be investigated. In contrast, it should be kept in mind that cryptogenic organizing pneumonia may develop as a prolonged finding of involvement that may occur in the lung parenchyma due to lung infections and/or cold weather triggering during the winter months. In this regard, further studies can be conducted in which allergens and/or the history of infection in patients and meteorological variables are also evaluated.

Importance of Histopathological Grading for Treatment Selection in Malignant Mesothelioma.

BACKGROUND: Complexities in TNM staging in epithelioid malignant pleural mesothelioma (MPM) may lead to errors in treatment selection, leading to major surgical interventions in patients with low survival expectations. METHODS: Sixty-nine stage I epithelioid MPM patients, including 27 patients treated with pleurectomy/decortication (P/D) and multimodal therapy (MMT) (the P/D [MMT] group), and 42 patients treated with chemotherapy or chemoradiotherapy (the CRT group), were included in the study. After an initial evaluation of overall survival, all patients were grouped in terms of histopathological parameters and treatment types, and then, a secondary survival evaluation was performed for the groups. RESULTS: Forty-one patients were male, the mean age was 61.8 years. The median survival time was 26 months in the P/D (MMT) group, and 19.6 months in the CRT group, but the difference was not statistically significant. After grouping according to pathological criteria, a median survival time of 32.4 ± 2.9 months in the P/D (MMT) group and 21.9 ± 3.2 months in the CRT group was obtained among patients with histopathological low-grade tumors. Among patients with high-grade tumors, the median survival time was 18.3 ± 2.6 months in the P/D (MMT) group and 17 ± 4.4 months in the CRT group. Among patients with low-grade tumors, the P/D (MMT) group had longer survival. Median survival times were similar among patients with high-grade tumors. CONCLUSION: In epithelioid MPM, histopathological grading by video-assisted thoracic surgery pleural biopsy can prove accurate in selecting patients for P/D and MMT.

Does cryptogenic organizing pneumonia change seasonal?

SUMMARY BACKGROUND AND AIM: Meteorological factors affect the respiratory system, and the most important factor is the change in ambient temperature and humidity. We aimed to investigate the seasonal characteristics of patients diagnosed with cryptogenic organizing pneumonia. METHODS: The study included 84 cryptogenic organizing pneumonia, 55 chronic obstructive pulmonary disease, and 42 asthma patients. To determine the characteristics of the disease according to the seasons, the number of attacks and admissions was grouped according to the seasonal characteristics and analyzed for three groups. RESULTS: Among cryptogenic organizing pneumonia and chronic obstructive pulmonary disease patients, males significantly predominated (p<0.001). The hospitalization rate was highest in chronic obstructive pulmonary disease patients but similar to cryptogenic organizing pneumonia and asthma patients (p<0.001). The highest admission rate in cryptogenic organizing pneumonia patients was observed in spring (39.3% in spring, 26.2% in fall, 22.6% in winter, and 11.9% in summer). In winter, cryptogenic organizing pneumonia patients were admitted less frequently than chronic obstructive pulmonary disease and asthma patients. The neutrophil-to-lymphocyte ratio was higher in cryptogenic organizing pneumonia patients than in asthma patients and similar to chronic obstructive pulmonary disease patients. CONCLUSION: As a result of our study, the high rate of diagnosis and admission in the spring in cryptogenic organizing pneumonia suggested that the effect of allergens on the formation of cryptogenic organizing pneumonia should be investigated. In contrast, it should be kept in mind that cryptogenic organizing pneumonia may develop as a prolonged finding of involvement that may occur in the lung parenchyma due to lung infections and/or cold weather triggering during the winter months. In this regard, further studies can be conducted in which allergens and/or the history of infection in patients and meteorological variables are also evaluated.

Could PD-L1 positivity be associated with venous thrombosis in patients with non-small cell lung cancer?

The risk of venous thromboembolism (VTE) is increased in non-small cell lung cancer (NSCLC), and defining at-risk patients is important. Thus, we aimed to assess the association between programmed cell death ligand 1 (PD-L1) expression and VTE [pulmonary embolism (PE), deep venous thrombosis (DVT)] in NSCLC. In this retrospective, observational multicentre study, 369 patients with NSCLC who had PD-L1 immunohistochemistry based on biopsies taken between January 2017 and December 2019, were divided as PD-L1-positive (n = 181) and -negative (n = 188) groups, and low-positive (n = 99) and high-positive (n = 82) PD-L1 groups. Among all population, 12.5% of them developed a VTE during a median follow-up of 474 days. The rates of DVT, PE, and PE + DVT were 5.7%, 6% and 0.8%, respectively. VTE (15.5% vs. 9.5%) and DVT (3.8% vs. 7.4%) were similar between two groups, while PE was significantly higher in PD­L1-positive group than those in PD-L1-negative group (11.1% vs 1%, p < 0.001). There were no significant differences between low- and high-positive groups in terms of VTE (14.1% vs. 17%), PE (12.1% vs. 9.8%), and DVT (2% vs. 6.1%). In the multivariate analysis, multiple metastases (Hazard ratio [HR] 4.02; 95% confidence interval [Cl] 1.18-13.63; p = 0.07) and PD-L1 positivity was associated with an increased PE risk (HR 8.39; 95% Cl 2.07-34.07; p = 0.003). In conclusion, PD-L1 positivity may be of important role in predicting the increased risk of PE in patients with NSCLC and thereby may be used to define patients likely to benefit from thromboprophylaxis.

Single versus multiple video-assisted thoracocopic lung biopsy for suspected interstitial lung disease: a perspective on diagnostic efficacy and length of hospital stay.

Background: Nearly one-third of the patients with interstitial lung disease (ILD) require surgical biopsy for a definite diagnosis. Video-assisted thoracoscopic surgical (VATS) biopsy has replaced open lung biopsy, but the number of biopsy required to achieve an accurate diagnose is controversial. Objectives: Our study aims to show that a well-planned single VATS biopsy is as effective as multiple biopsies for the accurate diagnosis of ILD by reduced days of hospital stay. Methods: We included 111 patients with suspected ILD who underwent VATS biopsy in our study. Patients were separated into three groups according to the number of biopsies obtained. The differences between groups for diagnostic yield, mean time for chest tube removal, perioperative complications, and approximate volume per biopsy were analyzed statistically. Results: Eighteen single, 74 double, and 19 triple biopsies were made. Mean times of chest tube removal and hospital stay for single, double, and triple biopsy were 3.5, 4.8, and 6.1 days respectively. The number of biopsy and length of hospital stay was strongly related (p = 0.02), but there was no difference for diagnostic yield between single and multiple biopsy groups (p > 0.05). There was no intraoperative complication or perioperative mortality. In postoperative period, eight patients with multiple biopsies had prolonged air leak. Conclusion: Although classical knowledge suggests multiple biopsies from different locations of the lung are essential, recent reports have shown that the site and the number of biopsy are not as effective as previously thought in achieving the diagnosis for ILD. Our results show that a "single" biopsy, decided with multidisciplinary evaluation, is an effective and safe diagnostic tool, with lesser days of hospital stay. Main novel aspects: 1. The classical knowledge that multiple biopsies should be taken from different regions of the lung in the diagnosis of interstitial lung diseases has changed over time.2. Diagnostic concordance between multiple biopsy specimens is above 85%.3. A "single" biopsy, decided with multidisciplinary evaluation, is an effective and safe diagnostic tool with lower days of hospital stay.

An Unusual Diagnosis in a Single-Lung Transplant Recipient: Secondary Amyloidosis.

Silicosis, a progressive, fibrotic occupational lung disease with no known treatment, is an uncommon indication for lung transplant. There is a paucity of research on patients with silicosis who have received lung transplants. The long-term consequences of the native lung in patients with severe chronic silicosis who have had a single-lung transplant are also of interest. We present a case of amyloidosis in a patient who underwent a single-lung transplant for silicosis.

Small cell lung cancer stem cells display mesenchymal properties and exploit immune checkpoint pathways in activated cytotoxic T lymphocytes.

Small cell lung cancer (SCLC) is an aggressive tumor type with early dissemination and distant metastasis capacity. Even though optimal chemotherapy responses are observed initially in many patients, therapy resistance is almost inevitable. Accordingly, SCLC has been regarded as an archetype for cancer stem cell (CSC) dynamics. To determine the immune-modulatory influence of CSC in SCLC, this study focused on the characterization of CD44+CD90+ CSC-like subpopulations in SCLC. These cells displayed mesenchymal properties, differentiated into different lineages and further contributed to CD8+ cytotoxic T lymphocytes (CTL) responses. The interaction between CD44+CD90+ CSC-like cells and T cells led to the upregulation of checkpoint molecules PD-1, CTLA-4, TIM-3, and LAG3. In the patient-derived lymph nodes, CD44+ SCLC metastases were also observed with T cells expressing PD-1, TIM-3, or LAG3. Proliferation and IFN-γ expression capacity of TIM-3 and LAG3 co-expressing CTLs are adversely affected over long-time co-culture with CD44+CD90+ CSC-like cells. Moreover, especially through IFN-γ secreted by the T cells, the CSC-like SCLC cells highly expressed PD-L1 and PD-L2. Upon a second encounter with immune-experienced, IFN-γ-stimulated CSC-like SCLC cells, both cytotoxic and proliferation capacities of T cells were hampered. In conclusion, our data provide evidence for the superior potential of the SCLC cells with stem-like and mesenchymal properties to gain immune regulatory capacities and cope with cytotoxic T cell responses. With their high metastatic and immune-modulatory assets, the CSC subpopulation in SCLC may serve as a preferential target for checkpoint blockade immunotherapy .

Rapidly Progressive Pulmonary Kaposi Sarcoma After Bilateral Sequential Lung Transplant: A Case Report.

Skin cancers are among the rarely seen complications after solid-organ transplant. Kaposi sarcoma invasion to an allograft is an uncommon condition. In this study, we present a case of Kaposi sarcoma in a 58-year-old patient diagnosed at 8 months after bilateral sequential lung transplant due to chronic obstructive pulmonary disease. Kaposi sarcoma showed rapid progression despite immunosuppressive drug modification, resulting in lung involvement and respiratory failure. Rapid and complete improvement was achieved with rapid diagnosis and aggressive treatment that included combined chemotherapy after surgery. The patient presented with no complications from Kaposi sarcoma at month 26 after transplant.

Pulmonary vascular alterations in explanted lung after transplantation.

Widespread pulmonary destruction and fibrosis can be seen in end-stage pulmonary diseases. This situation causes vascular remodeling of the pulmonary circulation and pulmonary hypertension. Lung transplantation is an alternative treatment for end-stage pulmonary diseases. The purpose of this study is to research pathological vascular alterations retrospectively in explanted lungs with or without pulmonary hypertension. 57 explanted lungs were evaluated for occlusive intimal fibroelastosis, smooth muscle proliferation, medial hypertrophy, intimal cellular or fibrous thickening, hemosiderosis, plexiform lesion, angiomatoid lesion, arteriosclerosis, venopathy, capillary duplication and arteriovenous malformation. Both systolic and mean pulmonary artery pressures were defined. The relationship between vascular patterns and pulmonary hypertension was investigated. Pathological vascular alterations in explanted lungs with or without pulmonary hyper- tension included medial hypertrophy (80.71%), intimal cellular or fibrous thickening (80.7%), arteriosclerosis (77.19%), smooth muscle proliferation (55.3%) and arteriovenous malformation (50.3%). Hemosiderosis (12.5%), plexiform lesion (14%) and venopathy (21%) were less frequent pathological vascular alterations. Capillary duplication was common in secondary pulmonary hypertension and was statistically meaningful. Although medial hypertrophy and intimal thickness were seen in pulmonary hypertension, they can also be observed in end-stage pulmonary diseases without pulmonary hypertension. Interstitial capillary duplication was an important histopathological finding in end-stage lung diseases with pulmonary arterial hypertension.

Diffuse Panbronchiolitis After Lung Transplantation: First Case in the Literature.

BACKGROUND: Diffuse panbronchiolitis is a chronic airway disease characterized by diffuse inflammation of respiratory bronchioles and peribronchial tissue. We present a case of diffuse panbronchiolitis developed after lung transplantation, which to our knowledge has not been previously described in the literature. CASE REPORT: A 52-year-old white woman was admitted with reports of weakness, shortness of breath, and productive cough 6 months after bilateral sequential lung transplantation. Thorax computed tomography revealed the appearance of a budding branch pattern in the lower lobes of both lungs. Repeated transbronchial lung biopsies were not diagnostic. A lower lobe wedge biopsy with thoracotomy was performed in the patient, whose respiratory function gradually deteriorated. Dense lymphocyte infiltration in the respiratory bronchiole wall and foamy macrophage groups in the adjacent interstitial area were detected in the histopathologic sections. The dramatic response was achieved with pulse steroid therapy in a short time. Rapidly worsening clinical course and response to the pulse steroid therapy suggested acute cellular rejection. CONCLUSIONS: Acute cellular rejection is expected within the first year in lung transplant recipients. Diffuse panbronchiolitis may be a kind of clinical presentation in lung recipients and should be considered in patients who develop severe graft function loss in a short time.

Contribution of 18F-FDG PET/CT in the Differential Diagnosis of Pulmonary Hamartomas and Pulmonary Carcinoids

Objectives: This study aimed to evaluate 18fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) findings in the differential diagnosis of pulmonary carcinoids and pulmonary hamartomas. Methods: 18F-FDG PET/CT findings of 34 patients with pulmonary carcinoids (12 atypical, 22 typical) and 32 patients with pulmonary hamartomas were retrospectively evaluated. Both mean diameter and mean maximum standardized uptake value (SUVmax) of hamartomas and carcinoids were compared by Mann-Whitney U and Kruskall-Wallis H tests. Results: The mean longest diameter of atypical carcinoids (3.5±1.7 cm) was higher than that of hamartomas (2.1±1 cm) (p=0.038). No significant difference was found between the mean diameter of typical carcinoids and mean diameter of hamartomas (p=0.128). The mean SUVmax of atypical carcinoids (5.97±3.7) and typical carcinoids (4.22±1.7) were higher than those of hamartomas (1.65±0.9) (p=0.002 and p=0.003, respectively). There were collapse/consolidation in 55.8%, bronchiectasis or mucoid impaction in 47%, and air trapping in 14.7% in the peripheral parenchyma of the 34 carcinoids. Collapse/consolidation was detected in a patient with endobronchial hamartoma, and other finding was not found in the parenchyma around hamartomas. Conclusion: The 18F-FDG uptake of pulmonary carcinoids can vary from minimal to intense. 18F-FDG uptake can be seen in pulmonary hamartomas. However, the mean SUVmax of atypical carcinoids and typical carcinoids were higher compared to hamartomas. Pulmonary carcinoid must be suspected in cases with accompanying bronchial obstruction findings in the periphery of the mass.

COVID-19 in a Lung Transplant Patient: Rapid Progressive Chronic Lung Allograft Dysfunction.

The pandemic of SARS-CoV-2, known as COVID-19, has continued to show its effect all over the world. The clinical course of the disease in solid-organ transplant recipients is a matter of concern. Lung transplant recipients also demonstrate special features because the graft encounters the COVID-19 pathogen directly as a result of inhalation, and the lungs are the most important organs affected by the disease. We shared the development process of acute rejection followed by rapid progression of chronic lung allograft dysfunction after COVID-19 in a recipient who was followed-up in the fifth year after lung transplant.

Is 18F-FDG PET/CT capable of differential diagnosis from tuberculous pleurisy from malignant mesothelioma?

AIM: 18F-Fluorodeoxyglucose (FDG) PET/computerized tomography (CT) is a valuable method in the diagnosis of malignant pleural mesothelioma (MPM). But, some infections, particularly tuberculosis, are known to mimic cancer. We aimed to compare the FDG PET/CT findings of tuberculosis pleurisy (TP) and malignant mesothelioma and evaluate its role of differential diagnosis. MATERIAL AND METHOD: We retrospectively reviewed the data from 85 patients (45 patients with MPM and 40 patients with TP) who underwent FDG PET/CT. All images were reevaluated and pleural thickening, maximum standardized uptake values (SUVmax), lymphatic uptake and accompanying parenchymal findings were noted. RESULTS: There was no significant difference in age and sex between the two groups. Pleural thickening was more prominent in the MPM group. Mean pleural thickness was 21.4 ± 18.6 mm in the MPM group and 6.8 ± 3.5 mm in the TP group (P = 0.0). Besides pleural pathology, lymph nodes involvement in the thoracic (P = 0.0) and extrathoracic area (P = 0.34) and parenchymal findings were prominent in the TP group (P = 0.0). However, there was no significant difference in pleural SUVmax values between the two groups (P = 0.61). CONCLUSION: Intense pleural FDG uptake can be observed in TP like malignant mesothelioma. For the evaluation of the pleural pathologies in the tuberculosis endemic countries, it should be considered that FDG PET/CT may have false-positive results. Evaluation of increased pleural FDG uptake together with the detected parenchymal findings and lymphatic involvement may help us to make more accurate interpretation of the diagnosis.