Identification of the most specific markers to differentiate primary pulmonary carcinoma from metastatic gastrointestinal carcinoma to the lung

Background A number of biomarkers have the potential of differentiating between primary lung tumours and secondary lung tumours from the gastrointestinal tract, however, a standardised panel for that purpose does not exist yet. We aimed to identify the smallest panel that is most sensitive and specific at differentiating between primary lung tumours and secondary lung tumours from the gastrointestinal tract. Methods A total of 170 samples were collected, including 140 primary and 30 non-primary lung tumours and staining for CK7, Napsin-A, TTF1, CK20, CDX2, and SATB2 was performed via tissue microarray. The data was then analysed using univariate regression models and a combination of multivariate regression models and Receiver Operating Characteristic (ROC) curves. Results Univariate regression models confirmed the 6 biomarkers’ ability to independently predict the primary outcome (p < 0.001). Multivariate models of 2-biomarker combinations identified 11 combinations with statistically significant odds ratios (ORs) (p < 0.05), of which TTF1/CDX2 had the highest area under the curve (AUC) (0.983, 0.960–1.000 95% CI). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 75.7, 100, 100, and 37.5% respectively. Multivariate models of 3-biomarker combinations identified 4 combinations with statistically significant ORs (p < 0.05), of which CK7/CK20/SATB2 had the highest AUC (0.965, 0.930–1.000 95% CI). The sensitivity, specificity, PPV, and NPV were 85.1, 100, 100, and 41.7% respectively. Multivariate models of 4-biomarker combinations did not identify any combinations with statistically significant ORs (p < 0.05). Conclusions The analysis identified the combination of CK7/CK20/SATB2 to be the smallest panel with the highest sensitivity (85.1%) and specificity (100%) for predicting tumour origin with an ROC AUC of 0.965 (p < 0.001; SE: 0.018, 0.930–1.000 95% CI).

Pulmonary blastoma in a pregnant woman: a case report and brief review of the literature

Background Pulmonary blastoma (PB) comprises a rare heterogeneous group of lung tumours typically containing immature epithelial and mesenchymal structures that imitate the embryonic lung tissue and extremely rarely occurs during pregnancy. Although cough and haemoptysis are the most common PB symptoms, they usually indicate other serious pregnancy-related complications. Case presentation The article presents the unusual case of a 22-year-old pregnant woman diagnosed with PB during pregnancy. Conclusions PB is characterized by poor prognosis and patients’ outcome relies on a rapid diagnosis. Surgery remains the most common and effective treatment. Due to the extreme rarity, the literature contains only single mentions of PB in pregnancy, thus its impact on the course of pregnancy and the developing fetus remains unknown.

Distinct cDC subsets co-operate in CD40 agonist response while suppressive microenvironments and lack of antigens subvert efficacy

Agonistic αCD40 therapy has shown to inhibit cancer progression, but only in a fraction of patients. Hence, understanding the cancer cell-intrinsic and microenvironmental determinants of αCD40 therapy response is crucial to identify responsive patient populations and design efficient combination treatments. Here, we showed that the therapeutic efficacy of αCD40 in responder melanoma tumours, relied on pre-existing cDC1-primed CD8+ T cells, however cDC1s were dispensable after αCD40 administration. Surprisingly, in response to αCD40 the abundance of activated cDCs, potentially derived from cDC2s increased, thereby further activating antitumour CD8+ T cells. Hence, distinct cDC subsets are required to induce αCD40 responses. By contrast, lung tumours, characterised by a high abundance of macrophages, were resistant to αCD40 therapy. Combining αCD40 therapy with macrophage depletion led to tumour growth inhibition only in the presence of strong neoantigens. Accordingly, treatment with immunogenic cell-death inducing chemotherapy sensitised non-immunogenic tumours to αCD40 therapy.

Toxicity and efficacy of stereotactic body radiotherapy for ultra-central lung tumours: a single institution real life experience

Objectives: The use of stereotactic body radiotherapy (SBRT) to treat ultra-central lung tumours remains more controversial than for peripheral and central tumours. Our objective was to assess toxicities, local control (LC) rate and survival data in patients with ultra-central lung tumours treated with SBRT. Methods: We conducted a retrospective and monocentric study about 74 patients with an ultra-central lung tumour, consecutively treated between 2012 and 2018. Ultra-central tumours were defined as tumours whose PTV (planning target volume) overlapped one of the following organs at risk (OAR): the trachea, right and left main bronchi, intermediate bronchus, lobe bronchi, oesophagus, heart. Results: Median follow-up was 25 months. Two patients (2.7%) showed Grade three toxicity. No Grade four or five toxicity was observed. 11% of patients experienced primary local relapse. Local control rate was 96.7% at 1 year and 87.6% at 2 years. Median progression free survival (PFS) was 12 months. Median overall survival (OS) was 31 months. Conclusions: SBRT for ultra-central tumours remains safe and effective as long as protecting organs at risk is treatment-planning priority. Advances in knowledge: The present study is one of the rare to describe exclusively ultra-central tumours through real-life observational case reports. Globally, literature analysis reveals a large heterogeneity in ultra-central lung tumours definition, prescribed dose, number of fractions. In our study, patients treated with SBRT for ultra-central lung tumours experienced few Grade three toxicities (2.7%) and no Grade four or five toxicities, due to the highest compliance with dose constraints to OARs. LC remained efficient.

CT Imaging of Primary Lung Tumours with CT Guided Fine Needle Aspiration Cytology Correlation among Guwahati, Assam Population

BACKGROUND The primary lung masses (tumours) are those that originate from the lung tissue. Although most primary pulmonary tumours are carcinomas, a large histological spectrum of benign and malignant tumours of the lung exists. Although chest xray is still considered to be the primary imaging modality of lungs, computed tomography (CT) not only shows the segments that are involved but also the extent of involvement. We wanted to study the sensitivity and specificity of CT in the diagnosis of primary neoplastic lesions of lung, study the CT patterns of different histological variants of bronchogenic carcinoma, and correlate CT findings with CT guided fine needle aspiration and cytology (FNAC) findings. METHODS The present descriptive cross-sectional study was conducted among 34 patients suspected clinically of having lung neoplasms, in Gauhati Medical College and Hospital, Guwahati, Assam from December 2010 to November 2011. RESULTS Considering FNAC / histopathological examination (HPE) as the gold standard, the positive predictive value and false negative value of CT scan for diagnosis of neoplastic lesions of lung were 97 % and 3 % respectively, in our study. Among our study population, mean age with lung tumours was 61 years, highest number of cases was seen in the age group of 51 - 60 years (35 %); Males and females affected were 27 (79.41 %), and 7 in number (20.59 %), respectively. CONCLUSIONS CT is more sensitive in the detection of neoplastic lesions of the lung and associated hilar / mediastinal adenopathy than chest roentgenography. CT has a high efficacy in detecting neoplastic lesions of lung, delineating its lobar and segmental anatomy, thereby helping surgical resection of lung. In this study, CT guided FNAC and cytological findings correlated well with CT diagnosis of primary neoplastic lesions of lung. KEYWORDS Primary Lung Tumour, Contrast Enhanced Computed Tomography (CECT), Fine Needle Aspiration and Cytology (FNAC)