Lung cancer biomarker testing : perspective from Europe

A questionnaire on biomarker testing previously used in central European countries was extended and distributed in Western and Central European countries to the pathologists participating at the Pulmonary Pathology Society meeting 26-28 June 2019 in Dubrovnik, Croatia. Each country was represented by one responder. For recent biomarkers the availability and reimbursement of diagnoses of molecular alterations in non-small cell lung carcinoma varies widely between different, also western European, countries. Reimbursement of such assessments varies widely between unavailability and payments by the health care system or even pharmaceutical companies. The support for testing from alternative sources, such as the pharmaceutical industry, is no doubt partly compensating for the lack of public health system support, but it is not a viable or long-term solution. Ideally, a structured access to testing and reimbursement should be the aim in order to provide patients with appropriate therapeutic options. As biomarker enabled therapies deliver a 50% better probability of outcome success, improved and unbiased reimbursement remains a major challenge for the future.Peer reviewe

Lung cancer in older patients with granulomatosis with polyangiitis: a report of three cases

Abstract Background Granulomatosis with polyangiitis (GPA) is characterized by necrotizing granulomatous inflammation with necrotizing vasculitis predominantly affecting small to medium vessels. The survival rates have drastically improved; however, GPA can be lethal, with older patients having a worse prognosis and higher mortality than younger patients. Moreover, the incidence of various cancers has been reported to increase in patients with GPA. We aimed to discuss possible associations between GPA and lung cancer and emphasize the associated diagnostic challenges. Case presentation We encountered three older patients with chronic GPA who developed lung cancer during long-term follow-up. Two of the patients had a smoking history, with one having silicosis and the other having chronic obstructive pulmonary disease. Furthermore, all of them had radiation exposure from repeated radiography/computed tomography. All the patients had confirmed GPA, and vasculitis relapse was first suspected when new lung lesions were noted during follow-up. However, they had no new clinical symptoms, and serum ANCA titer increased only in one patient. All the patients received standard immunosuppressive treatment but eventually died. Conclusions Lung cancer is uncommon in patients with GPA; however, the similarity between the imaging findings of lung cancer and GPA may pose a diagnostic challenge. Clinicians should be particularly vigilant when treating older patients with an increased risk of cancer, as they are often asymptomatic or have poorly apparent clinical features

Mediastinal lymphangioma in an adult with a tracheal bronchus

Introduction. Lymphangiomas, also known as cystic hygromas or cystic lymphangiomas, are cystic abnormalities of the lymph vessels and they are rare benign tumors. Tracheal bronchus (Bronchus suis or “pig bronchus”) is a very rare congenital anomaly. The aim of this work is to present а very rare case of а lymphangioma with tracheal bronchus. Case outline. The article presents the rare case of a 35-year-old otherwise healthy man, who was admitted to our thoracic surgery department with a mediastinal tumor. On performing bronchoscopy a tracheal bronchus was found. A thoracic CT scan revealed a well-circumscribed mass in the superior and anterior mediastinum measuring 37 x 39 x 59 mm. First a Carlens mediastinoscopy, and then a right parasternal Chamberlain mediastinotomy were performed. The final pathological diagnosis of lymphangioma was made. In this case, surgery was not performed because the patient was asymptomatic and the tumor did not grow larger during follow-up. Conclusion. The lymphangioma of the mediastinum in an adult is a rare and benign condition with a good prognosis, but it should be considered in a differential diagnosis of mediastinal tumors. We recommend only a minimally invasive diagnostic approach (parasternal mediastinotomy) when the patient is asymptomatic

Endobronchial ultrasound–guided transbronchial needle aspiration in the staging of lung cancer patients

Objective: Mediastinoscopy as diagnostic procedure for evaluation of mediastinum in patients with non-small-cell lung cancer has long been considered the reference standard. However, less invasive method has occurred. Endobronchial ultrasound–guided transbronchial needle aspiration came into widespread use and has resulted in controversy as to whether it is a good replacement for mediastinoscopy. We chose to demonstrate the usefulness of endobronchial ultrasound–guided transbronchial needle aspiration in evaluating the mediastinum in patients with non-small-cell lung cancer. Material and methods: Over a 48-month period, 1841 patients underwent endobronchial ultrasound–guided transbronchial needle aspiration at our healthcare centre. In all patients, 2964 biopsies from the lymph node group N2 and 783 from group N1 were taken. The mean short axis of the lymph nodes biopsied was 2.0 (range: 0.6–2.6). The mean number of lymph node stations biopsied per patient was 2.6. Patients with a negative result of endobronchial ultrasound–guided transbronchial needle aspiration underwent mediastinoscopy. All patients with a negative result in endobronchial ultrasound–guided transbronchial needle aspiration and mediastinoscopy underwent surgical resection with lymph node sampling. Results: The metastases to lymph nodes N2/N3 and N1 were found in 1111 (60.3%) and 199 (9.3%), respectively. Mediastinoscopy was performed in 730 patients with a positive result in 83 (11.4%) patients. In the group of operated patients, metastatic N1 disease was found in 264 (14.1%). In the group of the operated patients, mediastinal involvement of disease (N2) was found in 30 patients (4.5%). The sensitivity, negative predictive value and diagnostic accuracy for hilar lymph node staging for endobronchial ultrasound–guided transbronchial needle aspiration were 57%, 96% and 96%, respectively. The sensitivity, negative predictive value and diagnostic accuracy per patient for mediastinal lymph node staging for endobronchial ultrasound–guided transbronchial needle aspiration and mediastinoscopy were 91%, 85%, 93% and 73%, 95.5%, 97%, respectively. The specificity and positive predictive value of both tests were 100%. Conclusion: The clinical usefulness of endobronchial ultrasound–guided transbronchial needle aspiration is undeniable according to diagnostic performance data. Endobronchial ultrasound–guided transbronchial needle aspiration should be considered complementary to mediastinoscopy in the evaluation of patients with radiographically abnormal mediastinum

Targeted Next-Generation Sequencing of Thymic Epithelial Tumours Revealed Pathogenic Variants in KIT, ERBB2, KRAS, and TP53 in 30% of Thymic Carcinomas

A better understanding of the molecular pathogenesis of thymic epithelial tumours (TETs) could revolutionise their treatment. We evaluated thymomas and thymic carcinomas by next-generation sequencing (NGS) of somatic or germline single nucleotide variants (SNVs) in genes commonly mutated in solid tumours. In total, 19 thymomas and 34 thymic carcinomas were analysed for nonsynonymous SNVs in 15 genes by targeted NGS (reference genome: hg19/GRCh37). Ten SNVs in TP53 (G154V, R158P, L194H, R267fs, R273C, R306 *, Q317 *), ERBB2 (V773M), KIT (L576P), and KRAS (Q61L) considered somatic and pathogenic/likely pathogenic were detected in 10 of 34 (29.4%) thymic carcinomas. No somatic SNVs confirmed as pathogenic/likely pathogenic were found in thymomas. Rare SNVs of uncertain or unknown functional and clinical significance, to our knowledge not reported previously in TETs, were found in ERBB2 (S703R), KIT (I690V), and FOXL2 (P157S) in 3 of 19 (16%) thymomas. The most frequent germline SNVs were TP53 P72R (94% TETs), ERBB2 I655V (40% TETs), and KIT M541L (9% TETs). No significant difference in median disease-free survival (DFS) was found between thymic carcinoma patients with and without pathogenic SNVs (p = 0.190); however, a trend toward a longer DFS was observed in the latter (16.0 vs. 30.0 months, respectively). In summary, NGS analysis of TETs revealed several SNVs in genes related to the p53, AKT, MAPK, and K-Ras signalling pathways. Thymic carcinomas showed greater genetic dysregulation than thymomas. The germline and rare SNVs of uncertain clinical significance reported in this study add to the number of known genetic alterations in TETs, thus extending our molecular understanding of these neoplasms. Druggable KIT alterations in thymic carcinomas have potential as therapeutic targets

Pulmonary Tuberculosis Mimicking Lung Cancer Progression after 10 Years of Cancer Remission

Differentiation between pulmonary tuberculosis and lung cancer is often challenging for clinicians, especially that both conditions can coexist. This is due to the fact that the clinical and radiological symptoms of both diseases can be similar. Our Case Report presents a patient who was treated for advanced lung cancer 10 years earlier and currently has been hospitalized again because of a strong clinical and radiological suspicion of the cancer progression, but whose final diagnosis was tuberculosis

Lung cancer biomarker testing : perspective from Europe

A questionnaire on biomarker testing previously used in central European countries was extended and distributed in Western and Central European countries to the pathologists participating at the Pulmonary Pathology Society meeting 26-28 June 2019 in Dubrovnik, Croatia. Each country was represented by one responder. For recent biomarkers the availability and reimbursement of diagnoses of molecular alterations in non-small cell lung carcinoma varies widely between different, also western European, countries. Reimbursement of such assessments varies widely between unavailability and payments by the health care system or even pharmaceutical companies. The support for testing from alternative sources, such as the pharmaceutical industry, is no doubt partly compensating for the lack of public health system support, but it is not a viable or long-term solution. Ideally, a structured access to testing and reimbursement should be the aim in order to provide patients with appropriate therapeutic options. As biomarker enabled therapies deliver a 50% better probability of outcome success, improved and unbiased reimbursement remains a major challenge for the future

Dataset for reporting of thymic epithelial tumours:recommendations from the International Collaboration on Cancer Reporting (ICCR)

Aims: Thymic epithelial tumours (TET), including thymomas and thymic carcinomas and thymic neuroendocrine neoplasms, are malignant neoplasms that can be associated with morbidity and mortality. Recently, an updated version of the World Health Organization (WHO) Classification of Thoracic Tumours 5th Edition, 2021 has been released, which included various changes to the classification of these neoplasms. In addition, in 2017 the Union for International Cancer Control (UICC) / American Joint Committee on Cancer (AJCC) published the 8th Edition Staging Manual which, for the first time, includes a TNM staging that is applicable to thymomas, thymic carcinomas, and thymic neuroendocrine neoplasms. Methods and Results: To standardize reporting of resected TET and thymic neuroendocrine neoplasms the accrediting bodies updated their reporting protocols. The International Collaboration on Cancer Reporting (ICCR), which represents a collaboration between various National Associations of Pathology, updated its 2017 histopathology reporting guide on TET and thymic neuroendocrine neoplasms accordingly. This report will highlight important changes in the reporting of TET and thymic neuroendocrine neoplasms based on the 2021 WHO, emphasize the 2017 TNM staging, and also comment on the rigour and various uncertainties for the pathologist when trying to follow that staging. Conclusion: The ICCR dataset provides a comprehensive, standardized template for reporting of resected TET and thymic neuroendocrine neoplasms.</p