Handling and standardization of EBUS needle aspiration in NSCLC patients: The value of the cell block, a monoinstitutional experience.

BACKGROUND: Lung cancer is the main cause of cancer-related death worldwide, and 85% of all lung tumors are non-small cell lung cancers (NSCLC). More than 60% of all lung tumors are diagnosed at an advanced stage, leading to poor prognosis. Given the growing demand for NSCLC profiling for selection of the most appropriate therapy, the acquisition of adequate tumor samples has become increasingly crucial, mostly in advanced NSCLC patients due to old age and/or comorbidities. Being a mini-invasive sampling technique, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) represents a valuable alternative to traditional transthoracic or surgical sampling in these patients, and perfoming cell block (CB) could be crucial to maximize the potential biological information. The aim of this study is to describe a monoinstitutional interprofessional experience in handling EBUS-TBNA and CB in 464 patients. METHODS: We retrospectively collected all the consecutive CBs obtained from EBUS TBNA performed between 2014 and 2021 on the lung lesions or mediastinal lymph nodes. All the CBs were handled in a standardized method. RESULTS: A total of 95.5% (448/464 samples) of adequacy for site and 92.6% (430/464) of adequacy for diagnosis were observed. Moreover, in the adenocarcinoma histotype, ALK, ROS1 and tumor proportion score (TPS) PD-L1 assessment by IHC was possible in 96% (140/146) of cases, and molecular profile was obtained in 93.8% (137/146) of cases. In the squamous cell carcinoma histotype, TPS PD-L1 assessment was possible in 81% (13/16) of cases. All four CB results obtained from carcinoma NOS were adequate for ALK, ROS1 and PD-L1 assessment and molecular profiling. All 39 metastatic samples from extra-pulmonary primary were adequate for immunohistochemical characterization and molecular profiling. Finally, reporting of the tumor sample adequacy to the clinicians took a median time of about 30 h (range: 24-80 h). CONCLUSION: Careful cytological smear management together with the handling and standardization of CB obtained from EBUS-TBNA could represent an effective method to increase the adequacy of the tumor specimen for both diagnosis and molecular profile.

Mixed Pulmonary Adenocarcinoma and Atypical Carcinoid: A Report of Two Cases of a Non-codified Entity With Biological Profile.

Pulmonary carcinoids combined with a non-neuroendocrine component have rarely been described, and this histological subtype is not included as a specific entity in the current World Health Organization classification of pulmonary neoplasms. Here, we described the molecular and histological features of two rare cases of mixed lung neoplasms, composed of atypical carcinoid and adenocarcinoma. The targeted next-generation sequencing analysis covering single nucleotide variations, copy number variations, and transcript fusions in a total of 161 cancer genes of the two different tumor components shows a similar molecular profile of shared and private gene mutations. These findings suggest their monoclonal origin from a transformed stem/progenitor tumor cell, which acquires a divergent differentiation during its development and progression and accumulates novel, specific mutations.

NRG1 and NRG2 fusions in non-small cell lung cancer (NSCLC): seven years between lights and shadows.

INTRODUCTION: Fusions in neuregulin 1 (NRG1) and neuregulin 2 (NRG2) genes are molecular features of non-small cell lung cancer (NSCLC). These rearrangements enhance ectopic expression of the NRG/ErbB receptor-ligand and induce the triggering of downstream pathways. Evidence suggests the involvement of the NRG1/ErbB3 axis deregulation in the progression and treatment resistance of NSCLC cancer (NSCLC) and that NRG1 fusions are prognostic/predictive markers for targeted therapy. AREAS COVERED: Biological and prognostic/predictive value of NRG1 and NRG2 fusions in NSCLC and their related cellular pathways are described and discussed. Publications in English language, peer-reviewed, high-quality international journals were identified on PubMed, as well as scientific official sites were used to update the international clinical trials progress. EXPERT OPINION: NRG1 and NRG2 fusions should be considered as novel markers for biological therapy targeting ErbB2/ErbB3. There is evidence for the involvement of the NRG1/ErbB3 axis deregulation in cancer stem cell phenotype, tumor progression, and resistance to NSCLC therapy. Neuregulin fusions are very complex, hence many question marks must be tackled before translating these molecular lesions into clinical practice. Biology, and aggressiveness of the NRG1 and NRG2 fusions warrant further investigations.

Neuroendocrine-Related Circulating Transcripts in Small-Cell Lung Cancers: Detection Methods and Future Perspectives.

No well-established prognostic or predictive molecular markers of small-cell lung cancer (SCLC) are currently available; therefore, all patients receive standard treatment. Adequate quantities and quality of tissue samples are frequently unavailable to perform a molecular analysis of SCLC, which appears more heterogeneous and dynamic than expected. The implementation of techniques to study circulating tumor cells could offer a suitable alternative to expand the knowledge of the molecular basis of a tumor. In this context, the advantage of SCLC circulating cells to express some specific markers to be explored in blood as circulating transcripts could offer a great opportunity in distinguishing and managing different SCLC phenotypes. Here, we present a summary of published data and new findings about the detection methods and potential application of a group of neuroendocrine related transcripts in the peripheral blood of SCLC patients. In the era of new treatments, easy and rapid detection of informative biomarkers in blood warrants further investigation, since it represents an important option to obtain essential information for disease monitoring and/or better treatment choices.

Mediastinal Nodular Lesions Synchronous to Lung Carcinoma on Frozen Section: Trap and Lesson.

Thymoma is the most frequent neoplasm arising in the anterior mediastum. It usually presents as an enlarged central mass. In the literature, multiple thymoma is described as an unusual finding; rare variants have also been described, like the signet ring-like cell variant. Evidence of co-existence of signet ring-like cells and lymphocytes in small biopsies from nodular mediastinal lesions can lead to a diagnosis of metastatic carcinoma, mostly at frozen sections. Thymoma and pulmonary carcinoma are very rarely associated neoplasms. We present a case of two mediastinal lesions discovered during pulmonary carcinoma staging. At frozen section, a diagnosis of 'epithelioid proliferation associated to lymphoid tissue' was advanced on a sample of nodular lesions and of 'carcinoma' on pulmonary biopsy. Double AB Type Thymoma with a signet ring cell-like component, synchronous to pulmonary adenocarcinoma, was the diagnosis made on formalin fixed-paraffin embedded samples. Reporting the coexistence of these two entities can help pathologists and surgeons to establish the best management of similar patients.