[Chinese expert consensus on the pathological diagnosis of interstitial lung disease with transbronchial lung cryobiopsy specimens].

Transbronchial lung cryobiopsy (TBLC) is an applicable technique that can provide a histologic diagnosis of interstitial lung disease(ILD). The general sample size of TBLC is much smaller than that of surgical lung biopsy (SLB), which raises more concerns about the procedure's diagnostic accuracy. A guiding consensus and guidelines on the pathological procedure of ILD with TBLC are required to better guide pathologists in diagnostic practice. The Respiratory Pathology Working Group of the Respiratory Physicians Branch of the Chinese Medical Doctor Association and the Thoracic Diseases Group of the Pathological Branch of the Chinese Medical Association, jointly organized by experts, have worked together to discuss and formulated the consensus. The consensus is based on literature review, clinical practice, collection of clinical issues, and discussion during a series of meetings. Experts approved the final proposed consensus with more than 70% of votes in favor (Delphi). The consensus summarized the delivery requirements, quality evaluation and artificial phenomena of TBLC specimens. It also proposed the diagnostic principles and procedures, types of ILD corresponding to major pathological changes, and major corresponding differential diagnoses of TBLC specimens. Finally, the consensus formed 14 recommendations for clinical diagnosis and multidisciplinary discussion. We suggest that the TBLC clinical manipulators should observe and measure the size of the specimen in time. The specimen size should be greater than 5 mm in diameter, and multiple pieces(3 to 5 pieces)are recommended. Pathologists should record the number of blocks of tissue submitted for examination and the volume, color, and texture of each specimen. Evaluation of the proportion of alveolar parenchyma/airway components under the microscope, analysis of the type and distribution of lesions will facilitate making diagnostic suggestions. The size of TBLC specimens is significantly smaller than SLB and may not show sufficient features of ILD or secondary changes. It is more necessary to combine the evaluation of clinical changes and lesion distribution assessed by HRCT for a comprehensive diagnosis. Common microscopic artefacts of TBLC specimen are mass of red blood cells, proteinaceous fluid and fibrin exudation. In the absence of hemosiderin cells or clinical signs of hemoptysis symptoms, the diagnosis of pulmonary hemorrhagic disease should be considered with caution. TBLC is not a suggested diagnosis when the pathological changes are mainly located in the pleural or subpleural lung tissues, ., pleuroparenchymal fibroelastosis. The principle of pathological diagnosis of ILD in TBLC is consistent with SLB, with a description of the main pathological morphological change and a tendentious pathological diagnosis; if the lesion is not fully shown, only a pathological description is given. A well-sampled TBLC specimen may show patchy fibrosis and fibroblast foci in UIP, supporting a pathological diagnosis of a probable UIP pattern. TBLC may not display sufficient features of the distribution of subpleural and peripheral lung lesions in UIP, as well as secondary lesions. TBLC specimens show diffuse inflammation and fibrosis with well-preserved lung tissue structure, which may support a pathological diagnosis of NSIP; if the distribution of lesions and lung tissue structure are difficult to evaluate, it is recommended that a pathological diagnosis of fibrotic ILD or cellular ILD be made. TBLC specimens may show pathological features of NSIP accompanied by organization, but it is difficult to accurately evaluate the proportion of organization area. In this scenario, a descriptive diagnosis of NSIP accompanied by organization is suggested. It is recommended to diagnose organizing pneumonia if only distal airway organization is present in TBLC; in addition to organization, if pathological histology is accompanied by obvious interstitial fibrosis and lung tissue remodelling, granuloma formation, obvious neutrophil infiltration or accompanied with abscess formation, obvious eosinophil infiltration, tissue necrosis, hyaline membrane formation or vasculitis, secondary OP should be considered. It is recommended to diagnose acute fibrinous and organizing pneumonia (AFOP) if lesions on TBLC show features of organizing pneumonia and fibrin balls. A diagnosis of smoking-related ILD (RB-ILD or DIP) is suggested when a good sampling of TBLC shows a significant accumulation of histocytes or smoker's macrophages in the alveolar spaces, and without specific changes sufficient for other diagnoses. If the lesions are confined to the lumen of respiratory bronchioles and the immediate peribronchiolar airspaces, RB-ILD is supported; if the distribution is diffuse, DIP should be considered. If it is difficult to determine the distribution of the lesions, it is necessary to integrate clinical and chest CT imaging findings to differentiate RB-ILD from DIP. A well-sampled TBLC specimen can display the pathological features of DAD and then also support such a pathological diagnosis. Lymphoid interstitial pneumonia (LIP) should show diffuse lymphocyte infiltration and lymphoid follicle formation in the lung interstitium in TBLC specimens. It is recommended that chest CT imaging be combined to determine whether the lesion is diffuse to differentiate from other lymphoproliferative diseases.