Retrospective Analysis Of Pathological Features And Gene Research Of Bronchiolar Adenoma

Objective:Bronchiolar adenoma(BA)is a newly reported solid lung tumor.In 2018,the diagnostic term BA was proposed based on the concept of ciliated muconodular papillary tumor(CMPT).Since the proposal of BA is very latest,comprehensive analyses on its nature,morphology,genetic changes and prognosis are scant.In recent years,the gradually accumulated understanding of the morphological and genetic characteristics of BA stimulates the increased demand for the diagnosis and differential diagnosis.Therefore,in-depth studies on clinical manifestations,pathological characteristics,immunophenotypes and genetic features of BA are necessary for the accurate diagnosis.Methods:Three cases of BA diagnosed in the Affiliated Hospital of Guizhou Medical University from January 2018 to December 2020 were recruited.Their clinical data were collected,and immunohistochemical staining and genetic testing were performed.In addition,relevant studies about BA and CMPT published before February 2021 were searched in online databases.Through data extraction and analyses,the clinical characteristics,medical history,imaging features,pathological manifestations,diagnosis and treatment,prognosis and differential diagnosis of BA and CMPT were thoroughly investigated,thus elucidating the understanding of BA,and exploring its key research issues.SPSS software was used for statistical analyses.Results:Through systematic retrospective analysis of the 255 cases reported in the literatures and 3 recruited in our hospital,it is found that the incidence of BA is slightly higher in women than that of men,and the mean age of onset was 63.7±12.4years.Most of cases were admitted because of small nodules in the lungs in CT images during physical examinations,which were mainly distributed in the lower lobes of the lung,especially the right lung.Clinical symptoms and signs of BA/CMPT are lacked,with occasional chest discomforts like coughing,chest tightness and pain.Imaging manifestations of BA/CMPT were solid,partially solid or ground-glass nodules in the surrounding lungs.The dual-layer structure composed of luminal cells and basal cells could be observed under the microscope.In particular,luminal cells were mainly composed of ciliated cell,mucous cells,club cells and/or type II alveolar cells.Immunohistochemistry staining showed positive expressions of P40,P63 and CK5/6 in basal cells,and positive expressions of TTF-1 and CK7 in luminal cells,and a part of cells were stained Napsin-A positive.Mutations in the BRAF,EGFR or KRAS genes were usually examined.These patients were usually treated with the wedge pneumonectomy of the lung or lobectomy,showing a good prognosis without metastases.Conclusions:BA/CMPT belongs to uncertain malignant potential tumors that originate from the bronchulus,manifesting as discontinuous basal cells with an unclear boundary with surrounding tissues.Mutations in BRAF,EGFR,KRAS and other drivers by next-generation sequencing indicated for further biological examinations.The pathogenesis of BA/CMPT is still inconclusive.Most patients lack obvious clinical symptoms,and they usually ask for medical treatment because of lung nodules found in physical examinations of CT imaging.The imaging and laboratory findings of BA/CMPT are not specific,and its diagnosis relies on pathological examination.It is mainly differentiated from lung adenocarcinoma,especially the presence of ciliated cells during intraoperative frozen diagnosis.So far,the wedge pneumonectomy of the lung is preferred to BA/CMPT patients.Since clinical cases of BA/CMPT are relatively few and most of them are described in case reports,the natural course and prognosis of BA/CMPT require explorations in the future.