BACKGROUND Bronchiolar adenoma(BA)and ciliated muconodular papillary tumor are rare tumors that have bilayered cell proliferation and continuous expression of p40 and CK5/6 in the basal cell layer.Diagnosis is difficu...BACKGROUND Bronchiolar adenoma(BA)and ciliated muconodular papillary tumor are rare tumors that have bilayered cell proliferation and continuous expression of p40 and CK5/6 in the basal cell layer.Diagnosis is difficult because of the limited knowledge of these tumors and their morphological similarities to malignant tumors,including invasive mucinous adenocarcinoma,especially based on the histopathology of intraoperative frozen sections.These tumors are now considered to be benign neoplasms,with malignant transformation reported in only a few cases.CASE SUMMARY A 57-year-old woman presented with a 17.0 mm×7.0 mm nodule in the lower lobe of the left lung.Hematoxylin-eosin staining and immunohistochemistry of a surgical specimen were performed.The tumor consisted of a BA area and a mucinous adenocarcinoma(MA)area.In the BA area,the tumor had a bilayered structure of luminal cells and basal cells.The basal cells were positive for CK5/6 and p40,but the MA area was negative for these biomarkers.The Ki-67 proliferation index was low(1%-2%).The patient was diagnosed with BA accompanied by MA,and had a favorable outcome.CONCLUSION The present study indicated that BA may be carcinogenic,and suggests that clinicians should be aware of its potential for malignant transformation.展开更多
BACKGROUND The clinicopathological features,immunohistochemical characteristics,and genetic mutation profile of two unusual cases of distal bronchiolar adenoma are retrospectively analyzed and the relevant literature ...BACKGROUND The clinicopathological features,immunohistochemical characteristics,and genetic mutation profile of two unusual cases of distal bronchiolar adenoma are retrospectively analyzed and the relevant literature is reviewed.CASE SUMMARY Case 1 was a 63-year-old female patient who had a mixed ground-glass nodule,with mild cells in morphology,visible cilia,and bilayer structures in focal areas.Immunohistochemical staining for P63 and cytokeratin(CK)5/6 revealed the lack of a continuous bilayer structure in most areas,and no mutations were found in epidermal growth factor receptor,anaplastic lymphoma kinase,ROS1,Kirsten rat sarcoma,PIK3CA,BRAF,human epidermal growth factor receptor-2(HER2),RET,and neuroblastoma RAS genes.Case 2 was a 58-year-old female patient who presented with a solid nodule,in which most cells were observed to be medium sized,the nuclear chromatin was pale and homogeneous,local cells had atypia,and cilia were found locally.Immunohistochemical staining for P63 and CK5/6 showed no expression of these proteins in mild cell morphology whereas the heteromorphic cells showed a bilayer structure.The same nine genes as above were analyzed,and HER2 gene mutation was identified.CONCLUSION Some unresolved questions remain to be answered to determine whether the lesion is a benign adenoma or a part of the process of malignant transformation from benign adenoma of the bronchial epithelium.Furthermore,whether lesions with atypical bilayer structures are similar to atypical hyperplastic lesions of the breast remains to be elucidated.Moreover,clarity on whether these lesions can be called atypical bronchiolar adenoma and whether they are invasive precursor lesions is needed.Future studies should examine the diagnostic significance of HER2 gene mutation as a prognostic indicator.展开更多
Objective Bronchiolar adenoma(BA)is a peripheral pulmonary neoplasm characterized by a bilayered cell structure com-posed of basal cells and luminal cells.Owing to its low incidence and limited research data,clinician...Objective Bronchiolar adenoma(BA)is a peripheral pulmonary neoplasm characterized by a bilayered cell structure com-posed of basal cells and luminal cells.Owing to its low incidence and limited research data,clinicians and pathologists still have an insufficient understanding of this disease.This study aims to characterize the morphological,immunohistochemical,and genetic features of BA and its variants,and to determine whether BA can progress to a malignancy.Methods Among these 33 cases,21 were histologically characterized by double-layered tumors with continuous basal cell layers.Six patients exhibited a partial classic bilayer,transitioning from a bilayer to a monolayer in certain lesion areas(mixed-type BAs).Six other BA-like tumors with monolayered components might represent the early stage of malignant transformation of BA.Next-generation sequencing analysis was conducted on 33 cases to elucidate the genetic spectrum.Results All the cellular components exhibited a relatively mild morphology.Immunohistochemical analysis revealed that basal cells coexpressed p40 and cytokeratin 5/6.Thyroid transcription factor 1 was expressed in the double-cell layer,which consists of ciliated columnar epithelial cells,basal cells,nonciliated columnar epithelial cells,and cuboidal epithelial cells.The pan-cancer gene panel was used to observe driver alterations in 9 of 21 classic bilayered BAs(43%),2 of 6 mixed-type BAs(33%),and 3 of 6 monolayered BA-like lesions(50%).Genetically,monolayered BA-like lesions shared some alterations with classic BAs in mutational signatures,whereas NKX2-1 mutations were enriched only in monolayered BA-like lesions.Conclusion These findings underscore the histopathological and genetic characteristics of BA and its variants,suggesting that monolayered BA-like lesions have the potential to develop into lung adenocarcinoma.In the future,more cases should be recruited to further explore the malignant transformation of this specific entity via the multidimensional spectrum.展开更多
基金Supported by the Science and Technology Plan Project of Wenzhou,China,No.Y20190117the Natural Science Foundation of Zhejiang Province,China,No.LQ21H090017。
文摘BACKGROUND Bronchiolar adenoma(BA)and ciliated muconodular papillary tumor are rare tumors that have bilayered cell proliferation and continuous expression of p40 and CK5/6 in the basal cell layer.Diagnosis is difficult because of the limited knowledge of these tumors and their morphological similarities to malignant tumors,including invasive mucinous adenocarcinoma,especially based on the histopathology of intraoperative frozen sections.These tumors are now considered to be benign neoplasms,with malignant transformation reported in only a few cases.CASE SUMMARY A 57-year-old woman presented with a 17.0 mm×7.0 mm nodule in the lower lobe of the left lung.Hematoxylin-eosin staining and immunohistochemistry of a surgical specimen were performed.The tumor consisted of a BA area and a mucinous adenocarcinoma(MA)area.In the BA area,the tumor had a bilayered structure of luminal cells and basal cells.The basal cells were positive for CK5/6 and p40,but the MA area was negative for these biomarkers.The Ki-67 proliferation index was low(1%-2%).The patient was diagnosed with BA accompanied by MA,and had a favorable outcome.CONCLUSION The present study indicated that BA may be carcinogenic,and suggests that clinicians should be aware of its potential for malignant transformation.
文摘BACKGROUND The clinicopathological features,immunohistochemical characteristics,and genetic mutation profile of two unusual cases of distal bronchiolar adenoma are retrospectively analyzed and the relevant literature is reviewed.CASE SUMMARY Case 1 was a 63-year-old female patient who had a mixed ground-glass nodule,with mild cells in morphology,visible cilia,and bilayer structures in focal areas.Immunohistochemical staining for P63 and cytokeratin(CK)5/6 revealed the lack of a continuous bilayer structure in most areas,and no mutations were found in epidermal growth factor receptor,anaplastic lymphoma kinase,ROS1,Kirsten rat sarcoma,PIK3CA,BRAF,human epidermal growth factor receptor-2(HER2),RET,and neuroblastoma RAS genes.Case 2 was a 58-year-old female patient who presented with a solid nodule,in which most cells were observed to be medium sized,the nuclear chromatin was pale and homogeneous,local cells had atypia,and cilia were found locally.Immunohistochemical staining for P63 and CK5/6 showed no expression of these proteins in mild cell morphology whereas the heteromorphic cells showed a bilayer structure.The same nine genes as above were analyzed,and HER2 gene mutation was identified.CONCLUSION Some unresolved questions remain to be answered to determine whether the lesion is a benign adenoma or a part of the process of malignant transformation from benign adenoma of the bronchial epithelium.Furthermore,whether lesions with atypical bilayer structures are similar to atypical hyperplastic lesions of the breast remains to be elucidated.Moreover,clarity on whether these lesions can be called atypical bronchiolar adenoma and whether they are invasive precursor lesions is needed.Future studies should examine the diagnostic significance of HER2 gene mutation as a prognostic indicator.
基金supported by Xi'an Jiaotong University Medical Development Fund(No.XJYG2025-SFJJ011)Natural Science Foundation of Inner Mongolia Autonomous Region(No.2023LHMS08027).
文摘Objective Bronchiolar adenoma(BA)is a peripheral pulmonary neoplasm characterized by a bilayered cell structure com-posed of basal cells and luminal cells.Owing to its low incidence and limited research data,clinicians and pathologists still have an insufficient understanding of this disease.This study aims to characterize the morphological,immunohistochemical,and genetic features of BA and its variants,and to determine whether BA can progress to a malignancy.Methods Among these 33 cases,21 were histologically characterized by double-layered tumors with continuous basal cell layers.Six patients exhibited a partial classic bilayer,transitioning from a bilayer to a monolayer in certain lesion areas(mixed-type BAs).Six other BA-like tumors with monolayered components might represent the early stage of malignant transformation of BA.Next-generation sequencing analysis was conducted on 33 cases to elucidate the genetic spectrum.Results All the cellular components exhibited a relatively mild morphology.Immunohistochemical analysis revealed that basal cells coexpressed p40 and cytokeratin 5/6.Thyroid transcription factor 1 was expressed in the double-cell layer,which consists of ciliated columnar epithelial cells,basal cells,nonciliated columnar epithelial cells,and cuboidal epithelial cells.The pan-cancer gene panel was used to observe driver alterations in 9 of 21 classic bilayered BAs(43%),2 of 6 mixed-type BAs(33%),and 3 of 6 monolayered BA-like lesions(50%).Genetically,monolayered BA-like lesions shared some alterations with classic BAs in mutational signatures,whereas NKX2-1 mutations were enriched only in monolayered BA-like lesions.Conclusion These findings underscore the histopathological and genetic characteristics of BA and its variants,suggesting that monolayered BA-like lesions have the potential to develop into lung adenocarcinoma.In the future,more cases should be recruited to further explore the malignant transformation of this specific entity via the multidimensional spectrum.