Comparison Of Clinicopathological Features Between SMARCA4-deficient Undifferentiated And Poorly Differentiated Carcinomas In The Chest

Objective:Smarca4-deficient tumors are rare and aggressive tumors,which are often misdiagnosed as poorly or undifferentiated tumors due to primitive differentiation.These tumors have distinctive morphologic,immunohistochemical and molecular genetic features.The aim of this study is to investigate the clinicopathological features,immunohistochemical features,diagnosis,differential diagnosis and significance of SMARCA4-deficient tumors of the lung and mediastinum through a series of cases.Methods: The clinical,imaging and follow-up data of 11 SMARCA4-deficient undifferentiated tumors and 16 SMARCA4-deficient poorly differentiated carcinomas diagnosed at the First Affiliated Hospital of China Medical University from 2015 to2023 were collected.The clinicopathological features and prognosis were analyzed by histological and immunohistochemical staining.Results:1.Smarca4-deficient undifferentiated tumor cells were diffusely distributed in sheets with obvious necrosis.Focal tumor cells could be rhabdoid in shape,loosely arranged,poorly adherent,round or oval in shape,with eosinophilic cytoplasm,nuclear asymmetry,loss of cell adhesion,and some were epithelioid in shape,with abundant clear or pale pink cytoplasm,vesicular nuclei,and prominent nucleoli.Mitotic figures were common,nuclear cytoplasmic ratio was high,and some showed neuroendocrine features.Poorly differentiated SMARCA4-deficient carcinoma cells were epithelioid or syncytioid,arranged in nests or nodules,with abundant clear or eosinophilic cytoplasm.Some cells showed rhabdoid or undifferentiated morphology,obvious atypia,some clear nucleoli,binucleated or multinucleated cells,vacuolated chromatin,common mitotic figures,and eosinophilic globules.There were many inflammatory cells infiltrating the interstitium,often accompanied by flake necrosis.Most of SMARCA4-deficient undifferentiated tumors were negative for CK and CK7,positive for Vimentin,negative for Claudin-4,and positive for SALL4.Smarca4-deficient poorly differentiated carcinomas were mostly positive for CK,CK7,Vimentin,Claudin-4,and SALL4.The expression of SMARCA4,TTF-1 and P63 was negative in both tumors.The average percentage of Ki67 proliferation index in SMARCA4-deficient undifferentiated tumors was 64.10%,and that in SMARCA4-deficient poorly differentiated carcinomas was 44.06%.There was a significant difference in Ki67 proliferation index between SMARCA4-deficient undifferentiated and poorly differentiated carcinomas(P<0.05).The median survival time of SMARCA4-deficient undifferentiated tumors was 3 months,and the response to radiotherapy and chemotherapy was not significant.The half-year survival rate of SMARCA4-deficient undifferentiated tumors was 30.3%,and that of SMARCA4-deficient poorly differentiated tumors was 78.8%.Conclusion:Smarca4-deficient undifferentiated tumors and SMARCA4-deficient poorly differentiated carcinomas have different histomorphology and immunohistochemistry,which can be used to distinguish SMARCA4-deficient undifferentiated tumors from SMARCA4-deficient poorly differentiated carcinomas.The half-year survival rate of SMARCA4-deficient undifferentiated tumors was30.3%,and that of SMARCA4-deficient poorly differentiated tumors was 78.8%.The survival time of SMARCA4-deficient undifferentiated tumors was significantly worse than that of SMARCA4-deficient poorly differentiated carcinomas.