Biomarkers, Tumor ; DNA Helicases ; Humans ; Neoplasms ; Nuclear Proteins/genetics* ; Transcription Factors

Objective: To investigate the clinicopathological features, immunophenotype and differential diagnoses of SMARCA4-deificient undifferentiated carcinoma (SMARCA4-DUC) of the gastrointestinal tract. Methods: The clinicopathological data and immunohistochemical profiles of nine cases of SMARCA4-DUC of the gastrointestinal tract diagnosed in Fudan University Shanghai Cancer Center, from 2018 to 2021, were analyzed retrospectively. The relevant literature was reviewed. Results: There were seven males and two females with age at presentation ranging from 39 to 74 years (mean 58 years, median 64 years). The tumor occurred in the stomach (6 cases), right hemicolon (2 cases) and duodenum (1 case). The main symptoms included dysphagia, abdominal pain, diarrhea and melena. Five cases were resected, and the tumor sizes ranged from 5.0 to 8.7 cm (mean 6.7 cm). Microscopically, the tumor was composed of sheets of undifferentiated round to epithelioid cells with large vesicular nuclei harboring prominent nucleoli and displaying brisk mitotic activity. Foci of dyscohesive rhabdoid cells were also noted. The tumor cells were generally uniform; however, prominent pleomorphism and spindle cell component was present in one case each. Five cases contained areas of coagulative necrosis, and one case showed myxoid change of the stroma. By immunohistochemistry, eight cases showed complete loss of BRG1 (SMARCA4) and BRM (SMARCA2) expression. Whereas the expression of these two markers was lost in the epithelioid component of one case, it remained in the spindle cell component (mosaic pattern). Apart from one case with partial expression of pan-cytokeratin, all other eight cases showed either limited (<5%, n=5) or totally negative (n=3) staining of pan-cytokeratin. In addition, four cases also expressed CD34, SOX2 and SALL4. Six patients had follow-up data: four died of disease within 1 year. Conclusions: SMARCA4-DUC of the gastrointestinal tract represents a highly aggressive malignancy with poor outcome. Due to lack of cell-specific differentiation, it is not uncommonly misdiagnosed as a wide variety of poorly-differentiated or undifferentiated tumors. Increased recognition of this rare but distinctive entity not only facilitates the diagnosis and differential diagnosis, but also provides important therapeutic and prognostic information for the clinicians.
Biomarkers, Tumor/genetics* ; Carcinoma/pathology* ; China ; DNA Helicases ; Female ; Gastrointestinal Tract/pathology* ; Humans ; Keratins ; Male ; Nuclear Proteins ; Retrospective Studies ; Transcription Factors