BACKGROUND SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting(SWI/SNF)complexes and plays an essential role in oncogenesis.SMARCA4-deficient malignancies arising from the gastrointestinal t...BACKGROUND SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting(SWI/SNF)complexes and plays an essential role in oncogenesis.SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis.There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies.Programmed death 1(PD-1)antibodies,known as immune checkpoint inhibitor antibodies,potentially play a role in treating gastrointestinal tract malignancies.CASE SUMMARY We present two patients with SMARCA4 deficiency and TP53 gene mutation in advanced undifferentiated carcinomas of the duodenum.For both patients,SMARCA4 deficiency was confirmed by immunohistochemical staining for the BRG1 protein,while TP53 gene mutations were observed via next-generation sequencing.Both patients were administered chemotherapy in combination with an anti-PD-1 antibody.The two patients exhibited completely different responses to treatment and had different prognoses.Case 1 experienced rapid progression after PD-1 infusion and chemotherapy,case 2 experienced a remarkable response after treatment,and the progression-free survival was more than 6 months.CONCLUSION This study described our clinical and pathological observations of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum.PD-1 combined with chemotherapy showed a certain efficacy in select patients,providing options for treating these highly malignant tumors.Patients with liver metastases had a worse prognosis than did those with only lymph node metastasis.展开更多
BACKGROUND SMARCA4-deficient undifferentiated tumors(SMARCA4-DUTs)present with diverse clinical manifestations and progress to metastasis and even cause death within a few months.This novel subset of undifferentiated ...BACKGROUND SMARCA4-deficient undifferentiated tumors(SMARCA4-DUTs)present with diverse clinical manifestations and progress to metastasis and even cause death within a few months.This novel subset of undifferentiated tumors occurs in the middle-aged population and is strongly associated with a smoking history.Distin-guishing it from other malignancies is challenging.CASE SUMMARY A 62-year-old man presented with chest pain for 7 d.The patient had no respiratory symptoms and normal pulmonary function test results.The patient had been a smoker for 8 years and quit smoking 2 years ago.Chest computed tomography revealed a huge mass involving the left upper and lower lung lobes with pericardial invasion and multiple metastases.Tumor samples were obtained using open frozen biopsy,after several unsuccessful attempts.The tumor was composed of sheets of undifferentiated disclosive cells with vesicular nuclei and prominent nucleoli.The differential diagnosis included high-grade lymphoma,germ cell tumor,NUT carcinoma,undifferentiated carcinoma,and sarcoma.The tumor cells were large,arranged in sheets,and did not exhibit glandular or squamous differentiation.Frequent foci of necrosis were noted.There was no evidence of epithelial differentiation on immunohistochemical staining.The SMARCA4 stain showed complete loss of expression of SMARCA4,which is diagnostic.CONCLUSION In the present case,thoracic SMARCA4-DUT was diagnosed based on clinical features,absence of epithelial differentiation,and negative SMARCA4 expression.展开更多
Atypical teratoid/rhabdoid tumors (AT/RTs) are lethal central nervous system tumors, which are primarily diagnosed in infants. Current treatments for AT/RTs include surgery, radiotherapy, and chemotherapy;these treatm...Atypical teratoid/rhabdoid tumors (AT/RTs) are lethal central nervous system tumors, which are primarily diagnosed in infants. Current treatments for AT/RTs include surgery, radiotherapy, and chemotherapy;these treatments have poor prognoses and challenging side effects. The pivotal genetic event in AT/RT pathogenesis comprises the inactivation ofSMARCB1 orSMARCA4. Recent epigenetic studies have demonstrated mutual and subtype-specific epigenetic derangements that drive tumorigenesis;the exploitation of these potential targets might improve the dismal treatment outcomes of AT/RTs. This review aims to summarize the literature concerning targeted molecular therapies for pediatric AT/RTs.展开更多
文摘BACKGROUND SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting(SWI/SNF)complexes and plays an essential role in oncogenesis.SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis.There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies.Programmed death 1(PD-1)antibodies,known as immune checkpoint inhibitor antibodies,potentially play a role in treating gastrointestinal tract malignancies.CASE SUMMARY We present two patients with SMARCA4 deficiency and TP53 gene mutation in advanced undifferentiated carcinomas of the duodenum.For both patients,SMARCA4 deficiency was confirmed by immunohistochemical staining for the BRG1 protein,while TP53 gene mutations were observed via next-generation sequencing.Both patients were administered chemotherapy in combination with an anti-PD-1 antibody.The two patients exhibited completely different responses to treatment and had different prognoses.Case 1 experienced rapid progression after PD-1 infusion and chemotherapy,case 2 experienced a remarkable response after treatment,and the progression-free survival was more than 6 months.CONCLUSION This study described our clinical and pathological observations of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum.PD-1 combined with chemotherapy showed a certain efficacy in select patients,providing options for treating these highly malignant tumors.Patients with liver metastases had a worse prognosis than did those with only lymph node metastasis.
基金Supported by a grant from Yeungnam University,No.222A580017.
文摘BACKGROUND SMARCA4-deficient undifferentiated tumors(SMARCA4-DUTs)present with diverse clinical manifestations and progress to metastasis and even cause death within a few months.This novel subset of undifferentiated tumors occurs in the middle-aged population and is strongly associated with a smoking history.Distin-guishing it from other malignancies is challenging.CASE SUMMARY A 62-year-old man presented with chest pain for 7 d.The patient had no respiratory symptoms and normal pulmonary function test results.The patient had been a smoker for 8 years and quit smoking 2 years ago.Chest computed tomography revealed a huge mass involving the left upper and lower lung lobes with pericardial invasion and multiple metastases.Tumor samples were obtained using open frozen biopsy,after several unsuccessful attempts.The tumor was composed of sheets of undifferentiated disclosive cells with vesicular nuclei and prominent nucleoli.The differential diagnosis included high-grade lymphoma,germ cell tumor,NUT carcinoma,undifferentiated carcinoma,and sarcoma.The tumor cells were large,arranged in sheets,and did not exhibit glandular or squamous differentiation.Frequent foci of necrosis were noted.There was no evidence of epithelial differentiation on immunohistochemical staining.The SMARCA4 stain showed complete loss of expression of SMARCA4,which is diagnostic.CONCLUSION In the present case,thoracic SMARCA4-DUT was diagnosed based on clinical features,absence of epithelial differentiation,and negative SMARCA4 expression.
文摘Atypical teratoid/rhabdoid tumors (AT/RTs) are lethal central nervous system tumors, which are primarily diagnosed in infants. Current treatments for AT/RTs include surgery, radiotherapy, and chemotherapy;these treatments have poor prognoses and challenging side effects. The pivotal genetic event in AT/RT pathogenesis comprises the inactivation ofSMARCB1 orSMARCA4. Recent epigenetic studies have demonstrated mutual and subtype-specific epigenetic derangements that drive tumorigenesis;the exploitation of these potential targets might improve the dismal treatment outcomes of AT/RTs. This review aims to summarize the literature concerning targeted molecular therapies for pediatric AT/RTs.
