Transformed lymphoma occurs when indolent lymphoma transforms into more aggressive lymphoma usually associated with poor prognosis. In this study, we analysed the immunophenotypes, prognostic factors and outcomes of 35 patients with transformed lymphoma from among 306 marginal zone lymphoma (MZL), 544 follicular lymphoma (FL) and 871 chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) cases. In addition, we performed whole-exome sequencing study of seven transformed MZL (tMZL) cases. Our results demonstrate that the median time from indolent lymphoma diagnosis to transformed DLBCL was 35 months (range, 14–53 months). The 5-year overall survival (OS) and progression-free survival (PFS) rates after histological transformation (HT) were 50% and 26%, respectively. Kaplan–Meier survival analysis revealed that asynchronous HT and transformed CLL/SLL (tCLL/SLL) were significant adverse prognostic factors for OS after DLBCL HT. We identified mutations involvement in chromatin remodelling (CREBBP and EP300) and regulators of NF-κB signalling (TNFAIP3, BCL10, MYD88, CD79B and CARD11) were affected in tMZL. Whole-exome sequencing and copy-number analysis revealed that tMZL derives from the divergent evolution of an ancestral common progenitor clone (CPC). Collectively, this study provides clinicopathological characteristics of three common types of transformed lymphomas and the genetic profile of tMZL with diagnostic and therapeutic implications.

Transformed lymphoma occurs when indolent lymphoma transforms into more aggressive lymphoma usually associated with poor prognosis. In this study, we analysed the immunophenotypes, prognostic factors and outcomes of 35 patients with transformed lymphoma from among 306 marginal zone lymphoma (MZL), 544 follicular lymphoma (FL) and 871 chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) cases. In addition, we performed whole-exome sequencing study of seven transformed MZL (tMZL) cases. Our results demonstrate that the median time from indolent lymphoma diagnosis to transformed DLBCL was 35 months (range, 14–53 months). The 5-year overall survival (OS) and progression-free survival (PFS) rates after histological transformation (HT) were 50% and 26%, respectively. Kaplan–Meier survival analysis revealed that asynchronous HT and transformed CLL/SLL (tCLL/SLL) were significant adverse prognostic factors for OS after DLBCL HT. We identified mutations involvement in chromatin remodelling (CREBBP and EP300) and regulators of NF-κB signalling (TNFAIP3, BCL10, MYD88, CD79B and CARD11) were affected in tMZL. Whole-exome sequencing and copy-number analysis revealed that tMZL derives from the divergent evolution of an ancestral common progenitor clone (CPC). Collectively, this study provides clinicopathological characteristics of three common types of transformed lymphomas and the genetic profile of tMZL with diagnostic and therapeutic implications.

Downregulation of lncRNA H19 (H19) expression is associated with an unfavorable prognosis in some cancers. However, little was known as to whether there was an association between H19 and minimally invasive follicular thyroid carcinoma (MI-FTC). In our study, we used quantitative real-time polymerase chain reaction (qRT-PCR) to determine H19 expression in 186 patients with MI-FTC who underwent initial surgery. Of the 186 patients with MI-FTC, 21 patients show distant metastasis （M+）at the initial operation established the diagnosis of MI-FTC. Of the 165 patients who did not show distant metastasis at diagnosis during the follow-up period (≥10 years), 28 patients undergone M+ and 137 patients has no distant metastasis（M-）after the initial operation. Low H19 expression was associated with large tumor size, vascular invasion, and distant metastasis. Univariate analysis showed that gender (male), age (45 years or older), primary tumor size (4 cm or more), vascular invasion and H19 level (<1.12) were significant prognostic factors related to postoperative distant metastases. Multivariate analysis showed that age, primary tumor size (4 cm or more) and vascular invasion was a significant prognostic factor for survival. Patients with low H19 expression showed a poorer outcome in MI-FTC patients. Receiver-operating characteristic (ROC) curve analysis demonstrated H19 could distinguish M+ from M- patientswith a value of area under the curve (AUC). Our findings suggest that H19 is a potential prognostic factor for evaluating prognosis and the metastatic potential of MI-FTC at an initial operation stage.

Downregulation of lncRNA H19 (H19) expression is associated with an unfavorable prognosis in some cancers. However, little was known as to whether there was an association between H19 and minimally invasive follicular thyroid carcinoma (MI-FTC). In our study, we used quantitative real-time polymerase chain reaction (qRT-PCR) to determine H19 expression in 186 patients with MI-FTC who underwent initial surgery. Of the 186 patients with MI-FTC, 21 patients show distant metastasis （M+）at the initial operation established the diagnosis of MI-FTC. Of the 165 patients who did not show distant metastasis at diagnosis during the follow-up period (≥10 years), 28 patients undergone M+ and 137 patients has no distant metastasis（M-）after the initial operation. Low H19 expression was associated with large tumor size, vascular invasion, and distant metastasis. Univariate analysis showed that gender (male), age (45 years or older), primary tumor size (4 cm or more), vascular invasion and H19 level (<1.12) were significant prognostic factors related to postoperative distant metastases. Multivariate analysis showed that age, primary tumor size (4 cm or more) and vascular invasion was a significant prognostic factor for survival. Patients with low H19 expression showed a poorer outcome in MI-FTC patients. Receiver-operating characteristic (ROC) curve analysis demonstrated H19 could distinguish M+ from M- patientswith a value of area under the curve (AUC). Our findings suggest that H19 is a potential prognostic factor for evaluating prognosis and the metastatic potential of MI-FTC at an initial operation stage.