The main unifying feature of cases with frontotemporal dementia (FTD) is the p attern of brain atrophy. Surprisingly, there are a variety of underlying histopa thologies in cases with the clinical features and typical...The main unifying feature of cases with frontotemporal dementia (FTD) is the p attern of brain atrophy. Surprisingly, there are a variety of underlying histopa thologies in cases with the clinical features and typical pattern of atrophy cha racterizing FTD. This suggests that the degenerative mechanism(s) associated wit h pyramidal cell loss and gliosis in FTD is likely to be similar in the differen t histopathological forms of the disease. In this study we tested this hypothesi s by analysing a common cell death mechanism, apoptosis, in cases of FTD with ei ther Picks disease (PiD) (n = 9) or frontotemporal lobar degeneration (FTLD) ( n = 7) compared with normal controls (n = 10). Tissue sections from previously a nalysed cases were stained using anti activated caspase-3 immunohistochemistry , TUNEL, propidium iodide, and cell and pathology specific labels. These marke rs of apoptosis identified both astrocytes and neurons in regions vulnerable to degeneration in all cases of FTD. However, neuronal apoptosis was rare (<2 %of neurons), even at early disease stages where there is considerably less fro ntotemporal atrophy or pyramidal cell loss. This suggests that other cell death mechanisms account for the progressive neuronal loss in FTD. In contrast, astroc ytes with beaded processes and other apoptotic features were very frequent in bo th PiD and FTLD, with the severity of astrocytosis and astrocytic apoptosis corr elating with both the degree of neuronal loss and the stage of disease. These fi ndings provide evidence that astrocytic apoptosis occurs as an early event in di fferent histopathological forms of FTD. Furthermore, this astrocytic apoptosis d irectly relates to the degree of degeneration in FTD, and becomes the overwhelmi ng pathological feature as the disease progresses.展开更多
目的探讨系统性ALK阴性间变性大细胞淋巴瘤(anaplastic large cell lymphoma,ALCL)的临床病理特点、分子特征、治疗和预后。方法回顾性分析18例系统性ALK^(-)ALCL的临床病理特征、免疫表型特点,行HE、免疫组化染色、FISH和NGS检测,并复...目的探讨系统性ALK阴性间变性大细胞淋巴瘤(anaplastic large cell lymphoma,ALCL)的临床病理特点、分子特征、治疗和预后。方法回顾性分析18例系统性ALK^(-)ALCL的临床病理特征、免疫表型特点,行HE、免疫组化染色、FISH和NGS检测,并复习相关文献。结果系统性ALK^(-)ALCL好发于老年男性,常位于进展期,以淋巴结病变为主,结外原发部位包括原发胰腺、原发胸椎;形态学显示17例呈普通型,1例呈“霍奇金样”型。免疫表型:肿瘤细胞中CD30均弥漫强阳性(>75%),CD2(16/17)、CD3(13/18)、CD5(4/18)、CD7(8/18)、CD4(14/18)、TIA-1(16/18)、CD8(2/16)、GATA-3(10/12)、EMA(3/5)、MUM1(12/12)、CD43(6/6)和CD56(2/8)不同程度阳性,Ki67增殖指数30%~90%,PD-L1(22C3)(TPS=0~100%),ALK、CD15、CD79α和CD20均阴性;FISH检测:5例TP63缺失,2例DUSP22缺失。NGS检测:16例发生基因突变,基因突变频率0~11个,平均4.2个基因突变;伴TP63重排的ALK^(-)ALCL更易发生于女性,多发于淋巴结,临床分期晚,易伴p53基因异常。结论伴TP63重排的系统性ALK^(-)ALCL与诸多不良因素相关,临床过程多呈侵袭性,预后不佳。展开更多
文摘The main unifying feature of cases with frontotemporal dementia (FTD) is the p attern of brain atrophy. Surprisingly, there are a variety of underlying histopa thologies in cases with the clinical features and typical pattern of atrophy cha racterizing FTD. This suggests that the degenerative mechanism(s) associated wit h pyramidal cell loss and gliosis in FTD is likely to be similar in the differen t histopathological forms of the disease. In this study we tested this hypothesi s by analysing a common cell death mechanism, apoptosis, in cases of FTD with ei ther Picks disease (PiD) (n = 9) or frontotemporal lobar degeneration (FTLD) ( n = 7) compared with normal controls (n = 10). Tissue sections from previously a nalysed cases were stained using anti activated caspase-3 immunohistochemistry , TUNEL, propidium iodide, and cell and pathology specific labels. These marke rs of apoptosis identified both astrocytes and neurons in regions vulnerable to degeneration in all cases of FTD. However, neuronal apoptosis was rare (<2 %of neurons), even at early disease stages where there is considerably less fro ntotemporal atrophy or pyramidal cell loss. This suggests that other cell death mechanisms account for the progressive neuronal loss in FTD. In contrast, astroc ytes with beaded processes and other apoptotic features were very frequent in bo th PiD and FTLD, with the severity of astrocytosis and astrocytic apoptosis corr elating with both the degree of neuronal loss and the stage of disease. These fi ndings provide evidence that astrocytic apoptosis occurs as an early event in di fferent histopathological forms of FTD. Furthermore, this astrocytic apoptosis d irectly relates to the degree of degeneration in FTD, and becomes the overwhelmi ng pathological feature as the disease progresses.
文摘目的探讨系统性ALK阴性间变性大细胞淋巴瘤(anaplastic large cell lymphoma,ALCL)的临床病理特点、分子特征、治疗和预后。方法回顾性分析18例系统性ALK^(-)ALCL的临床病理特征、免疫表型特点,行HE、免疫组化染色、FISH和NGS检测,并复习相关文献。结果系统性ALK^(-)ALCL好发于老年男性,常位于进展期,以淋巴结病变为主,结外原发部位包括原发胰腺、原发胸椎;形态学显示17例呈普通型,1例呈“霍奇金样”型。免疫表型:肿瘤细胞中CD30均弥漫强阳性(>75%),CD2(16/17)、CD3(13/18)、CD5(4/18)、CD7(8/18)、CD4(14/18)、TIA-1(16/18)、CD8(2/16)、GATA-3(10/12)、EMA(3/5)、MUM1(12/12)、CD43(6/6)和CD56(2/8)不同程度阳性,Ki67增殖指数30%~90%,PD-L1(22C3)(TPS=0~100%),ALK、CD15、CD79α和CD20均阴性;FISH检测:5例TP63缺失,2例DUSP22缺失。NGS检测:16例发生基因突变,基因突变频率0~11个,平均4.2个基因突变;伴TP63重排的ALK^(-)ALCL更易发生于女性,多发于淋巴结,临床分期晚,易伴p53基因异常。结论伴TP63重排的系统性ALK^(-)ALCL与诸多不良因素相关,临床过程多呈侵袭性,预后不佳。
