Abstract：
OBJECTIVE: First described in 2014, renal cell carcinoma (RCC) with TFEB amplification (6p21) is a rare molecular subgroup whose diagnosis is challenging. The prognosis and therapeutic implications remain unclear.
METHODS: We report here the clinical, histological, immunohistochemical, and genetic features of nine novel cases. The pathological and immunohistochemical features were centrally reviewed by expert uropathologists. Fluorescence in situ hybridisation (FISH) confirmed the diagnosis and comparative genomic hybridisation (CGH) was performed to determine quantitative genomic alterations. We also performed an exhaustive review of the literature and compiled our data.
RESULTS: TFEB-amplified RCC were locally advanced, with initial lymph node involvement in one case and liver metastasis in another case. They were high-grade eosinophilic tumours with papillary/pseudopapillary architecture, frequent positivity for melanocytic markers, and frequent PDL1 expression. FISH demonstrated high-level TFEB amplification in six cases. One case showed concomitant TFEB translocation. CGH analysis identified complex alterations with frequent losses of 1p, 2q, 3p, 6p, and frequent 6p and 8q gains. VEGFA coamplification was identified in all cases with a lower level than TFEB. The prognosis was poor, with five patients having lymph node or distant metastases.
CONCLUSIONS: TFEB-amplified RCC is a rare molecular subgroup with variable morphology whose diagnosis is confirmed by FISH analysis. The complex alterations identified by CGH are consistent with an aggressive clinical behaviour. The coamplification of VEGFA and the expression of PDL1 could suggest a potential benefit from antiangiogenics and targeted immunotherapy in combination for these aggressive tumours.
METHODS: We report here the clinical, histological, immunohistochemical, and genetic features of nine novel cases. The pathological and immunohistochemical features were centrally reviewed by expert uropathologists. Fluorescence in situ hybridisation (FISH) confirmed the diagnosis and comparative genomic hybridisation (CGH) was performed to determine quantitative genomic alterations. We also performed an exhaustive review of the literature and compiled our data.
RESULTS: TFEB-amplified RCC were locally advanced, with initial lymph node involvement in one case and liver metastasis in another case. They were high-grade eosinophilic tumours with papillary/pseudopapillary architecture, frequent positivity for melanocytic markers, and frequent PDL1 expression. FISH demonstrated high-level TFEB amplification in six cases. One case showed concomitant TFEB translocation. CGH analysis identified complex alterations with frequent losses of 1p, 2q, 3p, 6p, and frequent 6p and 8q gains. VEGFA coamplification was identified in all cases with a lower level than TFEB. The prognosis was poor, with five patients having lymph node or distant metastases.
CONCLUSIONS: TFEB-amplified RCC is a rare molecular subgroup with variable morphology whose diagnosis is confirmed by FISH analysis. The complex alterations identified by CGH are consistent with an aggressive clinical behaviour. The coamplification of VEGFA and the expression of PDL1 could suggest a potential benefit from antiangiogenics and targeted immunotherapy in combination for these aggressive tumours.
摘要：
目的：2014年首次描述，具有TFEB扩增（6p21）的肾细胞癌（RCC）是一种罕见的分子亚群，其诊断具有挑战性。预后和治疗意义仍不清楚。
方法：我们在这里报告临床，组织学,免疫组织化学，和9个新病例的遗传特征。泌尿系专家对病理和免疫组织化学特征进行了集中审查。荧光原位杂交（FISH）证实了诊断，并进行了比较基因组杂交（CGH）以确定定量基因组改变。我们还对文献进行了详尽的回顾，并汇编了我们的数据。
结果：TFEB扩增的肾癌局部晚期，1例初始淋巴结受累，另一例肝转移。它们是高度嗜酸性细胞肿瘤，伴有乳头状/假乳头状结构，黑素细胞标志物频繁阳性，和频繁的PDL1表达。FISH在6例中显示了高水平的TFEB扩增。1例合并TFEB易位。CGH分析确定了复杂的改变，频繁损失1便士，2q,3p,6p,以及频繁的6p和8q增益。在所有情况下，VEGFA共扩增的水平均低于TFEB。预后很差,5例患者有淋巴结或远处转移。
结论：TFEB扩增的RCC是一种罕见的具有可变形态的分子亚群，其诊断通过FISH分析得到证实。CGH鉴定的复杂改变与侵袭性临床行为一致。VEGFA的共扩增和PDL1的表达可能表明抗血管生成素和靶向免疫疗法联合治疗这些侵袭性肿瘤的潜在益处。
方法：我们在这里报告临床，组织学,免疫组织化学，和9个新病例的遗传特征。泌尿系专家对病理和免疫组织化学特征进行了集中审查。荧光原位杂交（FISH）证实了诊断，并进行了比较基因组杂交（CGH）以确定定量基因组改变。我们还对文献进行了详尽的回顾，并汇编了我们的数据。
结果：TFEB扩增的肾癌局部晚期，1例初始淋巴结受累，另一例肝转移。它们是高度嗜酸性细胞肿瘤，伴有乳头状/假乳头状结构，黑素细胞标志物频繁阳性，和频繁的PDL1表达。FISH在6例中显示了高水平的TFEB扩增。1例合并TFEB易位。CGH分析确定了复杂的改变，频繁损失1便士，2q,3p,6p,以及频繁的6p和8q增益。在所有情况下，VEGFA共扩增的水平均低于TFEB。预后很差,5例患者有淋巴结或远处转移。
结论：TFEB扩增的RCC是一种罕见的具有可变形态的分子亚群，其诊断通过FISH分析得到证实。CGH鉴定的复杂改变与侵袭性临床行为一致。VEGFA的共扩增和PDL1的表达可能表明抗血管生成素和靶向免疫疗法联合治疗这些侵袭性肿瘤的潜在益处。
