- 7 例 BRAF V600E 阴性后肾腺瘤（女 5、男 2，中位 43 岁），均无包膜、呈典型 MA 组织学；4/7 见分支扩张小管围绕密集小腺泡的叶状结构，3/7 见甲状腺滤泡样和/或微囊/网状模式，多数间质稀少。
- IHC：WT1、CD57 均弥漫阳性，BRAF V600E（VE1）阴性，CK7、AMACR 基本阴性。
- 靶向 RNA 测序：CCDC6::RET 2 例、ANKRD26::RET 1 例、STRN::ALK 2 例、RDX::ROS1 1 例、CUX1::BRAF 1 例，均保留激酶结构域；FISH/RT-PCR 验证。对照 7 例 V600E 突变型 MA 无融合。
- 实用意义：经典 MA 形态而 VE1 阴性时，可用靶向 RNA 测序找这些融合作为辅助诊断；全部肾部分切除后随访（中位 18 个月）无病。
收录范围：PubMed 英文摘要及中文翻译（abstract-only）。Unpaywall 无 OA 版本、Ovid 页无开放全文，未采集全文与图表。
摘要
后肾腺瘤（metanephric adenoma，MA）是一种罕见的肾脏良性肿瘤，约 80%–90% 的病例具有复发性 BRAF V600E 突变。BRAF V600E 阴性 MA 的分子驱动因素仍知之甚少，尽管已有罕见激酶融合的报道。本文报告一组多机构、经证实携带激酶融合的 BRAF V600E 阴性 MA 共 7 例。患者包括女性 5 例、男性 2 例，中位年龄 43 岁（范围 24–62 岁）。全部肿瘤均无包膜，呈典型 MA 组织学。值得注意的是，7 例中 4 例可见由分支状扩张小管围绕密集小腺泡构成的叶状结构，7 例中 3 例可见甲状腺滤泡样结构和/或微囊/网状模式。多数病例水肿性或纤维性间质明显稀少。免疫组化方面，全部病例 WT1 与 CD57 弥漫阳性，BRAF V600E（克隆 VE1）阴性，CK7 与 AMACR 基本阴性。靶向 RNA 测序检出涉及 RET（CCDC6::RET 2 例，ANKRD26::RET 1 例）、ALK（STRN::ALK 2 例）、ROS1（RDX::ROS1 1 例）和 BRAF（CUX1::BRAF 1 例）的融合。所有融合均保留了相应基因的激酶结构域。在有条件的病例中，荧光原位杂交或逆转录 PCR 证实了重排。与之相对，对 7 例 BRAF V600E 突变型 MA 进行靶向 RNA 测序，未发现激酶融合。全部患者均接受肾部分切除术，随访期间（中位 18 个月，范围 14–115 个月）均无病生存。我们的结果表明，包括 RET、ALK、ROS1 和 BRAF 在内的激酶融合是 BRAF V600E 阴性 MA 的替代驱动因素，拓展了 MA 的分子谱。对于具有经典 MA 组织学而 VE1 阴性的病例，针对这些融合的靶向 RNA 测序可作为有用的辅助诊断手段。
- Seven BRAF V600E-negative metanephric adenomas (5 women, 2 men; median age 43), all uncapsulated with typical MA histology; leaf-like structures in 4/7, thyroid follicle-like and/or microcystic/reticular patterns in 3/7, mostly scant stroma.
- IHC: diffuse WT1 and CD57, VE1 negative, largely CK7- and AMACR-negative.
- Targeted RNA-seq: CCDC6::RET (2), ANKRD26::RET (1), STRN::ALK (2), RDX::ROS1 (1), CUX1::BRAF (1), all kinase-domain-preserving, confirmed by FISH/RT-PCR; none in 7 V600E-mutant controls.
- Practical point: in VE1-negative cases with classic MA histology, targeted RNA sequencing for these fusions is a useful diagnostic adjunct; all patients disease-free after partial nephrectomy (median 18 months).
Scope: PubMed abstract only. Unpaywall lists no OA copy and the Ovid page shows no open full text, so full text, figures and tables were not collected.
Abstract
Metanephric adenoma (MA) is a rare benign renal neoplasm characterized by recurrent BRAF V600E mutations in ∼80% to 90% of cases. The molecular drivers in BRAF V600E‑negative MAs remain poorly understood, although rare kinase fusions have been reported. Here, we present a multi‑institutional series of 7 BRAF V600E‑negative MAs with confirmed kinase fusions. The patients included 5 women and 2 men, with a median age of 43 years (range: 24 to 62 y). All tumors were uncapsulated and exhibited typical MA histology. Notably, leaf‑like structures formed by branching dilated tubules surrounding dense small acini were observed in 4 of 7 cases, and thyroid follicle‑like structures and/or microcystic/reticular patterns were observed in 3 of 7 cases. The majority of cases showed marked paucity of edematous or fibrous stroma. By immunohistochemistry, all cases were diffusely positive for WT1 and CD57, negative for BRAF V600E (clone VE1), and largely negative for CK7 and AMACR. Targeted RNA sequencing identified fusions involving RET (CCDC6::RET in 2 cases, ANKRD26::RET in 1), ALK (STRN::ALK in 2), ROS1 (RDX::ROS1 in 1), and BRAF (CUX1::BRAF in 1). All fusions preserved the kinase domain of the respective genes. Fluorescence in situ hybridization or reverse‑transcriptase PCR confirmed the rearrangements in available cases. In contrast, targeted RNA sequencing of 7 BRAF V600E‑mutant MAs revealed no kinase fusions. All patients underwent partial nephrectomy and remained disease‑free during follow‑up (median: 18 mo, range: 14 to 115 mo). Our findings demonstrate that kinase fusions, including RET, ALK, ROS1, and BRAF, represent alternative drivers in BRAF V600E‑negative MAs, expanding the molecular spectrum of MA. In VE1-negative cases with classic MA histology, targeted RNA sequencing for these fusions may serve as a useful diagnostic adjunct.