Institute of Pathology, Erlangen University Hospital, Friedrich Alexander University of Erlangen-Nuremberg, Comprehensive Cancer Center, European Metropolitan Area Erlangen-Nuremberg (CCC ER-EMN), Erlangen, Germany.
Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.
Histopathology. 2024 Nov;85(5):783-793. doi: 10.1111/his.15304. Epub 2024 Aug 21.
A subset of exceptionally rare primary renal perivascular epithelioid cell tumours (PEComas) that harbour Xp11.2 translocation have been reported, but no larger series devoted to this topic have been published.
We describe the clinicopathological and molecular features of 10 renal PEComas, collected from our routine and consultation files. There were five female and five male patients aged 14-65 (median: 32 years). One patient had a history of childhood neuroblastoma, but no patients were known to have a tuberous sclerosis complex or other hereditary disorder. Complete surgical excision was the treatment for all patients. The available follow-up in five patients indicated a favourable outcome in 4/5 cases. Tumour size ranged from 2.8 to 15.2 cm (median, 5.2 cm). Immunohistochemistry revealed consistently strong TFE3 expression in all tumours, whereas PAX8 and keratin cocktails were uniformly negative. Other positive markers included HMB45 (7/9 tumours), CathepsinK (7/9 tumours), and CD117 (KIT) (3/5 tumours). TFE3 rearrangements were detected in 8/9 tumours (by targeted RNA sequencing in seven and by FISH in one). The identified fusion partners included SFPQ (n = 2) and one tumour each with ASPSCR1, ZC3H4, MED15, RBMX, and PRCC. One tumour that lacked TFE3 rearrangement by next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH) revealed a large intrachromosomal deletion involving PKD1 and TSC2 by DNA-based NGS.
This study highlights the morphologic and genetic diversity of TFE3-rearranged primary renal PEComas and underlines the value of surrogate TFE3 immunohistochemistry in identifying them. The lack of PAX8 and keratin expression represents the mainstay for distinguishing these tumours from MiTF-associated renal cell carcinomas. In addition, we report rare (ZC3H4, RBMX) and novel (MED15) TFE3 fusion partners in PEComa.
已经报道了一组罕见的原发性肾血管周上皮样细胞瘤（PEComa）亚类，这些肿瘤存在 Xp11.2 易位，但尚未有更大规模的相关研究。
我们描述了从常规和会诊病例中收集的 10 例肾 PEComa 的临床病理和分子特征。患者为 5 名女性和 5 名男性，年龄 14-65 岁（中位数：32 岁）。1 例患者有儿童期神经母细胞瘤病史，但无患者患有结节性硬化症或其他遗传性疾病。所有患者均接受了完全手术切除。对 5 例患者的随访显示，4/5 例患者的预后良好。肿瘤大小从 2.8 至 15.2cm（中位数，5.2cm）不等。免疫组织化学显示所有肿瘤均持续强烈表达 TFE3，而 PAX8 和角蛋白组合均为阴性。其他阳性标志物包括 HMB45（7/9 例肿瘤）、CathepsinK（7/9 例肿瘤）和 CD117（KIT）（3/5 例肿瘤）。在 8/9 例肿瘤中检测到 TFE3 重排（7 例通过靶向 RNA 测序，1 例通过 FISH）。鉴定的融合伙伴包括 SFPQ（n=2）和 1 例各与 ASPSCR1、ZC3H4、MED15、RBMX 和 PRCC 融合的肿瘤。1 例通过下一代测序（NGS）和荧光原位杂交（FISH）均未发现 TFE3 重排的肿瘤，通过基于 DNA 的 NGS 发现其存在涉及 PKD1 和 TSC2 的大片段染色体内缺失。
本研究强调了 TFE3 重排的原发性肾 PEComa 的形态和遗传多样性，并强调了替代 TFE3 免疫组化在识别它们中的价值。缺乏 PAX8 和角蛋白表达是将这些肿瘤与 MiTF 相关的肾细胞癌区分开来的主要依据。此外，我们报告了 PEComa 中罕见（ZC3H4、RBMX）和新的（MED15）TFE3 融合伙伴。
