- 115 例子宫间叶肿瘤中，9/9 PEComa 弥漫中至强 GPNMB 阳性；但 LMS（47%）、UUS（40%）、IMT（67%）亦可达诊断阈值。
- 严格标准：>75% 肿瘤体积、中至强强度；低水平局灶/弱着色常见，易误读。
- 结论：敏感但不特异，不可单独用于鉴别，须结合形态与更广 IHC 面板。
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摘要
背景：GPNMB 是一种溶酶体跨膜蛋白，已成为微眼相关转录因子家族（TFE3 与 TFEB）驱动及 mTOR 通路激活肿瘤的诊断标志物。弥漫、中至强阳性的 GPNMB 已被提出可作为易位驱动及 mTOR 通路激活肿瘤（含 PEComa）的替代标志。本研究评估 GPNMB 免疫组化在鉴别子宫 PEComa 与常见形态学拟态（子宫间叶源性肿瘤）中的诊断效用。
材料与方法：分析 115 例子宫间叶源性肿瘤，包括 9 例 PEComa 及广泛鉴别诊断谱系：平滑肌肉瘤（LMS，n=19）、STUMP（n=20）、平滑肌瘤（n=10）、低级别子宫内膜间质肉瘤（LG ESS，n=18）、高级别 ESS（HG ESS，n=13）、腺肉瘤（n=11）、未分化子宫肉瘤（UUS，n=5）、炎性肌纤维母细胞瘤（IMT，n=3）以及一组罕见实体（1 例 UTROSCT、3 例 KAT6B/A::KANSL1-、2 例 PLAG1- 与 1 例 NTRK 重排肉瘤）。行 GPNMB 免疫组化；仅当弥漫着色（>75% 肿瘤体积）且强度为中至强时严格定义为阳性。
结果：所有子宫 PEComa（9/9；100%）呈弥漫中至强 GPNMB 阳性。然而，诊断意义的表达亦见于 LMS（9/19；47%）、UUS（2/5；40%）、IMT（2/3；67%）及 LG ESS（1/18；6%）。其余实体缺乏诊断性 GPNMB 表达，呈阴性，或仅局灶（1%–75% 肿瘤细胞），或弥漫但弱着色。低水平 GPNMB 表达常见，非阳性肿瘤中 65%（60/92）呈局灶或弱着色，支持采用严格判读标准。
结论：尽管对子宫 PEComa 高度敏感，GPNMB 特异性不足以将其与主要子宫间叶拟态（尤其 LMS、IMT 与 UUS）区分。严格判读标准（>75% 肿瘤细胞中至强阳性）可减少假阳性解释，但 GPNMB 不应作为单独鉴别标志物，而应结合形态学及更广的免疫组化面板综合解读。
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Abstract
Background. GPNMB is a lysosomal transmembrane protein that has emerged as a diagnostic marker for tumours driven by the microphthalmia-associated transcription factor family (TFE3 and TFEB) and mTOR pathway activation. Diffuse, moderate-to-strong GPNMB positivity has been proposed as a surrogate marker for both translocation-driven and mTOR pathway-activated neoplasms, including PEComas. This study investigated the diagnostic utility of GPNMB immunohistochemistry in differentiating uterine PEComas from common morphological mimics among uterine mesenchymal tumours.
Materials and methods. We analysed a cohort of 115 uterine mesenchymal tumours, which included nine PEComas and a broad panel of differential diagnoses, comprising leiomyosarcoma (LMS, n = 19), STUMP (n = 20), leiomyoma (n = 10), low-grade endometrial stromal sarcoma (LG ESS, n = 18), high-grade ESS (HG ESS, n = 13), adenosarcoma (n = 11), undifferentiated uterine sarcoma (UUS, n = 5), inflammatory myofibroblastic tumour (IMT, n = 3) and a collection of rare entities (1 UTROSCT, 3 KAT6B/A::KANSL1-, 2 PLAG1- and 1 NTRK-rearranged sarcomas). Immunohistochemistry (IHC) for GPNMB was performed, and a case was strictly defined as positive only if it showed diffuse staining (>75% of tumour volume) of moderate to strong intensity.
Results. All uterine PEComas (9/9; 100%) showed diffuse moderate to strong GPNMB positivity. However, diagnostically significant expression was also observed in LMS (9/19; 47%), UUS (2/5; 40%), IMT (2/3; 67%) and LG ESS (1/18; 6%). All other entities lacked diagnostic GPNMB expression, showing negative or only focal (1%-75% of tumour cells) or diffuse but weak staining. Low-level GPNMB expression was common, with focal or weak staining present in 65% of non-positive tumours (60/92), supporting the use of strict scoring criteria.
Conclusions. Although highly sensitive for uterine PEComa, GPNMB lacks sufficient specificity for distinguishing PEComa from its principal uterine mesenchymal mimics, particularly LMS, IMT and UUS. Although strict scoring criteria (moderate-to-strong positivity in >75% of tumour cells) reduce false-positive interpretation, GPNMB should not be used as a standalone discriminatory marker but interpreted in conjunction with morphology and a broader immunohistochemical panel.