The nested variant of urothelial carcinoma, a frequent mimic of benign lesions on limited specimens, has been associated with high-stage disease including metastases at presentation. While PAX8 immunohistochemistry has been noted to be infrequently present in urothelial carcinoma in general, it has not been studied specifically in a cohort of nested urothelial carcinomas. Furthermore, TERT promoter mutation status is a potentially valuable biomarker for diagnosis of urothelial carcinoma and for noninvasive disease monitoring that has been observed in a majority of urothelial carcinoma and has previously been seen to be prevalent in multiple variant morphologies of urothelial carcinoma, including the nested variant. Twenty-five primary and three metastatic samples of nested urothelial carcinoma, along with 16 benign cases, were identified in a multicenter retrospective record review. PAX8 immunohistochemical stain was performed on all cases. In addition, TERT mutation analysis by allele-specific PCR was performed on 21 of the primary nested urothelial carcinoma cases and all benign cases. Positive PAX8 expression was identified in 52% (13 of 25) primary cases and 67% (2 of 3) metastatic cases of nested urothelial carcinoma; 50% (1 of 2) cases of large nested urothelial carcinoma were positive for PAX8. PAX8 expression was negative in the benign urothelium in all cases. TERT promoter mutation was observed in 83% (15 of 18) nested urothelial carcinoma cases and in 6% (1 of 16) of the benign cases. Recognition of the prevalence of positive PAX8 staining in this clinically relevant variant of urothelial carcinoma is essential to avoiding inaccurate or delayed diagnosis during the diagnostic workup of bladder lesions suspicious for nested variant of urothelial carcinoma. Moreover, the prevalence of TERT promoter mutations in nested urothelial carcinoma is similar to that of conventional urothelial carcinoma, further supporting its use as a biomarker that is stable across morphologic variants of urothelial carcinoma.

中文翻译：

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尿路上皮癌嵌套变体中的 PAX8 表达和 TERT 启动子突变：具有免疫组织化学和分子相关性的临床病理学研究。

尿路上皮癌的嵌套变体是有限标本上良性病变的常见模仿，与包括就诊时转移在内的晚期疾病有关。虽然 PAX8 免疫组织化学已被注意到一般不常出现在尿路上皮癌中，但尚未在一组巢状尿路上皮癌中进行专门研究。此外，TERT 启动子突变状态是一种潜在有价值的生物标志物，可用于诊断尿路上皮癌和用于非侵入性疾病监测，已在大多数尿路上皮癌中观察到，并且以前曾被认为在尿路上皮癌的多种变异形态中普遍存在，包括巢状变种。25 个原发性和三个转移性巢状尿路上皮癌样本，以及 16 个良性病例，在多中心回顾性记录审查中确定。对所有病例进行 PAX8 免疫组化染色。此外，对 21 例原发性巢状尿路上皮癌病例和所有良性病例进行了等位基因特异性 PCR 的 TERT 突变分析。在 52%（25 例中的 13 例）原发病例和 67%（3 例中的 2 例）巢状尿路上皮癌转移病例中鉴定出阳性 PAX8 表达；50%（2 个中的 1 个）大型巢状尿路上皮癌病例为 PAX8 阳性。在所有病例中，PAX8 表达在良性尿路上皮中均为阴性。在 83%（18 个中的 15 个）巢状尿路上皮癌病例和 6%（16 个中的 1 个）良性病例中观察到 TERT 启动子突变。识别这种临床相关的尿路上皮癌变体中阳性 PAX8 染色的流行对于避免在疑似尿路上皮癌嵌套变体的膀胱病变的诊断检查期间做出不准确或延迟的诊断至关重要。此外，嵌套式尿路上皮癌中 TERT 启动子突变的发生率与常规尿路上皮癌相似，进一步支持其用作跨尿路上皮癌形态学变异稳定的生物标志物。