低恶性潜能的乳头状尿路上皮肿瘤（PUN-LMP）：在 2019 年，对于 Ta、非浸润性膀胱肿瘤，它仍然是一个有意义的组织病理学分级类别吗？
Papillary urothelial neoplasm of low malignant potential (PUN-LMP): Still a meaningful histo-pathological grade category for Ta, noninvasive bladder tumors in 2019?
机构信息
Urology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Surgical Oncology (Urology), Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.
Surgical Oncology (Urology), Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands; Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany; Surgical Oncology (Urology), University Health Network, Princess Margaret Cancer Center, University of Toronto, Toronto, Canada.
出版信息
Urol Oncol. 2020 May;38(5):440-448. doi: 10.1016/j.urolonc.2019.10.002. Epub 2019 Nov 5.
BACKGROUND
Papillary urothelial neoplasm of low malignant potential (PUN-LMP) was introduced as a noninvasive, noncancerous lesion and a separate grade category in 1998. Subsequently, PUN-LMP was reconfirmed by World Health Organization (WHO) 2004 and WHO 2016 classifications for urothelial bladder tumors.
OBJECTIVES
To analyze the proportion of PUN-LMP diagnosis over time and to determine its prognostic value compared to Ta-LG (low-grade) and Ta-HG (high-grade) carcinomas. To assess the intraobserver variability of an experienced uropathologist assigning (WHO) 2004/2016 grades at 2 time points.
MATERIALS AND METHODS
Individual patient data of 3,311 primary Ta bladder tumors from 17 hospitals in Europe and Canada were available. Transurethral resection of the tumor was performed between 1990 and 2018. Time to recurrence and progression were analyzed with cumulative incidence functions, log-rank tests and multivariable Cox-regression stratified by institution. Intraobserver variability was assessed by examining the same 314 transurethral resection of the tumorslides twice, in 2004 and again in 2018.
RESULTS
PUN-LMP represented 3.8% (127/3,311) of Ta tumors. The same pathologist found 71/314 (22.6%) PUN-LMPs in 2004 and only 20/314 (6.4%) in 2018. Overall, the proportion of PUN-LMP diagnosis substantially decreased over time from 31.3% (1990-2000) to 3.2% (2000-2010) and to 1.1% (2010-2018). We found no difference in time to recurrence between the three WHO 2004/2016 Ta-grade categories (log-rank, P = 0.381), nor for LG vs. PUN-LMP (log-rank, P = 0.238). Time to progression was different for all grade categories (log-rank, P < 0.001), but not between LG and PUN-LMP (log-rank, P = 0.096). Multivariable analyses on recurrence and progression showed similar results for all 3 grade categories and for LG vs. PUN-LMP.
CONCLUSIONS
The proportion of PUN-LMP has decreased to very low levels in the last decade. Contrary to its reconfirmation in the WHO 2016 classification, our results do not support the continued use of PUN-LMP as a separate grade category in Ta tumors because of the similar prognosis for PUN-LMP and Ta-LG carcinomas.
背景
低恶性潜能乳头状尿路上皮肿瘤（PUN-LMP）于 1998 年被引入作为一种非浸润性、非癌性病变，并作为一个单独的分级类别。随后，世界卫生组织（WHO）2004 年和 2016 年的膀胱癌分类标准再次确认了 PUN-LMP。
目的
分析 PUN-LMP 诊断随时间的比例，并确定与 Ta-LG（低级别）和 Ta-HG（高级别）癌相比，其预后价值。评估一位经验丰富的泌尿病理学家在 2 个时间点分配（WHO）2004/2016 分级的观察者内变异性。
材料和方法
来自欧洲和加拿大 17 家医院的 3311 例原发性 Ta 膀胱癌患者的个体患者数据可用。肿瘤经尿道切除术（TURT）于 1990 年至 2018 年进行。采用累积发生率函数、对数秩检验和多变量 Cox 回归分析复发和进展时间，按机构分层。观察者内变异性通过检查同 314 例 TURT 切片两次来评估，一次在 2004 年，一次在 2018 年。
结果
PUN-LMP 占 3.311 例 Ta 肿瘤的 3.8%（127/3311）。同一位病理学家在 2004 年发现了 71/314（22.6%）的 PUN-LMP，而在 2018 年仅发现了 20/314（6.4%）。总体而言，PUN-LMP 的诊断比例随着时间的推移从 31.3%（1990-2000 年）大幅下降至 3.2%（2000-2010 年）和 1.1%（2010-2018 年）。我们发现，在三种 WHO 2004/2016 Ta 分级类别之间（对数秩，P=0.381），以及在 LG 与 PUN-LMP 之间（对数秩，P=0.238），复发时间无差异。所有分级类别的进展时间均不同（对数秩，P<0.001），但 LG 与 PUN-LMP 之间无差异（对数秩，P=0.096）。复发和进展的多变量分析对所有 3 个分级类别和 LG 与 PUN-LMP 均显示出相似的结果。
结论
在过去十年中，PUN-LMP 的比例已降至非常低的水平。与 2016 年 WHO 分类标准中的重新确认相反，我们的结果不支持继续将 PUN-LMP 作为 Ta 肿瘤的单独分级类别使用，因为 PUN-LMP 和 Ta-LG 癌的预后相似。
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