- Histopathology（Pacheco、Chan 等，斯坦福大学）：25 例患者 37 份整块经尿道切除标本，研究高级别乳头状尿路上皮癌（PUC）基底旁扁平延伸的非典型尿路上皮——侧向延伸（LE）。
- 13 例有 LE：低级别形态 10 例、与 PUC 相似的高级别 3 例；平均 4.7 mm（1.5–10.8 mm），12/13 延伸到黏膜切缘。
- 配对 NGS：9/11 与 PUC 共享致病改变，支持克隆相关；LE 的 CK20 异常 11/11、p53 异常 3/11，可出现类似 CIS 的免疫表型。
- 读片提示：LE 可延伸 ≥1 cm，追求完整切除时宜放宽切缘；认识 LE 有助于避免在既往乳头状肿瘤背景下过度诊断 CIS。本站仅获摘要。
收录范围：PubMed 摘要中英对照。原文为 Wiley 订阅内容，本站未获全文与图表。
摘要
引言
膀胱乳头状尿路上皮癌（PUC）的侧向延伸（LE）是指非典型尿路上皮从乳头状肿瘤基底部以扁平形态向侧方延伸的现象。LE 已为人所知但定义不清，导致病理医师之间的诊断和解读不一致，从非典型增生到原位癌（CIS）不等。本研究利用整块经尿道切除标本，旨在更好地描述高级别 PUC 中的 LE。
方法
我们复阅了 25 例患者的 37 份整块切除标本，对 PUC 及 LE 成分进行了全面的形态学、分子和免疫组化特征分析。
结果
共见三种形态模式：无 LE（n = 24）；LE 的细胞形态级别低于邻近 PUC（低级别 LE，n = 10）；LE 的细胞形态与邻近 PUC 相似（高级别 LE，n = 3）。LE 平均长度 4.7 mm（范围 1.5–10.8 mm）。12/13（92%）的 LE 延伸至黏膜切缘。在 13 例有 LE 的肿瘤中，对 11 例配对的 PUC 与邻近 LE 成分进行了差异性二代测序。9/11（82%）中 LE 与 PUC 至少共享部分致病/可能致病性改变，支持两种成分之间的克隆相关性；5 例肿瘤另有 PUC 特有的改变，伴或不伴 LE 特有的改变。CK20 和 p53 免疫组化显示，11/11 例肿瘤的 LE 均有 CK20 异常，3/11（27%）p53 异常。PUC 与 LE 的 p53 染色模式在 10/11（91%）标本中一致，而 CK20 仅 6/11（55%）一致。
结论
LE 可从 PUC 基底部延伸至少 1 cm，提示若希望完整手术切除，应考虑更宽的切缘。此外，分子与免疫组化结果均显示，大多数病例中 LE 与 PUC 存在克隆相关，但关系具有异质性。值得注意的是，LE 可呈现与通常报道的 CIS 相似的免疫组化表现。认识 LE 可提高诊断一致性，并减少既往有乳头状肿瘤情况下对 CIS 的过度诊断。
- Histopathology (Pacheco, Chan and colleagues, Stanford): 37 en bloc transurethral resection specimens from 25 patients, characterising lateral extension (LE) — flat atypical urothelium extending from the base of high-grade papillary urothelial carcinoma (PUC).
- LE was present in 13: lower-grade cytomorphology in 10 and PUC-like higher grade in 3; mean length 4.7 mm (1.5–10.8 mm), reaching mucosal margins in 12/13.
- Paired NGS showed shared pathogenic alterations in 9/11, supporting clonality; LE had abnormal CK20 in 11/11 and aberrant p53 in 3/11, an immunoprofile that can resemble CIS.
- Practice point: LE can extend ≥1 cm, so wider margins may be needed for complete resection; recognising LE may reduce CIS overdiagnosis after prior papillary tumours. Abstract only.
Scope: the PubMed abstract. The article is Wiley subscription content; the full text and figures were not obtained.
Abstract
Introduction
Lateral extension (LE) in urinary bladder papillary urothelial carcinoma (PUC) refers to the phenomenon where atypical urothelium is seen extending laterally in a flat configuration from the base of the papillary tumour. LE is recognized but poorly defined, resulting in inconsistent diagnoses and interpretations amongst pathologists, ranging from atypia to carcinoma in situ (CIS). Herein, we aim to better characterize LE in high-grade PUC, utilizing en bloc transurethral resection specimens.
Methods
We reviewed 37 en bloc specimens from 25 patients and performed comprehensive morphological, molecular and immunohistochemical characterization of PUC and LE components.
Results
Three morphological patterns were seen: no LE (n = 24), LE with lower-grade cytomorphology compared to adjacent PUC (lower-grade LE, n = 10), and LE with cytomorphology similar to adjacent PUC (higher-grade LE, n = 3). Mean LE length was 4.7 mm (range 1.5–10.8 mm). LE extended to mucosal margins in 12/13 (92%). Differential next-generation sequencing was performed on paired PUC and adjacent LE components in 11/13 tumours with LE. In 9/11 (82%), LE and PUC showed at least a subset of shared pathogenic/likely pathogenic alterations, supporting clonality between the two components; in five tumours, there were additional alterations specific to PUC, with and without LE-specific alterations. Immunohistochemical staining for CK20 and p53 showed LE with abnormal CK20 in all 11/11 tumours and aberrant p53 in 3/11 (27%). PUC and LE showed concordant p53 staining patterns in 10/11 (91%) and CK20 in only 6/11 (55%) specimens.
Conclusion
We find that LE can extend at least 1 cm from the base of PUC, suggesting consideration for wider resection margins if complete surgical resection is desired. Additionally, LE is clonally related to PUC in most cases, albeit with heterogeneous relationships, as evidenced by both molecular and immunohistochemical findings. Notably, LE can show immunohistochemical findings similar to those commonly reported for CIS. Recognition of LE may improve diagnostic consistency and reduce overdiagnosis of CIS in the setting of prior papillary tumours.