Intraductal spread of urothelial carcinoma (UC) is not an uncommon finding in bladder cancer that requires appropriate clinical management. The presence of prostatic stromal invasion in non–muscle-invasive bladder cancer upstages the disease, necessitating cisplatin-based neoadjuvant chemotherapy and subsequent cystroprostatectomy. However, the identification of prostatic stromal invasion can be challenging, especially in biopsy and transurethral resection specimens. We assess the utility of D2-40, CK5/6, and high–molecular-weight cytokeratin (HMWCK) immunohistochemistry as an ancillary tool to differentiate prostatic stromal invasion from intraductal UC spread. We reviewed 13 cystoprostatectomies performed for UC with prostatic involvement. The presence of stromal invasion was histologically determined by the presence of circumferential retraction artifact, paradoxical differentiation, complex architecture, and desmoplastic reaction. The areas of interest were subsequently stained with D2-40, CK5/6, and HMWCK (clone 34βE12). Four bladder biopsies were used as a control to assess labeling in the benign urothelium. Nine cases had histologic evidence of prostatic stromal invasion (4 transmurally through bladder wall). D2-40 highlighted basal cells in all benign prostatic ducts and was consistently negative in UC, benign urothelium, prostatic adenocarcinoma, and benign luminal prostatic epithelium. D2-40 and CK5/6 performed similarly for intraductal UC, labeling only the basal cell layer with the exception of 1 case with squamous differentiation where CK5/6 exhibited full thickness staining. HMWCK diffusely stained 9 of 10 intraductal UCs without squamous differentiation and 1 intraductal UC with squamous differentiation. All 8 cases of invasive UC without squamous differentiation were negative for D2-40. Seven of these cases had focal CK5/6 and diffuse HMWCK staining. In 1 case of invasive UC with squamous differentiation, all stains were positive. D2-40 is expressed in prostatic basal cells, but it is not expressed in the benign or neoplastic urothelium. D2-40 and CK5/6 effectively highlight the intraductal spread of UC. While invasive UC is negative for D2-40, CK5/6 is usually patchy and localized to the periphery of the tumor nests. HMWCK often demonstrates diffuse staining in both scenarios. However, these stains do not perform well in cases of UC with squamous differentiation. Thus, D2-40 can be used as an ancillary tool to rule out prostatic stromal invasion.

尿路上皮癌 (UC) 的导管内扩散在膀胱癌中并不罕见，需要适当的临床治疗。非肌层浸润性膀胱癌中前列腺间质浸润的存在会导致疾病进展，因此需要基于顺铂的新辅助化疗和随后的膀胱前列腺切除术。然而，前列腺间质侵犯的识别可能具有挑战性，特别是在活检和经尿道切除标本中。我们评估了 D2-40、CK5/6 和高分子量细胞角蛋白 (HMWCK) 免疫组织化学作为区分前列腺间质侵袭和导管内 UC 扩散的辅助工具的效用。我们回顾了 13 例因 UC 累及前列腺而进行的膀胱前列腺切除术。间质侵入的存在通过组织学上的圆周回缩伪影、矛盾的分化、复杂的结构和促纤维增生反应的存在来确定。随后用 D2-40、CK5/6 和 HMWCK（克隆 34βE12）对感兴趣的区域进行染色。使用四个膀胱活检作为对照来评估良性尿路上皮的标记。9 例有前列腺间质侵犯的组织学证据（4 例经膀胱壁透壁）。D2-40 突出显示所有良性前列腺管中的基底细胞，并且在 UC、良性尿路上皮、前列腺腺癌和良性管腔前列腺上皮中始终呈阴性。D2-40 和 CK5/6 对于导管内 UC 的表现类似，仅标记基底细胞层，但 1 例鳞状分化病例除外，其中 CK5/6 表现出全层染色。HMWCK 对 10 个无鳞状分化的导管内 UC 中的 9 个和 1 个有鳞状分化的导管内 UC 进行了广泛染色。所有8例无鳞状分化的侵袭性UC病例D2-40均为阴性。其中 7 例具有局灶性 CK5/6 和弥漫性 HMWCK 染色。1例伴有鳞状分化的浸润性UC，所有染色均呈阳性。D2-40 在前列腺基底细胞中表达，但在良性或肿瘤性尿路上皮中不表达。D2-40 和 CK5/6 有效地突出了 UC 的导管内扩散。虽然侵袭性 UC 的 D2-40 呈阴性，但 CK5/6 通常呈斑片状，且位于肿瘤巢的外围。HMWCK 通常在这两种情况下都表现出弥漫性染色。然而，这些染色剂在具有鳞状分化的 UC 病例中表现不佳。因此，D2-40可以用作排除前列腺间质侵袭的辅助工具。