Robert J Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH.
Boca Raton Regional Hospital/Florida Atlantic University College of Medicine, Boca Raton, FL.
Am J Surg Pathol. 2020 Oct;44(10):1322-1330. doi: 10.1097/PAS.0000000000001532.
Trophoblastic differentiation (including choriocarcinoma) arising in urothelial carcinoma has been described in numerous case reports, but never in a single series. We present a series of these tumors, describing the morphologic spectrum, applying traditional and novel immunohistochemical stains, and characterizing clinical follow-up. We identified 16 cases, arising predominantly in the bladder (N=14), but also the ureter (N=1) and prostatic urethra (N=1). Six of our cases (38%) contained invasive urothelial carcinoma with admixed syncytiotrophoblasts, 8 cases (50%) consisted of invasive urothelial carcinoma with choriocarcinoma, 1 case (6%) showed urothelial carcinoma in situ with associated choriocarcinoma, and 1 case (6%) consisted of pure choriocarcinoma. Other subtypes of variant morphology were seen in 5 of our cases (31%) and included squamous, glandular, lipoid, chordoid/myxoid, and sarcomatoid features. Given the limited specificity of human chorionic gonadotropin immunohistochemistry, we also studied the expression of a novel specific trophoblastic marker, hydroxyl-δ-5-steroid dehydrogenase, as well as Sal-like protein 4. Human chorionic gonadotropin expression was seen in nearly all cases (93%) but was often not limited to the trophoblastic component, staining the urothelial component also in 85% of the cases. Expression of hydroxyl-δ-5-steroid dehydrogenase was more sensitive and more specific, staining 100% of the cases and limited to trophoblasts in all but 1 case. Sal-like protein 4 expression was variable, staining trophoblast in only 50% of cases and staining the urothelial carcinoma component in 43% of those positive cases. Most of our tumors presented at a high stage and were associated with poor clinical outcomes, with at least muscle-invasive disease (pT2) in 10 of the 14 bladder tumors (71%), periureteric fat invasion in the ureter tumor (pT3), distant metastases in 7 of 16 cases (44%) and death of disease in 3 of the 15 patients with follow-up (20%). Our study describes a series of urothelial carcinomas with trophoblastic differentiation, demonstrating the morphologic spectrum of this entity, its frequent association with other subtypes of variant morphology, its characteristic immunoprofile, and its aggressive clinical behavior.
尿路上皮癌中发生的滋养细胞分化（包括绒毛膜癌）在众多病例报告中已有描述，但从未在单一系列中出现。我们报告了一系列此类肿瘤，描述了形态学谱，应用了传统和新型免疫组织化学染色，并对临床随访进行了特征描述。我们共发现 16 例肿瘤，主要发生于膀胱（N=14），也发生于输尿管（N=1）和前列腺尿道（N=1）。我们的 6 例（38%）病例含有混合有合体滋养层的浸润性尿路上皮癌，8 例（50%）为浸润性尿路上皮癌伴绒毛膜癌，1 例（6%）为伴有绒毛膜癌的原位尿路上皮癌，1 例（6%）为单纯绒毛膜癌。我们的 5 例（31%）病例还存在其他亚型的变异形态，包括鳞状、腺性、脂性、索状/黏液样和肉瘤样特征。鉴于人绒毛膜促性腺激素免疫组织化学的特异性有限，我们还研究了一种新型特定滋养层标志物羟基-δ-5-类固醇脱氢酶以及 Sal 样蛋白 4 的表达。我们几乎在所有病例（93%）中都观察到人绒毛膜促性腺激素的表达，但该表达并不局限于滋养层成分，在 85%的病例中也染色尿路上皮成分。羟基-δ-5-类固醇脱氢酶的表达更敏感且更特异，除 1 例外，所有病例均为 100%阳性，且仅限于滋养层。Sal 样蛋白 4 的表达呈可变型，仅在 50%的病例中染色滋养层，在阳性病例中 43%染色尿路上皮癌成分。我们的大多数肿瘤分期较高，临床结局较差，14 例膀胱肿瘤中有 10 例（71%）为至少肌层浸润性疾病（pT2），输尿管肿瘤有输尿管周围脂肪浸润（pT3），7 例（44%）有远处转移，15 例有随访的患者中有 3 例（20%）死于疾病。我们的研究描述了一系列具有滋养细胞分化的尿路上皮癌，展示了该实体的形态学谱，其常见的伴发其他变异形态亚型，其特征性免疫表型以及侵袭性临床行为。
