小细胞膀胱癌（SCBC）是尿路上皮癌（UC）的一种罕见的分化形式。我们旨在确定纯SCBC（n = 16）和混合型（SCBC和UC; n = 30）肿瘤在病理学、基因表达特征、遗传改变和临床结果方面是否有差别。40名（87％）患者接受了一线化疗。29名患者在诊断时没有转移性疾病，并接受了彻底膀胱切除术。纯和混合肿瘤之间的年龄、性别、种族分布、肿瘤大小、表示阶段、治疗反应、病理下分期至≤ypT1N0、总体或无进展生存期（PFS）等没有差异。化疗后病理下分期至≤ ypT2N0M0的肿瘤与无反应肿瘤（≥ypT2≥yN1M1）之间的PFS更长（P = 0.001）。通过新辅助化疗（NAC）实现病理下分期的患者（n = 10）在诊断时为cT2N0M0阶段，并在最后一次随访时存活（中位推后37个月），而未能实现病理下分期的患者中有46％在最后一次随访时存活（中位推后38个月; P = 0.008）。RNA测序显示，混合SCBC的UC与纯SCBC具有类似的神经表达标志。DNA测序揭示了TERT（83％）、P53（56％）、ARID1A（28％）、RB1（22％）和BRCA2（11％）的变化。RB1的免疫组化显示，在18/19例（95％）患者中表达丧失，表明尽管RB1突变的患病率较低，但通路下调较为频繁。纯SCBC和混合型SCBC患者的结果类似，并且这些结果取决于RC的病理分期，对于经NAC后实现病理下分期的患者来说效果最好。©2023 John Wiley＆Sons Ltd。

Small cell bladder carcinoma (SCBC) is a rare, divergent form of urothelial carcinoma (UC). We aimed to determine whether pure (n = 16) and mixed (SCBC and UC; n = 30) tumours differed in pathology, gene expression characteristics, genetic alterations, and clinical outcomes.Forty (87%) patients received first-line chemotherapy. Twenty-nine patients had no metastatic disease at diagnosis and underwent radical cystectomy. There were no differences in age, sex, race distribution, tumour size, stage at presentation, therapy response with pathological downstaging to ≤ypT1N0, or overall or progression-free survival (PFS) between pure and mixed tumours. There was a longer PFS among downstaged chemotherapy-responding tumours ≤ypT2N0M0 than among unresponsive tumours ≥ypT2 ≥ yN1M1 (P = 0.001). Patients who achieved pathological downstaging with neoadjuvant chemotherapy (n = 10) were stage cT2N0M0 at the time of diagnosis and were alive at the last follow-up (median 37 months), while 46% of patients who failed to achieve pathological downstaging were alive at the last follow-up (median 38 months; P = 0.008). RNA sequencing showed that the UC of mixed SCBC had similar neural expression signatures to pure SCBC. DNA sequencing revealed alterations in TERT (83%), P53 (56%), ARID1A (28%), RB1 (22%), and BRCA2 (11%). Immunohistochemistry for RB1 showed loss of expression in 18/19 (95%) patients, suggesting frequent pathway downregulation despite a low prevalence of RB1 mutation.Patients with pure and mixed SCBC have similar outcomes and these outcomes are determined by the pathological stage at RC and are best among patients who have pathological downstaging after NAC.© 2023 John Wiley & Sons Ltd.