Parimi Vamsi, Choi Woonyoung, Feng Mingxiao, Fong Megan, Hoffman-Censits Jean, Kates Max, Lombardo Kara A, Comperat Eva, McConkey David J, Hahn Noah M, Esteves Rodrigo Salgado, Matoso Andres
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Department of Urology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Histopathology. 2023 Jun;82(7):991-1002. doi: 10.1111/his.14883. Epub 2023 Feb 21.
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.
小细胞膀胱癌（SCBC）是尿路上皮癌（UC）的一种罕见的、不同类型。我们旨在确定纯（n = 16）和混合（SCBC与UC；n = 30）肿瘤在病理、基因表达特征、基因改变和临床结局方面是否存在差异。
40例（87%）患者接受一线化疗。29例患者诊断时无转移性疾病并接受了根治性膀胱切除术。纯肿瘤与混合肿瘤在年龄、性别、种族分布、肿瘤大小、就诊时分期、治疗反应及病理降期至≤ypT1N0、总生存期或无进展生存期（PFS）方面均无差异。降期至≤ypT2N0M0的化疗反应性肿瘤的PFS长于未反应肿瘤≥ypT2≥yN1M1（P = 0.001）。新辅助化疗后实现病理降期的患者（n = 10）诊断时为cT2N0M0期，最后一次随访时仍存活（中位时间37个月），而未实现病理降期的患者中46%在最后一次随访时仍存活（中位时间38个月；P = 0.008）。RNA测序显示，混合性SCBC的UC具有与纯SCBC相似的神经表达特征。DNA测序显示TERT（83%）、P53（56%）、ARID1A（28%）、RB1（22%）和BRCA2（11%）存在改变。RB1免疫组化显示18/19例（95%）患者表达缺失，提示尽管RB1突变发生率低，但该通路频繁下调。
纯和混合SCBC患者的结局相似，这些结局由根治性膀胱切除术时的病理分期决定，在新辅助化疗后实现病理降期的患者中最佳。
