目的:肿块型肝内胆管癌(MF-iCCAs),涉及小胆管,赫林的胆管或运河,仍然被视为一个单一的实体。我们旨在研究组织学的多样性,MF-ICCAs的表型和肿瘤脉管系统。
结果:基于形态学和免疫表型,我们将MF-ICCAs分类为小胆管(SBD),胆管癌(CLC),导管板畸形(DPM)和肝细胞癌(HCC)样亚型。通过多区域肿瘤测序检查了组织学亚型之间的遗传相关性。在62个MF-iCCAs中具有不同比例的组织学亚型的肿瘤组中,比较了血管和其他临床病理特征。纯SBD的情况下,CLC,DPM和HCC样亚型编号为18(29%),七(11.3%),无(0%)和两个(3%),其余35例(56.4%)分别由几个部分组成。遗传改变,异柠檬酸脱氢酶(IDH)1/2,KRAS,TP53,聚溴-1(PBRM1)和BRCA1相关蛋白1(BAP1),在SBD之间共享,CLC,肿瘤内的DPM和肝样成分。我们发现了SBD之间不同的血管化机制,CLC和DPM亚型在CLC肿瘤中具有突出的血管共同选择。具有DPM模式的iCCA具有最高的血管密度(平均微血管密度,140/mm2;动脉血管密度,18.3/mm2)。CLC组分增加与总生存时间延长相关(r=0.44,P=0.006)。与具有CLC模式的MF-iCCA相比,纯SBD肿瘤的5年总生存率较低(30.5对72.4%,P=0.011)。
结论:MF-iCCAs包含四种组织学亚型。鉴于他们共享一些驱动基因改变,表明它们可以有共同的细胞起源,SBD,CLC和DPM亚型,然而,细胞分化不同,组织学,表型或肿瘤脉管系统。
OBJECTIVE: Mass-forming intrahepatic cholangiocarcinomas (MF-iCCAs), involving small bile ducts, bile ductules or canals of Hering, remain treated as a single entity. We aimed to examine the diversity in histology, phenotype and tumour vasculature of MF-iCCAs.
RESULTS: Based on morphology and immunophenotype, we classified MF-iCCAs into small bile duct (SBD), cholangiolocarcinoma (CLC), ductal plate malformation (DPM) and hepatocellular carcinoma (HCC)-like subtypes. Genetic correlations among the histological subtypes were examined by multi-region tumour sequencing. Vasculatures and other clinicopathological features were compared among tumour groups with various proportions of the histological subtypes in 62 MF-iCCAs. Cases of pure SBD, CLC, DPM and HCC-like subtypes numbered 18 (29%), seven (11.3%), none (0%) and two (3%), respectively; the remaining 35 (56.4%) cases comprised several components. Genetic alterations, isocitrate dehydrogenase (IDH)1/2, KRAS, TP53, polybromo-1 (PBRM1) and BRCA1-associated protein 1 (BAP1), were shared among SBD, CLC, DPM and hepatoid components within a tumour. We uncovered distinct vascularisation mechanisms among SBD, CLC and DPM subtypes with a prominent vessel co-option in CLC tumours. iCCA with a DPM pattern had the highest vascular densities (mean microvascular density,140/mm2 ; arterial vessel density, 18.3/mm2 ). Increased CLC component was correlated with longer overall survival time (r = 0.44, P = 0.006). Pure SBD tumours had a lower 5-year overall survival rate compared with MF-iCCA with CLC pattern (30.5 versus 72.4%, P = 0.011).
CONCLUSIONS: MF-iCCAs comprise four histological subtypes. Given their sharing some driver gene alterations, indicating they can have a common cell origin, SBD, CLC and DPM subtypes, however, differ in cell differentiation, histology, phenotype or tumour vasculature.