Nakanuma Yasuni, Sasaki Motoko, Kakuda Yuko, Harada Kenichi, Sato Yasunori, Sugino Takashi
Division of Pathology, Shizuoka Cancer Center, Shizuoka, Japan; Department of Diagnostic Pathology, Fukui Prefecture Saiseikai Hospital, Fukui, Japan.
Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
Hum Pathol. 2025 Jul;161:105865. doi: 10.1016/j.humpath.2025.105865. Epub 2025 Jul 2.
To characterize "neoplastic ductal plate malformation pattern (N-DPMP)" of intrahepatic cholangiocarcinoma (iCCA) and to evaluate whether or not von Meyenburg complexes (VMCs) and VMC-mimics characterized by dysplasia/carcinoma in situ were related to the development of iCCA.
N-DPMP composed of low-grade neoplastic biliary epithelia and showing ductal plate malformation (DPM) features, VMCs, and VMC-mimics were surveyed in 144 small duct-type (SD)-iCCA cases and 47 large duct-type (LD)-iCCA cases. Genetic alterations were examined by direct sequencing and immunohistochemistry. 536 autopsied livers were used as controls.
N-DPMP was found in 27 cases of SD-iCCA but not in LD-iCCA (p < 0.05). While a tumor totally composed of N-DPMP was found in 4 cases, a tumor composed of N-DPMP and anastomosing CCA and/or conventional CCA was found in the remaining 23 cases, with the latter being larger than the former (p < 0.05). Genetic alterations in N-DPMP parts were also found in anastomosing parts in two cases of N-DPMP with anastomosing CCA, supporting that anastomosing CCA may develop in N-DPMP. VMCs were found frequently in 49 cases of SD-iCCA than in 16 cases of autopsy livers (p < 0.01). VMC-mimics, which were found in 5 of 144 SD-iCCA cases, frequently showed mixture of atypical and benign epithelia with an abrupt transition, suggesting that VMC-mimics may reflect cancerization of VMCs by iCCA.
N-DPMP may be an early neoplastic lesion in approximately one-fifth of SD-iCCA. VMCs may be frequently associated with SD-iCCA, but there is no evidence that VMCs are a precursor of SD-iCCA.
描述肝内胆管癌（iCCA）的“肿瘤性胆管板畸形模式（N-DPMP）”，并评估以发育异常/原位癌为特征的von Meyenburg复合体（VMCs）和VMC模拟物是否与iCCA的发生有关。
在144例小胆管型（SD）-iCCA病例和47例大胆管型（LD）-iCCA病例中，对由低级别肿瘤性胆管上皮组成并表现出胆管板畸形（DPM）特征的N-DPMP、VMCs和VMC模拟物进行了研究。通过直接测序和免疫组织化学检测基因改变。536例尸检肝脏用作对照。
27例SD-iCCA病例中发现了N-DPMP，而LD-iCCA病例中未发现（p<0.05）。4例病例中发现肿瘤完全由N-DPMP组成，其余23例病例中发现肿瘤由N-DPMP与吻合性CCA和/或传统CCA组成，后者比前者大（p<0.05）。在2例伴有吻合性CCA的N-DPMP病例中，吻合部位也发现了N-DPMP部分的基因改变，支持吻合性CCA可能在N-DPMP中发生。49例SD-iCCA病例中VMCs的发现频率高于16例尸检肝脏（p<0.01）。在144例SD-iCCA病例中的5例中发现了VMC模拟物，其常表现为非典型上皮和良性上皮的混合且有突然转变，提示VMC模拟物可能反映了iCCA对VMCs的癌变作用。
N-DPMP可能是约五分之一的SD-iCCA中的早期肿瘤性病变。VMCs可能经常与SD-iCCA相关，但没有证据表明VMCs是SD-iCCA的前体。
