Aishima Shinichi, Nishihara Yunosuke, Kuroda Yousuke, Taguchi Kenichi, Iguchi Tomohiro, Taketomi Akinobu, Maehara Yoshihiko, Tsuneyoshi Masazumi
Department of Pathology, Hamanomachi, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Am J Surg Pathol. 2007 May;31(5):783-91. doi: 10.1097/01.pas.0000213421.53750.0a.
The morphologic characteristics and biologic behavior of small liver cancers with hepatic and biliary differentiation, and their histogenesis, remain unclear. In this study, 35 cases of hepatocellular carcinoma (HCC) smaller than 3 cm in diameter with biliary differentiation were divided into 3 groups, group 1 [cytokeratin (CK) 19-negative/mucin-negative], group 2 (CK 19-positive/mucin-negative), and group 3 (CK 19-positive/mucin-positive). Sixty-one HCCs without biliary differentiation were used as controls. We compared the histologic features of these tumors and the postoperative outcomes. Three morphologic features of HCCs with biliary differentiation were respectively observed in 40% (14/35), 60% (21/35), and 42.9% (15/35) as follows: (1) cancer cells with intermediate morphology, (2) prominent inflammatory cell infiltrate, (3) desmoplastic stroma; neural cell adhesion molecule and c-kit expression were noted in 25.7%(9/35) and 8.6%(3/35), respectively. Extrahepatic tumor recurrence after surgery occurred in 0% (0/16) of group 1, 33.3% (3/9) of group 2, 40.0% (4/10) of group 3, and 8.2% (5/61) of the ordinary HCCs. The tumor-related survival of group 3 patients was worse than that of patients with ordinary HCCs, but there were no differences between the survival of group 1, or group 2 patients and those with ordinary HCCs. Our results suggest that the biliary differentiation does occur even in small HCC, and a mucin-producing cancer cells indicates aggressive tumor behavior. The combination of intermediate cancer cells, inflammatory cell infiltrate, and desmoplastic stroma is likely to be related to the biliary differentiation of HCC.
具有肝和胆管分化的小肝癌的形态学特征、生物学行为及其组织发生仍不清楚。在本研究中，将35例直径小于3 cm且具有胆管分化的肝细胞癌（HCC）分为3组，第1组[细胞角蛋白（CK）19阴性/黏蛋白阴性]，第2组（CK 19阳性/黏蛋白阴性），第3组（CK 19阳性/黏蛋白阳性）。61例无胆管分化的HCC用作对照。我们比较了这些肿瘤的组织学特征和术后结果。具有胆管分化的HCC的三种形态学特征分别在40%（14/35）、60%（21/35）和42.9%（15/35）中观察到，如下：（1）具有中间形态的癌细胞，（2）显著的炎性细胞浸润，（3）促纤维增生性间质；神经细胞黏附分子和c-kit表达分别在25.7%（9/35）和8.6%（3/35）中被观察到。术后肝外肿瘤复发在第1组为0%（0/16），第2组为33.3%（3/9），第3组为40.0%（4/10），普通HCC为8.2%（5/61）。第3组患者的肿瘤相关生存率低于普通HCC患者，但第1组或第2组患者与普通HCC患者的生存率无差异。我们的结果表明，即使在小HCC中也会发生胆管分化，产生黏蛋白的癌细胞表明肿瘤行为具有侵袭性。中间型癌细胞、炎性细胞浸润和促纤维增生性间质的组合可能与HCC的胆管分化有关。
