Objective: To analyze the correlation between the histological classification of hepatocellular carcinoma (HCC), especially macrotrabecular-massive (MTM), tumor invasiveness, and prognosis. Methods: The clinical and follow-up data of 246 consecutive HCC cases who met the inclusion criteria from 2015 to 2018 were retrospectively analyzed. They were divided into trabecular/pseudoglandular, trabecular/patchy, and MTM types according to the histological classification. The relationship between each type and related clinicopathological features was analyzed. The Kaplan-Meier method was used to plot tumor-free survival (DFS) and overall survival (OS) curves. Log rank tests, COX univariate, and multivariate regression analyses were conducted to analyze the relationship between clinical features, including histological classification, DFS, and OS. Results: Trabecular/pseudoglandular, trabecular/nodular, and MTM type proportions were 44.7% (110 cases), 32.9% (81 cases), and 22.4% (55 cases), respectively. The results of the clinicopathological features showed that MTM-type HCC was significantly more invasive than the other two types, with alpha-fetoprotein (AFP) ≥400 ng/ml, tumor diameter≥8 cm, no tumor capsule, poor differentiation, and MVI positivity proportions, and the differences were statistically significant (P < 0.05).The proportion of MTM-type HCC patients with American Joint Committee on Cancer TNM Stage III to IV and Chinese Liver Cancer Staging (CNLC) II to II was significantly higher than that of the first two types, and the differences were statistically significant (P < 0.05). In addition, the proportion of MTM subtypes undergoing transcatheter arterial chemoembolization was also raised (P < 0.05). The DFS and OS were significantly lower for MTM-type HCC compared to trabecular/pseudoductal-type HCC at 1-, 3-, and 5-years, and the differences were statistically significant (P < 0.05). Univariate analysis indicated that strongly invasive clinical pathological features such as alpha fetoprotein (AFP) ≥400 ng/ml, tumor diameter ≥ 8 cm, no tumor capsule, poor differentiation, positive microvascular invasion, tumor stage, and MTM staging were all risk factors affecting DFS and OS (P < 0.05). Multivariate COX analysis showed that MTM histological staging, AFP ≥ 400 ng/ml, tumor non-encapsulation, satellite nodules, CNLC stages II~III, and TNM stages III~IV were independent risk factors for DFS (P < 0.05), while AFP ≥ 400 ng/ml, tumor non-encapsulation, and CNLC stage II~III were independent risk factors for OS ( P < 0.05). Conclusion: Histological classification is highly correlated with tumor invasiveness and HCC prognosis. Trabecular/pseudoglandular types have lower malignancy and a better prognosis, while MTM types exhibit strong invasive features and a poor prognosis.
目的： 分析肝细胞癌（HCC）组织学分型，特别是粗梁实体（MTM）型与肿瘤侵袭性及预后的相关性。 方法： 回顾性分析2015至2018年符合纳入标准连续246例HCC患者的临床和随访资料，依据组织学分型分为细梁/假腺管型、粗梁/团片型、MTM型，分析各型与相关临床病理特征关系，Kaplan-Meier法绘制无瘤生存率（DFS）和总生存率（OS）曲线并行Log-rank检验，COX单因素及多因素回归分析包括组织学分型在内的临床特征与DFS和OS关系。 结果： 细梁/假腺管型、粗梁/团片型、MTM型比例分别为44.7%（110例）、32.9%（81例）和22.4%（55例）。结果显示，MTM型HCC中提示高侵袭性的临床病理特征甲胎蛋白（AFP） ≥ 400 ng/ml、肿瘤直径≥ 8 cm、无肿瘤包膜、分化差、微血管侵犯（MVI）阳性比例显著高于其他2种类型，差异均有统计学意义（P值均< 0.05）。MTM型HCC TNM III～IV期和中国肝癌分期（CNLC）II～II期患者的比例显著也高于其他2种类型，差异均有统计学意义（P值均< 0.05），且MTM亚型行经导管动脉化疗栓塞术比例也较高（P < 0.05）。MTM型HCC的1、3、5年DFS和OS显著低于细梁/假腺管型HCC的1、3、5年DFS和OS，差异均有统计学意义（P值均< 0.05）。单因素分析提示高侵袭性的临床病理特征甲胎蛋白（AFP） ≥ 400 ng/ml、肿瘤直径≥ 8 cm、无肿瘤包膜、分化差、微血管侵犯阳性、肿瘤分期和MTM分型均是影响DFS和OS的危险因素（P值均< 0.05）。多因素COX分析显示MTM组织学分型、AFP ≥ 400 ng/ml、肿瘤无包膜、卫星灶、CNLC II～III期及TNM III～IV期是DFS的独立危险因素（P值均< 0.05）；而AFP ≥ 400 ng/ml、肿瘤无包膜和CNLC II～III期是OS的独立危险因素（P值均< 0.05）。 结论： 组织学分型与HCC肿瘤侵袭性和预后高度相关，细梁/假腺管型恶性程度较低，预后较好，而MTM型则表现出强侵袭性特征，预后不良。.
Keywords: Aggressiveness; Hepatocellular carcinoma; Histological classification; Macrotrabecular-massive subtype; Prognosis.