Macrotrabecular-Massive Subtype Is Associated with a High Risk of the Recurrence of Hepatocellular Carcinoma

<b>Background</b>: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide, mainly due to its high recurrence rate after curative treatments. The macrotrabecular-massive (MTM) subtype has recently been recognized as an aggressive histologic variant associated with vascular invasion and poor differentiation. This study aimed to investigate the prognostic impact of the MTM subtype on recurrence after surgical resection of HCC. <b>Methods</b>: We retrospectively reviewed 171 patients who underwent curative hepatic resection for HCC between January 2007 and December 2017 at Gangnam Severance Hospital, Seoul, Korea. Clinicopathologic parameters, including immune-related features such as lymphoid infiltration and tertiary lymphoid structures (TLSs), were evaluated. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox regression analyses. <b>Results</b>: During a median follow-up of 4.4 ± 3.4 years, 74 patients (43.3%) experienced recurrence. The MTM subtype was significantly more frequent in the recurrence group than in the non-recurrence group (47.3% vs. 21.6%, <i>p</i> < 0.001). Multivariate analysis identified MTM subtype as an independent predictor of recurrence (hazard ratio, 1.88; 95% CI, 1.14-3.10; <i>p</i> = 0.013). Lymphoid infiltration and TLSs were not associated with prognosis. Kaplan-Meier analysis showed higher recurrence in MTM-positive cases (<i>p</i> = 0.001), whereas OS did not differ significantly (<i>p</i> = 0.094). <b>Conclusions</b>: The macrotrabecular-massive subtype is an independent histopathologic predictor of recurrence after curative resection in HCC. Incorporating MTM subtype recognition into postoperative risk assessment may enhance patient stratification and inform future adjuvant therapy strategies.