Woo HY, Rhee H, Yoo JE, et al. - Pathological features of metastatic hepatocellular carcinomas (HCCs) to various organs differed. Vessels encapsulating tumor clusters (VETC) and macrotrabecular-massive (MTM) subtypes were correlated with lung metastasis, whereas lymph node metastasis was associated with K19 expression, epithelial-mesenchymal transition (EMT)-high features with fibrous tumor stroma and high immune cell infiltration.

• The authors collected samples from patients with intrahepatic HCC (cohort 1, n = 322) and extrahepatic metastatic HCC (cohort 2, n = 130).

• BCLC stage B–C, microvascular invasion, VETC-HCC, K19 and fibroblast-associated protein (FAP) expression, and CD163+ macrophage infiltration were all independent factors for extrahepatic metastasis.

• The proportion of VETC-HCC and MTM-HCC was highest in lung metastases (n = 63).

• Lymph node metastases (n = 19) had significantly higher rates of EMT-high features, such as K19 expression, fibrous tumor stroma with SMA and FAP expression, high immune cell infiltration, PD-L1 expression (combined positive score), CD3+, CD8+, Foxp3+ T cell, and CD163+ macrophage infiltration.

• EMT-high HCCs had higher rates of K19 expression, fibrous tumor stroma, high immune cell infiltration, PD-L1 expression, and CD3+ T cell infiltration in both cohorts, whereas EMT-low HCCs were more common in VETC-HCCs.

• The overall phenotypic features of paired primary-metastatic HCCs (n = 32) were not significantly different.