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Updated: Oct 21, 2025
Pathological Analysis of Lung Metastasis Following Lateral Tail-Vein Injection of Tumor Cells
Published on: May 20, 2020
Lung and lymph node metastases from hepatocellular carcinoma: Comparison of pathological aspects
Ha Young Woo1,2, Hyungjin Rhee3, Jeong Eun Yoo1
1Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Insights
Extrahepatic metastasis from hepatocellular carcinoma (HCC) shows distinct organ-specific pathology. Lung metastases are linked to VETC-HCC and MTM-HCC, while lymph node metastases exhibit EMT-high features and increased immune infiltration.
Area of Science:
- Oncology
- Pathology
- Cancer Metastasis
Background:
- Hepatocellular carcinoma (HCC) metastasis to organs outside the liver is a critical clinical event.
- Understanding the specific pathological characteristics of these extrahepatic metastases is crucial but remains unclear.
Purpose of the Study:
- To characterize the pathological features of HCC metastases in various organs.
- To identify factors associated with extrahepatic spread and organ-specific metastatic patterns.
Main Methods:
- Collected intrahepatic HCC (n=322) and extrahepatic metastatic HCC (n=130) samples.
- Performed clinicopathological evaluation and immunostaining for K19, CD34, αSMA, FAP, CAIX, VEGF, PD-L1, CD3, CD8, Foxp3, CD163, and EMT markers.
Main Results:
- Extrahepatic metastasis was associated with BCLC stage B-C, microvascular invasion, VETC-HCC, K19, FAP expression, and CD163+ macrophage infiltration.
- Lung metastases showed high proportions of VETC-HCC and MTM-HCC.
- Lymph node metastases displayed high rates of EMT-high features, K19 expression, fibrous stroma (αSMA, FAP), and significant immune cell infiltration (PD-L1, CD3+, CD8+, Foxp3+, CD163+).
Conclusions:
- Metastatic HCC exhibits diverse pathological features depending on the target organ.
- VETC and MTM subtypes correlate with lung metastasis.
- K19 expression, EMT-high features, fibrous stroma, and immune cell infiltration are linked to lymph node metastasis.
Background & Aims:
Extrahepatic metastasis from hepatocellular carcinoma (HCC) is a catastrophic event, yet organ-specific pathological characteristics of metastatic HCC remain unclear. We aimed to characterize the pathological aspects of HCC metastases to various organs.
Methods:
We collected intrahepatic HCC (cohort 1, n = 322) and extrahepatic metastatic HCC (cohort 2, n = 130) samples. Clinicopathological evaluation and immunostaining for K19, CD34, αSMA, fibroblast-associated protein (FAP), CAIX, VEGF, PD-L1, CD3, CD8, Foxp3, CD163 and epithelial-mesenchymal transition (EMT)-related markers were performed.
Results:
Independent factors for extrahepatic metastasis included BCLC stage B-C, microvascular invasion (MVI), vessels encapsulating tumour clusters (VETC)-HCC, K19 and FAP expression, and CD163+ macrophage infiltration (cohort 1, P < .05 for all). Lung metastases (n = 63) had the highest proportion of VETC-HCC and macrotrabecular-massive (MTM)-HCC. Lymph node metastases (n = 19) showed significantly high rates of EMT-high features, K19 expression, fibrous tumour stroma with αSMA and FAP expression, high immune cell infiltration, PD-L1 expression (combined positive score), CD3+, CD8+, Foxp3+ T cell and CD163+ macrophage infiltration (adjusted P < .05 for all). In both cohorts, EMT-high HCCs showed higher rates of K19 expression, fibrous tumour stroma, high immune cell infiltration, PD-L1 expression and CD3+ T cell infiltration, whereas EMT-low HCCs were more frequent among VETC-HCCs (P < .05 for all). Overall phenotypic features were not significantly different between paired primary-metastatic HCCs (n = 32).
Conclusions:
Metastatic HCCs to various organs showed different pathological features. VETC and MTM subtypes were related to lung metastasis, whereas K19 expression, EMT-high features with fibrous tumour stroma and high immune cell infiltration were related to lymph node metastasis.
