Assessment of Stromal Invasion for Correct Histological Diagnosis of Early Hepatocellular Carcinoma

Figure 1

Various features of stromal invasion of hepatocellular carcinoma (HCC) and pseudo-invasion (A) Crossing type. Cancer tissue (HCC) invades across fibrous septa (f) of tumor nodule. (B) Longitudinal type. Tumor cells grow longitudinally within fibrous septa (arrowheads). (C) Irregular type. Portal areas are irregularly invaded by tumor cells (Masson trichrome stain). (D) A non-cancerous area without invasion, and a portal area and fibrous septa are clearly seen. (E) Pseudo-invasion. Benign non-cancerous cells are found in the fibrous stroma (Masson trichrome stain). (F) Macroscopic view of stromal invasion. In the non-cancerous area without invasion (area of (a)), fibrous septa are clearly seen. In the area of tumor spread (area of (b)), septa are indistinct. (G) A panoramic view of stromal invasion. In the same way as in (F), the non-cancerous area without invasion (area of (a)) shows distinct fibrous septa. The area of tumor spread (area of (b)) shows indistinct septa because stromal invasion of longitudinal type and irregular type ((B), (C)) reduced the amount of fibrous component. (H) Continuity of fibrous invasion and vascular invasion. The arrows show portal vein (p) invasion. Vascular invasion is continuous to stromal invasion of fibrous tissue of the portal “tract” and fibrous septum (Masson trichrome stain). (I) Masson trichrome staining of pseudoinvasion. (J) Silver staining of the same specimen as (I). Liver cells are clearly surrounded by reticulin fibers. (K) Masson trichrome staining of true invasion. (L) Silver staining of the same specimen as (K). Carcinoma cells are not surrounded by reticulin fibers. (M) (N) Cytokeratin (CK) 7 immunostaining in a non-cancerous area (M) and cancerous area (N). (M) Ductular reaction, confirmed by CK 7 staining, is clearly seen in a non-cancerous, non-invasive area. (N) Ductular reaction is not found in the invasive area. (N) Adapted from Y. Kondo et al. [2], F. Kondo et al. [3], and from F. Kondo [11].