Immunophenotypes and Tumor Immune Microenvironment in Hepatocellular Carcinoma With Macrotrabecular Massive and Vessels Encapsulating Tumor Clusters.

BACKGROUND/AIM: Recently, vessels encapsulating tumor clusters (VETC) pattern and macrotrabecular massive (MTM) pattern of hepatocellular carcinoma (HCC) have been reported as aggressive histological types. These histological patterns showed an immunosuppressive tumor immune microenvironment (TIME). Since there have been no reports on the differences of these two subtypes simultaneously, this study examined the immunophenotypes and TIME of MTM-HCC and VETC-HCC immunohistochemically. PATIENTS AND METHODS: Seventy-four cases of previously diagnosed HCC, including 32 MTM-HCCs, 21 VETC-HCCs, and 21 conventional HCCs, were enrolled in immunohistochemical analysis. We conducted immunohistochemical analysis. RESULTS: We found that MTM-HCC showed less frequent expression of HepPar-1, which is one of the most common hepatocytic markers. In MTM-HCC, the frequency of high expression levels of Keratin19, carbonic anhydrase (CA) IX, and PD-L1 was higher compared to VETC-HCC and conventional HCC. PD-L1 expression was found in 34.4% of MTM-HCC, 0% of VETC-HCC, and 19.0% of conventional HCC. The rate of PD-L1 expression in MTM-HCC was significantly higher than the others (p=0.0015). PD-L1 expression was significantly associated with epithelial cell adhesion molecules and CA IX expression, which are representative markers of tumor stemness and hypoxic conditions, respectively. The CD8 infiltration in VETC-HCC was significantly lower than that in conventional HCC. CONCLUSION: MTM-HCC had different immunophenotypes and TIMEs compared to HCC with the VETC pattern. Although both had immunosuppressive TIME, the elements forming TIME were quite different. To enhance the immune checkpoint inhibitor efficacy, changing TIME from a suppressive to an active form is essential.

Clinicopathological characteristics and molecular analysis of lymphocyte-rich hepatocellular carcinoma.

Lymphocyte-rich hepatocellular carcinoma (LR-HCC), a newly proposed subtype of HCC, is characterized with abundant lymphocyte infiltration in the tumor. LR-HCC has a relatively good prognosis and is quite rare (<1% of all HCC). We examined LR-HCC clinicopathological and molecular characteristics by analyzing 451 surgically resected HCC cases without any prior treatment history at our hospital between 2012 and 2021. Clinicopathological features of LR-HCC and other HCCs (non-LR-HCC) were compared. Neoplastic and nonneoplastic hepatocytes from LR-HCC (n = 4) were collected with a laser microdissection system; RNA was extracted, followed by microarray analysis to examine lymphocytic infiltration-related molecular targets. Immunohistochemical staining of identified molecular target was performed in LR-HCC and non-LR-HCC. CD3, CD20, and CD8 immunostaining was also performed in LR-HCCs. There were 28 cases of LR-HCC (6%). No statistically significant differences were found in clinicopathological features, except for gross type, between LR-HCC and non-LR-HCC cases. The LR-HCC 5-year survival rate was >90%. Microarray analysis revealed high CCL20 expression in LR-HCC cases; immunohistochemical study showed significantly higher CCL20 expression in LR-HCC (P < 0.01) than in non-LR-HCC. CCR6, the only CCL20 receptor, was observed in infiltrating lymphocytes and HCC cells in LR-HCC. There were significantly more CD3-positive cells than CD20-positive cells (P < 0.0001) in tumor-infiltrating lymphocytes, most of which were CD8-positive T cells. In conclusion, there were no significant differences in clinicopathological characteristics between LR-HCC and non-LR-HCC, except for gross and LR microscopic features. CCL20 expression in LR-HCC may contribute to infiltration of large numbers of CD8-positive lymphocytes.

Prognostic impact of vessels encapsulating tumor clusters and macrotrabecular patterns in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) shows a high mortality rate. A macrotrabecular (MT) pattern and vessels encapsulating tumor clusters (VETC) pattern have been reported as aggressive histological patterns in HCC. However, their cut-off values have been contentious. METHOD: Nine hundred eighty-five cases of previously diagnosed HCC were enrolled. The percentage areas of the MT and/or VETC pattern with ≥ 5% at every 10% increment were assessed. Clinicopathological analysis including patients' prognosis was conducted. RESULT: One hundred fifty-eight and eighty-four cases were accompanied by 5-49% and ≥ 50% MT components, respectively. Two hundred six and twenty-nine cases had 5-49% and ≥ 50% VETC components, respectively. Cases with these histological patterns in common had aggressive characteristics and worse prognosis compared to cases with none of these patterns. The presence of 5-49% VETC pattern was independent worse prognostic factor in overall survival (P = 0.046). HCCs with the MT pattern and the VETC pattern were significantly accompanied by the VETC pattern and the MT pattern (P < 0.001), respectively. CONCLUSION: As even 5% of the MT pattern and/or VETC pattern affected the prognosis of patients with HCC, the amount of these pattern should be described in pathological reports. This information could be useful in expecting patients' prognosis and providing proper post-operative treatments.

Clinicopathological Analysis of Non-B Non-C Hepatocellular Carcinoma Focusing on Cellular Proliferation.

BACKGROUND/AIM: Non-B non-C hepatocellular carcinomas (NBNC-HCCs) are larger than hepatitis virus-related HCCs. We conducted a clinicopathological study of patients who underwent curative NBNC-HCC resection, including proliferative activity assessments, such as nuclear grade and Ki-67 labelling index (LI). MATERIALS AND METHODS: Histopathological findings of 197 patients were examined, including 56 NBNC-HCCs, 45 hepatitis B virus (HBV)-related HCCs (HBV-HCC), and 96 hepatitis C virus (HCV)-related HCCs (HCV-HCC). RESULTS: NBNC-HCCs were significantly larger than HCV-HCCs, but not significantly different from HBV-HCCs. Mitotic counts, nuclear grade, and Ki-67 LI of NBNC-HCCs were not significantly different from those of HCV-HCCs, but were significantly lower than those of HBV-HCCs. Recurrence-free survival was significantly better in the NBNC-HCC group than in the HBV-HCC group in cases with mild liver fibrosis. CONCLUSION: NBNC-HCCs were significantly larger in diameter, but their nuclear grade or Ki-67 LI were not significantly different from those of other HCCs, suggesting that they do not have a higher proliferative activity.

Experimental Determination of Relationship between Intramolecular O-D Bond Length and Its Stretching Vibrational Frequency of D2O Molecule in the Liquid State.

Experimental evidence has been obtained for the structure-spectra relationship of hydrogen bonds in aqueous solutions. Intramolecular O-D distance, rOD, has been determined by the least-squares fitting analysis of the neutron interference term in the high-Q region observed for pure D2O and concentrated aqueous solutions. The average O-D stretching frequency, νOD, has been obtained from the position of the center of gravity of the observed ATR-IR O-D stretching band. The linear relationship between rOD and νOD has been confirmed in the liquid state. The slope of dνOD/drOD is evaluated to be -21 000 ± 1000 cm-1 Å-1.

The prognostic impact of combined pulmonary fibrosis and emphysema in patients with clinical stage IA non-small cell lung cancer.

PURPOSE: We evaluated the long-term outcomes of clinical stage IA non-small cell lung cancer (NSCLC) patients with combined pulmonary fibrosis and emphysema (CPFE) who underwent lobectomy. METHODS: We reviewed the chest computed tomography (CT) findings and divided the patients into normal, fibrosis, emphysema and CPFE groups. We evaluated the relationships among the CT findings, the clinicopathological findings and postoperative survival. RESULTS: The patients were classified into the following groups based on the preoperative chest CT findings: normal lung, n = 187; emphysema, n = 62; fibrosis, n = 8; and CPFE, n = 17. The patients with CPFE were significantly older, more likely to be men and smokers, had a higher KL-6 level and lower FEV 1.0% value and had a higher rate of squamous cell carcinoma. The 5-year overall survival (OS) and disease-free survival rates were as follows: normal group, 82.5 and 76.8%; emphysema group, 80.0 and 74.9%; fibrosis group, 46.9 and 50%; and CPFE group, 36.9 and 27.9%, respectively (p < 0.01). A univariate and multivariate analysis determined that the pathological stage and CT findings were associated with OS. CONCLUSIONS: CPFE is a significantly unfavorable prognostic factor after lobectomy, even in early-stage NSCLC patients with a preserved lung function.

Breast carcinoma originating from a silicone granuloma: a case report.

Breast carcinoma rarely occurs in cases of foreign body granulomas following liquid silicone injection. Although the Food and Drug Administration (FDA) banned the use of all silicone injection products in 1992, liquid silicone injection for breast augmentation continues to be performed illegally. We herein report a case of breast carcinoma following liquid silicone injection in a 67-year-old female.A total of 45 years after liquid silicone injection, the patient had felt a breast mass in the right breast. Mammography showed a smooth mass that retracted the right nipple. Due to the presence of a marked acoustic shadow caused by the granulomas, evaluating the mass on ultrasonography was difficult. However, magnetic resonance imaging (MRI) showed a lobulated mass under the right nipple. The mass exhibited low signal intensity (SI) on T1-weighted images and intermingled high and low SI on T2-weighted images. Heterogeneous early enhancement with central low intensity was noted on dynamic contrast-enhanced MRI. Several oval-shaped low SI structures in the adipose tissue and disruption of the pectoralis major muscle were also observed. We diagnosed the patient with invasive ductal carcinoma based on a stereotactic-guided Mammotome® (a vacuum-assisted biopsy system manufactured by DEVICOR MEDICAL JAPAN, Tokyo, Japan) biopsy and subsequently performed mastectomy and axillary lymph node dissection (with a positive result for the sentinel node biopsy). Histologically, invasive ductal carcinoma was observed in the silicone granuloma.The development of foreign body granulomas following breast augmentation usually makes it difficult to detect breast cancer; thus, various devices are required to confirm the histological diagnosis of breast lesions. The stereotactic-guided Mammotome® biopsy system may be an effective device for diagnosing breast cancer developing in the augmented breast.