TREM-2 defends the liver against hepatocellular carcinoma through multifactorial protective mechanisms.

OBJECTIVE: Hepatocellular carcinoma (HCC) is a prevalent and aggressive cancer usually arising on a background of chronic liver injury involving inflammatory and hepatic regenerative processes. The triggering receptor expressed on myeloid cells 2 (TREM-2) is predominantly expressed in hepatic non-parenchymal cells and inhibits Toll-like receptor signalling, protecting the liver from various hepatotoxic injuries, yet its role in liver cancer is poorly defined. Here, we investigated the impact of TREM-2 on liver regeneration and hepatocarcinogenesis. DESIGN: TREM-2 expression was analysed in liver tissues of two independent cohorts of patients with HCC and compared with control liver samples. Experimental HCC and liver regeneration models in wild type and Trem-2-/- mice, and in vitro studies with hepatic stellate cells (HSCs) and HCC spheroids were conducted. RESULTS: TREM-2 expression was upregulated in human HCC tissue, in mouse models of liver regeneration and HCC. Trem-2-/- mice developed more liver tumours irrespective of size after diethylnitrosamine (DEN) administration, displayed exacerbated liver damage, inflammation, oxidative stress and hepatocyte proliferation. Administering an antioxidant diet blocked DEN-induced hepatocarcinogenesis in both genotypes. Similarly, Trem-2-/- animals developed more and larger tumours in fibrosis-associated HCC models. Trem-2-/- livers showed increased hepatocyte proliferation and inflammation after partial hepatectomy. Conditioned media from human HSCs overexpressing TREM-2 inhibited human HCC spheroid growth in vitro through attenuated Wnt ligand secretion. CONCLUSION: TREM-2 plays a protective role in hepatocarcinogenesis via different pleiotropic effects, suggesting that TREM-2 agonism should be investigated as it might beneficially impact HCC pathogenesis in a multifactorial manner.

Pathogenesis of Cholangiocarcinoma.

Cholangiocarcinoma (CCA) encompasses a group of malignancies that can arise at any point in the biliary tree. Although considered a rare cancer, the incidence of CCA is increasing globally. The silent and asymptomatic nature of these tumors, particularly in their early stages, in combination with their high aggressiveness, intra- and intertumor heterogeneity, and chemoresistance, significantly compromises the efficacy of current therapeutic options, contributing to a dismal prognosis. During the last few years, increasing efforts have been made to unveil the etiologies and pathogenesis of these tumors and to develop more effective therapies. In this review, we summarize current findings in the field of CCA, mainly focusing on the mechanisms of pathogenesis, cells of origin, genomic and epigenetic abnormalities, molecular alterations, chemoresistance, and therapies.

A comprehensive diagnosis of a desmoplastic small round cell tumor of unusual location based on fine-needle aspiration cytology: Report of a case arising in the parotid gland and review of the literature.

Desmoplastic small round cell tumor (DSRCT) is rare and a highly aggressive neoplasm that typically involves the soft tissues of the abdomen or pelvis in children or young adults, showing a male predilection. Although it can occurs over a wide age range, the peak incidence is in the third decade of life. DSRCT usually shows widespread abdominal serosal involvement, and overall patient survival is poor. On the other hand, extra-abdominal DSRCT is very rare. DSRCT in major salivary glands has been reported, but it is extremely rare. In the majority of reported series diagnosis is made by the histological analysis of FFPE tissues together with immunohistochemistry (IHC) and molecular analysis, particularly the demonstration of chromosomal translocation involving EWSR1. Very few cases have been diagnosed so far by Fine Needle Aspiration (FNA) cytology. Moreover ancillary studies have been performed in all reported cases in FFPE samples. There is still controversy and lack of consensus regarding the suitability of cytological samples especially smears for immunocytochemical (ICC) and fluorescence in situ hybridization (FISH), what makes its standardization difficult. We report a case of a primary DSRCT of parotid gland in a 17-year-old male diagnosed by FNA cytology. The cytomorphological diagnosis was coupled with ICC and FISH analysis performed on stained smears. We emphasize the feasibility and reliability of cytological smears for the application of immunocytochemical and molecular techniques.