Remarkable advancements in techniques of genomic profiling and bioinformatics have led to the accumulation of vast amounts of knowledge on the genomic profiles of biliary tract cancer (BTC). Recent largescale molecular profiling studies have not only highlighted genomic differences characterizing tumors of the intrahepatic and extrahepatic bile ducts and gallbladder, but have also revealed differences in genomic profiles pertaining to associated risk factors. Novel genomic alterations such as FGFR2 fusions and IDH1/2 mutations in intrahepatic cholangiocarcinoma (ICC) and ERBB2 alterations in gallbladder cancer (GBCA) are emerging as targeted therapy options capable of advancing precision medicine for the care of these patients. Moreover, variable genomic alterations also appear to impact prognosis and overall disease outcome independent from their therapy selection value. High mutational burden and increased expression of immune checkpoint-related proteins observed in a subset of BTC also show a potential for guidance of immunotherapy. Thus, comprehensive genomic profiling (CGP) is rapidly achieving status as an integral component of precision medicine and is starting to become invaluable in guiding the management of patients with BTC, a rare disease with dismal outcome.

Precursor lesions of invasive adenocarcinoma of the bile duct (cholangiocarcinoma) have been increasingly recognized during the past decade because of the results of multiple studies on the carcinogenesis of cholangiocarcinoma, technologic advancements in diagnostic imaging modalities, and an increase in the volume of elective procedures. The two main precursor lesions of cholangiocarcinoma that have evolved are biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. These lesions demonstrate histomorphologic similarities to pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm of the pancreas, respectively, whereas mechanisms of carcinogenesis and risk of progressive disease appear distinct. An enhanced understanding of the clinical presentation and pathologic features of precursor lesions of the biliary tract and use of the correct terminology will facilitate efficient communication between surgeons, oncologists, and pathologists and improve quality of patient care.

Idiopathic Non-Cirrhotic Portal Hypertension and Porto-Sinusoidal Vascular Disease: Review of Current Data

Colorectal cancer is the third leading cause of cancer-related death, and its incidence is rising in the younger patient population. In the past decade, research has unveiled several processes (underlying tumorigenesis, many of which involve interactions between tumor cells and the surrounding tissue or tumor microenvironment (TME). Interactions between components of the TME are mediated at a sub-microscopic level. However, the endpoint of those interactions results in morphologic changes which can be readily assessed at microscopic examination of biopsy and resection specimens. Among these morphologic changes, alteration to the tumor stroma is a new, important determinant of colorectal cancer progression. Different methodologies to estimate the proportion of tumor stroma relative to tumor cells, or tumor stroma ratio (TSR), have been developed. Subsequent validation has supported the prognostic value, reproducibility and feasibility of TSR in various subgroups of colorectal cancer. In this manuscript, we review the literature surrounding TME in colorectal cancer, with a focus on tumor stroma ratio.

Idiopathic noncirrhotic portal hypertension is a poorly defined clinical condition of unknown etiology. Patients present with signs and symptoms of portal hypertension without evidence of cirrhosis. The disease course appears to be indolent and benign with an overall better outcome than cirrhosis, as long as the complications of portal hypertension are properly managed. This condition has been recognized in different parts of the world in diverse ethnic groups with variable risk factors, resulting in numerous terminologies and lack of standardized diagnostic criteria. Therefore, although the diagnosis of idiopathic noncirrhotic portal hypertension requires clinical exclusion of other conditions that can cause portal hypertension and histopathologic confirmation, this entity is under-recognized clinically as well as pathologically. Recent studies have demonstrated that variable histopathologic entities with different terms likely represent a histologic spectrum of a single entity of which obliterative portal venopathy might be an underlying pathogenesis. This perception calls for standardization of the nomenclature and formulation of widely accepted diagnostic criteria, which will facilitate easier recognition of this disorder and will highlight awareness of this entity.