Cancer cells often encounter hypoxic and hypo-nutrient conditions, which force them to make adaptive changes to meet their high demands for energy and various biomaterials for biomass synthesis. As a result, enhanced catabolism (breakdown of macromolecules for energy production) and anabolism (macromolecule synthesis from bio-precursors) are induced in cancer. This phenomenon is called “metabolic reprogramming,” a cancer hallmark contributing to cancer development, metastasis, and drug resistance. HCC and cholangiocarcinoma (CCA) are 2 different liver cancers with high intertumoral heterogeneity in terms of etiologies, mutational landscapes, transcriptomes, and histological representations. In agreement, metabolism in HCC or CCA is remarkably heterogeneous, although changes in the glycolytic pathways and an increase in the generation of lactate (the Warburg effect) have been frequently detected in those tumors. For example, HCC tumors with activated β-catenin are addicted to fatty acid catabolism, whereas HCC tumors derived from fatty liver avoid using fatty acids. In this review, we describe common metabolic alterations in HCC and CCA as well as metabolic features unique for their subsets. We discuss metabolism of NAFLD as well, because NAFLD will likely become a leading etiology of liver cancer in the coming years due to the obesity epidemic in the Western world. Furthermore, we outline the clinical implication of liver cancer metabolism and highlight the computation and systems biology approaches, such as genome-wide metabolic models, as a valuable tool allowing us to identify therapeutic targets and develop personalized treatments for liver cancer patients. Export

The 4H syndrome (hypomyelination, hypodontia, hypogonadotro-pic hypogonadism) is a newly recognized leukodystrophy. The classical form is characteriz

Context.—: Nonalcoholic fatty liver disease (NAFLD) encompasses steatosis and steatohepatitis. The cause may be multifactorial, and diagnosis requires correlation with clinical information and laboratory results. Objective.—: To provide an overview of the status of histology diagnosis of steatosis, steatohepatitis, and associated conditions. Data Sources.—: A literature search was performed using the PubMed search engine. The terms ‘‘steatosis,'' ‘‘steatohepatitis,'' ‘‘nonalcoholic fatty liver disease (NAFLD),'' ‘‘nonalcoholic steatohepatitis (NASH),'' “alcoholic steatohepatitis (ASH),” ‘‘type 2 diabetes (T2DM),'' “cryptogenic cirrhosis,” “drug-induced liver injury (DILI),” “immune checkpoint inhibitor therapy,” and “COVID-19 and liver” were used. Conclusions.—: Nonalcoholic fatty liver disease has become the most common chronic liver disease in the United States. NASH is the progressive form of nonalcoholic fatty liver disease. The hallmarks of steatohepatitis are steatosis, ballooned hepatocytes, and lobular inflammation. NASH and alcoholic steatohepatitis share similar histologic features, but some subtle differences may help their distinction. NASH is commonly seen in patients with metabolic dysfunction but can also be caused by other etiologies. Examples are medications including newly developed immune checkpoint inhibitors and viral infections such as coronavirus disease 2019 (COVID-19). NASH is also a common cause of cryptogenic cirrhosis but can be reversed. The results from recent clinical trials for NASH treatment are promising in reducing the severity of steatosis, ballooning, and fibrosis.

Background: Warthin-like mucoepidermoid carcinoma is a newly recognized rare entity and could be misdiagnosed as a benign Warthin tumor. We report such a case of a 36-year-old male who presented with a left parotid gland mass. Case Report: Fine-needle aspiration showed features suggestive of Warthin tumor. Following parotidectomy, grossly there was a 1.6 cm well-circumscribed multilobular mass with focal areas of cystic change. Microscopically, at low magnification it had histological features resembling Warthin tumor, while lining with squamoid cells with scattered mucocytes demonstrating mild cytologic atypia was observed at high magnification. Immunohistochemically, the tumor cells were positive for p40, p63, cytokeratin 5/6, cytokeratin 7, and cancer antigen 125, but negative for discovered on GIST-1 (DOG1). Mucicarmine stain highlighted intracellular mucin within mucocytes. Rearrangement of mastermind like transcriptional coactivator 2 (MAML2) (11q21) gene was shown to be present in tumor cells by fluorescence in situ hybridization, supporting the diagnosis of a low-grade Warthin-like mucoepidermoid carcinoma. The patient was disease-free 12 months after surgery. Conclusion: Warthin-like mucoepidermoid carcinoma has not been widely recognized and can be misdiagnosed as Warthin tumor. Testing for MAML2 rearrangement provides essential support for diagnosis in difficult cases.

New insights in diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms