A Rare Case of Metastatic Hepatocellular Carcinoma to the Hard Palate.

Extrahepatic metastasis of hepatocellular carcinoma (HCC) to the head and neck is unusual, especially the oral cavity/maxillofacial region. Metastatic HCC to the hard palate, however, is particularly rare. The most common site of HCC metastasis is the lung, followed by lymph nodes, bone, and adrenal gland. Importantly, oral cavity metastatic HCC may be misdiagnosed as a primary malignancy, such as a salivary gland carcinoma. In this article, we describe a young woman with metastatic HCC to the hard palate that was initially diagnosed as an acinic cell carcinoma.

A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis.

Obesity and insulin resistance are associated with deposition of triglycerides in tissues other than adipose tissue. Previously, we showed that a missense mutation (I148M) in PNPLA3 (patatin-like phospholipase domain-containing 3 protein) is associated with increased hepatic triglyceride content in humans. Here we examined the effect of the I148M substitution on the enzymatic activity and cellular location of PNPLA3. Structural modeling predicted that the substitution of methionine for isoleucine at residue 148 would restrict access of substrate to the catalytic serine at residue 47. In vitro assays using recombinant PNPLA3 partially purified from Sf9 cells confirmed that the wild type enzyme hydrolyzes emulsified triglyceride and that the I148M substitution abolishes this activity. Expression of PNPLA3-I148M, but not wild type PNPLA3, in cultured hepatocytes or in the livers of mice increased cellular triglyceride content. Cell fractionation studies revealed that approximately 90% of wild type PNPLA3 partitioned between membranes and lipid droplets; substitution of isoleucine for methionine at position 148 did not alter the subcellular distribution of the protein. These data are consistent with PNPLA3-I148M promoting triglyceride accumulation by limiting triglyceride hydrolysis.

Sclerosing Extramedullary Hematopoietic Tumor: A Case Report.

Sclerosing extramedullary hematopoietic tumor (SEMHT) is a rare disease that was originally named fibrous hematopoietic tumor or myelosclerosis. The process typically occurs in patients with a history of chronic myeloproliferative disorders and may afflict the skin, lung, breast, gastrointestinal tract, breast, kidney, lymph node, and thyroid gland. In this article, we report the case of a 37-year-old female with more than 5 years history of acute B-cell lymphoblastic leukemia who presented with right upper quadrant pain and tenderness. Computed tomography scan showed multiple new ring-enhancing low-density lesions within the right and left hepatic lobes. A computed tomography-guided liver core biopsy was performed on one of the new liver lesions and showed extramedullary hematopoiesis with atypical megakaryocytes and sinusoidal capillarization with associated fibroblastic proliferation. Numerous atypical megakaryocytes were scattered in the background of haphazard collagen deposition. No significant blasts or a leukemic process were identified. Bone marrow aspiration and biopsy showed extensive reticulin fibrosis (MF-3), trilineage dysplasia, increased blasts (10% to 19%), and hypercellularity (close to 100%), which was consistent with MDS-EB-2. Cytogenetics was reported as follows: 44~46,XX,-3,add(3)(p13),-5,-6,-7,17,del(17)(p12),+1~5mar[cp9]/46,XX. Molecular analysis was negative for both JAK2 V617F and CALR exon 9 activating mutations. In summary, we contributed a new case of SEMHT diagnosis in a synchronous presentation with poor clinical evolution associated chromosome 7 deletion and intact JAK2 and CALR exon 9. Care should be taken when diagnosing intraabdominal and retroperitoneal soft tissue masses with the history of hematological disorders.

Peribiliary hepatic cysts presenting as hilar cholangiocarcinoma in a patient with end-stage liver disease.

Peribiliary cysts are cystic dilatations of peribiliary glands in the liver. They are present in ~50% of cirrhotic patients, but are underrecognized because they are usually asymptomatic and rarely present as obstructive jaundice. A 63-year-old male with hepatitis C cirrhosis, awaiting liver transplantation, had a new finding of intrahepatic dilatation on magnetic resonance imaging. This was initially concerning for cholangiocarcinoma, but was ultimately diagnosed as peribiliary cysts. Peribiliary cysts can imitate cholangiocarcinoma on imaging. Therefore, awareness of this condition is essential because misdiagnosis may lead to inappropriate delay or denial for liver transplantation. The ideal imaging modalities to identify peribiliary cysts are magnetic resonance cholangiography and drip infusion cholangiographic computed tomography, though hepatic dysfunction may limit the usefulness of the latter. Peribiliary cysts should be considered in cirrhotic patients with cholestasis, biliary dilatations and negative biopsy of the biliary system for malignancy.

Phytosterols differentially influence ABC transporter expression, cholesterol efflux and inflammatory cytokine secretion in macrophage foam cells.

Phytosterol supplements lower low-density lipoprotein (LDL) cholesterol, but accumulate in vascular lesions of patients and limit the anti-atherosclerotic effects of LDL lowering in apolipoprotein E (Apo E)-deficient mice, suggesting that the cholesterol-lowering benefit of phytosterol supplementation may not be fully realized. Individual phytosterols have cell-type specific effects that may be either beneficial or deleterious with respect to atherosclerosis, but little is known concerning their effects on macrophage function. The effects of phytosterols on ABCA1 and ABCG1 abundance, cholesterol efflux and inflammatory cytokine secretion were determined in cultured macrophage foam cells. Among the commonly consumed phytosterols, stigmasterol increased expression of ABCA1 and ABCG1 and increased efflux of cholesterol to apolipoprotein (Apo) AI and high-density lipoprotein (HDL). Campesterol and sitosterol had no effect on ABCA1 or ABCG1 levels. Sitosterol had no effect on cholesterol efflux to Apo AI or HDL, whereas campesterol had a modest but significant reduction in cholesterol efflux to HDL in THP-1 macrophages. Whereas stigmasterol blunted aggregated LDL (agLDL) induced increases in tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1ß secretion, sitosterol exacerbated these effects. The presence of campesterol had no effect on agLDL-induced inflammatory cytokine secretion from THP-1 macrophages. In conclusion, the presence of stigmasterol in modified lipoproteins promoted cholesterol efflux and suppressed inflammatory cytokine secretion in response to lipid loading in macrophage foam cells. While campesterol was largely inert, the presence of sitosterol increased the proinflammatory cytokine secretion.