Hepatocellular Carcinoma Arising in an HNF-1α-Mutated Adenoma in a 23-Year-Old Woman with Maturity-Onset Diabetes of the Young: A Case Report.

Hepatocyte nuclear factor-1α mutated hepatocellular adenomas (H-HCA) are thought to have no to minimal malignant potential. This report describes a 23-year-old woman with maturity-onset diabetes of the young who developed a 12.5-cm hepatic mass with a radiographically and pathologically distinct 3.0-cm region. Histologically and immunohistochemically, the bulk of the mass was an H-HCA with extensive pseudoglandular formation and only focal steatosis. The 3.0-cm nodule showed small cell change, thickened hepatocyte plates, pleomorphic and hyperchromatic nuclei, reticulin loss, and stromal and vascular invasion, diagnostic of hepatocellular carcinoma (HCC). Immunohistochemically, increased expression of glutamine synthetase in tumor cells and CD34 expression in sinusoidal endothelial cells were seen in the HCC component. Nuclear expression of ß-catenin, and exon 3 of CTNNB1 and TERT promoter mutations were absent in this case. Thus, we report a HCC arising in an H-HCA; although cases appear exceedingly rare, they reinforce the potential of H-HCA for malignant transformation.

Significance of complement split product C4d in ABO-compatible liver allograft: diagnosing utility in acute antibody mediated rejection.

Diagnosis of liver allograft antibody-mediated rejection (AMR) is difficult and requires a constellation of clinical, laboratory and histologic features that support the disease and exclude other causes. Histologic features of AMR may intermix with those of biliary obstruction, preservation/reperfusion injury, and graft ischemia. Tissue examination for complement degradation product 4d (C4d) has been proved to support this diagnosis in other allografts. For this reason, we conducted a retrospective review of all ABO compatible/identical re-transplanted liver patients with primary focus on identifying AMR as a possible cause of graft failure and to investigate the utility of C4d in liver allograft specimens. We reviewed 193 liver samples obtained from 53 consecutive ABO-compatible re-transplant patients. 142 specimens were stained with C4d. Anti-donor antibody screening and identification was determined by Luminex100 flow cytometry. For the study analysis, patients were stratified into 3 groups according to time to graft failure: group A, patients with graft failure within 0-7 days (n=7), group B within 8-90 days (n=13) and C >90 days (n=33). Two patients (3.7%) met the diagnostic criteria of acute AMR. Both patients experienced rapid decline of graft function with presence of donor specific antibodies (DSA), morphologic evidence of humoral rejection and C4d deposition in liver specimens. C4d-positive staining was identified in different medical liver conditions i.e., acute cellular rejection (52%), chronic ductopenic rejection (50%), recurrent liver disease (48%), preservation injury (18%), and hepatic necrosis (54%). Univariate analysis showed no significant difference of C4d-positive staining among the 3 patients groups, or patients with DSA (P>.05). In conclusion, AMR after ABO-compatible liver transplantation is an uncommon cause of graft failure. Unlike other solid organ allografts, C4d-positive staining is not a rugged indicator of humoral rejection, thus, interpretation should be done with caution to avoid diagnostic dilemmas.

Risk for renal cell carcinoma in chronic hepatitis C infection.

BACKGROUND: Chronic infection with hepatitis C virus (HCV) confers increased risk for chronic renal disease, and numerous reports suggest an association with renal cell carcinoma (RCC), a cancer with rapidly rising global incidence. We sought to determine whether HCV infection confers an increased risk for developing RCC. METHODS: With the use of administrative data from a large, integrated, and ethnically diverse healthcare system, we did a cohort study of 67,063 HCV-tested patients between 1997 and 2006 who were followed for the development of RCC until April 2008. RESULTS: A search of the health system cancer registry for patients with the diagnosis of kidney cancer showed that RCC was diagnosed in 0.6% (17 of 3,057) of HCV-positive patients versus 0.3% (177 of 64,006) of HCV-negative patients. The mean age at RCC diagnosis was much younger in HCV-positive individuals (54 versus 63; P < 0.001). The univariate hazard ratio for RCC among HCV patients was 2.20 (95% confidence interval, 1.32-3.67; P = 0.0025). In a multivariate model that included the risk factors age, African-American race, male gender, and chronic kidney disease, the overall hazard ratio for RCC among HCV patients was 1.77 (95% confidence interval, 1.05-2.98; P = 0.0313). CONCLUSION: Chronic HCV infection confers a risk for the development of RCC. IMPACT: Clinicians should consider newly identified renal lesions in patients with chronic HCV infection with a heightened suspicion for neoplasm, and newly diagnosed cases of RCC may require more careful surveillance for the presence of HCV infection. Additional studies are required to confirm these findings and to explore potential mechanisms of oncogenesis.