The Banff Working Group on Liver Allograft Pathology reviewed and discussed literature evidence regarding antibody-mediated liver allograft rejection at the 11th (Paris, France, June 5-10, 2011), 12th (Comandatuba, Brazil, August 19-23, 2013), and 13th (Vancouver, British Columbia, Canada, October 5-10, 2015) meetings of the Banff Conference on Allograft Pathology. Discussion continued online. The primary goal was to introduce guidelines and consensus criteria for the diagnosis of liver allograft antibody-mediated rejection and provide a comprehensive update of all Banff Schema recommendations. Included are new recommendations for complement component 4d tissue staining and interpretation, staging liver allograft fibrosis, and findings related to immunosuppression minimization. In an effort to create a single reference document, previous unchanged criteria are also included.

The goal of this study was to determine whether a panel of tumor suppressor gene markers of allelic loss could serve as a representative indicator of gene damage and thereby provide further discriminative power over current staging systems for recurrence-free prognostication in patients undergoing liver transplantation in the presence of hepatocellular carcinoma. The paraffin blocks from 103 cases of hepatocellular carcinoma were obtained, and cellular targets were selected for tissue microdissection genotyping. Tumor suppressor gene loss was based on loss of heterozygosity situated within or adjacent to specific genes of interest (APC, CDKN2A, DCC, MET, MYC1, OGG1, p34, p53, PTEN). Microdissected tissue was amplified using polymerase chain reaction (PCR) with flanking oligonucleotides bearing fluorescent labels designed for GeneScan fragment analysis; PCR products were separated by capillary electrophoresis. Normal microdissected tissue samples for each case were evaluated for informative status with respect to individual alleles for 18 microsatellites at 10 genomic loci-1p, 3p, 5q, 7q, 8q, 9p, 10q, 17p, 17q, 18q. The measure of allelic loss of heterozygosity combined with tumor number, tumor size, vascular invasion, lobar distribution, and patient gender provide a highly discriminatory model for predicting cancer recurrence after liver transplantation. Using our previously developed artificial neural network model in combination with the genotyping results, unambiguous predictions were made for 91 of the103 patients (88.3%).Of these, 1 was lost to follow-up, and 9 died recurrencefree less than 3 years posttransplantation. For the remaining 81, the combined models predicted tumor recurrence outcomes with complete accuracy. Microdissection genotyping provides powerful supplementary discriminative information for tumor-free survival. (Liver Transpl 2003; 9:664-671.)

Expression of hepatocyte growth factor (HGF) and c-Met (HGF receptor) has been reported in many neoplasms. We investigated coexpression of HGF and c-Met to determine the role of the HGF/c-Met pathway in breast carcinoma, especially at the cancer front. Eighty-eight cases of carcinoma of the breast were studied by immunohistochemistry and by in situ hybridization for HGF and c-Met expression. The staining pattern was termed "front accentuation pattern" when it was most conspicuous at the cancer front. HGF and c-Met proteins were expressed in cancer and stromal cells, with autocrine and paracrine patterns. The front accentuation pattern of c-Met was observed in cancer cells, but not in stromal cells. The front accentuation pattern was not observed in HGF. Coexpression of HGF and c-Met at the cancer front was correlated with histologic grade, reduced patient survival and a high Ki-67 labeling index. Our findings suggest that the HGF/c-Met pathway acts primarily as a mitogen, especially at the cancer front, in a paracrine manner and affects some clinical factors, including patient survival.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The macroscopic growth pattern of HCC is subdivided into three categories: nodular, massive, and infiltrative. Infiltrative HCC accounts for 7%-20% of HCC cases and is confirmed at pathologic analysis on the basis of the spread of minute tumor nodules throughout large regions of the liver. Infiltrative HCC may represent a diagnostic challenge because it is often difficult to distinguish from background changes in cirrhosis at imaging. Infiltrative HCC usually spreads over multiple hepatic segments, occupying an entire hepatic lobe or the entire liver, and it is frequently associated with portal vein tumor thrombosis. The tumor is usually ill defined at ultrasonography and shows minimal and inconsistent arterial enhancement and heterogeneous washout at contrast material-enhanced computed tomography and magnetic resonance (MR) imaging. The tumor may be more visible among the surrounding liver parenchyma at diffusion-, T1-, and T2-weighted MR imaging. Several liver diseases can mimic the infiltrative appearance of this malignancy, including focal confluent fibrosis, hepatic fat deposition, hepatic microabscesses, intrahepatic cholangiocarcinoma, and diffuse metastatic disease (pseudocirrhosis). The prognosis for patients with infiltrative HCC is poor because the tumor is often markedly advanced and associated with vascular invasion at presentation. Survival after surgical resection is decreased; thus, infiltrative HCC is a contraindication for resection and transplantation. Knowledge of the key tumor characteristics and imaging findings will help radiologists formulate a correct and timely diagnosis to improve patient management.

C4d-assisted recognition of antibody-mediated rejection (AMR) in formalin-fixed paraffin-embedded tissues (FFPE) from donor-specific antibody-positive (DSA+)renal allograft recipients prompted study of DSA+ liver allograft recipients as measured by lymphocytotoxic crossmatch (XM) and/or Luminex. XM results did not influence patient or allograft survival, or cellular rejection rates, but XM+ recipients received significantly more prophylactic steroids. Endothelial C4d staining strongly correlates with XM+ (<3 weeks posttransplantation) and DSA+ status and cellular rejection, but not with worse Banff grading or treatment response. Diffuse C4d staining, XM+, DSA+ and ABO-incompatibility status, histopathology and clinical-serologic profile helped establish an isolated AMR diagnosis in 5 of 100 (5%) XM+ and one ABO-incompatible, recipients. C4d staining later after transplantation was associated with rejection and nonrejection-related causes of allograft dysfunction in DSA-and DSA+ recipients, some of whom had good outcomes without additional therapy. Liver allograft FFPE C4d staining: (a) can help classify liver allograft dysfunction; (b) substantiates antibody contribution to rejection; (c) probably represents nonalloantibody insults and/or complete absorption in DSA-recipients and (d) alone, is an imperfect AMR marker needing correlation with routine histopathology, clinical and serologic profiles. Further study in late biopsies and other tissue markers of liver AMR with simultaneous DSA measurements are needed.