Molecular testing for the clinical diagnosis of fibrolamellar carcinoma

• DOI: 10.1038/modpathol.2017.103
• Publication Date: 2017-09-01T11:41:05Z
• Authors: Rondell P Graham; Matthew M Yeh; Dora Lam-Himlin; Lewis R Roberts; Luigi Terracciano; Michael W Cruise; Patricia T Greipp; Riyam T Zreik; Dhanpat Jain; Nida Zaid; Safia N Salaria; Long Jin; Xiaoke Wang; Jeanette G Rustin; Sarah E Kerr; William R Sukov; David A Solomon; Sanjay Kakar; Emily Waterhouse; Ryan M Gill; Linda Ferrell; Venancio AF Alves; Deniz Nart; Funda Yilmaz; Stephanie Roessler; Thomas Longerich; Peter Schirmacher; Michael S Torbenson
• Keywords: Hematopathology; Cytopathology

Fibrolamellar carcinoma has a distinctive morphology and immunophenotype, including cytokeratin 7 CD68 co-expression. Despite the distinct findings, accurate diagnosis of fibrolamellar continues to be challenge. Recently, carcinomas were found harbor characteristic somatic gene fusion, DNAJB1-PRKACA. A break-apart fluorescence in situ hybridization (FISH) assay was designed detect this fusion event examine its diagnostic performance large, multicenter, multinational study. Cases initially classified as based on histological features reviewed from 124 patients. Upon central review, 104 cases histologically typical carcinoma, 12 'possible carcinoma' 8 'unlikely carcinoma'. PRKACA FISH positive for rearrangement 102 103 (99%) carcinomas, 9 carcinomas' 0 carcinomas'. Within morphologically group two tumors with unusual patterns also identified. Both had DNAJB1-PRKACA, but one amplification heterozygous deletion normal locus. In addition, 88 conventional hepatocellular evaluated all negative. These findings demonstrate that is clinically useful tool confirm high sensitivity specificity. more when plus confirmatory testing than alone.