PMID- 37859468 OWN - NLM STAT- MEDLINE DCOM- 20231207 LR - 20231221 IS - 1533-4058 (Electronic) IS - 1533-4058 (Linking) VI - 32 IP - 1 DP - 2024 Jan 1 TI - Arginase-1 is More Specific Than Hepatocyte Paraffin 1 for Differentiating Hepatocellular Carcinomas With Cytoplasmic Clearing from Nonhepatocellular Clear Cell Tumors in Liver Biopsies. PG - 37-43 LID - 10.1097/PAI.0000000000001169 [doi] AB - Arginase-1 (Arg1) and hepatocyte paraffin antigen 1 (HepPar1) are specific and sensitive markers of hepatocellular differentiation. HepPar1 is a granular cytoplasmic immunostain that may be negative in hepatocellular carcinoma (HCC) with cytoplasmic clearing. Arg1 shows uniform cytoplasmic positivity and frequent nuclear positivity. This study was undertaken to determine the staining pattern of Arg1 in HCC with cytoplasmic clearing and compare its use to HepPar1. Fifteen resected HCCs with cytoplasmic clearing and 31 biopsies of clear cell liver tumors (14 HCCs and 17 nonhepatocellular tumors) were identified. Resections were stained with Arg1 to characterize the pattern, intensity, and extent of Arg1 positivity. Biopsies were stained with Arg1 (n=31) and HepPar1 (n=28). In all, 13/15 resected and 11/14 biopsied HCCs with cytoplasmic clearing showed nuclear positivity for Arg1. Both Arg1 and HepPar1 stained significantly more HCCs than nonhepatocellular tumors (13/14 and 11/12, respectively, with P <0.0001 and P =0.0018, respectively). However, HepPar1 stained significantly more nonhepatocellular tumors (5/12) than Arg1 (0/17, P =0.0445). Arg1 frequently displayed nuclear positivity, and interobserver agreement was better for Arg1 ( K =0.93 vs. 0.79). Overall, Arg1 is more specific than HepPar1 for differentiating HCC with cytoplasmic clearing from nonhepatocellular clear cell tumors in the liver. Its staining characteristics, including nuclear positivity, make it easier to interpret in combination with morphology, improving interobserver variability, and it stains significantly fewer mimics than HepPar1. CI - Copyright (c) 2023 Wolters Kluwer Health, Inc. All rights reserved. FAU - Larson, Brent K AU - Larson BK AD - Department of Pathology and Laboratory Medicine Cedars-Sinai Medical Center, Los Angeles, CA. FAU - Dhall, Deepti AU - Dhall D AD - Department of Pathology, University of Alabama at Birmingham, Birmingham, AL. FAU - Guindi, Maha AU - Guindi M AD - Department of Pathology and Laboratory Medicine Cedars-Sinai Medical Center, Los Angeles, CA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231020 PL - United States TA - Appl Immunohistochem Mol Morphol JT - Applied immunohistochemistry & molecular morphology : AIMM JID - 100888796 RN - 8002-74-2 (Paraffin) RN - EC 3.5.3.1 (Arginase) RN - 0 (Biomarkers, Tumor) SB - IM MH - Humans MH - *Carcinoma, Hepatocellular/pathology MH - Paraffin MH - *Liver Neoplasms/pathology MH - Arginase MH - Biomarkers, Tumor/analysis MH - Immunohistochemistry MH - Hepatocytes/pathology MH - Biopsy MH - Diagnosis, Differential COIS- The authors declare no conflict of interest. EDAT- 2023/10/20 06:42 MHDA- 2023/12/07 12:42 CRDT- 2023/10/20 03:43 PHST- 2021/11/07 00:00 [received] PHST- 2023/09/25 00:00 [accepted] PHST- 2023/12/07 12:42 [medline] PHST- 2023/10/20 06:42 [pubmed] PHST- 2023/10/20 03:43 [entrez] AID - 00129039-990000000-00142 [pii] AID - 10.1097/PAI.0000000000001169 [doi] PST - ppublish SO - Appl Immunohistochem Mol Morphol. 2024 Jan 1;32(1):37-43. doi: 10.1097/PAI.0000000000001169. Epub 2023 Oct 20.