A Practical Diagnostic Panel for Distinguishing between Hepatocellular Lesions
Farshid Siadat, Phillip Williams, Celia Margingean. Ottawa Hospital and University of Ottawa, Ottawa, ON, Canada
Background: Histopathologic distinction between well differentiated hepatocellular carcinoma (HCC), hepatocellular adenoma (HA) and focal nodular hyperplasia (FNH) can be challenging, especially on small biopsies. We studied the immunohistochemical (IHC) expression of Hepatocyte Specific Antigen (HSA), Insulin-Like Growth Factor II mRNA-Binding Protein 3 (IMP3), Glypican-3 (GPC3), and Glutamine Synthetase (GS) in order to determine their diagnostic value in the distinction between hepatocellular mass lesions.
Design: A total of 59 liver lesions were stained for the four antibodies, including 26 well differentiated HCC (23 resections; 3 biopsies), 13 HA (12 resections; 1 biopsy) and 20 FNH (14 resections; 6 biopsies). IHC was performed using HSA (Abcam), IMP3 (DAKO), GPC3 (Santa Cruz) and GS (Millipore, MAB302). Cytoplasmic granular staining was considered positive for HSA, IMP3 and GS and cytoplasmic, and/or membranous staining was considered positive for GPC3. The percentage and distribution of immunoreactive tumour cells was recorded for all antibodies and the staining intensity was graded as weak (1+), moderate (2+), or strong (3+).
Results: Strong HSA reactivity was detected in 19/20 (95%) of FNH, all HA (100%), and 23/26 (88%) of HCC. Staining for IMP3 was observed in all HCC (100%) and none of the FNH or HA. IMP3 showed a stronger (3+) staining at the periphery of the tumours. GPC3 showed strong (3+) reactivity in 18/26 (69%) of HCC, in 1/13 (8%) HA and was negative in all FNH.GS was strong and diffuse in all HCC (100%), strong and diffuse in 2/13 (15%) of HA, and showed a typical strong reactivity in “map-like” pattern in all FNH (100%).
Conclusions: HSA is a strong marker of hepatocytic lineage, however it is not useful in the differential diagnosis of HCC, HA and FNH. GPC3 and IMP3 are positive in most HCC and negative in the benign lesions. GPC3 staining may be focal in HCC, and lack of staining does not exclude a well differentiated HCC, in keeping with previous published results. GS is strongly positive in all HCC, weak or negative in the majority of HA and shows a typical “map-like” pattern in all FNH, evident even in small biopsies. In summary, morphology associated with a panel including GPC3, IMP3 and GS can differentiate between well differentiated hepatocellular lesions, even when limited tissue is available.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 110, Wednesday Morning