Immunohistochemical Glutamine Synthetase As a Surrogate Marker for Beta Catenin (Exon 3 Deletion) in a Rare Case of Hepatic Adenomatosis with Early Malignant Transformation to Well Differentiated Hepatocellular Carcinoma

Abstract Introduction/Objective Hepatic adenomatosis (HA) is a rare entity defined by ≥ 10 hepatocellular adenomas (HCAs). About half of HA cases are asymptomatic and incidentally found. Compared to individual HCAs, HA carries a higher risk of complications including: tumor rupture, bleeding, and an approximate 4.2% overall frequency of malignant transformation. Methods/Case Report A 29-year-old woman presented to the emergency department (ED) requesting a CT scan. She was seen by a gastroenterologist days prior to her ED visit for ongoing sharp rectal pain for 2-3 months. After a recent rectal exam, she was recommended to have a CT abdomen/pelvis to rule out a potential abscess. CT did not show a perianal or perirectal abscess but instead identified a 9.1 cm right hepatic lobe mass. A liver MRI showed a 6.4 x 8.5 cm mass with arterial enhancement. The patient had a prior history of OCP use. She underwent robotic wedge resection of liver segment 6 with cholecystectomy. Gross examination showed a 6 cm tumor with many smaller nodules ranging in size from 0.5-2.2 cm. Our case was submitted entirely for histologic examination. Microscopy demonstrated well differentiated hepatocellular carcinoma (WDHCC) confirmed with positive immunohistochemical (IHC) staining for HepPar1 and Arginase. Tumor cells showed mild patchy cytological atypia, occasional pseudoglands, and architectural atypia with “nodule in nodule growth.” There was reticulin loss in multiple areas and CD34 showed strong diffuse sinusoidal staining. Glypican 3, CRP, and HAA were negative. Low Ki-67, LFABP retention, and absent nuclear staining of beta catenin (BC) were noted. Glutamine synthetase (GS) was diffuse and homogeneous. The gallbladder was unremarkable. Results (if a Case Study enter NA) NA Conclusion This case emphasizes that, despite negative nuclear BC staining, diffuse homogenous staining of GS is a quality surrogate marker for BC mutations (ex. exon 3 deletions). Thorough gross, microscopic, and molecular examination in HA cases is essential for identifying transformation to WDHCC.