Clathrin Heavy Chain Expression in Atypical Hepatic Adenomas
Elizabeth McMillen, Jay Lefkowitch, Fei Bao. Columbia University Medical Center, New York, NY
Background: Hepatic adenomas (HAs) are benign neoplasms with the potential to undergo malignant transformation. One of 3 immunophenotypically characterized subtypes of HAs, beta-catenin mutated HAs with glutamine synthetase (GS) overexpression, is considered the most likely to become malignant. The criteria for histologic atypia in HAs and their corresponding immunohistochemical (IHC) profiles to define malignant potential are not well established. Clathrin heavy chain (CHC) has recently been established as a marker for the diagnosis of hepatocellular carcinoma, but its staining profile in HAs has not yet been investigated. In this study of atypical HAs, we sought to establish immunophenotypical criteria for atypical HAs, including the new marker CHC.
Design: We searched our database for all HAs from 1994 to 2011 and identified 5 out of 27 cases of HAs with atypical features by light microscopy. All cases were free of disease in the surrounding liver. Architectural atypia was defined as the presence of trabecular or pseudoacinar formation. Cytologic atypia was defined as nuclear pleomorphism, prominent nucleoli, and increased mitotic activity. Reticulin special stain and immunostains for CD34, GS and CHC were performed.
Results: Atypical HAs were seen in five patients including 2 females (ages 7 and 11) and 3 males (ages 22-66). Two patients had multiple adenomas. The HAs averaged 12 cm in greatest dimension. On histology, all five were classified as beta-catenin activated HAs. No steatotic or inflammatory HAs had atypical features morphologically. No stromal invasion was identified in any of the atypical HAs. By IHC analysis, four specimens were positive for GS and one was positive for Serum Amyloid A (SAA). SAA reactivity was also seen in 3 cases which were GS positive. All five cases were positive for CHC with >40% staining in the neoplastic cells. Interestingly, the CHC staining was stronger in areas of increased cytologic and architectural atypia. Focal loss of reticulin staining and increased vascularization by CD34 was seen in three of five cases.
Conclusions: This preliminary study identifies 5 out of 27 (19%) HAs show morphologically atypia and majority of the atypical HAs have GS overexpression and likely to be beta-catenin activated. All atypical HAs express CHC and the expression appears to correlate with the degree of cytologic or architectural atypia. Further analysis of CHC expression in other types of HAs is underway. Clincal follow up information and larger prospective study is needed to help indentify the risk of malignant transformation in patients with atypical HAs.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 254, Tuesday Morning