CAP Carcinoma: A Distinct Subtype of Hepatocellular Carcinoma with Unique Morphologic and Molecular Features
Laura D Wood, Christopher M Heaphy, Hubert J Daniel, Bita Naini, Charles R Lassman, Alan K Meeker, May R Arroyo, Michael Torbenson. Johns Hopkins Univ., Baltimore, MD; Univ. of California Los Angeles, Los Angeles, CA; Univ. of Florida, Gainesville, FL
Background: Hepatocellular carcinomas (HCCs) exhibit heterogeneous morphologies. While some morphologies represent variations in growth patterns, others may represent unrecognized variants of HCC with unique clinical and/or molecular features.
Design: Two pathologists independently screened a cohort of 242 unselected HCCs with varying morphologies. Each pathologist divided the cases into separate candidate morphologic variants, and the possible variants were compared. The most consistent candidate variants were further evaluated using both histologic and molecular techniques.
Results: A distinct morphologic variant was characterized by a unique and consistent set of shared histological features: smooth chromophobic cytoplasm, abrupt focal nuclear anaplasia (small clusters of tumor cells with marked nuclear anaplasia in a background of tumor cells with bland nuclear cytology), and scattered microscopic pseudocysts. Therefore, we designate this variant as CAP carcinoma (Chromophobic cytoplasm, Abrupt anaplasia, Pseudocysts). Thirteen cases were identified in the HCC cohort: 6 men and 7 women with a mean age of 59 years. Six of the carcinomas occurred in cirrhotic livers, and alpha-fetoprotein (AFP) was markedly elevated in 6 of the 9 cases for which pre-operative AFP levels were available. There were a variety of underlying liver diseases: hepatitis B (6 cases), hepatitis C (1 case), alcoholic cirrhosis (1 case), cryptogenic cirrhosis (1 case), none (2 cases), and unavailable (2 cases). Based on previous studies that included a small number of CAP carcinomas (before they were recognized as such), we next investigated CAP carcinomas for the alternative lengthening of telomeres (ALT) phenotype. ALT is a telomerase-independent mechanism of telomere maintenance involving homologous recombination which has a distinctive appearance by telomere-specific FISH. ALT is found in approximately 7% of all HCCs. Interestingly, the ALT phenotype was strongly enriched in CAP carcinomas - 11/12 (92%) cases were ALT positive: 9 strongly and 2 weakly (p<0.0001).
Conclusions: CAP carcinoma is a newly defined subtype of HCC with unique morphologic and molecular features. Morphologically, it is characterized by chromophobic cytoplasm, abrupt anaplasia, and pseduocysts. On a molecular level, CAP carcinomas exhibit the ALT phenotype. This is the first report of a high prevalence of the ALT phenotype in a morphologically distinct carcinoma subtype.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 258, Monday Morning