Lymphocyte-Rich Primary Carcinomas: Rare Tumors of the Liver
Z Meriden, HR Makhlouf, H Daniel, TT Wu, MM Yeh, MS Torbenson. Johns Hopkins Hospital, Baltimore, MD; AFIP, Washington, DC; Mayo Clinic, Rochester, MN; Univ. of Washington, Seattle, WA
Background: Lymphocyte-rich primary carcinomas of the liver are rare entities with a variety of morphologies, from hepatocellular carcinoma (HCC) to cholangiocarcinoma to lymphoepithelial-like carcinoma (LELC). LELC's in the head and neck are commonly associated with either Epstein-Barr virus (EBV) or human papilloma virus (HPV). To better understand the clinicopathologic spectrum of lymphocyte-rich primary carcinomas of the liver, cases were collected from 4 institutions and characterized at the clinical, histological, and molecular levels.
Design: A total of 9 cases were collected and reviewed. Eight cases had tissue available for molecular testing. Immunohistochemistry for p53, β-catenin, and p16 was performed on cases with available tissue (6/9). In-situ hybridization for EBV (EBER) was performed, as well as PCR on microdissected paraffin-embedded tissues for EBV and HPV. Exon 3 of CTNNB1 (encoding β-catenin) and exon 7 of TP53 (encoding p53) were also sequenced.
Results: The average age was 57 years at resection, 60% of individuals were women, and the average tumor size was 6 cm. Four of 7 cases (57.1%) arose in a background of hepatitis C. Two cases had a classic LELC morphology, 5 had an HCC morphology with marked lymphocytosis, and 2 were cholangiocarcinomas. Immunohistochemistry for β-catenin nuclear accumulation was negative in all cases, and tested cases were negative for exon 3 CTNNB1 mutations. In 4/5 cases, sparse p53 nuclear accumulation was seen, but sequencing for mutations in exon 7 of TP53 was negative in all tested cases. EBV was detected in 4/9 cases. Two cases were strongly EBV-positive (1 high-copy by real-time PCR, 1 by EBER); and both had a non-HCC morphology, one being a LELC and the other a cholangiocarcinoma. In contrast, the remaining two cases had low-copy EBV positivity by real-time PCR and had HCC morphologies. P16 was positive in 2 cases, with 5-25% of tumor cells showing positivity; however, HPV PCR was negative in all tested cases.
Conclusions: To our knowledge, this is the largest case series and only multi-institutional study of these rare tumors, which demonstrate a spectrum of morphologies. Unlike LELC's of the head and neck, lymphocyte-rich primary carcinomas of the liver are not HPV-associated; however, EBV is detectable in 30% of cases. High-copy EBV -positive tumors show non-HCC morphology, while low-copy EBV-positive tumors can have classic HCC features.
Category: Liver & Pancreas
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 235, Tuesday Morning