Hepatocellular Carcinoma in Fanconi-Bickel Syndrome

Author:

Pogoriler Jennifer1,O’Neill Allison F2,Voss Stephan D3,Shamberger Robert C4,Perez-Atayde Antonio R1

Affiliation:

1. Department of Pathology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

2. Division of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA

3. Department of Radiology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

4. Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

Abstract

Fanconi-Bickel syndrome is a rare autosomal recessive disorder due to mutations in the facilitative glucose transporter 2 ( GLUT2 or SLC2A2) gene resulting in excessive glycogen storage predominantly in the liver and kidney. Previous case reports of this condition have described liver biopsies with glycogen storage and variable steatosis and/or fibrosis. Unlike in other types of glycogen storage disease, hepatocellular adenomas and carcinomas have not been described to date in this syndrome. A 6-year-old boy with consanguineous parents had short stature, poorly controlled rickets, hepatosplenomegaly, and renal tubular dysfunction clinically consistent with Fanconi-Bickel Syndrome. Sequencing of the SLC2A2 gene showed a homozygous variant of unknown significance [c.474A > C (p.Arg158Ser)] causing a missense mutation in an evolutionarily conserved residue. An incidental single hepatic lesion was discovered on imaging, and subsequent resection showed a 2.6 cm well-differentiated hepatocellular carcinoma with moderate atypia, diffuse immunoreactivity for glypican-3, and nuclear b-catenin, and with focal complete loss of the reticulin framework. The non-neoplastic liver showed marked glycogen accumulation with mild periportal fibrosis, rare bridging fibrosis, and no regenerative or adenomatous nodules. By electron microscopy, tumor cells had pleomorphic nuclei, prominent nucleoli, and scant cytoplasm with numerous mitochondria. Well-developed canaliculi were occasionally seen. The non-neoplastic liver showed glycogenosis with abundant cytoplasmic free (non-membrane bound) glycogen. Hepatocellular carcinoma should be considered as a possible complication of Fanconi-Bickel syndrome. This well differentiated carcinoma did not appear to be associated with hepatic adenomatosis as has been described in some hepatocellular carcinomas associated with other hepatic glycogen storage disorders. The nuclear beta-catenin immunoreactivity indicates a role for the Wnt signaling pathway in the pathogenesis of this tumor.

Publisher

SAGE Publications

Subject

General Medicine,Pathology and Forensic Medicine,Pediatrics, Perinatology and Child Health

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3