Aberrant von Willebrand Factor (vWF) Expression of Sinusoidal Endothelial Cells in Nodular Regenerative Hyperplasia and Obliterative Portal Venopathy
Xuchen Zhang, Thomas D Schiano, Swan N Thung, Stephen C Ward, M Isabel Fiel. Yale University School of Medicine, New Haven, CT; Mount Sinai Medical Center, New York, NY
Background: Nodular regenerative hyperplasia (NRH) and obliterative portal venopathy (OPV) are under-recognized diseases of uncertain etiology that result in noncirrhotic portal hypertension (NCPH). The diagnosis can be easily missed on needle liver biopsy. CD34 and vWF are commonly used endothelial markers. vWF is released by activated endothelial cells and plays a crucial role in primary hemostasis and in the development of thrombotic vascular obliteration. Liver sinusoidal endothelial cells (LSEC) are unique in that the expression of CD34 and vWF are confined only to periportal areas in the normal liver. We sought to investigate the potential utility of these two immunomarkers in helping make the diagnosis of NRH and OPV. Additionally, the immunoexpression pattern may further elucidate the pathogenesis of these conditions.
Design: Re-review of the histology of liver wedge and needle biopsies of clinically proven NCPH cases was undertaken. NRH is defined as small hyperplastic nodules centered around portal tracts compressing adjacent atrophic hepatocytes and sinusoids whereas OPV, although having heterogeneous histology, commonly demonstrates different degrees of phlebosclerosis and dense portal fibrosis. Cases with combined OPV and NRH on biopsy were also noted. Immunohistochemical staining for CD34 and vWF (DAKO, Carpinteria, CA) was performed using standard methods.
Results: There were 15 NRH, 25 OPV and 5 normal liver biopsies (acting as controls). Among the 25 OPV, 20 had concurrent features of NRH (80%). CD34 (+) staining was mainly confined to small vessels in the portal tracts as well as LSECs in periportal areas in both NRH and OPV, similar to that in the normal control biopsies. Unlike CD34, expression of vWF in LSECs was (+) along the dilated sinusoids of NRH, and in a patchy or geographic pattern, particularly prominent in the perivenular areas of OPV as opposed to vWF expression being confined to periportal areas in the controls.
Conclusions: NRH and OPV are commonly seen together in the same liver biopsy. The aberrant expression of vWF in NRH and OPV suggest that LSEC activation is involved in their pathogenesis and that NRH and OPV may share a common pathway of vascular injury. The aberrant expression pattern of vWF may also aid in the histologic diagnosis and recognition of NRH and OPV on liver biopsy.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 112, Wednesday Afternoon