Pulmonary Pathology

1888 Role of von Willebrand Factor Sequestration and Glycoprotein 1b Expression in Wilms Tumor-Associated Acquired von Willebrand Syndrome: An Immunohistochemical Study Alexander Thurman, Jamal Benhamida, Scott Kogan. University of California, San Francisco Medical Center, San Francisco, CA. Background: Acquired von Willebrand syndrome (AvWS) represents an acquired quantitative or qualitative defect in von Willebrand factor (vWF) that may result in clinical bleeding. AvWS is known to be associated with various disease states, including myeloproliferative disorders, paraproteinemias, solid tumors, autoimmune disorders, and hormonal alterations. Specifi cally, AvWS has been well-described in pediatric patients with Wilms tumor (WT). The incidence of this complication is high, with estimates of laboratory-confi rmed AvWS ranging from 8 to 30 percent. The pathogenesis underlying this association is unknown, although mechanisms involving secreted hyaluronic acid and/or sequestration of vWF by tumor cells have been proposed. We herein present (1) the largest immunohistochemical study to date of surface vWF labeling in WT and (2) to our knowledge, the fi rst study to explore a potential etiologic link between WT and AvWS—namely, the expression of glycoprotein 1b (GP1b), a component of the canonical vWF-binding GP1b-9-5 surface receptor complex, by WT cells. Design: We retrospectively collected 28 cases of WT and 26 control cases from the archived clinical specimens of the Department of Pathology at the University of California, San Francisco Medical Center. Control cases consisted of 16 clear cell renal cell carcinomas (RCCs), 5 papillary RCCs, 2 chromophobe RCCs, 2 clear cell papillary RCCs, and 1 rhabdoid tumor of kidney. AvWS-related clinical and laboratory data were obtained for all patients. Immunohistochemical (IHC) staining for both vWF and GP1b were performed on all cases at ARUP Laboratories (Salt Lake City, Utah). Results: 7 of 28 patients with WT (25%) experienced clinical bleeding episodes which were suspicious for a bleeding diathesis. AvWS laboratory parameters were available in only 1 WT patient with clinical bleeding but were not diagnostic for AvWS. Tumor cells from WT and control cases did not exhibit membranous staining with either vWF or GP1b. Patchy, nonspecifi c cytoplasmic staining for vWF was noted in a minority of cases, predominantly occurring in stromal cells. Conclusions: Our results are consistent with prior immunohistochemical and indirect immunofl uorescence studies of vWF labeling performed on clinical samples from patients with WT and AvWS. Lack of staining with both vWF and GP1b provides compelling evidence against a role for vWF sequestration or aberrant GP1b expression in the pathogenesis of WT-associated AvWS.