von Hippel-Lindau disease-related neoplasia with an emphasis on renal manifestations

被引:2
作者
Tekin, Burak [1 ]
Erickson, Lori A. [1 ]
Gupta, Sounak [1 ]
机构
[1] Mayo Clin, Dept Lab Med & Pathol, 200 First St SW, Rochester, MN 55905 USA
关键词
Clear cell renal cell carcinoma; Hemangioblastoma; Hypoxia-inducible factor; Immunohistochemistry; VHL; von Hippel -Lindau disease; CENTRAL-NERVOUS-SYSTEM; COMMON BILE-DUCT; CELL CARCINOMA; PAPILLARY CYSTADENOMA; IMMUNOHISTOCHEMICAL MARKERS; DIFFERENTIATING HEMANGIOBLASTOMA; NEUROENDOCRINE TUMORS; INHIBIN-ALPHA; VHL; EXPRESSION;
D O I
10.1053/j.semdp.2023.11.003
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
von Hippel-Lindau (VHL) disease is characterized by biallelic inactivation of the VHL gene leading to abnormal or absent VHL protein function, and constitutive activation of hypoxia-inducible factors (HIF) that leads to protumorigenic signaling. Individuals with VHL disease develop numerous cysts and tumors involving multiple organs including the kidneys, central nervous system, endolymphatic sac, lungs, pancreatobiliary system, adrenal glands, epididymis, and/or broad ligament. On histologic examination, these lesions show morphologic overlap as they are frequently characterized by cells with clear cytoplasm and prominent vascularity. In addition to distinguishing non-renal tumors from metastatic clear cell renal cell carcinoma, understanding site-specific histopathologic and immunophenotypic features of these tumors has several applications. This includes distinguishing VHL-related tumors from those that arise sporadically and lack VHL gene alterations, guiding further genetic workup, and helping distinguish between different genetic predisposition syndromes. In this context, immunohistochemical studies for markers such as paired box 8 (PAX-8), carbonic anhydrase 9 (CA9), and glucose transporter 1 (GLUT-1) have an important role in routine clinical practice and represent cost-effective diagnostic tools. The recent development of targeted therapeutics directed against HIF-mediated signaling represents a significant milestone in the management of VHL disease and highlights the importance of accurately diagnosing and characterizing the wide spectrum of VHL disease-associated lesions.
引用
收藏
页码:20 / 27
页数:8
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