title: PAX8 expression in sporadic hemangioblastoma of the kidney supports a primary renal cell lineage: implications for differential diagnosis.
abstract: Hemangioblastoma is a benign, morphologically distinctive neoplasm of disputed histogenesis that typically occurs in the central nervous system either in the setting of von Hippel-Lindau disease or more often sporadically. Extraneural hemangioblastoma is exceptional and raises a challenging differential diagnosis. Herein, we report a primary renal hemangioblastoma occurring in 51-year-old woman without stigmata of von Hippel-Lindau disease. Histologically, the tumor was composed of sheets of polygonal epithelioid stromal cells with ample pale or eosinophilic, vacuolated cytoplasm in an arborizing capillary network. Tumor cells showed variable nuclear pleomorphism, intranuclear cytoplasmic invaginations, scattered hyaline globules, and psammoma-like calcifications. Some areas showed branching hemangiopericytoma-like vessels with tumor cells radiating from the wall, while other areas were edematous and hyalinized with sparse stromal cells and abundant reticular vessels. Immunohistochemically, the tumor cells reacted strongly and diffusely with antibodies to PAX8, CD10, α-inhibin, S100 protein, neuron-specific enolase, and vimentin, and they showed focal positivity with antibodies to epithelial membrane antigen and AE1/AE3. Tumor cells were negative for CK7, CK8/18, RCC antigen, synaptophysin, chromogranin, c-kit, D2-40, HMB45, melan-A, cathepsin K, SMA, desmin, CD31, CD34, and estrogen and progesterone receptors. Positive immunoreactivity for PAX8 is unexpected and contrasts to central nervous system (CNS) hemangioblastomas, which are essentially always negative for PAX8. This novel finding adds support to the hypothesis that the immunoprofile of extraneural hemangioblastoma varies with site of origin, perhaps as a result of tumor cell lineage and retention of organ-specific markers or acquisition of site-specific antigens due to local factors.
authors.affiliation: Department of Pathology, Ningbo Yinzhou Second Hospital, Ningbo, Zhejiang 315100, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Sean R
authors.initials: SR
authors.lastname: Williamson
authors.forename: Jingjing
authors.initials: J
authors.lastname: Yu
authors.forename: Wenping
authors.initials: W
authors.lastname: Xia
authors.forename: Changshui
authors.initials: C
authors.lastname: Li
authors.forename: Jiangjiang
authors.initials: J
authors.lastname: Zheng
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhu
authors.forename: Ke
authors.initials: K
authors.lastname: Sun
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002114:Calcinosis / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000378:metabolism; D019070:Cell Lineage; D002467:Cell Nucleus / Q000473:pathology; D003593:Cytoplasm / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D018325:Hemangioblastoma / Q000175:diagnosis* / Q000378:metabolism / Q000601:surgery; D006801:Humans; D007668:Kidney / Q000166:cytology; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000601:surgery; D008875:Middle Aged; D009928:Organ Specificity; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors
keywords: Differential diagnosis; Hemangioblastoma; Kidney; PAX8 immunohistochemistry; Renal neoplasm; von Hippel–Lindau disease