title: Immunohistochemical markers to distinguish between hemangioblastoma and metastatic clear-cell renal cell carcinoma in the brain: utility of aquaporin1 combined with cytokeratin AE1/AE3 immunostaining.
abstract: Distinguishing hemangioblastomas from metastatic clear-cell renal cell carcinomas (CCRCCs) in the brain is a diagnostic challenge owing to similar clinical and morphologic presentations. Inhibin-alpha and aquaporin1 were shown as positive markers of hemangioblastoma, but are not totally reliable distinguishing hemangioblastoma from metastatic CCRCC. This study shows that the diagnosis can be achieved using a combination of markers. To identify the panel of markers useful for this differential, 67 hemangioblastomas and 34 metastatic CCRCCs were analyzed using a panel of antibodies including aquaporin1, inhibin-alpha, D2-40, cytokeratin AE1/AE3, epithelial membrane antigen, and CD10. The study confirms the usefulness of aquaporin1 (97% sensitivity, 83% specificity) and inhibin-alpha (88% sensitivity, 79% specificity) as positive markers of hemangioblastoma and shows that aquaporin1 is a superior positive marker versus inhibin-alpha for the differential. Positivity of tumor cells with cytokeratin AE1/AE3 is the signature of a metastatic CCRCC (100% specificity, 88% sensitivity) and CD10 expression as well (100% specificity, 79% sensitivity). The combined use of aquaporin1 and AE1/AE3 yields a high degree of sensitivity and specificity to differentiate between hemangioblastoma and metastatic CCRCC. All tumors but one aquaporin1 positive and cytokeratin AE1/AE3 negative (65/66) correspond to hemangioblastomas (97% sensitivity, 97% specificity, 98.5% diagnostic positive predictive value). Tumors with the opposite profile, aquaporin1 negative, and cytokeratin AE1/AE3 positive, (25/25), correspond to metastatic CCRCC (74% sensitivity, 100% specificity, 100% diagnostic positive predictive value). In summary, aquaporin1 is the most sensitive positive marker of hemangioblastoma. Despite its moderate specificity, when used in combination with epithelial marker AE1/AE3, it allowed to reliably distinguish hemangioblastoma from metastatic CCRCC.
authors.affiliation: Department of Pathology, Nancy University Hospital, Nancy, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Weinbreck
authors.forename: Béatrice
authors.initials: B
authors.lastname: Marie
authors.forename: Aude
authors.initials: A
authors.lastname: Bressenot
authors.forename: Karine
authors.initials: K
authors.lastname: Montagne
authors.forename: Antony
authors.initials: A
authors.lastname: Joud
authors.forename: Cédric
authors.initials: C
authors.lastname: Baumann
authors.forename: Olivier
authors.initials: O
authors.lastname: Klein
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Vignaud
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051398:Aquaporin 1 / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000556:secondary; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000175:diagnosis* / Q000556:secondary; D002648:Child; D003937:Diagnosis, Differential; D005260:Female; D018325:Hemangioblastoma / Q000737:chemistry / Q000175:diagnosis*; D006801:Humans; D007633:Keratins / Q000032:analysis; D007680:Kidney Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor; D051398:Aquaporin 1; D007633:Keratins