Editor: Mahmut Akgul (

2022-40/October 17

Contributors: Ankur Sangoi

Middle-aged male with large renal mass, undergoes nephrectomy. Representative H&E sections of the renal mass shown here along with a single paired immunohistochemical assay. CLICK ON THE BELOW THUMBNAILS TO ENLARGE PHOTOS.



In more viable areas of the tumor away from necrotic foci, the morphology was in keeping with papillary renal cell carcinoma (RCC). Moreover, other immunostains not shown here showed strong diffuse nuclear positivity for PAX8, strong diffuse membranous positivity for CK7, and strong diffuse positivity for AMACR.

Carbonic anhydrase 9 (CA9) is a transmembrane protein and member of the zinc metalloenzyme family, involved in conversion between carbon dioxide and bicarbonate. Membranous pattern (not cytoplasmic) immunohistochemical expression of this marker is often used in the assessment of renal epithelial neoplasms, with strong complete membranous pattern expression (“box-like”) typical of clear cell renal cell carcinoma (RCC), “cup-like” membranous pattern expression often seen in clear cell papillary renal tumor, often negative expression seen in chromophobe and MiTF RCC, and showing variable expression in papillary RCC. Notably, as this marker is under control of the hypoxia inducible factor 1 (HIF1), expression of CA9 antibody can be overexpressed in areas of tissue hypoxia, as seen in this case of papillary RCC around tumor foci surrounding necrosis. Caution should be noted when using this marker among a panel of immunohistostains for cases lacking a straightforward morphologic diagnosis. It should also be noted that while this marker can be helpful in favoring clear cell RCC subtype in metastasis (particularly in cases with a history of RCC but unknown/unverified subtype or in patient’s with an unsampled renal mass and concurrent biopsied metastasis), it is NOT specific for RCC, and can be seen various neoplasms, including non-carcinomatous.

Luong-Player A, Liu H, Wang HL, Lin F. Immunohistochemical reevaluation of carbonic anhydrase IX (CA IX) expression in tumors and normal tissues. Am J Clin Pathol. 2014 Feb;141(2):219-25.

Ankur Sangoi
El Camino Hospital
Mountain View, CA


CA9, renal cell carcinoma, hypoxia, necrosis