The Diagnosis of Clear Cell Renal Cell Carcinoma (CRCC) on Needle Core Biopsies (NCB) of the Kidney: How Specific Is Carbonic Anhydrase IX (CA9) Immunohistochemistry (IHC)?
Rajen Goyal, Bing Zhu, Shreenath Bishu, Vamsi Parimi, Xiaoqi Lin, Ximing J Yang, Stephen M Rohan. Northwestern University Feinberg School of Medicine, Chicago, IL
Background: NCB of renal masses are becoming more common in clinical practice. NCB are often done in patients with contraindications to surgery prior to ablative therapies or in clinical trials of neoadjuvant targeted therapies. In the latter case, trial enrollment is often dependent on proper subclassification of a tumor. The modern classification of renal cell carcinoma (RCC) recognizes numerous subtypes of which CRCC is the most common. Many IHC markers useful in differentiating RCC subtypes have been described. IHC expression of CA9 is seen in most CRCC secondary to alteration of the VHL/HIF pathway. The expression of CA9 in CRCC is well known in the clinical literature in which the use of radiolabeled CA9 and PET/CT for the preoperative diagnosis of CRCC with high specificity has been documented. In the pathology literature it has been suggested that CA9 is not specific for CRCC and that CA9 expression is often seen in papillary RCC (PRCC) and other renal tumors. The aim of our study was to evaluate the utility of CA9 IHC in the diagnosis of CRCC on NCB.
Design: Thirty-two cases of renal tumors that had undergone NCB and then subsequent resection were evaluated. CA9 IHC was performed on the NCB in each case. Only membranous CA9 labeling was considered positive. The staining was graded from 0 to 3+ (0, no staining; 1+, 1-25% cells positive; 2+; 26-50%; and 3+, >50%). The final pathology of the resection specimen was used as the “gold standard” diagnosis. The presence or absence of necrosis was noted in each case.
Results: The final pathologic diagnoses included 21 CRCC, 4 PRCC, 4 chromophobe RCC, 2 unclassified RCC, and 1 oncocytoma. 95% (20/21) CRCC exhibited 3+ CA9 IHC. Three cases had discordant NCB and final pathology diagnoses (table 1). The sensitivity and specificity for CA9 labeling in CRCC were: 95% and 73% respectively.
|NCB DX||Final DX||CA9||Necrosis|
|Case 1||Unclassified RCC||PRCC||2+||Present|
|Case 2||Unclassified RCC||PRCC||2+||Present|
|Case 3||CRCC||Unclassified RCC||3+||Present|