Oncocytic renal tumors with CD117 negative, cytokeratin 7 positive immunoprofile are different from eosinophilic chromophobe renal cell carcinoma (CHRRCC) and oncocytoma
Trpkov K, Williamson SR, Martinek P, Cheng L, Fraile PSM, Yilmaz A, and Hes O. Oncocytic renal tumors with CD117 negative, cytokeratin 7 positive immunoprofile are different from eosinophilic chromophobe renal cell carcinoma (CHRRCC) and oncocytoma. Lab Invest 2018; 98:393.
Background: Positive staining for CD117 is often used to support diagnoses of oncocytoma or ChrRCC. Greater extent of cytokeratin 7 (CK7) labeling is generally considered in favor of ChrRCC; however, the extent of CK7 labelling in oncocytic tumors is usually limited compared to classic ChrRCC. We have encountered occasional oncocytic tumors that are unexpectedly CD117 negative, but diffusely CK7 positive. Design: Prompted by 2 index cases with oncocytic morphology that were CD117 negative and CK7 diffusely positive, we searched 4 large renal tumor archives for similar cases. In particular, we reviewed the cases labelled as “consistent with (or favor) eosinophilic ChRCC”, “oncocytic tumor, favor oncocytoma, or with hybrid features” and “low-grade oncocytic tumor (unclassified)”, all of which showed negative CD117 and diffusely positive CK7. We collected clinicopathologic and follow-up (F/U) data and, in addition to CD117 and CK7, we performed the following immunostains: PAX8, CD10, AMACR, e-cadherin, CK20, CA9, AE1/AE3, vimentin, BerEP4, and MOC31. Muller-Mowry colloidal iron stain was also done. In 7 cases with available paraffin tissue, we performed array CGH (aCGH) evaluation. Results: We identified 19 cases with male-to-female ratio of 1:1.7, and median age of 66 years (range 53-78y). Median tumor size was 30 mm (range 11-135 mm); all were single tumors. Grossly, the cut surface was tan-brown and solid. On microscopy, all cases showed solid or compact nested growth and often loosely arranged tumor cells in areas of edematous stroma. The cells exhibited oncocytic cytoplasm with uniformly round to oval, but not irregular or crumpled nuclei, with focal delicate (or absent) perinuclear halos, as shown in Figures 1 and 2. Uniform reactivity was found for: AE1/AE3, PAX8, e-cadherin, BerEP4 and MOC31. Negative stains included: CA9, CK20, and vimentin; CD10 and AMACR were either negative or focal. Muller- Mowry stain was either negative or apical positive. aCGH showed common deletions on 19p (7/7), 1p36 (5/7) and 19q (4/7), but no other consistent gains or losses. F/U was available for 15/19 patients (median 21 mo, range 3-118); all were alive with no disease progression. Conclusions: Oncocytic tumors that are CD117 negative and CK7 positive show remarkably consistent morphology and immunoprofile, which does not fit completely into either oncocytoma or eosinophilic ChrRCC. These tumors are indolent and show frequent losses of 1p36 and 19q, and uniform loss of 19p, but no other consistent losses or gains. (Figure Presented).