GATA3 as a valuable marker to distinguish clear cell papillary renal cell carcinomas from morphologic mimics

Publication date: Available online 11 July 2017
Source:Human Pathology
Author(s): Jose G. Mantilla, Tatjana Antic, Maria Tretiakova
Clear cell papillary renal cell carcinoma (CCPRCC) is a low-grade, indolent neoplasm, with no reported cases of death from disease or metastasis. These lesions can show clinical, morphologic and immunophenotypic overlap with several aggressive forms of renal cell carcinoma (RCC), including clear cell (CCRCC), translocation RCC and papillary RCC (PRCC) with cytoplasmic clearing. Given the difference in behavior, it is important to reliably separate these entities.We retrospectively reviewed 47 tumors from 45 patients with morphologic features of CCPRCC. All cases were stained against CK7, CAIX and GATA3. Cases inconsistent with CCPRCC were reclassified. Additionally, we stained tissue microarrays with 103 typical CCRCC and 62 PRCC, each in triplicate. 25 cases were morphologically and immunophenotypically consistent with CCPRCC; all of them showed diffuse CK7 expression and cup-like reactivity with CAIX. Of these, 19 (76%) showed strong nuclear reactivity for GATA3. Although some non-CCPRCC neoplasms showed at least partial CK7/CAIX co-expression, none were immunopositive for GATA3. All background normal kidneys studied showed GATA3 expression in the distal tubules, collecting ducts and retention cysts of the distal nephron. On follow-up, none of the patients with CCPRCC had recurrences or metastasis. Sensitivity and specificity for GATA3 staining in the diagnosis of CCPRCC were 76% and 100%, with positive and negative predictive values of 100% and 74%.In conclusion, GATA3 is specific and sensitive for CCPRCC, and can be used for accurate distinction from its main mimickers. Co-expression of GATA3 and CK7 in most CCPRCC provides evidence of their origin from distal nephron.

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