The Use of Immunohistochemistry in the Diagnosis of Metastatic Clear Cell Renal Cell Carcinoma

Abstract

The diagnosis of metastatic clear cell renal cell carcinoma may be difficult in some cases, particularly in the small image-guided biopsies that are becoming more common. As targeted therapies for renal cell carcinoma are now standard treatment, the recognition and diagnosis of renal cell carcinoma has become even more critical. Many adjunctive immunohistochemical markers of renal epithelial lineage such as CD10 and RCCma have been proposed as aids in the diagnosis of metastatic renal cell carcinoma, but low specificities often limit their utility. More recently described markers (PAX-2, PAX-8, human kidney injury molecule-1, hepatocyte nuclear factor-1-β, and carbonic anhydrase-IX) offer the potential for greater sensitivity and specificity in this diagnostic setting; however, knowledge of their expected staining in other neoplasms and tissues is critical for appropriate use. In this review, we discuss the most widely used immunohistochemical markers of renal lineage with an emphasis on their sensitivity and specificity for metastatic clear cell renal cell carcinoma. Subsequently, we present a variety of organ-specific differential diagnostic scenarios in which metastatic clear cell renal cell carcinoma might be considered and we propose immunopanels for use in each situation.

PAX2 and PAX8: Useful Markers for Metastatic Effusions

“…Other studies have shown that PAX8 is more sensitive (88-100%) for metastatic RCCs than other commonly used markers, such as CD10 (59-82%), EMA (67-77%) and RCC marker (72-95%) [8]. Sangoi et al [6] proposed replacing CD10 and RCC markers with PAX2 and PAX8 as markers in the workup for potential metastatic renal tumors, and Ozcan et al [7] supported this by suggesting that PAX2 and PAX8 are the best markers for metastatic RCCs. An additional use for PAX8 is that, since PAX8 is expressed in thyroid follicular cells, it will be positive in cytologic specimens of metastatic thyroid malignancies [1,12,22,28].…”

“…In müllerian tract malignancies, WT-1, ER, PR, and CA125 stain positive, although these markers are limited in their specificity [4,5]. For metastatic RCC, immunohistochemical stains such as the RCC marker and CD10 have been used; however, markers with a better sensitivity and specificity are also needed [6,7,8]. …”

“…Recent studies have examined PAX2 and PAX8 as immunohistochemical markers for metastatic RCCs and metastatic müllerian carcinomas [1,6,7,9,10,11,12,13,14,15,16]. PAX2 and PAX8 are transcription factors of the paired box gene (PAX) family that serve as important developmental regulators.…”

Isolated Nail Dystrophy: An Unlikely Presentation of Metastatic Renal Cell Carcinoma

“…2e), and PAX8 is a transcription factor that is sensitive and specific for RCC (Fig. 2f) [6]. Based on the immunohistochemistry with positive CD10, PAX8, AE1/AE3, and negative GATA-3, the diagnosis of metastatic RCC was made.…”

“…2a–f). CK 5/6 and p63 are markers for squamous cell carcinoma, SOX-10 and pan-melanocytic cocktail are markers for melanoma, and adipophilin is positive in sebaceous lesions but can also be a sensitive marker for RCC [5, 6]. CD10 is a metallomembrane endopeptidase that is highly sensitive but not specific for RCC (Fig.…”