Original ContributionUseful immunohistochemical panel for differentiating clear cell papillary renal cell carcinoma from its mimics
Introduction
Clear cell papillary renal cell carcinoma (CCPRCC) is a recently described low-grade renal cell tumor [1], [2], [3], [4]. This unique type of tumor can occur in both end-stage [4] or normal [2] kidneys. Histologically, this tumor can display various architectural patterns: true papillae, branching tubules, solid acinar nests, or ribbons. The tumor cells have clear cytoplasm and low Fuhrman nuclear grade. The nuclei are characteristically located away from the basement membrane to show a “piano-key-like” pattern [3]. The outcome data are limited; however, the available data suggest that this tumor is not aggressive and patients with this type of tumor usually have a good prognosis [1].
Paired box 8 (PAX-8) is a member of PAX family transcription factors, which has a conserved paired box, a DNA binding domain of 128 amino acids located at the N-terminus [5], and plays an important role in regulating cell proliferation, differentiation, apoptosis, migration, and stem cell maintenance [6]. It is involved in the normal development of renal, thyroid, and müllerian tissues [7], [8]. PAX-8 has been shown to be specifically expressed in tumors of thyroid, müllerian, and renal origin [9], [10], [11], [12], [13], [14]. Expression of PAX-8 has been demonstrated in major renal epithelial neoplasms [11] and is a useful marker in determining the primary origin of a neoplasm. No previous study has been done to investigate the expression of this marker in CCPRCC.
In this study, we evaluated the expression of this marker as well as carbonic anhydrase IX (CA IX), α-methylacyl-CoA-racemase (AMACR), and CK7 in this tumor. We demonstrate that this panel is useful in differentiating this tumor from its 2 most frequent mimics: conventional clear cell renal cell carcinoma and papillary renal cell carcinoma.
Section snippets
Materials and methods
In this study design, we investigated the expression of PAX-8, CA IX, CK7, and AMACR in CCPRCC in a group of 20 cases by immunohistochemistry (IHC). The cases of CCPRCC were retrieved from the pathology archives of the Hospital of the University of Pennsylvania. The study was approved by the Institutional Review Board of the University of Pennsylvania. The cases were reviewed by 2 pathologists to confirm the diagnosis using the criteria described in the literature [4].
Formalin-fixed and
Results
Twenty cases of CCPRCC were stained for PAX-8, CA IX, AMACR, and CK7. Of the 20 cases, 8 were from female patients, and 12 were from male patients. The age of the patients ranged from 27 to 76 years with an average of 59 ± 13 years. Thirteen tumors were from the left side; 5, from the right side; 2, bilateral. Seven patients underwent a radical nephrectomy; the remainder were removed via partial nephrectomy. Among the 7 patients who had a radical nephrectomy, 3 had end-stage renal disease; the
Discussion
Clear cell papillary renal cell carcinoma is a low-grade renal tumor and is often cystic [3]; however, only 5 (25%) of the 20 cases in our study were cystic lesions. The tumor cells show clear cytoplasm and low Fuhrman nuclear grade. The nuclei show characteristic polarization in a linear array away from the basement membrane. There are very limited data regarding the genetic abnormality of this tumor [15]. It does not show the characteristic chromosome abnormality of 3p deletion, which is a
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