Original Contribution
Useful immunohistochemical panel for differentiating clear cell papillary renal cell carcinoma from its mimics

https://doi.org/10.1016/j.anndiagpath.2013.05.004Get rights and content

Abstract

Clear cell papillary renal cell carcinoma (CCPRCC) is a recently described low-grade renal cell tumor. In this study, we investigated the expression of paired box 8 (PAX-8), carbonic anhydrase IX (CA IX), CK7, and α-methylacyl-CoA-racemase (AMACR) in this tumor by immunohistochemistry in a group of 20 cases of CCPRCC. Clear cell papillary renal cell carcinoma showed diffuse (70%) or intermediate (30%) nuclear positivity for PAX-8 in each case, with predominantly moderate intensity (50%). Ninety percent of the cases showed some degree of cytoplasmic staining for CA IX, predominantly with moderate intensity (50%). In addition, each case of CCPRCC also showed diffuse membranous staining for CK7. Most CCPRCCs (95%) were negative for AMACR. PAX-8, CA IX, CK7, and AMACR comprise a concise panel for distinguishing CCPRCC from its mimics. PAX-8 positivity helps to confirm the renal origin of this tumor. Positivity for CA IX and CK7 differentiate CCPRCC from conventional clear cell renal cell carcinoma, which is usually CA IX positive while CK7 negative. The CK7-positive and AMACR-negative pattern seen in CCPRCC differentiates it from papillary renal cell carcinoma, which is usually positive for both AMACR and CK7.

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

References (30)

  • S.K. Tickoo et al.

    Spectrum of epithelial neoplasms in end-stage renal disease: an experience from 66 tumor-bearing kidneys with emphasis on histologic patterns distinct from those in sporadic adult renal neoplasia

    Am J Surg Pathol

    (2006)
  • C.G. Li et al.

    PAX genes in cancer; friends or foes?

    Front Genet

    (2012)
  • V. Frost et al.

    Self-regulated Pax gene expression and modulation by the TGFbeta superfamily

    Crit Rev Biochem Mol Biol

    (2008)
  • B.A. Alexiev et al.

    Nephrogenic adenoma of the urinary tract: a review

    Int J Surg Pathol

    (2012)
  • J.C. Carvalho et al.

    p63, CK7, PAX8 and INI-1: an optimal immunohistochemical panel to distinguish poorly differentiated urothelial cell carcinoma from high-grade tumours of the renal collecting system

    Histopathology

    (2012)
  • Cited by (14)

    • Immunohistochemistry for the diagnosis of renal epithelial neoplasms

      2022, Seminars in Diagnostic Pathology
      Citation Excerpt :

      More importantly, diffuse keratin 7 (Fig. 5C) expression contrasts to the vast majority of clear cell RCC.53, 89, 90 CD10 (Fig. 5D) and AMACR are typically negative in clear cell papillary RCC, contrasting to clear cell RCC and papillary RCC, respectively.53, 89, 90 Tumors also frequently label for keratin 34βE1291 and GATA3,92 suggesting a phenotype more of the distal than proximal nephron.

    • Ureter, Urinary Bladder, and Kidney

      2021, Gattuso’s Differential Diagnosis in Surgical Pathology
    • The evolving classification of renal cell neoplasia

      2015, Seminars in Diagnostic Pathology
      Citation Excerpt :

      AMACR, CD10, and RCC marker are all negative. There may also be patchy positivity for high-molecular-weight cytokeratin.24,40–45 Genetic studies relating to clear cell (tubulo) papillary RCC are limited.

    View all citing articles on Scopus
    View full text