Nephrogenic adenoma identified on urine cytology using PAX‐2 immunostaining

Abstract

Urine cytology is a sensitive and specific method in detecting urothelial carcinoma of the urinary bladder, particularly the high-grade ones. However, the cytologic features of nonneoplastic lesions of the lower urinary tract, including nephrogenic adenoma, are nonspecific and may cause false positive diagnosis. Recent evidence has demonstrated that nephrogenic adenoma is a true ''nephrogenic'' lesion derived from the exfoliated and implanted renal tubular cells in the urinary tract. This has promoted the use of immunostaining of renal transcription factor PAX2 in tissue biopsies to differentiate nephrogenic adenoma from the common malignant tumors of the lower urinary tract. We report here that PAX2 immunostaining can also be used in urine cytology specimen to identify nephrogenic adenoma. Combination of PAX2 immunostaining and cytologic analysis may increase the accuracy in identifying this benign lesion in urine cytology specimen and therefore reduce unnecessary repeat cystoscopy and biopsy procedures. This may be a cost effective followup method for patients with an established diagnosis of nephrogenic adenoma. Diagn. Cytopathol. 2008;36:47-49. ' 2007 Wiley-Liss, Inc.Key Words: PAX2; nephrogenic adenoma; urine cytology Nephrogenic adenoma (NA) is an uncommon lesion of the urinary tract often associated with renal transplant, anatomic anomaly, or a history of traumatic injury of the urinary tract. 1 It was traditionally considered to be a metaplastic lesion of the urothelium. However, recent evidence has suggested that NA is a truly ''nephrogenic'' lesion derived from exfoliated and implanted renal tubular cells in the urinary tract. 2 The histologic features of NA are well described and the diagnoses in most cases are straightforward. 3-5 Urine cytology is frequently used to evaluate urinary bladder cancer and constitutes a large portion of cytology specimens. However, the cytologic features of NA are less well defined and it contributes to false positive diagnoses in urine cytology. [6][7][8] In addition, NA may coexist with or develop after the treatment of malignant tumors of the urinary tract, thus further complicating the recognition of this benign lesion. Several immunohistochemical markers have been used to assist in the differential diagnosis of NA. Recently, we reported that the renal transcription factor PAX2 is a reliable marker to distinguish NA from common carcinomas of the urinary tract on tissue sections. 9 We report here our experience utilizing PAX2 antibody in a urine cytology specimen for one NA case. Report of a CaseThe patient was a 69-year-old woman with end stage renal disease secondary to diabetes and hypertension who was on a waiting list for kidney transplant. A 3-cm tumor was noted on the right lateral wall of the urinary bladder during the pretransplant evaluation. The patient underwent a partial cystectomy and the tumor was reportedly resected completely. The histological diagnosis was lowgrade papillary urothelial carcinoma, which resulted in her subsequent removal from the tra...

Novel round cells in urine sediment and their clinical implications

“…2B and C). One study found that PAX2 is expressed in tubular adenoma cells in the lower urinary tract [13], but the cells observed in the present study were positive for GGT1 and CD13, and can therefore be discriminated from tubular adenoma cells. Our results suggest that the round cells are undifferentiated cells.…”

PAX Genes in Cancer; Friends or Foes?

“…PAX2 is expressed in ovarian cancers, in renal cell carcinomas (RCC), and in some bladder carcinomas (Muratovska et al, 2003; Tong et al, 2007; Herlitz et al, 2008). In these cell types it appears to be important for tumor cell survival (Muratovska et al, 2003; Hueber et al, 2006), which has recently been shown to be because PAX2 regulates ADAM10 (Doberstein et al, 2011), and in RCC PAX2 expression is promoted by the loss of VHL and hypoxia (Luu et al, 2009).…”

Flat pattern of nephrogenic adenoma: previously unrecognized pattern unveiled using PAX2 and PAX8 immunohistochemistry

“…[4][5][6][7][8] Several studies have shown that PAX2 and PAX8 are expressed in nearly 100% of nephrogenic adenomas [9][10][11][12] and are helpful markers when the diagnosis of nephrogenic adenoma is difficult. In this study, we corroborated the frequent expression of PAX2 (93%) and PAX8 (100%) in our series of nephrogenic adenomas and identified a flat pattern associated with other traditional nephrogenic adenoma patterns that extended along the adjacent urothelium.…”

“…2,3 By immunohistochemistry, nephrogenic adenomas are positive for the renal tubule markers cytokeratin 7 (CK7), CD10, alpha-methylacyl-coenzyme A racemase (AMACR), PAX2 and PAX8, but negative for bladder urothelium or prostate antigens. [4][5][6][7][8] The transcription factors PAX2 and PAX8 (paired box genes) are crucial proteins during the embryonic and fetal development of several organs, particularly intermediate mesoderm and Mü llerian-derived tissues, and are expressed in nearly 100% of nephrogenic adenomas in some series. [9][10][11][12] Tong et al 13 have shown that urothelial cells from the upper genitourinary tract are PAX8 positive, whereas urinary bladder urothelium lacks PAX8 expression.…”