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Presented by Dr. A. Cimino-Mathews and prepared by Dr. J. Judd Fite
Clinical history: A 50 year-old male with history of low grade papillary urothelial carcinoma.
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1. Question
Week 639: Case 3
Clinical history: A 50 year-old male with history of low grade papillary urothelial carcinoma
Correct
Answer: C. Nephrogenic adenoma
Histology: The bladder biopsies show partially denuded benign urothelium that where intact displays small uniform nuclei with overlying umbrella cells. The lamina propria contains chronic inflammatory cells including eosinophils. One tissue fragments contains irregular glands/tubule-like structures located in the lamina propria immediately underneath benign surface urothelium. The glands are lined by hobnail cells with bland cytology. By immunohistochemistry, the glands are positive for Pax8 and negative for GATA3.
Discussion: The bladder biopsy contains a nephrogenic adenoma, a benign proliferation which is believed to be derived from renal tubule epithelium. Evidence supporting renal derivation of nephrogenic adenoma comes from both immunohistochemistry (positivity for PAX8 and PAX2), but also based on studies of nephrogenic adenomas in patients with renal transplants. In these studies, the X-chromosome status of the nephrogenic adenoma mirrored the gender of the kidney donor and not the host patient. Nephrogenic adenomas most commonly occur in the bladder but can also be seen elsewhere in the urinary tract such as the urethra, ureter or renal pelvis, and typically occur in patients with a history of prior genitourinary instrumentation (e.g., renal transplant, genitourinary surgery). Nephrogenic adenomas can have variable histologic appearances: the spaces may appear more tubular, glandular or vascular-like; the individual cells may be cuboidal, eosinophilic, mucinous or signet-ring like. Nephrogenic adenomas are typically bland with minimal mitotic activity, but they can show degenerative-type atypia. One primary diagnostic pitfall with nephrogenic adenoma is prostatic adenocarcinoma, but they can also mimic urothelial carcinoma with glandular differentiation, vascular lesions, and clear cell adenocarcinoma. By immunohistochemistry, nephrogenic adenomas are positive for PAX8, PAX2, and AMACR/Racemase; may be positive for PSA; and are negative for vascular markers (CD34, ERG, CD31) and urothelial markers (p63, GATA3). (Notice that nephrogenic adenomas may be PSA+, Racemase+ and p63-, thus mimicking the staining pattern of prostatic adenocarcinoma on a PIN4 stain!)
References:
1. Oliva E, Young RH. Nephrogenic adenoma of the urinary tract: a review of the microscopic appearance of 80 cases with emphasis on unusual features. Mod Pathol. 1995 Sep;8(7):722-30.
2. Mazal PR, Schaufler R, Altenhuber-Müller R, et al. Derivation of nephrogenic adenomas from renal tubular cells in kidney-transplant recipients. N Engl J Med. 2002 Aug 29;347(9):653-9.
3. Netto GJ, Epstein JI. Benign Mimickers of Prostate Adenocarcinoma on Needle Biopsy and Transurethral Resection. Surg Pathol Clin. 2008 Dec;1(1):1-41.Incorrect
Answer: C. Nephrogenic adenoma
Histology: The bladder biopsies show partially denuded benign urothelium that where intact displays small uniform nuclei with overlying umbrella cells. The lamina propria contains chronic inflammatory cells including eosinophils. One tissue fragments contains irregular glands/tubule-like structures located in the lamina propria immediately underneath benign surface urothelium. The glands are lined by hobnail cells with bland cytology. By immunohistochemistry, the glands are positive for Pax8 and negative for GATA3.
Discussion: The bladder biopsy contains a nephrogenic adenoma, a benign proliferation which is believed to be derived from renal tubule epithelium. Evidence supporting renal derivation of nephrogenic adenoma comes from both immunohistochemistry (positivity for PAX8 and PAX2), but also based on studies of nephrogenic adenomas in patients with renal transplants. In these studies, the X-chromosome status of the nephrogenic adenoma mirrored the gender of the kidney donor and not the host patient. Nephrogenic adenomas most commonly occur in the bladder but can also be seen elsewhere in the urinary tract such as the urethra, ureter or renal pelvis, and typically occur in patients with a history of prior genitourinary instrumentation (e.g., renal transplant, genitourinary surgery). Nephrogenic adenomas can have variable histologic appearances: the spaces may appear more tubular, glandular or vascular-like; the individual cells may be cuboidal, eosinophilic, mucinous or signet-ring like. Nephrogenic adenomas are typically bland with minimal mitotic activity, but they can show degenerative-type atypia. One primary diagnostic pitfall with nephrogenic adenoma is prostatic adenocarcinoma, but they can also mimic urothelial carcinoma with glandular differentiation, vascular lesions, and clear cell adenocarcinoma. By immunohistochemistry, nephrogenic adenomas are positive for PAX8, PAX2, and AMACR/Racemase; may be positive for PSA; and are negative for vascular markers (CD34, ERG, CD31) and urothelial markers (p63, GATA3). (Notice that nephrogenic adenomas may be PSA+, Racemase+ and p63-, thus mimicking the staining pattern of prostatic adenocarcinoma on a PIN4 stain!)
References:
1. Oliva E, Young RH. Nephrogenic adenoma of the urinary tract: a review of the microscopic appearance of 80 cases with emphasis on unusual features. Mod Pathol. 1995 Sep;8(7):722-30.
2. Mazal PR, Schaufler R, Altenhuber-Müller R, et al. Derivation of nephrogenic adenomas from renal tubular cells in kidney-transplant recipients. N Engl J Med. 2002 Aug 29;347(9):653-9.
3. Netto GJ, Epstein JI. Benign Mimickers of Prostate Adenocarcinoma on Needle Biopsy and Transurethral Resection. Surg Pathol Clin. 2008 Dec;1(1):1-41.