Fibromyxoid Nephrogenic Adenoma

Abstract

Nephrogenic adenoma is a benign epithelial lesion of the genitourinary tract that arises from the reimplantation and proliferation of shed renal tubular cells in areas of urothelial injury and denudation. Fibromyxoid nephrogenic adenoma is a rare variant that consists of compressed spindle-shaped renal epithelial cells in a fibromyxoid background. Only 14 observations of this variant are reported in the literature. We performed a retrospective analysis of fibromyxoid nephrogenic adenomas from 3 large reference centers. We identified 43 lesions in 6 women and 36 men (2 in 1 man) with a median age of 72 years (range, 31 to 94 y). Median lesion size was 0.7 cm (range, 0.2 to 5 cm). Nephrogenic adenomas were in the bladder (n=15), prostate/prostatic urethra (n=14), kidney (n=7), ureter (n=3), penile urethra (n=3), and urethral diverticulum (n=1). One of the kidney lesions developed in an end-stage kidney and radiologically mimicked cancer. Of 37 patients with information, 36 had predisposing conditions including prior biopsy, transurethral resection of bladder tumor, resection, Foley catheter, BCG treatment, urinary stones, (chemo)radiation, or diverticulum. Only 4/37 (10.8%) had a history of prior irradiation. Fifteen lesions had pure fibromyxoid morphology and 28 were admixed classic and fibromyxoid patterns. Three nephrogenic adenomas involved prostatic stroma, 3 renal sinus fat, 2 muscularis propria (1 bladder, 1 renal pelvis), 1 perinephric fat, and 1 corpus spongiosum. Ten fibromyxoid nephrogenic adenomas were intermixed with urothelial carcinoma, 1 with prostate adenocarcinoma, and 1 with malignant melanoma. By immunohistochemistry, PAX8 was positive in all the examined lesions (n=31). Napsin A was negative in all examined fibromyxoid nephrogenic adenomas (n=30). Twenty of them had classic nephrogenic adenoma component which was positive for napsin A. Similar to classic nephrogenic adenoma, fibromyxoid nephrogenic adenoma can occur anywhere along the urinary tract and is associated with a prior history that causes urothelial injury. In nearly a quarter of the cases, fibromyxoid nephrogenic adenoma extended beyond the lamina propria. Unlike previously suggested, fibromyxoid nephrogenic adenoma is not specifically related to prior radiation therapy. Awareness of this variant is important to avoid misdiagnosis and overtreatment.

Identification of uromodulin deposition in the stroma of perinephric fibromyxoid nephrogenic adenoma by mass spectrometry

“…10 PAX8 immunoreactivity, which is an immunohistochemical hallmark of classical NA, was also observed in the epithelial cells of fibromyxoid NA. 10 The characteristic background matrix of fibromyxoid NA was reported to be strongly periodic acid-Schiff (PAS)-positive but negative for amyloid (Congo red) and reticulin staining. 11 There have been few studies of the substance comprising the background matrix of fibromyxoid NA, and mass spectrometry (MS) has not been applied to address this issue.…”

“…10,11 A recent study by Li et al showed that this variant of NA occurs predominantly in the bladder (80%), followed by the urethra (15%) and ureter (5%). 10 The extent of fibromyxoid stromal change varies between cases, with 65% showing mixed classical and fibromyxoid NA morphology and the remaining 35% showing pure fibromyxoid morphology. 10 PAX8 immunoreactivity, which is an immunohistochemical hallmark of classical NA, was also observed in the epithelial cells of fibromyxoid NA.…”

Identification of Uromodulin Deposition in the Stroma of Perinephric Fibromyxoid Nephrogenic Adenoma by Mass Spectrometry

“…Focal bromyxoid morphology was noted in one of the three cases of perinephric NA documented by Diolombi et al [11]. In a series of bromyxoid NAs, Li et al also reported a case with involvement of perinephric fat [9]. Biopsy-associated perforation and extensive disruption due to hemorrhage or mechanical obstruction have been postulated as possible causes of these deep in ltrative NAs.…”

“…A recent study by Li et al showed that this variant of NA occurs predominantly in the bladder (80%), followed by the urethra (15%) and ureter (5%) [9]. The extent of bromyxoid stromal change varies between cases, with 65% showing mixed classical and bromyxoid NA morphology and the remaining 35% showing pure bromyxoid morphology [9]. PAX8 immunoreactivity, which is an immunohistochemical hallmark of classical NA, was also observed in the epithelial cells of bromyxoid NA [9].…”

“…The extent of bromyxoid stromal change varies between cases, with 65% showing mixed classical and bromyxoid NA morphology and the remaining 35% showing pure bromyxoid morphology [9]. PAX8 immunoreactivity, which is an immunohistochemical hallmark of classical NA, was also observed in the epithelial cells of bromyxoid NA [9]. The characteristic background matrix of bromyxoid NA was reported to be strongly periodic acid-Schiff (PAS)-positive but negative for amyloid (Congo red) and reticulin staining [10].…”