Search

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.

Intraductal spread of urothelial carcinoma (UC) is not an uncommon finding in bladder cancer that requires appropriate clinical management. The presence of prostatic stromal invasion in non-muscle-invasive bladder cancer upstages the disease, necessitating cisplatin-based neoadjuvant chemotherapy and subsequent cystroprostatectomy. However, the identification of prostatic stromal invasion can be challenging, especially in biopsy and transurethral resection specimens. We assess the utility of D2-40, CK5/6, and high-molecular-weight cytokeratin (HMWCK) immunohistochemistry as an ancillary tool to differentiate prostatic stromal invasion from intraductal UC spread. We reviewed 13 cystoprostatectomies performed for UC with prostatic involvement. The presence of stromal invasion was histologically determined by the presence of circumferential retraction artifact, paradoxical differentiation, complex architecture, and desmoplastic reaction. The areas of interest were subsequently stained with D2-40, CK5/6, and HMWCK (clone 34βE12). Four bladder biopsies were used as a control to assess labeling in the benign urothelium. Nine cases had histologic evidence of prostatic stromal invasion (4 transmurally through bladder wall). D2-40 highlighted basal cells in all benign prostatic ducts and was consistently negative in UC, benign urothelium, prostatic adenocarcinoma, and benign luminal prostatic epithelium. D2-40 and CK5/6 performed similarly for intraductal UC, labeling only the basal cell layer with the exception of 1 case with squamous differentiation where CK5/6 exhibited full thickness staining. HMWCK diffusely stained 9 of 10 intraductal UCs without squamous differentiation and 1 intraductal UC with squamous differentiation. All 8 cases of invasive UC without squamous differentiation were negative for D2-40. Seven of these cases had focal CK5/6 and diffuse HMWCK staining. In 1 case of invasive UC with squamous differentiation, all stains were positive. D2-40 is expressed in prostatic basal cells, but it is not expressed in the benign or neoplastic urothelium. D2-40 and CK5/6 effectively highlight the intraductal spread of UC. While invasive UC is negative for D2-40, CK5/6 is usually patchy and localized to the periphery of the tumor nests. HMWCK often demonstrates diffuse staining in both scenarios. However, these stains do not perform well in cases of UC with squamous differentiation. Thus, D2-40 can be used as an ancillary tool to rule out prostatic stromal invasion.

Radical prostatectomy (RP) outcomes have been studied in White and Black non-Hispanic men qualifying for Epstein active surveillance criteria (EASC). Herein, we first analyzed such outcomes in White Hispanic men. We studied 70 men with nonpalpable Gleason score 3+3 = 6 (Grade Group [GG] 1) prostate cancer (PCa) with ≤2 positive cores on biopsy who underwent RP. In 18 men, prostate-specific antigen (PSA) density (PSAD) was >0.15 ng/mL/g. Three of these had insignificant and 15 had significant PCa. The remaining 52 men qualified for EASC. One patient had no PCa identified at RP. Nineteen (37%) had significant PCa defined by volume (n = 7), grade (n = 7), and volume and grade (n = 5). Nine cases were 3+4 = 7 (GG 2) (5/9 [56%] with pattern 4 0.5 cm3. Significant PCa is either a larger-volume anterior disease that may be detected by multi-parametric magnetic resonance imaging-targeted biopsy or anterior sampling of the prostate or higher-grade smaller-volume posterior disease that in most cases should not pose immediate harm and may be detected by repeat template biopsies.

Mucinous mammary carcinoma (MC) is a tumor type with relatively favorable prognosis. Unlike the circumstances surrounding conventional invasive duct carcinoma, data are limited regarding precursor lesions for MC. This study characterizes patterns of mucinous ductal carcinoma in situ (DCIS) as a precursor lesion for MC. All slides from 130 cases of MC encountered between 2000 and 2011 at Henry Ford Hospital, Detroit, MI were reviewed to subclassify MC, identify DCIS, and explore transition patterns from DCIS to MC. Calponin, p63, chromogranin, synaptophysin, CD56, and MIB-1 immunostaining analyses were performed in 65 cases. Among 106 cases of pure (71 type A, 35 type B) and 24 cases of mixed MC, DCIS appeared in 88 (68%) specimens, with all but 4 showing luminal mucin accumulation. Dominant patterns of mucinous DCIS were cribriform/solid (66), cribriform and papillary (7), papillary (5), micropapillary (3), and flat (3). Fifty-seven (68%) cases of mucinous DCIS demonstrated transitions from DCIS to MC. Luminal mucinous distention, focal flattening and attenuation of the epithelium, and disruption of the duct wall resulting in a mucocele-like extravasation of malignant epithelia with escaping mucin was a transition pattern seen with all architectures of DCIS and in all types of MC. This was the only pattern of transition to type A MC. The epithelial outpouching, formation of a cleft with accumulation of mucin around the epithelium, and transition into mucin pools with floating tumor cell clusters was the second transition pattern that went from cribriform/solid DCIS to type B and mixed MC. DCIS preceding aggressive phenotypes of MC (type B and mixed) more often had a cribriform/solid architecture, higher nuclear grade, and higher Ki-67-labeling index (all P

Although rare, there are cases within reported series of men with Gleason score (GS) ≤6 on radical prostatectomies that show pelvic lymph node (LN) metastases. However, there are no studies on whether pelvic LN metastases occur in tumors with GS ≤6 using the International Society of Urological Pathology (ISUP) updated GS system. We performed a search of the radical prostatectomy databases at 4 large academic centers for cases of GS ≤6. Only prostatectomies submitted and embedded in entirety with pelvic LN dissections were included. A combined total of 14,123 cases were identified, of which 22 cases had a positive LN. Histopathologic review of 19 cases (3 cases unavailable for review) showed higher grade than originally reported by the pathologists in all cases. Of the 17 pre-ISUP reviewed cases, 2 were upgraded to 4+3=7 with both cribriform and poorly formed glands. One case was upgraded to 4+3=7 with tertiary pattern 5 displaying cribriform glands, poorly formed glands, and cords of single cells. Eleven cases were upgraded to 3+4=7 with glomeruloid structures and small to large cribriform glands (1 of these also had features of ductal adenocarcinoma). Two cases had tertiary pattern 4 with small cribriform glands. One case had a prominent colloid component that would currently be graded as 4+5=9 because of large cribriform glands and solid sheets of cells within the mucin. Of the 2 post-ISUP cases, 1 demonstrated tertiary pattern 4, and the other showed GS 3+4=7 with irregular cribriform glands. Undergrading is the primary reason for LN positivity with GS ≤6, which has decreased significantly since the adoption of the ISUP grading system in 2005. Of over 14,000 totally embedded radical prostatectomies from multiple institutions, there was not a single case of a GS ≤6 tumor with LN metastases. In contrast to prevailing assumptions, GS ≤6 tumors do not appear to metastasize to LNs. Rather, Gleason pattern 4 or 5, as better defined by the current ISUP updated grading system, is required for metastatic disease.