Distal Tubular Hyperplasia: A Proposal for a Unique Form of Renal Tubular Proliferation Distinct From Papillary Adenoma.

We identified an unusual pattern of renal tubular proliferation associated with chronic renal disease, found in 23 patients, diffusely (n=12), or focally (n=11). Incidence was 5% of end-stage renal disease kidneys from one institution (8/177) and 7/23 patients with acquired cystic kidney disease-associated renal cell carcinoma from another. Most (19 patients) had 1 or more neoplasms including papillary (n=9), acquired cystic kidney disease (n=8), clear cell (n=4), or clear cell papillary (n=3) renal cell carcinoma. All (20 men, 3 women) had end-stage renal disease. The predominant pattern (n=18) was the indentation of chronic inflammation into renal tubules forming small polypoid structures; however, 5 had predominantly hyperplastic epithelium with less conspicuous inflammation. In 14 patients both patterns were appreciable, whereas the remainder had only the inflammatory pattern. Immunohistochemistry was positive for cytokeratin 7, high-molecular-weight cytokeratin, PAX8, and GATA3. Staining for alpha-methylacyl-CoA racemase was negative or weak, dramatically less intense than papillary neoplasms or proximal tubules. CD3 and CD20 showed a mixture of B and T lymphocytes in the inflammatory areas. Fluorescence in situ hybridization showed no trisomy 7 or 17 or loss of Y (n=9). We describe a previously uncharacterized form of renal tubular proliferation that differs from papillary adenoma (with weak or negative alpha-methylacyl-CoA racemase, lack of trisomy 7 or 17, and sometimes diffuse distribution). On the basis of consistent staining for high-molecular-weight cytokeratin and GATA3, we propose the name distal tubular hyperplasia for this process. Future studies will be helpful to assess preneoplastic potential and etiology.

Pseudoangiosarcomatous urothelial carcinoma of the urinary bladder.

The pseudoangiosarcomatous pattern has been described mostly in cutaneous and some visceral squamous cell carcinomas and is unique for its striking morphologic resemblance to angiosarcoma. Herein, we describe the clinicopathologic features of 7 pseudoangiosarcomatous urothelial carcinomas that occurred in the urinary bladder. The patients included 6 men and 1 woman ranging in age from 47 to 87 years (median 70 y). The pseudoangiosarcomatous morphology was observed in 7 urothelial carcinomas including 3 with squamous differentiation and comprised 35% to 85% of the invasive tumor. Histologically, the pseudoangiosarcomatous carcinomas were characterized by tumor cell discohesion and lysis that created pseudolumina formations surrounded by attached residual tumor cells. Detached degenerating tumor cells variably admixed with inflammatory cells were common in the false lumina. Partly intact urothelial carcinoma nests contained irregular or cleft-like spaces and disintegrating tumor cells with stretched intercellular bridges. The tumor was commonly associated with a dense collagenous matrix, often surrounding the lytic nests. Similar tumor cell discohesion and breakdown were observed in 3 tumors with foci of squamous cell differentiation, distinguished by the presence of dyskeratosis and keratin formation. All 7 tumors contained other nonpseudoangiosarcomatous carcinoma components such as conventional urothelial carcinoma (5), squamous differentiation (4), sarcomatoid spindle cell carcinoma (2), small cell carcinoma (1), micropapillary carcinoma (1), and glandular differentiation (1). The pseudoangiosarcomatous urothelial carcinomas were all (7/7) diffusely CK7 positive, most (6/7) were GATA3 positive, and none (0/7) expressed vascular-associated markers. There was no evidence to suggest that apoptosis (by TUNEL assay and cleaved caspase-3 immunostaining) or loss of the adhesion molecules CD138 and e-cadherin were possible causes for the tumor cell discohesion and breakdown. All 7 tumors were high stage at cystectomy and included 1 pT3a, 2 pT3b, and 4 pT4a tumors, and 3 had pelvic lymph node involvement. Follow-up data available in 6 cases revealed a poor outcome with an overall median survival of 8.5 months. In conclusion, we present an unusual morphology of bladder carcinoma that has a striking resemblance to a malignant vasoformative tumor. Our series showed that bladder pseudoangiosarcomatous carcinoma morphology is associated with a higher tumor stage at cystectomy, commonly admixed with other aggressive carcinoma variant morphologies, and portend a poorer outcome. Knowledge of this pattern is also important to avoid misdiagnosis, particularly in limited tissue samples.

The utility of PAX-2 and renal cell carcinoma marker immunohistochemistry in distinguishing papillary renal cell carcinoma from nonrenal cell neoplasms with papillary features.

PAX-2, a homeogene expressed during kidney development, has been studied as a marker of renal origin in both primary and metastatic clear cell renal cell carcinoma (RCC), but not in papillary neoplasms or in comparison with RCC marker (RCCma). We studied immunohistochemical expression of PAX-2 and RCCma in 24 papillary RCC (PRCC) and 66 nonrenal cell papillary neoplasms (NRCPN) from a variety of organs. Of the PRCC, 16/24 (67%) were positive for PAX-2; 23/24 (96%) were positive for RCCma. Of the NRCPN, 9/66 (14%) is positive for PAX-2 [4/10 (40%) ovarian papillary serous carcinomas, 5/9 (56%) uterine papillary serous carcinomas]; RCCma was positive in 28/66 (42%), including 9/9 (100%) papillary thyroid carcinomas, 8/10 (80%) ovarian papillary serous carcinomas, 4/9 (44%) uterine papillary serous carcinomas, 1/10 (10%) papillary urothelial carcinomas, 1/2 (50%) intraductal papillary mucinous carcinomas of the pancreas, 3/3 (100%) choroid plexus papillomas, 1/1 (100%) pituitary adenoma with papillary features, and 1/2 (50%) lung adenocarcinomas with papillary features. The sensitivity of PAX-2+/RCCma+ immunophenotype for PRCC was 58% with a specificity of 54%. There is significant overlap between the expressions of these markers in PRCC and NRCPN; however, the positivity of RCCma and/or PAX-2 is 100% sensitive for PRCC and may prove useful in the initial work up of metastases of unknown primary. PAX-2 and RCCma immunohistochemistry should be interpreted with caution in papillary neoplasms, with particular attention to the possibility of ovarian and uterine papillary serous carcinomas, which can express both PAX-2 and RCCma.