Nested Urothelial Carcinoma: A Clinicopathologic and Immunohistochemical Analysis of 33 Cases
MJ Wasco, D Bradley, RB Shah. University of Michigan, Ann Arbor
Background: Urothelial carcinoma (UC) with nested growth pattern is a rare and less studied variant of UC, characterized by deceptively bland morphology resembling small von Brunn's nests, yet aggressive biology.
Design: We analyzed a series of 33 patients with nested UC who underwent definitive treatment to better understand its clinicopathological spectrum, immunophenotype and clinical outcome. Tumors demonstrating either pure or mixed nested morphology with variable component of conventional UC were included.
Results: Patients age ranged from 41 to 81 years (avg 65) with a male: female ratio of 2.7:1. Pure nested UC accounted for 33% of cases. When seen along with conventional UC, the nested component ranged from 30% to 90%. Of the 22 cases associated with conventional UC, 29% had an additional component of divergent differentiation. Muscle invasion at TURBT and extravesical disease (T3) at cystectomy were observed in 82% and 83% of cases respectively (p <0.0001 compared to non-nested UC). Angiolymphatic invasion was common (73%). In comparison to pure conventional high grade UC, nested UCs were associated with metastatic disease (72%), in the form of lymph node and/or distant metastases (compared to 16% for conventional UC, p <0.0001). Behavior was similarly aggressive whether tumor was pure nested or mixed nested. Despite overall bland morphology, focal areas of high grade morphology in the deeper invasive component were noted in most tumors. Nested component uniformly demonstrated random cytological atypia, and growth patterns ranging from haphazard small isolated nests to areas with confluent nested growth with minimal desmoplasia. When associated with conventional UC, the nested component was part of the deeply invasive tumor. 94% of cases were positive for CK7, 68% CK20 positive, 93% K903 positive, and 93% p63 positive. Follow-up was available on 31 patients, and ranged from 1 to 31 months (average 12). 18% of patients died of disease, and another 36% of patients were alive with disease at last follow-up. 16/33 patients (48%) received neoadjuvant chemotherapy. Only two of these patients responded to this therapy. 24 patients were treated with cystectomy, 1 with nephroureterectomy, another 3 were treated with TURBT only, and 5 received radiation. Seven (21%) patients received adjuvant chemotherapy.
Conclusions: UC demonstrating pure or variable component of nested morphology is an aggressive tumor with uniformly bad outcome. Increased awareness of the spectrum of this tumor and its early recognition is important due to its subtle and heterogeneous morphology.
Category: Genitourinary (including renal tumors)
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 107, Wednesday Morning