Lymph node metastases in patients with urothelial carcinoma variants: influence of the specific variant on nodal histology.

Objectives: The effect that the presence of urothelial variant (UV) histologies has on the behavior of urothelial carcinoma remains poorly defined. The goal of this study is to examine the relationship between different histologic variants and the presence and histology of lymph node metastases.

Materials And Methods: Our institutional bladder cancer database was examined for all patients demonstrating UV at cystectomy performed between 2001 and 2012. Patients with primary bladder sarcoma, primary bladder adenocarcinoma, and squamous cell carcinoma were excluded. The cystectomy and nodal pathology reports were reviewed in node-positive cases with the goal of determining the relative percentages of UVs in the bladder and lymph nodes.

Results: Overall, 292 patients demonstrated UV at cystectomy. After excluding patients with primary adenocarcinoma, sarcoma, and squamous variants, 141 patients remained, of which 65 demonstrated node-positive disease. Of these node-positive patients, 57 had slides available for review. Node positivity was most common in the micropapillary (MP), clear cell urothelial carcinoma (CC), and plasmacytoid (PC) variants. Remaining variants demonstrated node-positive rates ranging from 11.1% to 37.5%. When nodes were positive, the variants found in the nodal metastases most commonly were MP, CC, glandular, nested, and lymphoepitheliomalike. Median lymph node density was highest in PC (33%) and CC (35%) variants, although these differences were not statistically significant. Variant histology predominated the nodal metastases regardless of predominance in bladder for the MP (84%) and CC (100%) variants. The PC variant exhibited the high incidence of positive surgical margins.

Conclusion: Lymph node metastases were most common in the MP, CC, and PC variants. Variant histology was present and predominated nodal histology in most MP and CC cases. These results suggest that the variant histology itself may be driving lymphatic spread in MP and CC cases. Conversely, the PC variant may be a marker for locally advanced and aggressive disease rather than specifically influencing lymphatic spread.