Invasive urothelial carcinoma with chordoid features: a report of 12 distinct cases characterized by prominent myxoid stroma and cordlike epithelial architecture.

Urothelial carcinoma is morphologically heterogeneous and many variant forms have been described. We have encountered several invasive urothelial carcinomas with a unique chordoid morphology characterized by prominent cellular cording and associated myxoid stromal matrix, a pattern closely resembling extraskeletal myxoid chondrosarcoma. This morphologic appearance, to our knowledge, has not been formally described in urothelial carcinoma. A series of 166 consecutive invasive urothelial carcinomas were reviewed to identify cases with cellular cording and myxoid stroma. The patient age, sex, tumor stage, morphologic features, association with typical urothelial carcinoma, and clinical outcome were recorded. Immunostains for p63, cytokeratin (CK) 34BE12, CK20, calponin, glial fibrillary acidic protein, S-100 protein, oncofetal protein glypican-3, and brachyury were performed on 7 cases. Mucin histochemistry was performed on 8 cases to evaluate the extracellular myxoid material. Eleven of the 166 (7%) consecutive invasive urothelial carcinomas had areas with a chordoid appearance. A total of 12 cases were analyzed including the addition of a consult case. The patients' ages ranged from 50 to 85 years (mean: 68 y); there were 8 males and 4 females. The specimens consisted of 5 cystectomies, 6 transurethral resections, and 1 anterior exenteration with right nephroureterectomy. Morphologically, each case had at least focal areas in which acellular myxoid stroma was associated with the carcinoma cells. When well developed, the neoplastic cells had scant eosinophilic cytoplasm and were arranged into cords closely mimicking extraskeletal myxoid chondrosarcoma, chordoma, mixed tumor/myoepithelioma of soft tissue, and yolk sac tumor. The percentage of tumor with a chordoid appearance ranged from 5% to 95% (mean: 39%; median: 25%). No conventional sarcomatous differentiation, no intracytoplasmic mucin, and no glandular formation were present in any case. All 12 cases had foci of typical urothelial carcinoma present at least focally and a gradual transition to the chordoid pattern was commonly seen. Immunophenotypically, all 7 cases evaluated showed strong immunoreactivity for p63 (nuclear) and CK34BE12 (cytoplasmic). Immunostains for CK20, calponin, glial fibrillary acidic protein, oncofetal protein glypican-3, and brachyury and were negative in the 7 cases studied (0 out of 7), whereas S-100 protein had focal staining (<5%) in 1 case. The myxoid stromal component was diffusely colloidal iron and Alcian blue positive in all 8 cases examined; periodic acid Schiff was negative in all 8 cases, whereas mucicarmine was only focally positive in 2 of 8 cases. Most cases were high stage (pT4: 5, pT3: 4, pT2: 2, and pT1: 1), and 6 of 8 cases (75%) with nodal sampling had metastatic disease. In 1 case, the lymph node metastasis had areas with chordoid morphology. Nine of 12 patients had available follow-up: 2 were dead of disease (1 and 10 mo), 4 were alive with disease (5 to 8 mo) with distant metastasis in 3, and 3 had no evidence of disease at last follow-up (2 to 120 mo). In summary, we describe a morphologic pattern of urothelial carcinoma with a distinct chordoid appearance that may potentially mimic a spectrum of primary vesical and nonvesical neoplasms with myxoid or mucinous components. These carcinomas maintain an immunophenotype characteristic of urothelial carcinoma and usually present with high stage disease.