Urothelial carcinoma involving the gynecologic tract: a morphologic and immunohistochemical study of 6 cases.

Spread of urothelial carcinoma (UC) to the female genital tract occurs in a small subset of women with UC. We studied 6 patients with involvement of various gynecologic (GYN) sites and detailed natural history and pathologic features. Four patients initially presented with bladder lesions, including 1 high-grade pTa tumor, 2 pT1 tumors, and 1 pT2 tumor; 1 patient presented with pT2 disease of the renal pelvis and 1 with GYN involvement in the form of vulvar Paget's disease. For the 5 patients presenting with UC, time to GYN involvement was 2 to 8 years; vaginal bleeding (n=4) was the main presenting symptom, and the first site of involvement was the vagina (n=4) or cervix (n=1). GYN sites displayed an array of morphologies and growth patterns that may be seen in both UC and GYN primary tumors. The presence or absence of invasion in the original UC did not dictate whether GYN sites would exhibit invasive disease or whether disease would present as continuous or "skip" lesions. Immunohistochemistry for at least 1 GYN site per patient revealed diffuse, strong CK7 and focal to diffuse strong CK20 positivity in all cases, as well as at least focal p16 positivity in 5 of 6 cases. HPV in situ hybridization was negative in all cases. At last follow-up, 3 patients had died from UC and 3 were alive with recurrent disease/documented metastasis. Our findings highlight the morphologic and immunohistochemical overlap between primary GYN squamous lesions and GYN involvement by UC and hence the importance of clinical history in ensuring an accurate diagnosis.