Multifocal transitional cell cancer and p53 mutation analysis.

Abstract

Intravesical seeding of bladder cancer cells has been suggested as a possible explanation of tumor multifocality. The fact that monoclonality was shown to occur in bladder cancer supports the hypothesis of seeding from an initial localization.' We report a case of several superficial transitional cell carcinoma localizations, including 1 in the fornix vaginae. CASE REPORT A 72-year-old woman presented with microscopic hematuria and abdominal discomfort. Urethrocystoscopy revealed hematuria from the right ureter ostium and retrograde ureterography was suspicious for a lower pole caliceal tumor in the right kidney. In February 1996 right nephroureterectomy was performed. Histological examination showed pTaG2 transitional cell carcinoma in the pyelum and lower pole calices. The distal ureter resection margin was negative for cancer. Pulmonary x-ray revealed no lung metastases. In October the patient was examined by a gynecologist for vaginal blood loss. At physical examination no palpable abdominal masses were found. Vaginal examination revealed a tumorous lesion at the posterior fornix. A biopsy did not contain enough tissue for a reliable diagnosis. However, in the successive weeks papillary growth developed in the vaginal anterior wall. A biopsy from this lesion revealed fragments of a noninvasive high grade transitional cell tumor. The patient was further evaluated by a urologist, since metastases from transitional cell carcinoma were suspected. Urine cytology and urethrocystoscopy revealed no abnormalities. Computerized tomography and radiographic x-ray studies of the thorax did not show signs of metastases. In May 1997 vaginal blood loss recurred and at physical examination a lesion was found in the anterior vaginal fornix as well as on the cervix. A papillary lesion was seen at the urethral meatus. Biopsy of the vaginal and urethral lesions revealed pTaG2 transitional cell carcinoma. Urethrocystoscopy did not show tumor recurrence in the bladder. Both lesions were resected completely. The dorsal wall of the urethra was partially resected as was the vaginal wall, cervix and uterus. Histological evaluation revealed typical high grade papillary transitional cell carcinoma with focal superficial invasive growth at the cervix and vagina (pTlG2b). No areas of squamous metaplasia were found in the tumors, which would have confirmed diagnosis of papillary squamous cell carcinoma. Transitional metaplasia was not present in the nontumorous epithelia. The differential diagnoses of seeding of urothelial cell carcinoma from the urological tract, and primary papillary transitional cell carcinoma of the cervix and vagina were considered (fig. 1).* To study the possible monoclonal origin of all lesions, we evaluated p53 gene mutations using single strand conformational polymorphism analysis. The lesions from the right kidney, urethra, vagina and bladder were analyzed for p53 mutations as described previo~sly.~ In all 4 studied transitional cell carcinoma lesions a shift in exon 6 was found (fig.