Detection of pagetoid urothelial intraepithelial neoplasia extending to the vagina by cervical screening cytology: a case report with renewed immunochemical summary.

BACKGROUND: Pagetoid spread of urothelial carcinoma (UC) to the lower genital tract is quite a rare and diagnostically challenging condition. Pagetoid urothelial intraepithelial neoplasia extending to the vagina is difficult to diagnose, especially in remote recurrences without symptomatic or macroscopic lesions typical to Paget disease. However, its identification by cervical screening cytology is important because UC is often characterized by a long history of relapse. CASE PRESENTATION: A 68-year-old Japanese postmenopausal woman developed brown vaginal discharge after radical cystectomy for bladder cancer (high-grade UC, pT2a pN0 cM0 [Union for International Cancer Control, 8th edition]) concomitant with focal in-situ UC in the urethra. She had a history of left renal pelvis UC, which was surgically removed 9 months before the radical cystectomy. Gynecologic examination of the lower genital tract was unremarkable although cervical screening cytology demonstrated severely atypical cells with pleomorphism repeatedly. Cervical colposcopy and diagnostic conization revealed no cervical neoplasm. In retrospect, immunocytochemical p16/Ki-67 dual staining for the previous cervical screening was negative for p16 labeling, and the neoplastic cells were positive for cytokeratins 7 and 20, p63, and GATA binding protein 3. No high-risk human papillomavirus genotype was identified by an automated DNA chip system using liquid-based cytology samples. Eleven months post-cystectomy, punch biopsy of the vulva and vagina confirmed intraepithelial UC in the juxtaposed squamous epithelium with pagetoid spread demonstrating positivity for specific urothelial markers: uroplakins II and III and thrombomodulin. Concurrent invasive malignancy was ruled out, and CO2 laser vaporization of the vulvar and vaginal lesion was performed. The patient remained alive without evidence of invasive malignancy for 14 months after the radical cystectomy for bladder cancer. CONCLUSIONS: To detect recurrent pagetoid urothelial intraepithelial neoplasia with pagetoid spread in the lower genital tract, pathologists should recognize the history of prior UC with special attention to absence of p16 labeling in cervical cytology as a pointer to the diagnosis of urothelial cancer. Using further biopsy and immunohistochemical confirmation of UC relapse, investigation to rule out invasive malignancies and careful follow-up throughout the patient's lifetime is recommended.

Intraoperative lavage cytologic analysis of surgical margins as a predictor of local recurrence in pulmonary metastasectomy.

HYPOTHESIS: Cytologic analysis of intraoperative lavage at the surgical margin during wedge or segmental resection for pulmonary metastatic lesions predicts postoperative local failure at the surgical margin of the pulmonary parenchyma. DESIGN: Prospective nonrandomized trial. SETTINGS: Institution-based study. PATIENTS: Fifty-one consecutive patients undergoing wedge or segmental resection for 87 pulmonary metastatic lesions of various primary tumor types from November 1, 1997, through January 31, 2001, were prospectively enrolled. INTERVENTIONS: An intraoperative lavage cytologic technique at the surgical margin for each pulmonary metastasis was performed as described previously. MAIN OUTCOME MEASURES: Incidence of positive cytologic findings and postoperative local recurrence at the surgical margin. RESULTS: Of the examined lesions, 10 (11%) showed positive cytologic results at the surgical margin, despite a macroscopically safe margin in the attempted resection. Of these, metastasectomy was converted to segmentectomy in 3. An additional wedge resection and evaporation using an Nd:YAG laser in the surgical margin were performed in 1 and 4 lesions, respectively. Complications precluded further treatment in 2 lesions. By July 2001, although no local recurrence at the surgical margin area was found among the lesions with negative cytologic results, recurrence at the surgical margin occurred in 2 with positive cytologic results, including 1 receiving no treatment and 1 receiving Nd:YAG laser evaporation, indicating that a significant difference in the recurrence rate according to lavage cytologic status (P<.001). CONCLUSIONS: This intraoperative lavage cytologic technique in wedge or segmental resection of pulmonary metastases of various primary tumors may be a useful predictor of local recurrence at the surgical margin. With these test results, local recurrence at the surgical margin may be controllable in patients undergoing pulmonary metastasectomy.