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

Abstract

BackgroundPagetoid 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 presentationA 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.ConclusionsTo 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.

Vulvar Paget disease secondary to high-grade urothelial carcinoma with underlying massive vascular embolization and cervical involvement: case report of unusual presentation

“…Padhy et al presented a case of secondary Paget disease of urothelial origin without previous or concurrent urinary tract malignancy. Urothelial origin was determined based on the immunohistochemical profile, with expression of GATA3, uroplakin III, and p63, similar to our case and to other authors [11,14]. In our case, the previous urothelial carcinoma was of low grade and had been under control for years.…”

“…An interesting feature of the case reported here was the cervical involvement apparent on cervicovaginal cytology. Koyanagi et al presented a case of high grade urothelial carcinoma with pagetoid spread to the vagina, without accompanying Paget disease presentation [14]. The authors discuss the differences between pagetoid urothelial carcinoma, pagetoid colorectal carcinoma and extramammary Paget disease, highlighting the importance of cervical screening cytology.…”

Vulvar Extramammary Paget Disease Detected by Cytology for Cervical Cancer Screening: A Case Report and Literature Review

“…Articles eligible for the study included primary studies that reported EMPD with abnormal cervical cytology. From these, we reviewed 10 articles describing 11 cases that matched the above ( Table 1 ) [ 3 – 12 ]. It should be noted that among the 12 cases, 6 were primary EMPD, 5 were secondary EMPD derived from urothelial carcinoma, and 1 was secondary EMPD derived from a rectal carcinoma.…”

“…Secondary EMPD is subclassified into type I (secondary to anorectal or urothelial neoplasia) and type II (Paget disease secondary to adenocarcinomas or related tumors of other sites) [ 1 ]. There are reports of vulvar primary EMPD and secondary EMPD derived from the bladder or rectum spreading to the cervix through the epithelium, but only 11 cases of vulvar EMPD with abnormal cervical cytology have been reported in the English literature [ 3 – 12 ]. Herein, we present a case of type I secondary EMPD derived from urothelial carcinoma diagnosed after cytological examination for cervical cancer screening.…”

Extramammary Paget’s Disease: Diagnosis, Pathogenesis, and Treatment with Focus on Recent Developments

“…However, cases of secondary EMPD developed from urothelial carcinoma showing negative CK20 staining have also been reported [42], suggesting that the combination of CK7/CK20 staining is not an absolute method to discriminate primary from secondary EMPD. As for other markers, CDX-2, an intestinal cell marker, and uroplakin II and III, urothelial cell markers, could be also useful for the discrimination: both are usually negative for primary EMPD [40,[43][44][45]. Collectively, comprehensive evaluation using multiple markers, including CK7/20, GCDFP-15, CDX-2, and uroplakin II and III, is required for accurate discrimination of primary EMPD and secondary EMPD.…”