BACKGROUND:Although the incid ence of cervical ad enocarcinoma has consistently increased , especially among young women, there is no established best means for screening. This study evaluated the screening efficacy of CINtec PLUS (CINtec; p16/Ki67 d ouble immunocytochemistry) expression in cervical gland ular cells. METHODS: Cervical cytology was examined using abnormal gland ular cells. The CINtec status of 100 samples with correspond ing surgically resected specimens and 11 samples that exhibited negative results for intraepithelial lesion or malignancy at follow-up was analyzed . Ad d itionally, 31 negative samples containing benign glandular cells were included. RESULTS: Of the 142 samples, CINtec status was diffusely positive in 74, focally positive in 24, and negative in 44. The 74 d iffusely positive samples includ ed 70 ad enocarcinomas (62 cervical, seven uterine, and one ovarian) and four cases of high-grad e cervical intraepithelial neoplasia. The 24 focally positive samples included 15 adenocarcinomas (seven cervical, seven uterine, and one fallopian tube) and nine without malignancy. The 44 negative samples included nine adenocarcinomas (five uterine and four cervical) and 35 without malignancy.The sensitivity, specificity, positive predictive value, and negative predictive value of the CINtec diffusely or focally positive cases for cervical adenocarcinomas were 94.5%, 58.0%, 70.4%, and 90.9%, respectively. In CINtec diffusely positive cases, the respective values were 84.

Objective: The aim of this study was to evaluate the reliability of estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) expression levels in Cellprep® (CP). Study Design: We evaluated the stability of immunocytochemistry (ICC) of ER and HER2 for primary or recurrent breast cancer samples rinsed in CP vials. Samples were prepared from CP vials stored for 1–30 or 160–240 days. ER and HER2 statuses were determined after 1–30 days (26 and 25 tests, respectively) or 160–240 days (15 and 18 tests, respectively) with the same protocols as immunohistochemistry (IHC), and were compared with the corresponding surgically resected specimens. Results: ER statuses according to CP samples showed perfect agreement (1–30 days: kappa, κ = 1; 160–240 days: κ = 1). HER2 statuses also showed good agreement (1–30 days: κ = 0.79; 160–240 days: κ = 0.64), although there were more equivocal HER2 cases in CP than in the surgically resected specimens. Conclusion: ER ICC in CP vials is reliable regardless of the preservation period. HER2 ICC in CP has more equivocal cases than HER2 IHC in surgically resected specimens. Both improvement of the immunostaining protocol and further validation study of in situ hybridization are indispensable for the practical application of ICC in CP.

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.

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