The CINtec PLUS® system is an immunohistochemical cocktail composed of antibodies against p16(INK4a) (surrogate of HPV infection) and Ki-67 (proliferation marker) meant to improve the sensitivity and specificity for detecting high-grade dysplasia (HGD). In the presence of dysplasia, a red chromogen marks Ki-67 expression in the nucleus and a brown chromogen marks cytoplasmic p16(INK4a) expression. Only cells showing dual staining are interpreted as positive. This retrospective study examined the performance of CINtec PLUS testing when performed on ASC-US diagnosed samples. Comparison was made to high-risk HPV DNA test results and colposcopic biopsy results. Technical considerations in the interpretation of this immunohistochemical stain are additionally discussed. CINtec PLUS showed modest sensitivity (64%) and specificity (53%) in identifying the presence of HGD at surgical biopsy. Positive and negative predictive values for HGD were 28% and 83%, respectively. HR-HPV DNA test yielded sensitivity of 100% and specificity of 21%. During interpretation, squamous metaplasia and endocervical cells were seen to show individual staining for p16(INK4a) or Ki-67. Individual staining, when present within three dimensional cellular groups common to SurePath® preparations, can be time-intensive to interpret necessitating thoughtful examination at high power. The Pap test with HR-HPV DNA testing is a highly sensitive test. A specific test is needed to prevent false positives and over treatment. The CINtec® system provides a modest increase in specificity beyond HR-HPV DNA testing. Future study of its appropriateness and cost-ffectiveness in a treatment algorithm are warranted.

Objectives: To stratify patients with micropapillary urothelial carcinoma of the urinary bladder based on the percentage of micropapillary component and to correlate tumor volume with other clinicopathological features. Methods: Cases of micropapillary urothelial carcinoma of the urinary bladder from 2002 to 2009 were identified. Only patients with available follow-up information were included in the analysis. Tumor volumes were stratified based on the percentage of micropapillary component (<50%, >50% and 100%). Results: Overall, 24 cases were analyzed. Mean patient age was 71 years (range 55-86 years), with a male to female ratio of 3:1. Six cases (6/24; 25%) were composed entirely of micropapillary component. A total of 12 cases (12/24; 50%) showed >50% micropapillary component. Six cases (6/24; 25%) showed <50% micropapillary component. A higher percentage of micropapillary urothelial carcinoma component was significantly associated with male sex, regional lymph node metastasis and pathological stage (P-values = 0.0005, 0.01 and 0.03, respectively). The percentage of the micropapillary component was, however, unrelated to patients' survival. Conclusions:The present study confirms that micropapillary urothelial bladder carcinoma is typically aggressive and presents with advanced stage disease in most cases. A quantification of the micropapillary component is to be recommended. An accurate diagnosis of this entity in relatively small biopsies or transurethral resection of bladder tumor specimens is especially critical to define the best treatment plan.

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