Histopathologic diagnosis of cervical biopsies determines clinical management of patients with an abnormal cervical cancer-screening test yet is prone to poor inter-observer reproducibility. Immunohistochemical staining for biomarkers related to the different stages of cervical carcinogenesis may provide objective standards to reduce diagnostic variability of cervical biopsy evaluations but systematic, rigorous evaluations of their potential clinical utility are lacking. To address diagnostic utility of HPV L1, p16 INK4a , and Ki-67 immunohistochemical staining for improving diagnostic accuracy, we conducted a community-and population-based evaluation using 1455 consecutive cervical biopsies submitted to the Department of Pathology at the University of Virginia during a period of 14 months. Thin-sections of each biopsy from 1451 of 1455 (99.7%) biopsies underwent evaluation of immunohistochemical stains for three biomarkers, masked to the original diagnosis, and the results were compared to an adjudicated, consensus diagnosis by 3 pathologists. p16 INK4a immunostaining, using the strongest staining as the cutpoint, was 86.7% sensitive and 82.8% specific for cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) diagnoses. The p16 INK4a performance was more sensitive (p < 0.001), less specific (p < 0.001), and of similar overall accuracy for CIN2+ compared to the combined performance of all pathologist reviews in routine clinical diagnostic service (sensitivity = 68.9%, specificity = 97.2%). Ki-67 immunostaining was also strongly associated with a CIN2+ diagnosis but its performance at all staining intensities was inferior to p16 INK4a immunostaining, and did not increase the accuracy of CIN2+ diagnosis when combined with p16 INK4a immunostaining compared to p16 INK4a immunostaining alone. We found no utility for L1 immunostaining in distinguishing between CIN and non-CIN. In conclusion, with a rigorous evaluation, we found immunohistochemical staining for p16 INK4a to be a useful and reliable diagnostic adjunct for distinguishing biopsies with and without CIN2+.

A uniform nomenclature for ZLL does not exist. Based on the results of this analysis, we suggest that the generic term idiopathic lymphoplasmacellular mucositis-dermatitis be considered to encompass the lymphoplasmacellular infiltrates in the skin and mucosal surfaces considered herein. This designation is morphologically descriptive and can be applied regardless of anatomic location.

HighlightsDesmoplastic small round cell tumor of the ovary is a rare clinical entity with poor prognosis.Accurate diagnosis utilizes a combination of histological, immunohistological, and cytogenetic findings.This disease should be kept on the differential diagnosis in young women with widespread disease on presentation.