The histopathologic distinction of cervical adenocarcinoma in situ (AIS) and invasive adenocarcinoma (AC) from some benign endocervical lesions can be challenging. The ProEx C antibody reagent targets nuclear proteins (minichromosome maintenance protein 2, MCM2 and topoisomerase II-alpha, TOP2A), which are over expressed during the aberrant S-phase induction of HPV infected and neoplastic cells. In this immunohistochemical study the utility of the ProEx C reagent in distinguishing AIS and AC from a variety of non-neoplastic glandular lesions was examined. ProEx C immunohistochemical staining was performed on sections from formalin-fixed, paraffin-embedded tissue of 65 cervical tissues including 48 non-neoplastic cervices (normal [n=10], microglandular hyperplasia [n=10], tubal metaplasia [n=11], cervical endometriosis [n=7], reactive endocervix [n=10]) and 17 cervices with glandular malignancy (AIS [n=12] and AC [n=5]). Both intensity and prevalence of immunoreactivity was scored. The median and distribution of scores for both prevalence and intensity was compared for AIS versus each of the 5 benign cervical lesions using a Mann-Whitney U test. The median and distribution of prevalence of immunohistochemical staining for AIS was different from all benign mimics, but the intensity of staining for AIS did overlap with some mimics as it was not significantly different from endometriosis, microglandular hyperplasia, and reactive endocervix. ProEx C reagent has potential as an adjunctive testing tool in the histopathologic diagnosis of both AIS and AC, particularly in difficult cases with small biopsies or foci of disease.
Our observed incidence of HM is greater than previous studies and is attributable to improved detection of PM cases. Molecular genotyping and cytogenetic evidence indicate that CM is almost half as common as PM. This ratio may be useful in benchmarking laboratory diagnosis and HM registries.
The molecular cytogenetic analysis of specimens (genotyping) suspicious for hydatidiform mole (HM) significantly improves diagnostic accuracy over histopathology and immunohistochemical analysis alone, particularly in the classification of partial mole. However, the implementation of this advance in diagnostics has been slow. This study sought to identify the major benefit and potential barriers to the adoption of genotyping. A pilot Placental Molar Diagnostic (PMD) Service was established combining histopathology, p57 immunohistochemistry, and molecular genotyping analysis for both in-house and referred-in cases suspicious for HM or with a preliminary diagnosis of HM. A retrospective analysis of 117 cases received in the first 16 mo was conducted to identify the utility of the PMD Service and factors or barriers which precluded optimal results. A final diagnosis of HM was made in 73 cases (37 complete HMs and 36 partial HMs). The remaining 44 cases were hydropic abortuses. Three potential barriers were identified that could lead to less than optimal results from a PMD Service: prevalence of noninformative genotyping, lack of any available or appropriate paraffin blocks, and inappropriate deferral of genotyping. The major utility of this pilot PMD Service was to increase the specificity of a diagnosis of HM, and avoid unnecessary clinical follow-up in 37% of cases with an initial suspicion or diagnosis of HM. Measures can be undertaken to address potential barriers to the implementation of a comprehensive placental diagnostic platform. Underutilization of molecular genotyping in the diagnosis of HM likely leads to inappropriate management and "downstream" costs in a significant proportion of patients suspected of having HM.
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