Mitotically Active Microglandular Hyperplasia of the Cervix: Absence of K-Ras Mutation and Implications for Differential Diagnosis
Rita Abi-Raad, Ahmed Alomari, Pei Hui, Natalia Buza. Yale University School of Medicine, New Haven, CT
Background: Microglandular hyperplasia (MGH) of the cervix is a benign lesion characterized by proliferation of tightly packed endocervical glands with relatively uniform nuclei and rare to absent mitoses. Endometrioid endometrial adenocarcinomas (EAC) with a microglandular pattern can closely mimic MGH of the cervix resulting in a significant diagnostic dilemma, especially when present in the endocervical curettage. Significant nuclear atypia and increased mitotic activity (>1 mitosis/10 high power field (HPF)) are generally considered to be in favor of EAC.
Design: The aim of this study was to review the morphologic features of MGH with special focus on mitotic activity and nuclear atypia in correlation with K-ras mutation analysis. A total of 380 cases of MGH were identified in our departmental archives between January 2005 and June 2012. Of those, 68 were identified in endocervical polyps, which were subjected to an initial screening to further select the final study population of 45 cases with extensive MGH arising in endocervical polyps. All available slides were reviewed by two gynecologic pathologists and the mitotic activity and degree of nuclear atypia were evaluated. Ten cases with increased mitotic activity (5 or more mitoses/ 10 HPF) were subjected to K-ras mutation analysis by single-strand conformation polymorphism. Clinical history and follow-up data were retrieved from the patients' electronic medical records. For a control group, we identified 10 cases of EAC with microglandular pattern, 7 of which were also subjected to K-ras mutation analysis.
Results: Fifteen of the 45 MGH cases (33.3%) had 5 or more mitoses/10 HPF. The highest mitotic count was 11/10 HPF, which was observed in 3 cases. Moderate cytologic atypia was seen in 13 MGH cases. Follow-up was available for 29 MGH patients (mean follow-up time 37 months), all of which were alive and well. K-ras mutation was absent in all 10 MGH cases tested. In the EAC group, 4 of the 7 cases tested positive for K-ras mutation.
Conclusions: MGH of the cervix may show significant mitotic activity (up to 11/10 HPF) in a relatively high proportion of cases without negatively affecting the clinical prognosis. Therefore, mitotic activity cannot be reliably used to differentiate between MGH and EAC in small biopsies. K-ras mutation analysis may be a helpful adjunct in difficult cases.
Category: Gynecologic & Obstetrics
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 167, Monday Morning