Outcome after Conization for Cervical Intraepithelial Neoplasia Grade III: Relation with Surgical Margins, Extension to the Crypts and Mitoses

Abstract

Aims and Background Factors linked to residual neoplasia and recurrence following conization of the uterine cervix for treating cervical intraepithelial neoplasia grade III (CIN III), such as the surgical margins, extension of CIN into the crypts and the number of mitoses, have been studied with contradictory results. We evaluated patients submitted to conization for CIN III and analyzed the aforementioned factors, relating them to recurrence and residual neoplasia in hysterectomy specimens. Methods The surgical specimen of cold-knife conization for CIN III performed in 63 patients (average age, 37.3 ± 9.3 years) was fixed in 4% formaldehyde. The ectocervical and endocervical margins were removed and the cone was cut into fragments perpendicular to the surface of the endocervical mucosa (1 mm thick). One histological section (5 μm thick) was cut from each block and stained with hematoxylin-eosin. We studied the total number of fragments from each cone and affected by CIN, endocervical and ectocervical margins, extension to the crypts, number of mitoses and tripolar mitoses in 100 microscope fields using a 100x objective. Results The endocervical margin was involved in 34.9% vs 9.5% (P = 0.001) of ectocervical margins. Recurrence affected 53.8% of cases presenting involved margins versus 12.9% in the cases without involved margins (P = 0.0078). The average interval to recurrence was 3.2 years. CIN was present in 2.5 to 100% (median, 28%) of the cone fragments (median no., 28; range, 7-95). A median of 44.4% and 25% of cone fragments presented CIN with and without recurrence, respectively. Correlation of the number of mitoses with tripolar mitoses and the percentage of fragments involved by CIN with the number of mitoses and tripolar mitoses showed, respectively, P = 0.02, 0.05 and 0.005. A median of 142 mitosis and 4 tripolar mitosis were observed per case with disease recurrence versus 104 and 3 (P = 0.02, 0.6), respectively, when recurrence did not occur. Of 14 patients who underwent hysterectomy after conization (mean, 3.6 ± 3 months afterwards) for endocervical or both margins involved by CIN in the cone specimen, 8 (57.1%) presented CIN III and one (7.1%) microinvasive carcinoma. In 96.8% of the conizations, the CIN extended to the crypts. Conclusions Involved margins and mitoses are associated with a greater recurrence rate for CIN. Residual neoplasia in the hysterectomy specimen after an involved margin with conization is frequent.