Examination of Sources of Diagnostic Error Leading to Cervical Cone Biopsies With No Evidence of Dysplasia

Abstract

At our institution, 17% of cervical conization specimens are reported as negative for dysplasia or malignancy. To identify sources of error, we reviewed 53 negative conization specimens and their prior and follow-up cytology, biopsy, and endocervical curettage specimens. Examination of deeper-level sections and p16 immunostaining were performed on all conization specimens and selected biopsy specimens. Dysplasia was detected in 26% (14/53) of conization specimens. Twenty-eight percent (15/53) of cones were truly negative, and the presurgical material had been overcalled as high-grade squamous intraepithelial lesions (HSIL). Forty-five percent (24/53) of cones were truly negative and HSIL was confirmed in the presurgical material. Of these, 11% (6/53) showed subsequent evidence of residual dysplasia and 26% (14/53) were negative on further follow-up. Deeper-level sections, p16 immunostains, and consensus review may help identify squamous dysplasia in conization specimens and may prevent the overdiagnosis of HSIL on cervical biopsies.

Predictors of Negative Cone Biopsies and Its Clinical Significance

“…This percentage is similar to other studies: 13.8% in the study by Livasy et al [9], 17.7% in the series by Ryu et al [10], 16% in the series by Rodriguez-Manfredi et al [11], 10% in the study by Witt et al [12], 17% by Carrig et al [13], and 18.2% in the study of Nam et al [16].…”

“…In conclusion, this study indicates that the incidence of white cone in our institution is 10% of all the cone biopsy; this incidence is similar to the series by Livasy et al [9], Ryu et al [10], Rodriguez-Manfredi et al [11], Witt et al [12], Carrig et al [13], and Nam et al [16] This series also confirms that women with low-risk cytology, minor changes in colposcopy, CIN 2, and no use of oral contraceptive have a high probability of having no lesions in the conization specimen. Women with negative cone and women with residual lesions as evidenced by LEEP have similar rates of persistent/recurrent disease.…”

Proton MRS of cervical cancer at 7 T

“…Tumor tissue characterization relies on histologic information, typically obtained by biopsy, which may be prone to sampling errors ranging from 10.6% to 43% . This means that, due to the intratumor heterogeneity, the biopsy location often mismatches the location of the tumor or highest grade as identified on post‐surgical histological specimens.…”

Adjunct p16INK4a Immunohistochemistry Aids the Detection of High-Grade Squamous Intraepithelial Lesions in Endocervical Curettage Specimens

“…Although inadequate sampling may be a reasonable explanation for the discrepancy, the possibility of the lesion not being adequately represented on the slide or being present on the slide and misinterpreted by the pathologist is of equal concern. A recently published study by Carrigg et al, 28 which examined the diagnostic reasons underlying negative cervical cone biopsies, addresses this latter concern. Their study found that 26% of cervical cone biopsy specimens initially diagnosed as negative were subsequently found to harbor dysplasia.…”

“…They concluded that the use of p16 INK4a IHC and recut levels, in addition to consensus group review, were useful in decreasing the false-negative rate of conization specimens. 28 The Working Group 4 of the LAST recommends against routine use of p16 INK4a for assessing biopsy specimens in the setting of histologic interpretations of negative, intraepithelial neoplasia I, and intraepithelial neoplasia III. 27 recommendation number 4a highlights the special circumstance for the use of p16 INK4a in high-risk patients (defined as prior cytologic diagnosis of HSIL, ASC-H, ASC/HPV16+, or atypical glandular cells) as an adjunct for evaluating biopsy specimens that are at risk for missed high-grade disease.…”