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

Dept of Pathology, UC San Diego Health System, 200 W Arbor Dr, MC8720, San Diego, CA 92103-8720
American Journal of Clinical Pathology (Impact Factor: 2.51). 04/2013; 139(4):422-7. DOI: 10.1309/AJCP6BSD0SNGQLHQ
Source: PubMed


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.

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    American Journal of Clinical Pathology 04/2013; 139(4):418-20. DOI:10.1309/AJCPU0UA5GYHXXIZ · 2.51 Impact Factor
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    ABSTRACT: Objectives: We questioned whether the use of p16(INK4a) immunohistochemistry in endocervical curettage (ECC) specimens would improve the detection of high-grade squamous intraepithelial lesions (HSIL) in a high-risk patient population. Methods: Papanicolaou test results were retrieved in 58 consecutive ECC specimens that were previously diagnosed as no histopathologic abnormality in patients with antecedent HSIL or atypical squamous cells, cannot exclude HSIL. An H&E recut and immunohistochemistry for p16(INK4a) were performed on all cases. Results: HSIL were found in 18 (31%) ECC specimens originally interpreted as negative. Of these 18 cases, three had moderate-sized fragments of ectocervical epithelium with HSIL seen on the recut H&E with concurrent positivity for p16(INK4a). Fourteen cases had rare to occasional clusters of atypical cells with strong immunoreactivity for p16(INK4a). A single case showed a medium-sized fragment of HSIL on the p16(INK4a)-stained section. Conclusions: The use of recuts and adjunct p16(INK4a) should be considered when evaluating ECC specimens in high-risk patient populations.
    American Journal of Clinical Pathology 03/2014; 141(3):342-7. DOI:10.1309/AJCPDXD41YLVAZZN · 2.51 Impact Factor
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    ABSTRACT: Cellular cycle proteins like the p16(INK4a) and the Ki67 proliferation nuclear antigen have been used as oncogenicity cellular markers. The E6 and E7 oncoproteins interact with tumor suppressor genes p53 and pRb, culminating with the p16(INK4a) overexpression. The objective of this study was to evaluate the presence of HPV-DNA in 174 cervical biopsies and correlate the different histological grades with the p16(INK4a) and Ki67 immunohistochemical expression (IHC). A cross-sectional study that enrolled a total of 174 women who underwent uterine cervical biopsies between February 2003 and December 2006, in southern Brazil, was performed. Cervical smear samples were analyzed for the presence of HPV-DNA through polymerase chain reaction (PCR), and biopsy samples were examined for p16(INK4A) and Ki67 expression through IHC techniques. The presence of HPV-DNA was observed in 89% of the tested patients, among which 52% were positive for high-risk (HR) viral types [16, 18 and 31]. Regarding p16(INK4a), an expression of 69% was observed, being expressed in 100% of the high-grade squamous lesions (HSIL) and HR-HPV-DNA positives. Ki67 expression was associated with the lesion grade, being more expressive in the most severe lesions (p<0.001). p16(INK4A) and Ki67 markers coexpression was present in 86% of the samples (p<0.001), being 100% among those positive to HR-HPV-DNA with HSIL (p<0.001). The results suggest an association between the presence of HR-HPV infection and the p16(INK4a) and Ki67 expression and which is even stronger among women with HSIL.
    Pathology - Research and Practice 04/2014; 210(8). DOI:10.1016/j.prp.2014.03.009 · 1.40 Impact Factor
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