Detection of Adenocarcinoma In Situ of the Cervix in Papanicolaou Tests: Comparison of Diagnostic Accuracy With Other High-Grade Lesions

2004 ◽  
Vol 128 (2) ◽  
pp. 153-157 ◽  
Author(s):  
Andrew A. Renshaw ◽  
Dina R. Mody ◽  
Richard L. Lozano ◽  
Emily E. Volk ◽  
Molly K. Walsh ◽  
...  

Abstract Context.—Adenocarcinoma in situ of the cervix is a recently recognized interpretation in the Bethesda 2001 system. Although specific morphologic criteria have been published, recognizing this entity is still difficult. Objective.—To compare pathologists' ability to correctly identify and categorize adenocarcinoma in situ with their ability to identify and categorize adenocarcinoma, high-grade squamous intraepithelial lesion, and squamous cell carcinoma. Design.—Pathologists' reviews in the 2001 and 2002 College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology Program, an interlaboratory comparison program for gynecologic cytology, were examined. Cases were usually reviewed by multiple pathologists. False-negative rates, the percentage of reviews with exact agreement with reference interpretations, and the percentage of cases in which all reviews were in exact agreement with the reference interpretation for adenocarcinoma in situ, adenocarcinoma, high-grade squamous intraepithelial lesion, and squamous cell carcinoma were compared. Results.—A total of 213 reviews of cases categorized as adenocarcinoma in situ were compared with 2821 reviews of adenocarcinoma, 7535 reviews of high-grade squamous intraepithelial lesion, and 1886 reviews of squamous cell carcinoma. The false-negative rate for adenocarcinoma in situ (11.7%) was significantly higher than that for high-grade squamous intraepithelial lesion (4.6%, P < .001) and squamous cell carcinoma (3.3%, P < .001) but not for adenocarcinoma (8.9%, P = .16). Of all the reviews of adenocarcinoma in situ cases, 46.5% were interpreted specifically as adenocarcinoma in situ, compared to 72.2% of reviews of adenocarcinoma, 73.2% of high-grade squamous intraepithelial lesion, and 75.1% of squamous cell carcinoma. No individual case of adenocarcinoma in situ was always specifically recognized as adenocarcinoma in situ; 26.5% of cases of adenocarcinoma were specifically recognized as such in all reviews. Findings were similar with and without the inclusion of high-grade squamous intraepithelial lesion/carcinoma, not otherwise specified, as an acceptable review interpretation for cases of adenocarcinoma, squamous cell carcinoma, and high-grade squamous intraepithelial lesion. Conclusion.—These data from expert-referenced and biopsy-proven cases suggest that adenocarcinoma in situ is not as easily recognized or categorized as other serious diagnoses.

2004 ◽  
Vol 128 (1) ◽  
pp. 17-22 ◽  
Author(s):  
Andrew A. Renshaw ◽  
Nancy A. Young ◽  
George G. Birdsong ◽  
Patricia E. Styer ◽  
Diane D. Davey ◽  
...  

Abstract Context.—Results of clinical trials suggest that interpretation of liquid-based cytology preparations is more accurate and is associated with less screening error than interpretation of conventional preparations. Objective.—In this study, the performance of participants in interpreting ThinPrep (TP) preparations was compared with participants' performance on conventional Papanicolaou tests in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology (PAP). Design.—The results of the PAP from the year 2002 were reviewed, and the discordancies to series and exact-match error rates for the 2 cytologic methods were compared. Results.—For this study, a total of 89 815 interpretations from conventional smears and 20 886 interpretations from TP samples were analyzed. Overall, interpretations of TP preparations had both significantly fewer false-positive (1.6%) and false-negative (1.3%) rates than those of conventional smears (P = .001 and P = .02, respectively) for validated or validated-equivalent slides, as assessed by concordance with the correct diagnostic series. In this assessment of concordance to series, interpretations of educational TP and conventional preparations were similar, except for high-grade squamous intraepithelial lesion, in which the performance was significantly worse for educational TP preparations (false-negative rate of 8.1% vs 4.1% for conventional smears, P < .001). When interpretations were matched to the exact diagnosis, validated-equivalent TP preparations were generally more accurate for diagnoses in the 100 series and 200 series than were conventional smears. Notably, for the reference diagnosis of squamous cell carcinoma, the exact-match error rate on validated equivalent TP slides was significantly greater than that of conventional slides (44.5% vs 23.1%, P < .001). Interpretations of educational TP preparations also had a significantly higher error rate in matching to the exact reference diagnosis for squamous cell carcinoma (33.7% vs 22.8%, P = .007). Conclusions.—Overall, TP preparations in this program were associated with significantly lower error rates than conventional smears for both validated and educational cases. However, unlike the negative for intraepithelial lesion and malignancy, not otherwise specified, low-grade squamous intraepithelial lesion, and adenocarcinoma cytodiagnostic challenges, participants' responses indicated some difficulty in recognizing high-grade squamous intraepithelial lesion and squamous cell carcinoma.


2006 ◽  
Vol 130 (3) ◽  
pp. 332-336 ◽  
Author(s):  
Andrew A. Renshaw ◽  
Dina R. Mody ◽  
Edward Wang ◽  
Jennifer Haja ◽  
Terence J. Colgan

Abstract Context.—The practice of gynecologic cytology requires that high-grade squamous intraepithelial lesion (HSIL) be precisely recognized. In this regard, hyperchromatic crowded groups are known to be difficult to classify in conventional gynecologic cytology, but whether this is true in ThinPrep specimens is uncertain. Objective.—To assess whether hyperchromatic crowded groups of cells in challenging HSIL cases are a problem in ThinPrep preparations, and whether these groups differ in appearance from those of conventional smears. Design.—Sixteen images were taken from both conventional smears and ThinPrep slides that had a reference diagnosis of HSIL in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology, but had performed poorly on subsequent participants' reviews. These 32 representative images were of hyperchromatic crowded groups and were classified by 20 Cytopathology Resource Committee members (17 pathologists and 3 cytotechnologists), who were masked to the reference diagnosis. A consensus classification was derived using the majority opinion of the individual reviewers. Finally, 5 cytologic features were assessed for those images that were interpreted as abnormal by the consensus classification. Results.—None of the 32 images was uniformly interpreted as either benign, squamous lesion, or glandular lesion on individual review. Only 27% of individual interpretations of conventional smear images and 15% of ThinPrep images were interpreted as HSIL/squamous cell carcinoma (P < .001). Individual interpretations of ThinPrep images as glandular lesions (60%) were more often made than those of conventional smears (44%, P < .001). The consensus interpretation of ThinPrep images was glandular lesion in 75% of cases, whereas fewer than 50% of the consensus interpretations of conventional smear images were in this category. Conventional smear images were characterized by elongate nuclei (43%) and large nuclei (71%), whereas ThinPrep images more often showed rounded smooth edges (53%) and small nuclei (80%), and were recognized as a glandular lesion. Conclusions.—Hyperchromatic crowded groups of cells are a source of difficulty in challenging HSIL cases for both conventional smears and ThinPrep specimens. In conventional smears, these groups are more likely to be labeled as a squamous lesion, owing to their elongate and large nuclei. In ThinPrep specimens, however, these groups are more likely to be labeled as glandular lesions, owing to their smooth contoured borders and small nuclei.


2019 ◽  
Vol 63 (5) ◽  
pp. 417-423 ◽  
Author(s):  
Caitlin Alexander ◽  
Marissa White ◽  
Zahra Maleki ◽  
Erika F. Rodriguez

Introduction: A causal link between infection with a high-risk strain of human papilloma virus (hrHPV) and the development of cervical squamous cell carcinoma (SCC) is well established. However, a small number of SCCs are hrHPV-negative by either HPV co-DNA testing and/or HPV-in situ hybridization (HPV-ISH) at the time of diagnosis. These apparently hrHPV-negative lesions are poorly understood, specifically whether hrHPV-positive precursor lesions exist, which would be detected through hrHPV-based screening. Methods: A search of the pathology archives at the Johns Hopkins Hospital identified women with a diagnosis of hrHPV-negative cervical SCC on surgical specimen. All prior pathologies, including cervical cytology and surgical pathology specimens, and associated hrHPV DNA test results, p16 immunohistochemistry, and HPV-ISH were reviewed. Results: A total of 25 women were identified having a surgical specimen diagnosed as SCC with either negative or equivocal HPV-ISH. Fifteen had a Pap test in the 6 months preceding a diagnosis of SCC, with cytology diagnoses as follows: high-grade squamous intraepithelial lesion n = 14/15; atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion n = 1/15. hrHPV co-testing was performed for 5 of these 15 women and was negative in 2/5 cases. Cervical biopsy was performed for 24 women. HPV-ISH testing, performed on 14 of the biopsy specimens, was negative for 11/14 patients. Of 15 specimens stained for p16, 14 were positive. Conclusion: A subset of patients exist in whom hrHPV is not detectable at or near the time of progression to SCC. Additional research is necessary to further describe this population and determine whether maintaining cytological screening would provide benefit.


Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 864-872
Author(s):  
Wenting Li ◽  
Bo Yang ◽  
Yiqun Li ◽  
Cuicui Wang ◽  
Xinzhi Fang

Abstract Background We investigated the expression and clinical significance of miR-141 and miR-340 in cervical squamous cell carcinoma (CSCC). Methods Expression of miR-141 and miR-340 in CSCC, high-grade squamous intraepithelial lesion (HSIL), and normal cervical squamous epithelium were detected by qRT-PCR. PTEN was assessed by immunohistochemistry. Their relationship with clinicopathological features was analyzed. Results The changes of miR-141 and miR-340 were different in CSCC, HSIL, and normal squamous epithelium (P = 0.030). miR-141 expression was statistically significant in gross type, differentiation, uterine corpus invasion, nerve invasion, vagina invasion, and FIGO stage in CSCC (P < 0.05). miR-340 expression was related to tumor size, differentiation, nerve invasion, lymph node metastasis, and FIGO stage in CSCC (P < 0.05). miR-141 and miR-340 expressions were statistically significant in different ages (P < 0.05) in HSIL. The AUC of miR-141 in CSCC diagnosis and that of miR-340 in HSIL diagnosis were 0.893 and 0.764, respectively. The sensitivity and the specificity of miR-141 for diagnosis of CSCC were 95.0% and 60.8%, respectively, while those of miR-340 for diagnosis of HSIL were 90.0 and 48.6%, respectively. miR-141 and miR-340 expressions are associated with PTEN expression (P = 0.002 and P < 0.001). Conclusion miR-141 and miR-340 may be associated with their target gene PTEN and involved in the carcinogenesis of cervical squamous epithelium.


2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Yue-Jie Li ◽  
Xin Qing ◽  
Qing-Xu Tao ◽  
Li Xiang ◽  
Li Gong ◽  
...  

Background. Vasculogenic mimicry (VM), as an endothelium-independent cancer microcirculation, has been observed in many malignancies including cervical cancer. Erythropoietin (EPO) and erythropoietin receptor (EPO-R) could produce an angiogenic effect to promote cervical squamous cell carcinoma (CSCC) progression. However, the association between VM formation and EPO/EPO-R expression in CSCC is poorly explored. Methods. Seventy-six paraffin-embedded CSCC samples, 25 high-grade squamous intraepithelial lesion (HSIL) samples, 20 low-grade squamous intraepithelial lesion (LSIL) samples, and 20 normal cervix samples were collected. Immunohistochemistry SP method was performed to detect EPO/EPO-R expression and CD31/periodic acid-Schiff (PAS) double staining was performed to detect VM formation. The associations of EPO/EPO-R and VM with clinicopathological parameters of CSCC were analyzed. The associations between VM formation and EPO/EPO-R expression were also analyzed. Results. The positive expression rates of EPO and EPO-R were gradually increasing along the progression of normal cervix-LSIL-HSIL-CSCC sequence (P<0.05). EPO and EPO-R expression were not significantly associated with clinicopathological parameters of CSCC patients (P>0.05). VM was significantly associated with FIGO stage, lymphovascular space involvement, and lymph node metastasis (P<0.05). VM was positively associated with EPO expression (r=0.284, P<0.05) but was not associated with EPO-R expression (P>0.05). Conclusion. These data suggest that increased EPO/EPO-R expression may play an important role in cervical carcinogenesis. EPO overexpression may promote VM formation in CSCC.


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