The Differential Diagnosis of Reparative Changes and Malignancy: Performance in the College of American Pathologists Pap Education and Proficiency Testing Programs

Abstract

Context.— Repair is a challenging diagnosis and a significant source of false-positive (FP) interpretations in cervical cytology. No large-scale study of performance of repair in the liquid-based era has been performed. Objective.— To evaluate the performance of repair in the College of American Pathologists Pap Education and Proficiency Testing (PT) programs. Design.— The FP rate for slides classified as repair was evaluated by preparation type, participant type (cytotechnologist, pathologist, or laboratory), and program. The specific misdiagnosis category and individual slide performance were also evaluated. The rate of misclassification of slides as repair by participants for other diagnostic categories in the Pap Education program was assessed. Results.— The overall FP rate was 1700 of 12 715 (13.4%). There was no significant difference by program or preparation type. Within the Education program there was no difference by participant type, but pathologists' FP rate in the PT program (47 of 514, 9.1%) was significantly better than cytotechnologists in the PT program (51 of 380, 13.4%) and pathologists in the Education program (690 of 4900, 14.1%). High-grade squamous intraepithelial lesions/cancers (HSIL+) accounted for 1380 of 1602 FP interpretations (86%) in Education, but 43 of 98 (43.9%) in PT. Most slides had a low rate of misclassification, but a small number were poor performers. False-negative diagnosis of HSIL+ as repair was less common, ranging from 0.7% to 1.8%. Conclusions.— Despite initial indications that liquid-based cytology might reduce the rate of misclassification of repair, FP interpretations remain common and are no different by preparation type. Misclassification is most commonly as HSIL or carcinoma, potentially resulting in significant patient harm.

Pitfalls in Gynecological Cytology: Review of the Common and Less Frequent Entities in Pap Test

“…Reparatory cells can look dramatic with the background of blood, leucocytes, and fibrin, which can give the impression of tumor diathesis. The main differentials of repair are HSIL and cancer [4,5,[12][13][14]. Morphological features of repair (shown in Fig.…”

Challenging lesions in cervical cytology: The elusive HSIL

“…Notably, repair may actually enter the differential diagnosis for invasive squamous cell carcinoma given that marked reactive/reparative processes may contain large nuclei with prominent and sometimes irregular nucleoli, and mitoses can be seen. Several studies have shown repair to be a significant source of both false‐positive and false‐negative cytological diagnoses, with the most common misclassifications being HSIL/carcinoma, adenocarcinoma, and adenocarcinoma in situ 31–36 . Included among the diagnostic clues, reparative cells typically have pale chromatin and tend to form more cohesive and well‐ordered sheets, and typically do not present as single atypical cells as may be seen with squamous cell carcinoma.…”