Dilip Gupta

Interobserver and Intraobserver Variability in the Cytologic Diagnosis of Normal and Abnormal Metaplastic Squamous Cells in Pap Smears

OBJECTIVE Interoberver variability has important implications for patient care, diagnostic error and medical litigation. In the management of any cervical epithelial abnormality, its biologic significance as well as diagnostic reproducibility is very important. Interobserver variability has not been measured adequately for metaplastic squamous lesions. We analyzed interobserver and intraobserver variability and diagnostic accuracy in the diagnosis of dysplastic metaplastic cells. STUDY DESIGN Sixty Pap smears from patients with abnormalities of metaplastic squamous cells of varying severity were selected from the files of Lankenau Hospital, Wynnewood, Pennsylvania, U.S.A., diagnosed between 1990 and 1996. These were reviewed by four observers with different levels of cytology experience. Each of the observers blindly and independently reviewed all Pap smears. Tabulated results were analyzed to determine interobserver and intraobserver variability and diagnostic accuracy. RESULTS Statistically significant interobserver reproducibility was found between both inexperienced observers as well as between observers 1 (experienced) and 3 (inexperienced) and between observers 2 (experienced) and 4 (inexperienced). The observed degree of agreement between both experienced observers (1 and 2) reflected random rating rather than reproducibility. There was no difference in interobserver reproducibility in low vs. high grade lesions. Intraobserver reproducibility had no significant correlation with experience of the observer. The sensitivity ranged from 0.69 to 0.97 (mean, 0.79), while the specificity ranged from 0.09 to 0.46 (mean, 0.30). Mean diagnostic accuracy was better in benign and low grade squamous intraepithelial lesions in comparison to high grade squamous intraepithelial lesions. CONCLUSION There was good interobserver agreement in classifying squamous metaplastic lesions. The agreement did not correlate with grade of dysplasia or experience of the cytopathologists. These findings should be considered in making treatment, quality assurance and legal decisions. A larger study is indicated to study interobserver and intraobserver variability and define cytologic criteria for lesions of metaplastic squamous cells.

Evaluation of HER-2/neu Gene Status in Osteosarcoma by Fluorescence In Situ Hybridization and Multiplex and Monoplex Polymerase Chain Reactions

CONTEXT Previous reports suggest that the human epidermal growth factor 2 (HER-2/neu) receptor may be overexpressed in osteosarcoma. OBJECTIVE To determine whether osteosarcomas have amplifications of the HER-2/neu gene. DESIGN We studied a series of osteosarcomas by fluorescence in situ hybridization (FISH) and by 2 real-time polymerase chain reaction assays that measure the amount of HER-2/neu DNA relative to a control gene. The HER-2/ neu monoplex and multiplex assays were capable of identifying those cases of breast cancer that were known to overexpress HER-2/neu as assessed by FISH. We initially studied 21 cases of osteosarcoma by FISH analysis (using a technique that included a probe for chromosome 17), 11 of which had their HER-2/neu gene amplification status previously reported. RESULTS None of these osteosarcoma cases showed HER-2/neu amplification by our FISH analysis and subsequent quantitative (multiplex) polymerase chain reaction. Apparent expression of HER-2/neu protein was observed in several of the cases but the immunoreactivity was localized to the cytoplasm and was not membranous in character. An additional 35 osteosarcoma specimens were subjected to monoplex polymerase chain reaction analysis, and amplifiable DNA was recovered from 19 specimens (54%). None of these samples had HER-2/neu amplification by monoplex PCR analysis and only one case had membranous immunoreactivity graded as 1+. CONCLUSION Although a small subset of osteosarcomas had weak noncircumferential membranous immunoreactivity for HER-2/neu protein, no osteosarcomas demonstrated positive (2+ or 3+) immunoreactivity for HER-2/ neu protein and none showed HER-2/neu gene amplification by either FISH or polymerase chain reaction.

ASCUS, Mature Metaplastic Type

OBJECTIVE To study the cytologic criteria for follow-up of mature metaplastic cells within the atypical squamous cells of undetermined significance (ASCUS) category. STUDY DESIGN Squamous epithelial abnormalities between January 1994 and June 1997 at our institution totaled 2,632 and included squamous carcinoma (1), high grade squamous intraepithelial lesions (278), low grade squamous intraepithelial lesions (875) and ASCUS (1,478). From the ASCUS group, 134 (9.06%) were metaplastic; 89 were selected for review. Criteria for case selection were follow-up with tissue biopsy or at least two Pap smears and no previous epithelial abnormality. Patients ranged from 27 to 70 years of age. Parameters tabulated included number of abnormal cells per slide, their architecture, cell size, shape, cytoplasmic hue and texture, nuclear size and contour, chromatin pattern and nucleoli. Additionally, specimens were reviewed for hormonal status and inflammation. The findings were correlated with follow-up data. RESULTS Cells generally appeared single or in loose, monolayered sheets of three to seven cells per group. The cells were well demarcated, polygonal or oval and ranged from 11 to 30 microns with cyanophilic or eosinophilic thickened cytoplasm. The round to oval nuclei with slight irregularity showed a minimally increased nuclear/cytoplasmic ratio with stippled chromatin. Upon review, 69 smears were confirmed as ASCUS-M. Follow-up revealed 42 with benign findings, 9 with persistent ASCUS/ASCUS-M and 18 with low grade squamous intraepithelial lesions. CONCLUSION In mature metaplastic cells with minimal atypia in patients with no previous or concurrent dysplasia, the follow-up details were similar to those described for ASCUS-superficial/immediate squamous cells. These patients could be followed conservatively.

Implementation and evaluation of a negation tagger in a pipeline-based system for information extraction from pathology reports

We have developed a pipeline-based system for automated annotation of Surgical Pathology Reports with UMLS terms that builds on GATE – an open-source architecture for language engineering. The system includes a module for detecting and annotating negated concepts, which implements the NegEx algorithm – an algorithm originally described for use in discharge summaries and radiology reports. We describe the implementation of the system, and early evaluation of the Negation Tagger. Our results are encouraging. In the key Final Diagnosis section, with almost no modification of the algorithm or phrase lists, the system performs with precision of 0.84 and recall of 0.80 against a gold-standard corpus of negation annotations, created by modified Delphi technique by a panel of pathologists. Further work will focus on refining the Negation Tagger and UMLS Tagger and adding additional processing resources for annotating freetext pathology reports.