Sherry Woodhouse

Atypical epithelial cells and specimen adequacy: Current laboratory practices of participants in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology

○ Context.-The Bethesda System for reporting cervical/ vaginal cytologic diagnoses introduced terminology for atypical squamous and glandular cells and categories for specimen adequacy. Objectives.-To analyze current laboratory reporting practices and compare trends to previous surveys. Design.-Questionnaire surveys were mailed to 2000 laboratories in 1996 and 1997. Participants.-Laboratories enrolled in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology. Main Outcome Measures.-Laboratory policies, criteria, and reporting rates for Bethesda System categories. Results.-The 1996 specimen adequacy survey had 1166 respondents, and 768 laboratories returned the 1997 questionnaire focusing on atypical squamous cells of undetermined significance (ASCUS) and glandular cells of undetermined significance (AGUS). Nearly all laboratories (92%) routinely reported specimen adequacy, an increase from the 66% rate in 1991. The median rate for unsatisfactory specimens was 0.5% (mean 0.95%), and the median rate for the satisfactory but limited category was 5.8% (mean 9.3%). The Bethesda criteria for designating a specimen unsatisfactory were used by more than 90% of laboratories. Nearly all laboratories (97%) used the term ASCUS in 1997, and more than 80% of laboratories used the Bethesda criteria for this category. Median reporting rates for epithelial abnormalities were as follows: ASCUS, 4.5%; AGUS, 0.3%; low-grade squamous intraepithelial lesion (SIL), 1.6%; and high-grade SIL, 0.5%. The median ASCUS/SIL ratio was 2.0, with 80% of laboratories reporting ratios between 0.64 and 4.23. The median ASCUS rate and ASCUS/SIL ratio were higher than 1993 survey results. Nearly all laboratories attempted follow-up studies on patients with abnormal cytology results, and midsized laboratories achieved the highest rates of follow-up. Median rates of abnormalities following an ASCUS or AGUS diagnosis were 20% and 15%, respectively. Laboratory respondents commonly used written recommendations in ASCUS/AGUS reports. Conclusions.-Most laboratories that responded to the surveys had adopted Bethesda terminology and criteria for specimen adequacy and ASCUS/AGUS. Reporting rates for SIL and adequacy categories have remained stable, but median ASCUS rates and ASCUS/SIL ratios are higher than in 1993. The AGUS category is reported infrequently, but can be associated with significant pathology.

Interobserver and Intraobserver Bias Exists in the Interpretation of Anal Dysplasia

AbstractINTRODUCTION: Natural history of progression from anal intraepithelial neoplasia to invasive carcinoma remains unproven. The risk of progression may be linked to the severity of dysplasia. Important therapeutic decisions are thus based on the severity of anal intraepithelial neoplasia. Consistency and reliability in the interpretation of anal intraepithelial neoplasia are unproven. METHODS: One hundred ninety anal biopsy specimens were identified for review of dysplasia with a six-point grade system from normal to invasive cancer, evidence of human papillomavirus infection, and quality of histology by three pathologists. RESULTS: Results revealed poor to moderate agreement on grading of quality of histology (weighted kappa score, 0.07–0.22), human papillomavirus status (weighted kappa score, 0.24–0.53), and dysplasia (weighted kappa score, 0.38–0.7). Complete agreement between the original pathology and the three pathologists was observed in only 32 percent of cases. Analysis of 86 slides previously read by one of the pathologists revealed only moderate agreement, with a weighted kappa score of 0.64. CONCLUSION: Significant interobserver and intraobserver bias exists in the interpretation of anal intraepithelial neoplasia. These inconsistencies may explain the uncertainty about the natural progression of anal intraepithelial neoplasia and the varied results of surgery reported for anal intraepithelial neoplasia in the literature.

Interobserver variability in subclassification of squamous intraepithelial lesions: Results of the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology.

OBJECTIVE To determine whether, on a national cytology proficiency test, a competent cytologist can consistently distinguish grades of squamous intraepithelial lesions. DESIGN Results for low- and high-grade squamous intraepithelial lesion referenced slides from the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology for 1996 and 1997 were analyzed including educational, nongraded vs graded validated slides. RESULTS The discrepant rate between low- and high- grade lesions ranged from 9.8% to 15% for cytotechnologist, pathologist, laboratory, and all responses. There was a statistically significant difference in performance on graded, validated slides vs educational slides with better performance on validated slides. CONCLUSION This significant interobserver variability in subclassification of squamous lesions should be considered in management guidelines for abnormal Papanicolaou test results and implementation of national cytology proficiency testing.

Effects of radiotherapy on different histopathological types of rectal carcinoma

Background  Down staging by pre‐operative chemoradiotherapy is currently considered part of the standard therapeutic approach to rectal carcinoma. The aim of this study was to assess the response to chemoradiotherapy of different histopathological types of rectal carcinoma with emphasis on the mucinous variant.

Enterochromaffin and serotonin cells are abnormal for patients with colonic inertia

PURPOSE: In recent studies, serotonin and several gut peptides have been shown to serve as regulators of colonic transit. Thus, the distribution, density, and intensity of cells secreting serotonin or certain gut peptides could be abnormal in patients with colonic inertia. The aim of this study was to evaluate the distribution, density, and staining intensity of enterochromaffin and serotonin cells in the colonic mucosa of patients with colonic inertia compared with a control group. METHODS: Between 1993 and 1998 tissue blocks from the right and left side of the colon were obtained in 19 consecutive patients (18 females; mean age, 43.7±11.5 years) who underwent subtotal colectomy for colonic inertia. The control group consisted of colonoscopic biopsies from the right and left colon of 15 patients (all females; mean age, 52.7±16.5 years) for indications other then constipation, inflammatory bowel diseases, or carcinoma. Immunocytochemical staining of enterochromaffin and serotonin cells were performed on 4 µm tissue sections with the primary rabbit antibody against chromogranin A or serotonin, and the biotinylated secondary antibody and enzyme-labeled-streptavidin. The average cell number per microscopic field (×200) was calculated and the proportion of cells with various staining distribution was expressed as the percentage of the entire positive cell population as low, moderate, and high intensity. Studentst-test and chi-squared test were used for statistical analysis, with significance level set atP<0.05. RESULTS: The quantity of both enterochromaffin cells (16.8±10.2) and serotonin cells (12.1±6.4) in the mucosa of the left colon in patients with colonic inertia was significantly higher when compared with the right side of the colon (enterochromaffin cells, 9.4±6.0; serotonin cells, 7.8±3.6;P<0.01). The percentage of both types of cells with low staining intensity was increased, whereas the cells with high and moderate staining intensity were decreased (P<0.01) in the left colon as compared with the right. The number of enterochromaffin cells in left-sided colonic mucosa was significantly higher in the colonic inertia group than in the control group (16.8±10.1vs. 10.4±6.0;P<0.05). Moreover, the numbers of serotonin cells in both the right and left colon was also significantly higher in the colonic inertia group than in the control group (right, 7.8±3.6vs. 4.1±2.4; left, 12.1±6.4vs. 5.8±3.7;P<0.01). In both sides of the colon, the percentage of enterochromaffin and serotonin cells with low staining was significantly higher, whereas percentage of those cells with high or moderate staining was significantly lower in the colonic inertia group than in the control group. In the colonic inertia group there was a significantly positive correlation between numbers of enterochromaffin and serotonin cells (right side,P<0.01; left side,P<0.05). CONCLUSION: In patients with colonic inertia, the number of both enterochromaffin and serotonin cells are significantly increased in the colonic mucosa, especially in the left colon. As indicated by staining distribution, enterochromaffin and serotonin cells contain significantly less hormone than do the same cells in the control group.

Altered serotonin immunoreactivities in the left colon of patients with colonic inertia

Serotonin is an important positive regulator of colonic motility and transit. Its quantity and distribution in the left colon could be abnormal in patients with colonic inertia (CI) and contribute to the disease.

Reparative Changes and the False-Positive/False-Negative Papanicolaou Test A Study From the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology

CONTEXT Reparative changes can be a diagnostic challenge on Papanicolaou tests and must be distinguished from epithelial cell abnormalities. Both squamous intraepithelial lesions (SIL) and carcinoma may be underdiagnosed as repair. This study examines laboratory and cytologist performance in the diagnosis of repair. OBJECTIVES To determine if laboratories and cytologists can consistently distinguish reparative changes from SIL and carcinoma and to document how often SIL and carcinoma are mistaken for repair in a standardized educational slide program. DESIGN Results for reparative changes, SIL, and carcinoma slides from the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology for 1998 were analyzed. Only results from validated referenced slide responses were used. RESULTS The concordancy rate for reparative-change slides, that is, any response of within normal limits or benign cellular changes, ranged from 91% to 94% for cytotechnologist, pathologist, and laboratory responses. False-negative rates for squamous carcinoma and adenocarcinoma, high-grade SIL, and low-grade SIL ranged from 0.47% to 5.41%; the proportion of false-negative diagnoses of reparative changes ranged from 24% to 62% of all discordant responses. CONCLUSIONS Of all benign cellular changes and within normal limits categories in the Interlaboratory Comparison Program in Cervicovaginal Cytology, repair most often elicits a false-positive laboratory response. Underdiagnosing epithelial abnormalities as repair is also a source of false-negative Papanicolaou test results.

Reduced expression of serotonin receptor(s) in the left colon of patients with colonic inertia

AbstractPURPOSE: Serotonin regulates colonic motility via receptors expressed on neural fibers and smooth muscle. Colonic inertia is characterized by delayed colonic transit. Abnormalities in serotonin receptor protein, as judged by immunoreactivity levels, could contribute to the origin of colonic inertia. The aim of this study was to investigate the expression of serotonin receptor(s) immunoreactivity in the left colon of patients with colonic inertia compared with controls. METHODS: Sixteen patients who underwent subtotal colectomy for colonic inertia were assessed. Colonic transit time was measured with the radiopaque marker technique and presented as the number of retained markers in the colon on Day 5. The control group consisted of 18 patients who underwent left hemicolectomy for colonic carcinoma; histologically normal tissues from the left colon were used. Immunohistochemical staining for serotonin receptor was performed with a rabbit anti-idiotypic antibody. The average positive area (square pixels) in the mucosa, muscularis mucosa, submucosa, and circular and longitudinal muscles per microscopic field (63×) was calculated based on measurement of the positively stained area in 20 randomly chosen microscopic fields in each related structure. The Scion Image computer analysis system was used. RESULTS: Serotonin receptor(s) immunoreactivity was mainly detected in the muscular mucosa, circular muscles, and longitudinal muscles and rarely in the mucosa and submucosa. In muscularis mucosa and circular muscle, the positive areas were significantly less in the colonic inertia group than in controls (muscularis mucosa: 29.1 ± 10.8 vs. 109.7 ± 28.2, P < 0.05; circular muscle: 25.6 ± 6.2 vs.90.2 ± 19.1, P < 0.01). There were significantly positive correlations in the control group in serotonin receptor(s) immunoreactivity levels between circular muscle and longitudinal muscle (r = 0.54, P < 0.05) and between muscular mucosa and longitudinal muscle (r = 0.57, P < 0.05) but not in colonic inertia patients. In addition, the positive areas in the circular muscle were positively correlated to the colonic transit time (Spearman’s rank correlation, 0.83; P < 0.01). CONCLUSION: In colonic inertia patients, the serotonin receptor(s) immunoreactivity level is lower in muscular mucosa and circular muscle. The absence of a correlation of serotonin receptor(s) immunoreactivity in the muscular mucosa and muscularis propria in the patient group implies that an uncoordinated expression of serotonin receptors may also contribute to colonic inertia. However, the positive correlation between serotonin receptor(s) immunoreactivity levels in the circular muscle and the transit time observed in colonic inertia patients suggests a decrease in stimulatory subtypes and at the same time an increase in inhibitory subtypes of serotonin receptors in this tissue.

Variability in serotonin and enterochromaffin cells in patients with colonic inertia and idiopathic diarrhoea as compared to normal controls

Aim To evaluate differences in distribution, density and staining intensity of enterochromaffin cells (EC) and serotonin cells (SC) in the colonic mucosa of patients with colonic inertia (CI), idiopathic diarrhoea (ID) and a control group.

Squamous cell carcinoma of the rectum in ulcerative colitis: case report and review of the literature

The majority of colorectal carcinomas diagnosed are adenocarcinomas. Squamous cell carcinomas (SCC) of the rectum are rare tumors, and were reported as rare complication of inflammatory bowel disease. Surgery is the most effective therapy; and adjuvant chemotherapy and radiotherapy should also be considered. We report two cases of ulcerative colitis-associated SCC of the rectum. The lesions were treated with chemoradiotherapy with complete response.