Cytotechnologists. Do we have enough?
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Cell Biology↗
Biomedical subjects
M U Prey
Publications and source records attributed to M U Prey.
Procedures used in the creation of the American Society of Cytopathology cervical Cytology Practice Guideline.
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Journal Article↗
Detection of high grade squamous intraepithelial lesions and tumors using the AutoPap System: results of a primary screening clinical trial.
BACKGROUND: The AutoPap System for the initial screening and quality control of conventional cervical cytology slides previously has shown superior performance for the detection of abnormal slides of low grade squamous intraepithelial lesions and above. This report presents data regarding the important category of high grade squamous intraepithelial lesions and above (HSIL+). METHODS: All slides were run through a Current Practice (CP) arm of manual screening with 10% random quality control followed by an AutoPap (AP) arm of device initial screening with approximately 25% of slides receiving no further review; 75% received a manual rescreen with AP ranking and QC rescreening of 15% of the top ranking negative manual screen slides was performed. Detection performance for truth-determined HSIL+ cases was compared between the two study arms. Available follow-up biopsy results were correlated for cases determined to be HSIL+. RESULTS: Of 25,124 analyzed slides, 70 slides had truth-determination at the HSIL+ level (67 HSILs, 1 adenocarcinoma in situ, and 2 invasive tumors). The AP arm identified 68 of 70 cases (including both invasive tumors). Neither false-negative HSIL+ was found in the 25% "No Further Review" population. The CP arm identified 65 of 70 cases (missing both invasive tumors). The results showed statistical equivalence between the two arms (P = 0.0129). Biopsy follow-up was available in 27 of 70 HSIL+ cases identified by AP and showed abnormality at some level in 100% of cases. CONCLUSIONS: The AP arm was statistically equivalent and showed numeric superiority to the CP arm for the category of HSIL+. Follow-up data confirmed the true-positive nature of these findings. These results are significant because any overall improvement in the performance of an initial screening device must be paralleled by at least equivalence in the clinically important subset category of HSIL+. Cancer (Cancer Cytopathol)
Adenocarcinoma↗
AutoPap system detection of infections and benign cellular changes: results from primary screener clinical trials.
Primary screening devices for cervical cytology must show performance data for the detection of infectious organisms and benign cellular changes (BCC) for cytologists who routinely report these findings. The data on infection and BCC from the AutoPap primary screening clinical trials are presented herein. The presence of infectious organisms (candida, trichomonas, shift in bacterial flora, herpes, actinomyces) and BCC were noted in each of the clinical trial arms (current practice, CP; AutoPap-assisted practice, AP). For the purposes of these analyses, a report of infection or BCC from either arm was considered to be "truth." In 25,124 slides analyzed, there were 2,925 cases of infection identified. Of these, CP identified 2,141, and AP identified 1,985. The overall detection results are statistically equivalent. Of 17 cases of actinomyces, CP detected 8, while AP detected 12. Of 1,282 cases of candida, CP detected 983, and AP detected 865. Of 1,375 cases of shift of bacterial flora, CP detected 897, and AP detected 869. Of 14 cases of herpes, CP detected 9, and AP detected 11. Of 343 cases of trichomonas, CP detected 293, and AP detected 275. There were 5,156 cases of BCC identified in the trial. CP detected 3,431, and AP detected 3,276. The detection rates for BCC are statistically equivalent. The results show that the AutoPap-assisted practice for the primary screening of conventional cervical cytology slides is equivalent to the current practice for the detection of cervical infections and benign cellular changes.
Actinomyces↗
The value of monoclonal antibody B72.3 for the diagnosis of breast carcinoma: experience with the first commercially available source.
One hundred cases of invasive breast carcinoma were studied using the commercially available monoclonal antibody Anti-Human Tumor-Associated Glycoprotein-72 (MAb B72.3, Biomedical Technologies Inc, Stoughton, MA) prediluted at 8.5 micrograms/mL. Forty-three cases displayed positive reactivity with this antibody. Intensity and distribution of positive staining varied among the tumor cells. Twenty-two cases had 1% or less reactive cells, while eight cases contained 40% or more positive tumor cells. Apical cell membrane and diffuse cytoplasmic staining were present. In fifteen cases intracytoplasmic lumina and extra-cellular secretory material were highlighted by positive staining. Thirty-five cases had benign breast tissue adjacent to the tumor. Benign ductal and lobular epithelial cells were nonreactive except for two cases in which small foci of apocrine metaplasia were positive. Reactivity with MAb B72.3 was not dependent upon histologic grade, nuclear grade, nodal status, or patient age. Excluding the lower number of positively stained cases, our findings were similar to other MAb B72.3 investigations. The number of positively stained cases and the intensity of the positivity were increased by using MAb B72.3 at 5.0 micrograms/mL with overnight incubation, or by using MAb B72.3 at 40.0 micrograms/mL with 2 hours of incubation. Our findings confirm that MAb B72.3 shows reliable reactivity with breast carcinoma that is sensitive to antibody concentration and incubation time without loss of specificity for tumor cells. Our results are also consistent with the view that MAb B72.3 probably detects epithelial membrane-related antigens in breast carcinoma, as do several other antibodies.
Antibodies, Monoclonal↗
Guidelines for practical utilization of intraoperative frozen sections.
We reviewed 4057 intraoperative frozen sections from 1980 through 1984 to assess the accuracy, strengths, and weaknesses of this technique. Breast, lymph node, and skin comprised half of the sites evaluated. Frozen-section and final diagnoses agreed in 91.5% and disagreed in 6.8% of the cases; 1.7% of the cases were deferred. False-negative frozen-section diagnoses were due to pathologist sampling or judgment errors and surgeon sampling errors. There were eight (0.15%) false-positive diagnoses, none of which altered patient treatment. We recommend that lymph nodes for lymphoproliferative disorders and breast tissue for which a malignant diagnosis will not result in an immediate mastectomy not be submitted for frozen-section diagnosis. Appropriate studies of these tissues can be carried out without an intraoperative diagnosis; such a policy will increase the cost-effectiveness of frozen sections without compromising patient care.
False Negative Reactions↗
Evaluation of three commercially available rotavirus detection methods for neonatal specimens.
Commercially available assay kits have now made detection of rotavirus in stool specimens possible as a routine laboratory test. One such kit, Rotazyme II (Abbott Laboratories, North Chicago, IL) has been reported to give a higher incidence of false positive results with neonatal stool than with stool from older patients. One hundred stool specimens from asymptomatic neonates (age range, two to five days) were tested by two ELISA methods and one latex agglutination method in order to evaluate the rate of false positivity in this group of patients. Negative staining electron microscopy was used as the reference method. The two ELISA methods were Rotazyme II and Rotavirus EIA (International Diagnostic Laboratories, St. Louis, MO), and the latex agglutination method was Meritec-Rotavirus (Meridian Diagnostics, Inc., Cincinnati, OH). The Rotavirus EIA and Meritec-Rotavirus tests gave 0% and 1% false positive results, respectively, while the Rotazyme II test gave a 4% false positive rate with an additional 19% equivocal results. This extensive comparative analysis of commercially available assays for detection of rotavirus in neonatal stool specimens suggests a false positive or equivocal rate with the Rotazyme II test that impairs clinical utility.
Diarrhea, Infantile↗
Breast carcinoma cell kinetics, morphology, stage, and host characteristics. A thymidine labeling study.
The thymidine labeling index (TLI) was measured in 757 primary, invasive breast carcinomas in women by an in vitro method that achieved intense labeling of S-phase cells. The frequency distribution of the TLI was positively skewed but could be normalized by taking logarithms. The mode was 2%; median, 5.2%; geometric mean, 4.5%; mean 7.1%. The TLI was significantly related to a number of pathological features. Carcinomas of large size, with inflammatory or otherwise locally aggressive, undifferentiated histologic and nuclear characteristics, necrosis, inflammatory cellular response, and circumscribed tumor border showed strong tendencies to have high TLIs. The TLI was not significantly related to race, axillary lymph nodal status, or invasion of lymphatics and blood vessels. Breast carcinomas replicated cells at high rates ("rapid growth") more often in young women than in aged women. Lack of either estrogen receptor (ER) or progesterone receptor (PgR) was associated with high TLI. Although the inverse relationship between TLI and PgR was more or less linear, and the relationship between TLI and ER was not, differences in TLI between PgR-negative and PgR-positive patients were no greater than between ER-negative and ER-positive tumors. The degree of inflammatory infiltrate was strongly related to both proliferative rate and evidence of cell-death, indicative of a secondary phenomenon rather than a role in regulation of tumor growth. The proliferative rate of breast carcinoma appears to be an important determinant of morphologic patterns. Although it modulates the pace of progress of the disease, it is at most a weak determinant of metastasis.
Adolescent↗
Heterogeneity of breast carcinomas determined by flow cytometric analysis.
Eight cases of primary breast carcinoma were studied for evidence of heterogeneity by flow cytometry using propidium iodide staining of DNA. Tumors ranged from 2.5 to 8.0 cm in greatest dimension, mean 4.2 cm. Five to 11 samples, determined by tumor size, were analyzed from each primary tumor in addition to 4 axillary lymph nodal metastases from 3 of the 8 cases. The presence of carcinoma was demonstrated histologically in each flow cytometric sample. Three of the carcinomas showed only diploid DNA content. Three showed the same single hyperdiploid population in each sample. Two carcinomas (2.5 and 3.5 cm) were heterogeneous and demonstrated 2 or 3 hyperdiploid populations. The 2 or 3 distinct hyperdiploid populations were present singly or sometimes in combination in one sample. Five of the 11 samples from 1 of the heterogeneous tumors and its axillary metastasis contained a single diploid population. Therefore, flow cytometric analysis of a single sample from a breast carcinoma may not be representative of the entire tumor. The study of multiple samples of breast carcinomas by flow cytometry is necessary for full characterization of the tumors.
Adult↗
Practical breast carcinoma cell kinetics: review and update.
The S-phase fraction (SP) measured by flow cytometry of DNA and the thymidine labeling index (TLI) measured autoradiographically indicate the proportion of carcinoma cells currently synthesizing DNA and reflect the rate of proliferation. The TLI and SPF are lognormally distributed. The median TLI performed to maximize precursor uptake is near 5% (5 labeled carcinoma cells per 100) the mean near 7%, and the range from less than 1% to near 40%. Corresponding values for the SPF measured by DNA flow cytometry are slightly higher when appropriate measures are taken to reduce background debris counts and other artefacts. Residual elevation of SPF above TLI may result from S-phase arrested cells. Flow cytometric histograms show that clearly aneuploid cell lines exist in 50-80% of primary breast carcinomas. Aneuploid breast carcinomas have higher mean TLI than diploid breast carcinomas, and therefore proliferate more rapidly. They also more frequently lack estrogen receptor (ER). Carcinomas with minimal nuclear anaplasia, particularly those of tubular, mucinous, infiltrating lobular and adenocystic types have low TLI and SPF, whereas carcinomas with highly anaplastic nuclei, including medullary carcinomas, have high TLI and SPF. TLI and SPF correlate inversely with ER and PgR content, have no relationship to axillary lymph nodal status, and have a weak positive correlation with tumor size and a weak negative correlation with age. High TLI predicts a high risk of early relapse after primary therapy for both node-negative and node-positive carcinomas. Carcinomas that produce brain metastases have particularly high TLI. Current evidence suggests that high SPF and aneuploidy may prove to have prognostic significance like TLI.
Aneuploidy↗
The AutoPap system for primary screening in cervical cytology. Comparing the results of a prospective, intended-use study with routine manual practice.
OBJECTIVE: To evaluate the effectiveness of the AutoPap System in detecting abnormal and normal cervical smears when used in a primary screening/quality control mode, as compared with currently established laboratory practices. STUDY DESIGN: Slides were obtained prospectively and were initially processed in the routine fashion with cytotechnologist screening followed by 10% random quality control rescreening. Slides were then processed on the AutoPap System and allocated into the following groups: (1) approximately 25% of the lowest-ranking slides were placed in the laboratory's archives as within normal limits; (2) the remaining approximately 75% of slides were subjected to manual screening. Approximately 15% of the highest-ranking slides in this group underwent quality control rescreening. For each slide needing manual screening, the cytotechnologist was supplied with a report giving the ranking score of that slide. All discrepant slides for either adequacy or diagnosis were subjected to a truth-determination process. The results obtained from the two arms of the protocol were then compared. RESULTS: The AutoPap System-assisted arm of the study was superior to the current practice arm for the identification of abnormal slides at the level of atypical squamous cells of undetermined significance and above (ASCUS+), low grade squamous intraepithelial lesion (LSIL) and higher LSIL+. AutoPap System-assisted practice was equivalent to current practice for the identification of unsatisfactory and satisfactory but limited by slides. All results showed statistical significance. In addition, AutoPap System-assisted practice in the study indicated improved specificity of diagnosis. CONCLUSION: AutoPap System-assisted practice shows superior sensitivity and specificity when compared to current practice. Its clinical use as a primary screening device should improve the overall practice of cervical cytology as well as provide potential enhancement in overall laboratory productivity.
Algorithms↗