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Biomedical subjects

D D Davey

Publications and source records attributed to D D Davey.

At least 37 records · Page 2Linked to original sources

Quality and liability issues with the Papanicolaou smear: the problem of definition of errors and false-negative smears.

A universally accepted definition for a false-negative Papanicolaou smear has not been established. Therefore, it is important to specify the criteria used to define false-negative smears when discussing the performance of clinical cytology. If these variables are not specified, there is potential for miscommunication. Variables include sampling versus laboratory false-negative errors, the definitions of what constitutes disease and the threshold to define an error, the time interval to detection, and the mechanism for detection of errors. False-negative error rate is defined as the number of false-negative Papanicolaou smears divided by the number of patients with disease. Discrepancy rate is often used interchangeably with false-negative rate, but the former does not factor in the prevalence of disease and the threshold used to define an error. The false-negative fraction is most useful for interlaboratory comparison. A reasonable definition of a laboratory false negative is a smear originally reported as negative or normal that is found to have sufficient numbers of carcinoma or dysplastic cells on review. The abnormal cells should be verifiable by more than one experienced cytologist in a blinded fashion, and it is ideal if the lesion is confirmed by biopsy or other confirmatory test.

Diagnostic Errors↗

Papanicolaou smear 5-year retrospective review: what is required by the Clinical Laboratory Improvement Amendments of 1988?

Five-year retrospective review of negative or normal smears in patients with newly diagnosed high-grade squamous intraepithelial lesions or cancer is a federal regulation for all laboratories practicing gynecologic cytology under the Clinical Laboratory Improvement Amendments of 1988. Amended reports are required when significant discrepancies are found that would affect patient care. The focus of this regulation is current patient care. Two studies have found a retrospective discrepancy rate of about 10% when the threshold for discrepancy was at least dysplasia. Higher rates are reported when missed atypical cases are counted as discrepancies. Retrospective review highlights problem areas for laboratory education and quality improvement efforts, but liability concerns have been a detrimental consequence of this regulation. Clarification that amended reports be issued only when current patient care is affected should aid laboratories in complying with this regulation.

Facility Regulation and Control↗

Atypical squamous cells of undetermined significance qualified: a follow-up study.

The Bethesda System recommends that the diagnosis of "atypical squamous cells of undetermined significance" (ASCUS) be qualified when possible to indicate whether a reactive process, or a squamous intraepithelial lesion (SIL), is favored. In order to evaluate the utility of this recommendation, 308 cervicovaginal smears diagnosed as ASCUS favoring a reactive (FR) or dysplastic (FD) process were identified. Concurrent or follow-up biopsies and cervicovaginal smear results were reviewed and compared to the follow-up of 103 cervicovaginal smears diagnosed as ASCUS without qualification. A follow-up diagnosis of SIL was found in 46.5%, 29.5% and 26.2% of the ASCUS FD, ASCUS FR, and ASCUS unqualified cases, respectively. A repeated ASCUS diagnosis was found in 20.4%, 21.8%, and 18.4% of the ASCUS FD, ASCUS FR, and ASCUS unqualified cases, respectively. Follow-up of each group was negative for dysplasia in 30.0%, 48.7%, and 54.4% of the ASCUS FD, ASCUS FR, and ASCUS unqualified cases, respectively. These results support the use of an ASCUS FD category for the increased detection of patients with dysplasia. The ASCUS FR category was not helpful in our laboratory. Follow-up studies of qualified ASCUS cases in individual practice settings may be useful in guiding patient management.

Carcinoma, Squamous Cell↗

Cytopathology and the pathology resident. A survey of residency program directors.

OBJECTIVE: To collect information on the status of cytopathology training in the United States. DESIGN: Questionnaire survey mailed in June 1994. SETTING: Pathology residency training programs in the United States. PARTICIPANTS: Pathology residency directors. MAIN OUTCOME MEASURES: Training length, numbers of cytology specimens, teaching methods and topics, and graduated responsibility. RESULTS: Of the 196 surveys mailed, 101 (52%) programs responded. The average length of required training was 3 months. The perceived optimal training time averaged 4.5 months, however, with 80% of programs requiring less than their stated optimum. The median numbers of gynecologic, nongynecologic, and fine-needle aspiration biopsy specimens examined per resident were 1100, 500, and 200, respectively. Cytopreparatory techniques, laboratory management, computer systems, and immunocytochemistry were included in over 75% of cytopathology training programs. Teaching at the microscope was rated as the most important teaching method by 90% of respondents. The majority of senior residents performed fine-needle aspiration biopsy procedures and screened and signed out cases with direct faculty supervision, but fewer than 20% of programs allowed senior residents to independently sign out specimens. CONCLUSIONS: Recommendations based on this review include a minimum training time of 3 months, improved training in both fine-needle aspiration biopsy techniques and gynecologic cytology, continuous exposure to cytopathologic techniques, and increased graded responsibility for senior residents.

Education, Medical, Graduate↗

Atypical squamous cells of undetermined significance. Current laboratory practices of participants in the College of American Pathologists Interlaboratory. Comparison Program in Cervicovaginal Cytology.

OBJECTIVE: To evaluate current laboratory practices and rates for atypical squamous cells of undetermined significance (ASCUS), a category of epithelial cell abnormality in the Bethesda System. DESIGN: Questionnaire surveys were mailed in December 1993 and March 1994. SETTING: Cytopathology laboratory participants in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology (PAP). RESULTS: Most responding laboratories (82.5%) limited the use of "atypia" terminology to abnormalities of undetermined significance. Nearly half of the laboratories employed only the term ASCUS for squamous epithelial changes in this category. The median rate of ASCUS in 1993 was 2.8%, with 10% of laboratories reporting rates greater than 9.0%. The median squamous intraepithelial lesion rate was 2.0%, with a median ASCUS-squamous intraepithelial lesion ratio of 1.3. The majority of laboratories qualified a portion of ASCUS cases and issued recommendations for follow-up when appropriate. Fifty-six percent of laboratories surveyed included patients diagnosed with ASCUS in follow-up programs. Laboratories estimated that about 20% (median response) of patients with ASCUS smears had a squamous intraepithelial lesion or equivalent diagnosis made within a year's follow-up. CONCLUSIONS: The ASCUS category is used by the majority of laboratories as recommended by the Bethesda System, but reporting rates vary. The results of this survey and associated surveys provide laboratories with useful benchmark figures for interlaboratory comparison of ASCUS practices.

Cervix Uteri↗

Comparison of immunoreactivity of neu oncoprotein in fine-needle aspirates and paraffin-embedded materials.

Expression of the neu oncogene has been extensively examined in frozen and paraffin section breast cancers; however, very few studies examine neu oncoprotein oncoprotein expression in fine-needle aspirates. To this effect, we compared the expression of neu oncoprotein in formalin-fixed paraffin-embedded breast cancers and the corresponding fine-needle aspirates of these cancers. There was 100% correlation between the expression of neu oncoprotein in the paraffin-embedded breast cancers and the fine-needle aspirates, indicating the suitability of fine-needle aspirates for the expression of neu oncoprotein in breast cancers.

Biopsy, Needle↗

Cytokeratin positivity in fine-needle aspirates of melanomas and sarcomas.

Cytokeratin (CK) positivity has been considered a specific marker for epithelial differentiation in cytologic specimens. After observing CK reactivity in fine-needle aspirate (FNA) specimens of melanoma and sarcoma, a retrospective study of melanomas and sarcomas was undertaken to investigate the frequency of anomalous CK staining in these neoplasms. Cell block sections and/or restained smears from 36 melanomas and sarcomas were retrospectively stained for CK. An appropriate internal positive control (HMB-45), S100 protein, or vimentin) was also used to insure antigen preservation. Of the smears from 19 melanomas, five revealed focal strong CK positivity of neoplastic cells, two cases showed faint or equivocal staining, 11 cases were negative for CK, and one could not be interpreted due to inadequate controls. Of the smears from 14 sarcomas, two showed positivity for CK (one fibrosarcoma and one condrosarcoma), 11 were negative, and one had inadequate controls. The number of CK positive cells was less than that observed with the appropriate internal positive control antibodies. Destained Papanicolaou smears were superior to Diff-Quik smears for retrospective immunocytochemical stains. Cell block sections from four of the melanomas and one sarcoma demonstrated no aberrant staining. Since cytokeratin positivity occasionally is seen in nonepithelial neoplasms, its presence alone cannot be used to make a definitive diagnosis of carcinoma. Therefore, a panel of immunocytochemical stains should be utilized in diagnosis of FNA specimens.

Biopsy, Needle↗

Lymphomas of the oral soft tissues are not preferentially associated with latent or replicative Epstein-Barr virus.

OBJECTIVES: Epstein-Barr virus is periodically shed in the saliva of persons infected by the virus. Epstein-Barr virus has been implicated in the pathogenesis of certain subtypes of lymphoma, particularly high-grade lymphomas. Because high-grade subtypes represent the majority of lymphomas that arise in oral soft tissues, we hypothesized that Epstein-Barr virus might be preferentially associated with oral lymphomas. STUDY DESIGN: A series of 34 oral lymphomas were diagnosed according to the revised European-American classification scheme. They were examined for the presence of latent Epstein-Barr virus by EBER1 in situ hybridization and for expression of the Epstein-Barr virus replicative protein, BZLF1, by immunohistochemistry. RESULTS: Epstein-Barr virus EBER1 transcripts were detected in 11 of 31 oral lymphomas including 7 of 10 AIDS-related lymphomas and only 4 of 21 lymphomas that occurred in nonimmunocompromised persons. The Epstein-Barr virus-containing lymphomas were all high-grade histologic subtypes, that is, diffuse large cell, immunoblastic, or Burkitt's lymphomas. In contrast, Epstein-Barr virus was not detected in any of five low-grade oral lymphomas. In the single case of T-cell lymphoma in this study, EBER1 was expressed in the tumor cells. A switch from viral latency to replication, as measured by EBV BZLF1 expression, was identified in rare lymphoma cells in only four cases. This rate of viral replication was not higher than what has been reported in lymphomas arising at other anatomic sites. Although one of our lymphomas arose at a site of previous oral hairy leukoplakia, there was no other evidence that Epstein-Barr virus replication predisposed to development or persistence of oral lymphomas. CONCLUSIONS: These data suggest that even though Epstein-Barr virus is frequently found in oral secretions, neither latent nor replicative Epstein-Barr virus is present more commonly in oral lymphomas than in lymphomas arising in other anatomic sites, when controlling for immunodeficiency status.

Adolescent↗

Etiologies for non-correlating cervical cytologies and biopsies.

To investigate the etiologies for discrepancies between cervicovaginal smear and corresponding cervical biopsy results, 615 patients with cytologic diagnoses of dysplasia or malignancy during 1 year were reviewed. Sixty-nine patients (11%) were identified in which the cytologic and histologic diagnoses differed. Utilizing an algorithm developed for the study, these cases were assigned an etiologic category for discrepancy: colposcopic biopsy or cytologic sampling, cytologic screening, histotechnical processing, histologic or cytologic interpretation. The most common cause for a discrepancy was colposcopic biopsy sampling (36 cases, 51%). There were nine errors (13%) in biopsy interpretation, with seven underdiagnoses and two overdiagnoses. Eight errors (11%) in cytologic interpretation occurred with half of these representing underdiagnoses. The other causes for discrepancy were less common--cytologic sampling (6 cases), histotechnical processing (3 cases), cytologic screening (2 cases), and a combination of factors (5 cases). Use of this algorithm allows laboratories to identify problem areas and design specific corrective protocols to improve diagnostic accuracy and patient care.

Algorithms↗

Comparative assessment of DNA analysis in effusions by image analysis and flow cytometry.

Cytologic evaluation of body cavity fluids is useful to detect malignancy within the pleural and peritoneal spaces. A definitive diagnosis cannot always be made on cytologic evaluation alone. As malignant processes may show abnormal DNA content, DNA analysis of effusions may be useful. Therefore, we determined the DNA content of 37 effusions by flow cytometry (FC) and image analysis (IA) using the CAS 200. Of the 37 fluids evaluated, 18 were cytologically malignant, 15 benign, and four atypical. Overall, 22 fluids (60%) showed concordance between FC and IA. None of the benign fluids were aneuploid. All showed diploid histograms or diploidy with increased proliferating cells. Three of four atypical fluids had increased proliferating cells by either FC or IA, whereas one was diploid by both methods. Aneuploidy was detected in 13 malignant fluids: five were aneuploid by both methods and eight by only one method. IA identified aneuploidy in five of those eight cases, while three were identified by FC. Three of the cytologically malignant fluids were diploid by both methods, and two showed increased proliferating cells by IA and diploidy by FC. The specificity of both methods was 100%. However, the sensitivity of identifying a malignant fluid by aneuploidy is low, 44% for FC and 55% for IA. IA appears to identify small aneuploid populations more frequently than FC. The detection of aneuploidy in effusions is highly suggestive of malignancy, and the combination of both techniques gives the highest detection rate (72%). However, neither are as sensitive as traditional cytologic evaluation with the occasional use of additional histochemical stains.

DNA, Neoplasm↗

Atypical squamous cells of undetermined significance: interlaboratory comparison and quality assurance monitors.

The Bethesda System recognizes "Atypical Squamous Cells of Undetermined Significance" (ASCUS) as a category of epithelial cell abnormality. Neither the acceptable rate of ASCUS nor the clinical follow-up are well defined. This study focused on interlaboratory comparison and quality assurance methods for evaluating the rate and outcome of ASCUS. Data was collected from questionnaire surveys from the College of American Pathologists Interlaboratory PAP Program and the four authors' laboratories. Most PAP laboratories (82.5%) limit the use of "atypia" terminology to abnormalities of undetermined significance. According to PAP data, the median rate of ASCUS in 1992 was 2.9%, with 10% of laboratories reporting rates greater than 9.0%. The median squamous intraepithelial lesion (SIL) rate was 2.2%, with a median ASCUS/SIL ration of 1.3. The authors' laboratories (university, independent, and hospital) revealed ASCUS rates of 1.6-9.0%, while SIL rates were 2.1-9.0%. The ASCUS/SIL ratio was less variable, 0.8-2.7. Follow-up of ASCUS patients in the authors' laboratories showed 10.3-43% with SIL, but less than 6% with high grade SIL. The ratio ASCUS/SIL may serve as a useful laboratory monitor. Peer review and follow-up studies of ASCUS serve to validate laboratory criteria and consequent clinical follow-up. Communication with clinicians is vital in ensuring optimal patient care.

Cell Nucleus↗

Proliferating cell nuclear antigen in prostatic adenocarcinoma: correlation with established prognostic indicators.

OBJECTIVE: The utility of an antibody to proliferating cell nuclear antigen (PCNA), a growth-specific nuclear protein, was assessed as a prognostic variable for prostatic adenocarcinoma. Its expression was correlated with established prognostic indicators, including tumor grade, stage, prostatic-specific antigen (PSA), and percent of tumor in the gland at excision. METHODS: Forty archival needle biopsies containing a minimum of four hundred tumor cells were analyzed. Immunoperoxidase staining of paraffin sections was performed for PCNA (PC10) after pretreatment in antigen retrieval solution. A proliferative index (PI) for each case was derived using image analysis with measurement of at least four hundred twenty-five nuclei. RESULTS: PI values ranged from 2.4 to 31.3 percent. Mean PI values varied significantly (ANOVA, p = 0.005) among cases with dominant Gleason grade (DGG) of 3 (mean PI = 9.3%), 4 (mean PI = 13.7%), and 5 (mean PI = 18.8%). By t test, significant differences were noted for PI in cases with DGG 2 and 3 versus those with DGG 4 and 5 (p = 0.0065). PI for cases with DGG 3 versus 5 showed significant difference (p = 0.0017). Tumors of Gleason scores 5 to 7 differed significantly from those with scores 8 to 10 (p = 0.014). A statistical relationship for PI and PSA, clinical stage, and percent tumor at resection could not be established by linear regression. CONCLUSIONS: These findings suggest that additional study of the PI, as determined by PCNA immunohistochemistry and image analysis, may be warranted to determine its usefulness as an adjunctive parameter in prostate adenocarcinoma. This technique may be particularly useful in needle biopsies where limited tumor may render assessment of grade difficult.

Adenocarcinoma↗

Assessment of cervicovaginal smear adequacy. The Bethesda System guidelines and reproducibility.

Criteria for assessing adequacy of cervicovaginal smears according to the Bethesda System include cellular composition and quantity, specimen preservation, fixation, and absence of obscuring elements. The reproducibility of adequacy assessment using these parameters was the focus of this study. Specimens were chosen to include a wide spectrum of clinical history and adequacy interpretations, but excluded cases with epithelial abnormalities and those judged "limited" because of insufficient transformation zone component. The 114 specimens were independently evaluated twice by five reviewers, with interceding randomization. Full interobserver concordance was obtained in 50.4% of cases, with consensus reached by three or more observers in 97.4% of cases. Of 2280 paired interpretations, 74% (1692) concurred. Pairwise kappa values for interobserver agreement ranged from .71 to .54 (very good to fair), with overall kappa = .61. Interobserver agreement for each category was near excellent for "satisfactory" (kappa = .73), good for "unsatisfactory" (kappa = .63), and only fair for "satisfactory but limited" (kappa = .48). Paired intraobserver reproducibility (agreement for two separate readings by the same observer) ranged from 69% to 77% (average, 74%), with good to fair kappa values (.66-.51). These findings indicate that the specimen adequacy guidelines of the Bethesda System provide good inter- and intraobserver reproducibility. The "satisfactory but limited" category appears to show the lowest concordance. Problem areas include evaluation of adequate minimum cellularity and estimation of number of cells obscured.

Female↗

Ductal abnormalities detected with galactography: frequency of adequate excisional biopsy.

OBJECTIVE: Galactography (ductography) is a contrast examination of the mammary ducts performed to identify and localize intraductal growths that may be the cause of spontaneous discharge from the nipple. The objective of this study was to correlate the radiologic-pathologic findings in patients with abnormal findings on galactograms in order to determine how often the biopsy specimens included the lesions seen at galactography. MATERIALS AND METHODS: We retrospectively studied all galactograms with abnormal findings obtained in women who subsequently had biopsy at our institution between 1981 and 1991. Galactograms and tissue specimens from 29 women who had 30 biopsies were included. The standard technique was used to perform galactography. Biopsies were performed by using standard surgical technique for duct excision. The histopathologic findings were retrospectively reviewed by a pathologist to determine whether the biopsy specimens included the lesions seen at galactography. RESULTS: In six (20%) of the 30 biopsies, the lesion shown by galactography was not seen on histopathologic review. In the other 80%, the lesion was successfully identified on histopathologic examination. CONCLUSION: Our finding that the abnormality shown by galactography was not completely excised in one in five cases indicates that greater cooperation between the surgeon, radiologist, and pathologist is essential to ensure that all lesions are properly removed.

Biopsy↗