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Biomedical subjects

D C Wilbur

Publications and source records attributed to D C Wilbur.

At least 37 records · Page 2Linked to original sources

High grade squamous cervical lesions following negative Papanicolaou smears: false-negative cervical cytology or rapid progression.

The cervical cytologic finding of a high grade squamous intraepithelial lesion (HGSIL) or carcinoma shortly following a negative smear is unusual. To determine if such cases are due to screening errors, inadequate sampling, or rapidly progressive lesions, a review of negative smears (immediately preceding a diagnosis of HGSIL or carcinoma by at most 2 yr) was performed on 17 patients (all such patients in our 1990-92 files, representing 6% (17/290) of such diagnoses). The time between negative smear and positive result averaged 9.3 mo. Eighty-eight percent of these patients had prior histories of a cytologic abnormality. Upon review, 16 of 17 "negative" smears contained a cytologic abnormality. Atypical immature squamous metaplastic type cells (AISMTs) were found in 11 of 16 cases, atypical squamous cells or slight dysplasia were found in 5 of 16, HGSIL was found in 5 of 16, and atypical cells of undetermined type and origin were noted in 1 of 16. Combinations of the above diagnoses were present in 6 of 16 cases. The number of abnormal cells per slide was estimated, with < 10 cells in 1 case, < 50 in 4 cases, 50-100 in 7 cases, 100-200 in 3 cases, and > 200 in 1 case. In this study, screening and/or evaluation errors were the dominant cause of false-negative cytologic diagnoses, with AISMTs accounting for the most commonly missed or misinterpreted cells. These cells are small and have hyperchromatic nuclei with elevated nucleus to cytoplasmic ratio and nuclear irregularities.

Adult↗

Endocervical glandular atypia: a "new" problem for the cytologist.

New patterns of cellular presentation on cervical smears have become more frequent since the introduction of new sampling devices which provide increased material from the upper portions of the endocervical canal. The normal histologic variability of the endocervical canal, as well as the presence of tubal metaplasia, infectious and inflammatory reactions, squamous lesions involving endocervical glands, and true endocervical neoplastic lesions in these areas, have presented the cytologist with a variety of cellular appearances which may cause difficulties in differential diagnosis. Recognition of these entities, their cytologic manifestations, and the effects of increased high endocervical sampling, will allow the cytologist to begin the process of gaining the experience necessary to assess these new cellular patterns. A potential management protocol for patient follow-up is presented which will allow the user to investigate such cases in an efficient and cost effective manner.

Cervix Uteri↗

Interobserver reproducibility of the Nottingham modification of the Bloom and Richardson histologic grading scheme for infiltrating ductal carcinoma.

The interobserver reproducibility of the Nottingham modification of the Bloom and Richardson histologic grading scheme for invasive breast carcinoma was tested. Six surgical pathologists from four institutions independently evaluated histologic grade and each of its three components for 75 infiltrating ductal carcinomas. The number of slides per case ranged from one to nine (median 3). Pairwise kappa values for agreement ranged from moderate to substantial (0.43-0.74) for histologic grade. Generalized kappa values indicated substantial agreement for tubule formation (0.64), moderate agreement for mitotic count (0.52), and near moderate agreement for nuclear pleomorphism (0.40). Normalizing the mitotic counts per mm2 showed only slight improvement in agreement over the published range of mitotic counts for three different field areas. The results suggest that steps to discriminate between categories for nuclear pleomorphism would likely be of benefit for improving the interobserver reproducibility of histologic grade. Nevertheless, the Nottingham modification of the Bloom and Richardson grading system is recommended as a suitable scheme for evaluating invasive breast carcinomas in the routine clinical setting.

Breast Neoplasms↗

ThinPrep Processor. Clinical trials demonstrate an increased detection rate of abnormal cervical cytologic specimens.

The authors compared the accuracy of conventionally prepared smears and smears prepared by an automated, fluid-based, thin-layer processing device in the detection of cytologic abnormalities. A total of 3218 patients from five centers took part in this study, in which a single cervical sample was split into a matched pair. The conventional smear was made in the routine fashion; the remainder of the cells on the sampling device were rinsed into a transport-fixation fluid. A slide was then prepared from the solution using the thin-layer processor. Diagnostic findings identified on the two preparations were compared in a blinded fashion, and a discrepancy resolution procedure was used to eliminate screening differences. Overall, there was a high correlation in the diagnoses of the two methods. For low-grade or more severe disease, the thin-layer method resulted in a 13% increase in the rate of detection, as compared with the conventional Papanicolaou smear technique.

Cell Biology↗

Late solitary cerebral metastases from renal cell carcinoma: report of two cases.

We report two cases of solitary cerebral metastases from renal cell carcinoma 15 and 18 years after nephrectomy. In a review of the literature, only two cases of solitary brain metastasis from renal cell carcinoma with latency periods greater than 10 years have been documented. Our two cases represent the longest latency periods reported between nephrectomy and detection of a solitary cerebral metastasis. Histologic examination and immunohistochemical profile of the primary renal tumors and metastatic cranial tumors showed identical morphology and immunophenotype.

Aged↗

The relationship of obesity to the frequency of pelvic examinations: do physician and patient attitudes make a difference?

Obese women are at higher risk for the development of both endometrial and ovarian carcinoma. Biochemical mechanisms represent documented causal factors but the role of psycho-social attitudes has received limited attention. This study examined the difference in the frequency of pelvic screening examinations between obese and non-obese women and the effect of physician and patient attitudes toward obesity on examination frequency. A total of 291 women subjects and 1316 physician subjects participated in this study. Data reported in this paper suggest that attitudes and behaviors are negatively influenced by weight. As subjects' weight went up, negative opinions about their appearance and reluctance to obtain pelvic examinations also increased while the likelihood of having annual pelvic examinations decreased. A substantial minority (17%) and an overwhelming majority (83%) of physicians indicated they were reluctant to perform pelvic examinations on obese and reluctant patients respectively. If physicians are more reluctant to perform pelvic examinations on obese and reluctant women and obese women are more reluctant to be examined, there may be a critical delay in detecting adenocarcinomas of the female genital tract.

Adult↗

Estrogen and progesterone receptor and c-erbB-2 oncoprotein analysis in pure in situ breast carcinoma: an immunohistochemical study.

The authors studied 30 consecutive archival cases of pure breast carcinoma in situ (CIS) for estrogen receptor (ER), progesterone receptor (PR), and c-erbB-2 oncogene product. Clinical factors of age and menstrual status and histologic features of tumor type and nuclear grade were determined. Some 77% represented ductal CIS, with 10% noninvasive papillary, and 13% lobular CIS. A total of 22 of 30 (73%) were ER+ and 19 (63%) were PR+; 24 (80%) were c-erbB-2+ with 11 (37%) showing strong staining; 75% of the ER-PR group had tumors of NG 3, versus 14% for the ER+PR+ plus ER+PR- groups. Nonstatistically significant trends correlating the strongly positive oncogene group with PM status, receptor negativity, and high nuclear grade were noted. The overall rate of receptor positivity, as well as the correlation with nuclear grade, is similar to that in invasive carcinomas c-erbB-2 protein expression shows a higher rate in in situ than is reported for invasive tumors, and shows a tendency to be expressed more strongly in tumors with other features of poor prognosis. Therefore, these factors may also have prognostic significance in CIS. Continued followup of this population to recurrence may provide further insight.

Adult↗

Estrogen and progesterone receptor detection in archival formalin-fixed, paraffin-embedded tissue from breast carcinoma: a comparison of immunohistochemistry with the dextran-coated charcoal assay.

The steroid receptor (estrogen (ER) and progesterone receptor (PR] status was studied in 94 cases of invasive breast carcinoma from three separate institutions. All cases had fresh tissue examined for ER and PR by the dextran-coated charcoal cytosolic assay (DCC), and each case was examined immunohistochemically for ER and PR from archival formalin-fixed, paraffin-embedded tissue. Immunohistochemical assays (IH) were reviewed blinded to the DCC results and scored in a semiquantitative fashion prior to comparison to the DCC results. Overall, there was agreement between DCC and IH in 89% of ER and in 87% of PR assays. Some 50% of the ER discorrelations were of the IH-positive DCC-negative type, while 27% of the PR discorrelations were of this type. In four cases, both ER and PR did not correlate between IH and DCC determinations, with two being IH (ER and PR) positive and DCC negative, and two of the opposite type. The results of the study show that steroid receptor assays performed on routinely processed formalin-fixed archival material are reliable and closely recapitulate the results of traditional biochemical assays. Results suggest that, in the cases where IH is positive while DCC is negative, the IH result may actually provide a more reliable receptor status of the tumor than does the DCC result. Semiquantitation of fixed tissue IH assays shows a trend toward quantitative correlation with DCC results, but this correlation is weak, and factors concerning fixation and processing are most likely to be responsible.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗

DNA ploidy in breast lesions. A comparative study using two commercial image analysis systems and flow cytometry.

DNA ploidy determinations on a series of 24 breast specimens were performed independently utilizing flow cytometry (FCM) and two separate commercially available computerized image analysis systems for image cytometry (ICM). The tissues analyzed were obtained from 20 carcinomas, 2 benign neoplasms and 2 benign reductive procedures. The results showed a close correlation between the DNA indices (DIs) obtained by all methods in 14 of the 24 cases. In four cases, all methods showed aneuploid peaks, but with differing DIs. In six cases (two benign and four malignant) FCM showed diploidy while ICM showed peridiploid cell populations. The results obtained with the two image analysis systems were in agreement for 20 of the 24 cases. ICM is an acceptable alternative to FCM for reproducible ploidy analysis. ICM-based measurements have the advantage of the visual discrimination of abnormal cells and therefore may have a greater sensitivity in identifying small aneuploid populations. Populations with DIs in the range of 1.0 to 1.3 need to be assessed carefully in ICM-based determinations due to the potential that these "aneuploid" peaks may represent shifted diploid populations.

Breast Diseases↗

Epithelial differentiation in meningiomas. An immunohistochemical, histochemical, and ultrastructural study--with review of the literature.

Meningiomas possess features indicative of epithelial differentiation. The present study further documents this finding by a multimodality approach on serial sections from 25 meningiomas of all histologic and clinical categories. Standard light microscopic examination, immunohistochemical staining with a variety of epithelial and nonepithelial markers, and histochemical staining for mucin were performed on each case. Directed electron microscopic examination was performed on selected examples of epithelial feature-positive and -negative cases. All cases were immunoreactive for vimentin and epithelial membrane antigen. Thirty-two percent were reactive for cytokeratin and 39% for S-100. Twenty percent showed mucin positivity by histochemistry. Electron microscopic examination of cytokeratin-positive cases showed either intracellular lumina (secretory areas) or cytoplasmic tonofibrils, whereas cytokeratin-negative tumors lacked lumina and tonofibrils. Previous studies showing epithelial features in meningiomas are reviewed with emphasis on the studies using immunohistochemistry. These histochemical, immunohistochemical, and ultrastructural characteristics are of utility in the examination of tumors of suspected meningeal origin, particularly when dealing with atypical presentations or histomorphologic features.

Antigens, Neoplasm↗

Quality control in immunohistochemistry. Report of a workshop sponsored by the Biological Stain Commission.

Although immunohistochemical methods are increasingly applied in diagnostic histopathology, there has been little standardization or quality control of immunoreagents; and published reports have not standardized Material and Methods for meaningful comparisons of results among clinicians. The Biological Stain Commission-sponsored workshop was convened to address the following issues: a manufacturers' testing program for probity of commercial antibodies, development of a manual for performance criteria and quality control assurance procedures, standardization of package inserts, standardization of information provided in the Materials and Methods sections of publications, establishment of a reagent and procedure clearing house, study of the effects of different fixation regimes on tissue antigens, and investigation of the environmental conditions needed for antigen-antibody interaction. The recommendations of the ad hoc committee and their implications for the future are discussed.

Antigen-Antibody Complex↗

Detection of infection by human papillomavirus in genital condylomata. A comparison study using immunocytochemistry and in situ nucleic acid hybridization.

One hundred eighty exophytic genital lesions clinically suspicious for infection by human papillomavirus (HPV) were analyzed by hematoxylin and eosin light microscopy, immunocytochemistry for HPV capsid antigen; and in situ nucleic acid hybridization for HPV messenger RNA (mRNA). Of 96 cases morphologically consistent with infection by HPV, 53% were antigen-positive, and 83% were mRNA positive (P less than 0.01). Of 55 cases suggestive but not diagnostic of HPV infection, 13% were antigen-positive and 26% were mRNA positive. Negative results were obtained in all lesions not believed to be indicative of HPV infection by morphologic criteria. In mRNA positive diagnostic cases, two thirds were of HPV type 6 and one third were HPV type 11. Two cases of coinfection with HPV types 6 and 16 were found. The study concludes that in situ hybridization for HPV mRNA is a more sensitive indicator of HPV infection, and in addition, provides HPV type, which may have prognostic significance.

Antigens, Viral↗

Continuity of human papillomavirus (HPV) type between neoplastic precursors and invasive cervical carcinoma. An in situ hybridization study.

Infection by the human papillomaviruses (HPV) represents an important risk factor in squamous lesions of various sites. More recently, data suggest that the glandular components of some tumors may also contain human papillomaviruses. This association may implicate HPVs in the genesis of these lesions as well. We present a longitudinal in situ hybridization study of HPV expression within a single patient, showing viral mRNA in squamous dysplasia, squamous and adenocarcinoma in situ, and in invasive adenosquamous carcinoma. There was continuity of the viral type (HPV 16) in the preinvasive and invasive portions of the lesions, and HPV mRNA was clearly demonstrable in the glandular components. The case illustrates the utility of in situ hybridization for the microscopic localization of viral gene expression, in addition to providing information about the viral type and perhaps the biologic potential of the lesion.

Adenocarcinoma↗

ASCUS and AGUS criteria. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: The conference participants addressed the following issues: (1) reporting of equivocal diagnoses, (2) strategies to minimize the use of such diagnoses, (3) morphologic criteria, and (4) management of women with equivocal diagnoses. CONSENSUS POSITION: Equivocal diagnoses should be minimized, to the extent possible, by emphasizing cytologist education and training, improved specimen collection and quality assurance monitoring of individual and laboratory diagnosis rates. Cases fulfilling criteria for other diagnostic entities should not be included in the equivocal category. Regardless of the term utilized, an equivocal diagnosis should be qualified in some manner to indicate that the diagnosis defines a patient at increased risk of a lesion, particularly for those cases which raise concern about a possible high grade lesion. Qualification of an equivocal diagnosis can also be accomplished by appending laboratory statistics of the likelihood of various clinical outcomes or recommendations for patient follow-up. In contrast to favoring a reactive process versus squamous intraepithelial lesion (SIL), a more rationale approach to qualification of atypical squamous cells of undetermined significance may be to separate cases equivocal for low grade SIL from those suspicious for high grade SIL. With regard to glandular lesions, the conference participants expressed unanimous support for the separation of adenocarcinoma in situ (AIS) from atypical endocervical cells of undetermined significance when sufficient criteria are present. However, the diagnosis of a precursor lesion to AIS, endocervical glandular dysplasia, was controversial. The majority of conference participants discourage the use of such terms as mild glandular dysplasia and low grade glandular dysplasia for cytologic diagnoses. ONGOING ISSUES: Conference participants agreed that a term reflecting diagnostic uncertainty is necessary to communicate findings that are equivocal. However, participants could not agree on the wording of such a term. Opinions differed as to: (1) use of atypical, abnormal or morphologic changes to describe cell changes, (2) whether the diagnosis should indicate a squamous or glandular origin of the cells in question when this determination can be made, and (3) the value of defining morphologic criteria for such a diagnosis. The debate over terminology, as well as morphologic criteria, is ongoing, and the readership is invited to communicate opinions to Acta Cytologica. Management of women with equivocal diagnoses varies widely from locale to locale and may differ based on how the equivocal diagnosis is qualified. Findings insufficient for the diagnosis of a high grade lesion may warrant more aggressive follow-up than cases equivocal for a low grade lesion. Where sensitivity of detection of lesions is of paramount importance, follow-up will generally consist of more frequent cytology screening or colposcopy and biopsy. However, in some countries it is considered unethical to have a high percentage of false positive diagnoses, which result in overtreatment and an unnecessary burden for women participating in cervical screening. Future studies may provide a morphologic, or perhaps molecular, basis for distinguishing true precursors of neoplasia from minor lesions of no significant clinical import; this would allow a more coherent and rational approach to diagnosis and management of women with equivocal cytologic findings.

Adenocarcinoma↗

Cell preparation methods and criteria for sample adequacy. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Cell Preparation Methods Standardized fixation and optimal staining Sampling of cervix, sampling error, homogenization of sample, subsampling Assessment of liquid-based preparations: efficacy and economic impact Training and transitional procedures before full implementation of new technologies Criteria for Sample Adequacy Clinician responsibility for collecting and providing representative sample to laboratory Collection instruments, number of slides Cellular content of samples: evidence of transformation zone (TZ) sampling, number of squamous cells present, obscuring factors Screening issues CONSENSUS POSITION The conventional cervical smear remains the standard method of cervical cancer screening but has limitations in individual test sensitivity and specificity. Sample takers should: (1) receive appropriate training in sample collection, (2) be held responsible for providing the laboratory with appropriate samples, and (3) have their performance monitored. The instruments used for sampling should collect cells from both the ectocervix and endocervix; optimally, TZ sampling, represented by the presence of endocervical or squamous metaplastic cells, should be identifiable in samples other than atrophic specimens. The adequacy of a specimen (as judged microscopically) does not guarantee that it is representative of the cervix. Each cytology report should include a comment on cellular content/adequacy of the specimen. Liquid-based preparations may overcome many of the inherent problems with the conventional cervical smear. ONGOING ISSUES: We need further data on the cost-effectiveness of making two slides from cervical specimens and/or using two samplers rather than a single one. Do we have enough information to make recommendations as to the appropriate type of sampler to be used in particular situations, such as routine screening? What is the best method of screening for/detecting endocervical glandular neoplasia? How are such terms as unsatisfactory and inadequate defined in cervical cytology classifications other than the Bethesda System? What number and types of epithelial cells should be present (visualized) in a cervical smear or liquid-based preparation for it to be considered adequate? Do we need to have evidence of TZ sampling in specimens taken during the follow-up period after treatment of squamous intraepithelial lesion or after detection of endocervical glandular neoplasia? What criteria for obscuring factors, such as blood and inflammation, should be used in assessing adequacy? Cost-benefit analyses of utilizing liquid-based preparations are needed. Should we inform women about the technical details of the test methods available or chosen by the laboratory? Are women in a position to decide which method is the most appropriate to assess their cervical scrape sample? We need to obtain more information about the properties of proprietary liquid fixative/transport media with respect to inactivation of viral pathogens, tuberculosis and other bacterial pathogens and suitability for immunobiologic and molecular tests, etc. We need to obtain more information on the use of stoichiometric stains and the limitations of Papanicolaou stain for image analysis systems. The use of liquid-based preparations for nongynecologic cytopathology and ancillary tests must be considered, including criteria for adequacy. We need to obtain more information on the time required for and best methods of training experienced cytotechnologists to become competent at assessing liquid-based cervical preparations.

Cell Biology↗