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PubMed1989

Coexistence of cytoplasmic and nuclear estrogen receptors. A histochemical study on human mammary cancer and rabbit uterus.

Consecutive serial cryostat-frozen sections of 157 human mammary carcinomas and the uteri of six immature New Zealand white rabbits were stained histochemically for cytoplasmic estrogen receptor (ER) and nuclear ER by a fluorescent estrogen compound (Fluorocep Estrogen, Zeus Technologies, Inc., Raritan, NJ) and by a monoclonal antibody immunoperoxidase technique (ER-ICA, Abbott Laboratories, North Chicago, IL), respectively. The percentage of the ER-positive cells in the cancer cell population under observation was estimated and recorded. The results of the cytoplasmic ER assay were compared with those of the nuclear ER assay in each tumor; all cancers with less than 10% ER-positive cancer cells were grouped together as ER-negative tumors, the cancers with 30% or more ER-positive cancer cells as ER-positive tumors, and those with 10% to 29% ER-positive cancer cells as borderline positive. According to this manner of classification, 94% to 97% of the ER-positive mammary carcinomas diagnosed by one histochemical assay would have been identified as such by the other with no more than 10% difference in the ER-positive cell counts. The majority of ER-positive breast cancer cells and practically all of the luminal lining cells of the immature rabbit endometrium had coexistent cytoplasmic and nuclear ER. In the mammary cancers containing less than 30% ER-positive cancer cells, there was a greater (up to 20%) discrepancy in positive cell counts between the cytoplasmic ER assay and the nuclear ER assay. This discrepancy may be due to sampling errors of small clones of ER-positive cancer cells in two adjacent sections, difference in antigenic determinants between the cytoplasmic and the nuclear ER, and the binding sites in the nuclear ER being preoccupied by estrogen. The findings of this study appear to support the hypothesis that there are ER in the cytoplasm and the nucleus of the mammary carcinoma cells and the epithelial cells of the endometrium.

Adult↗
PubMed1993

Dedifferentiation of locally recurrent prostate cancer after radiation therapy. Evidence for tumor progression.

BACKGROUND: Untreated or unsuccessfully treated prostatic adenocarcinoma may develop more malignant characteristics as time passes--the phenomenon of tumor progression. Whether this occurs after unsuccessful radiation therapy has not been answered. This study was designed to address that issue. METHODS: The histologic grades at initial diagnosis and at local recurrence were compared in 49 patients who experienced local recurrence after external beam radiation therapy. RESULTS: Tumor grades were assigned using the M. D. Anderson grading system. At the initial diagnosis, the grades were distributed as follows: Grade 1, 18 (37%), Grade 2, 22 (45%); Grade 3, 8 (16%); and Grade 4, 1 (2%). At recurrence, the grades were: Grade 1, 3 (6%); Grade 2, 14 (29%); Grade 3, 14 (29%); and Grade 4, 18 (37%). The shift to higher grades at recurrence was highly significant (P < 0.001). This dedifferentiation could not be accounted for by possible tissue sampling variability, and stepwise multiple variable logistic regression revealed that the only factor predicting for dedifferentiation was the time since treatment. The tumors that recurred later had a significantly higher likelihood to be dedifferentiated than those that recurred early. Patients whose tumors dedifferentiated had a poorer survival than those whose tumors retained their original grade. CONCLUSIONS: The possibilities were considered that the dedifferentiation could arise by tissue sampling error, by persistence and regrowth of high-grade components, by the development of new tumors, or by radiation-induced transformation. None of these mechanisms appeared to explain the data adequately, and it was concluded that the observed dedifferentiation was indeed a manifestation of time-dependent tumor progression. Eradication of the primary tumor is therefore important, not only to allay local symptoms, but also to prevent the emergence of more virulent and potentially lethal tumors.

Aged↗
PubMed1993

Cervical cytopathology. An evaluation of its accuracy based on cytohistologic comparison.

BACKGROUND: Although Papanicolaou cytology represents the most effective technique to prevent and detect precancerous conditions of the uterine cervix, its false-negative yield is still a reason of concern among pathologists and gynecologists. METHODS: Because histologic control is one of the best ways to assess the accuracy of cytology diagnosis, the authors have investigated 1000 women who had cervical smears and tissue sampling obtained during the same colposcopic evaluation between 1987 and 1990. RESULTS: Out of 1000 cases (average age, 34.6 years; range, 14-80 years), 918 had adequate, 62 had less than optimal, and 10 had unsatisfactory samples. Cytology unsatisfactory and less than optimal cases as well as inadequate histology cases have been disregarded from all calculations. After histologic comparison, confirmed negatives were 622 of 918 (67.8%). Cytologic diagnoses of cervical intra-epithelial neoplasia (CIN) I were 96, of CIN II were 44, of CIN III, inclusive of carcinoma in situ, were 39, and of invasive carcinoma were 2. Atypical cases were 56. The overall sensitivity was 76.3%, with group sensitivity rates increasing directly with CIN grade. Positive predictive value was 80.2%. Specificity was 93.0%, and negative predictive value was 91.3%. False-negatives were 59 of 681 (8.7%), basically due to sampling errors. Among true-positives, there was 1 category discrepancy in 30 cases (mostly undercalled or overcalled CIN II) and 2 category discrepancies in 4 cases. CONCLUSIONS: Cervical cytology has an overall accuracy close to that reported in studies employing indirect control methods, such as patient follow-up. Higher sensitivity rates emerged for CIN II, CIN III, and cervical carcinoma. Our figures of sensitivity and specificity may represent a useful reference source for future studies dealing with quality control in cervical cytopathology.

Adolescent↗
PubMed2001

Fine-needle aspiration cytology of Hodgkin disease: a study of 89 cases with emphasis on false-negative cases.

UNLABELLED: INTRODUCTION. Although the cytologic features of Hodgkin disease (HD) has been well described, HD accounts for most of the false-negative fine-needle aspiration (FNA) biopsies of malignant lymphomas. In this study, the authors examined the factors contributing to a false-negative diagnosis of HD. METHODS: Eighty-nine cases from 72 patients (23 females and 49 males) with HD evaluated by FNA were identified between 1990 and 1999. The patients' ages ranged from 5 to 90 years (median, 38 years). Eighty-five FNAs were from lymph nodes, and 4 were from extranodal sites. Histologic correlation was available for all patients. RESULTS: Based on the original cytologic diagnosis, 43 (48.3%) cases had a positive diagnosis of HD, 20 (22.5%) suspicious or atypical diagnosis, 13 (14.6%) a benign diagnosis (false-negative cases), and 10 (11.2%) were nondiagnostic. Three (3.4%) additional cases had a malignant diagnosis other than HD. After review, three false-negative cases were reclassified as HD and seven as atypical lymphoid proliferation. Three of these 10 cases also showed conspicuous collections of histiocytes mimicking poorly formed granulomas. In those "atypical" cases, only rare Reed-Sternberg (R-S) cells variants were identified. No R-S cells or its variants were identified in the remaining three false-negative cases; subsequent excisional biopsy showed partial involvement of the lymph node by HD in two cases. Among the nondiagnostic cases, nine cases showed considerable fibrosis in the resected lymph node. In addition, six cases were performed without on-site assessment. CONCLUSIONS: The cytologic diagnosis of HD can be challenging when classic R-S cells are absent. Contributing factors for a false-negative diagnosis include obscuring reactive inflammatory cells, fibrosis of the involved lymph nodes, partial involvement of the lymph node by HD, sampling error, and misinterpretation. On-site assessment significantly minimizes the false-negative diagnostic rate. Furthermore, additional material can be obtained for ancillary studies. Cancer (Cancer Cytopathol)

Adolescent↗
PubMed2001

Family and parenting interventions in children and adolescents with conduct disorder and delinquency aged 10-17.

BACKGROUND: Conduct disorder and delinquency are significant problems for children and adolescents and their families, with the potential to consume much of the resources of the health, social care and juvenile justice systems. A number of family and parenting interventions have been recommended and are used for these conditions. The aim of this review was to determine if these interventions are effective in the management of conduct disorder and delinquency in children and adolescents, aged 10-17. OBJECTIVES: To determine if family and parenting interventions improve the child/adolescent's behaviour; parenting and parental mental health; family functioning and relations; and have an effect on the long term psychosocial outcomes for the child/adolescent. SEARCH STRATEGY: Randomised controlled trials were identified through searching the Cochrane Controlled Trial Register (CCTR), databases (MEDLINE, EMBASE, PsycINFO, CINAHL, Sociofile, ERIC, Healthstar), reference lists of articles and contact with authors. SELECTION CRITERIA: Randomised controlled trials with a major focus on parenting and/or family functioning were eligible for inclusion in the review. Trials needed to include at least one objective outcome measure (e.g. arrest rates) or have used a measure that had been published in peer review publications and validated for the relevant purpose. Studies were required to have a control group, which could be a no intervention group, a wait list group or a usual intervention group (e.g. probation). Trials in children and adolescents aged 10 to 17 years with conduct disorder and/or delinquency and their families were considered. Conduct disorder was defined by a standardised psychological assessment (for example, using a child behaviour checklist), or a psychiatric diagnosis. Delinquency was defined by a referral from a juvenile justice or another legal system for a child/adolescent who has committed a serious crime e.g assault and/or offended on at least two occasions. DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed all eligible studies for inclusion, assessed study quality (allocation concealment, blinding, follow up, clinically important outcomes) and extracted data. Heterogeneity was assessed using the Chi squared test of heterogeneity along with visual inspection of the data. A significance level less than 0.1 was interpreted as evidence of statistically significant heterogeneity. For data where heterogeneity was found the reviewers looked for an explanation. If studies with heterogeneous results were thought to be comparable the statistical synthesis of the results was done using a random effects model. This model takes into account within-study sampling error and between-studies variation in the assessment of uncertainty and will give wider confidence intervals to the effect size and hence a more conservative result. Sensitivity analysis was performed to explore the effects of the varying quality of the studies included on the results. MAIN RESULTS: Of the nine hundred and seventy titles initially identified through the search strategy, eight trials met the inclusion criteria. A total of 749 children and their families were randomised to receive a family and parenting intervention or to be in a control group. In seven of these studies the participants were juvenile delinquents and their families and in only one the participants were children/adolescents with conduct disorder who had not yet had contact with the juvenile justice system. At follow up, family and parenting interventions significantly reduced the time spent by juvenile delinquents in institutions (WMD 51.34 days, 95%CI 72.52 to 30.16). There was also a significant reduction in the risk of a juvenile delinquent being re arrested (RR 0.66, 95%CI 0.44 to 0.98) and in their rate of subsequent arrests at 1-3 years (SMD -0.56, 95% CI -1.100 to - 0.03). For both of these outcomes there was substantial heterogeneity in the results suggesting a need for caution in interpretation. At present there is insufficient evidence that family and parenting interventions reduce the risk of being incarcerated (RR=0.50, 95% CI 0.20 to 1.21). No significant difference was found for psychosocial outcomes such as family functioning, and child/adolescent behaviour. REVIEWER'S CONCLUSIONS: The evidence suggests that family and parenting interventions for juvenile delinquents and their families have beneficial effects on reducing time spent in institutions. This has an obvious benefit to the participant and their family and may result in a cost saving for society. These interventions may also reduce rates of subsequent arrest but at present these results need to be interpreted with caution due to the heterogeneity of the results.

Adolescent↗
PubMed2004

Radiotherapy for neovascular age-related macular degeneration.

BACKGROUND: Radiotherapy has been proposed as a treatment to prevent new vessel growth in people with neovascular age-related macular degeneration (AMD). OBJECTIVES: The aim of this review was to examine the effects of radiotherapy on neovascular AMD. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group trials register) on The Cochrane Library Issue 2, 2004, MEDLINE (1966 to May 2004), EMBASE (1980 to June 2004) and LILACS (Latin American and Caribbean Health Sciences Literature Database) (May 2004). We also wrote to investigators of trials included in the review to ask if they were aware of any other studies. SELECTION CRITERIA: We included all randomised controlled trials in which radiotherapy was compared to another treatment, sham treatment, low dosage irradiation or no treatment in people with subfoveal choroidal neovascularisation secondary to AMD. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted the data. Relative risks were combined using a random effects model. The percentage of the variability in effect estimates that was due to heterogeneity, rather than sampling error, was estimated using I2. MAIN RESULTS: Eleven trials randomising a total of 1078 people were included in this review. All trials used a similar method of delivering the radiotherapy treatment (external beam). Dosage ranged from 7.5 to 24 Gy. Most trials found effects (not always significant) that favoured treatment. However, there was considerable inconsistency in the results between trials (I2 > 50%). As only 11 trials were included in the review and only some of these trials provided data for each outcome our ability to determine the causes of the heterogeneity between trials was limited. Subgroup analyses did not reveal any statistically significant interactions although with small numbers of trials in each subgroup (range two to four) this was not surprising. There was some indication that trials with no sham irradiation reported a greater effect of treatment as did trials with a greater percentage of participants with classic choroidal neovascularisation. REVIEWERS' CONCLUSIONS: This review currently does not provide evidence that external beam radiotherapy is an effective treatment for neovascular AMD. If further trials are to be considered to evaluate radiotherapy in AMD then adequate masking of the control group must be considered. Given the recent evidence that most lesions are amenable to treatment with photodynamic therapy if identified at a small lesion size, trials evaluating radiotherapy against photodynamic therapy are warranted.

Eye↗
PubMed1991

Alcohol, smoking, and occupational factors in cancer of the larynx: a case-control study.

A hospital-based case-control study of laryngeal cancer was conducted in Bremen in 1986 and 1987 with 100 prevalent male laryngeal cancer patients and 100 male hospital controls with diseases not considered to be related to smoking, alcohol, or occupational exposures, who were frequency matched by age. The odds ratio for heavy smoking (more than 30 pack-years) reached a value of 3.5 (95% confidence limits (CL) 1.1, 7.9). Ex-smokers showed a significant decrease in risk; this reached the level of those who had never smoked about 15 years after smoking cessation. For daily consumers of alcohol an odds ratio of 3.2 (95% CL 1.4, 7.5) was observed. Among the 17 occupations in which at least ten subjects had worked, excess risks were observed for stock keeping and transportation workers, and for leather and textile workers. The odds ratio was significantly increased for the latter (p less than 0.05). Among all those persons ever employed in a priori defined-risk occupations, an odds ratio of 2.74 (95% CL 1.23, 6.06) was observed. Considering responses to an exposure check-list, no increased risks could be shown for exposure to asbestos, coal tar, or welding fumes. On the other hand, excess risks were observed for exposures to diesel oil, gasoline, and mineral oil, controlling for smoking and alcohol. The findings in occupational and exposure subgroups were based on small numbers of cases and controls and, consequently, were subject to large sampling errors. Many of the results are consistent, however, with occupational risk factors reported from other studies.

Adult↗
PubMed2002

Unique case of mosaicism involving two morphologically similar marker chromosomes of different centric origin in a patient with developmental delay.

A five-year-old Caucasian male presented with developmental delay, minor dysmorphic features, and hyperactivity. Cytogenetic analysis showed the presence of a marker chromosome in the majority of cells analyzed. Fluorescence in situ hybridization (FISH) analyses using several alpha satellite probes, including D13Z1/D21Z1, did not reveal any signal on the marker chromosome. Subsequent multicolor FISH (M-FISH) indicated the marker to be derived from chromosome 13, and FISH with a chromosome 13 paint confirmed this finding. The absence of D13Z1/D21Z1 signal on the marker suggested that it was analphoid in nature. Comparative genomic hybridization (CGH) was utilized to further characterize the region of chromosome 13 from which the marker originated, and unexpectedly revealed a gain of chromosomal material at both the centromeric regions of chromosomes 3 and 13. In view of the CGH results, extensive FISH studies with D3Z1 and D13Z1/D21Z1 were performed and revealed the presence of four cell lines comprising one normal cell line (50.5%), a cell line with a chromosome 3 derived marker (19%), a cell line containing a marker derived from chromosome 13 (20%), and a cell line with both markers (10.5%). As the two markers appeared morphologically similar by GTG banding, all 47,XY metaphases in the initial analysis were thought to comprise only a single marker. This is the first report, to our knowledge, of the presence of a chromosome 3 and a chromosome 13 marker in mosaic condition in a congenital disorder. In light of our experience, we urge caution in interpreting karyotypes with marker chromosomes. Our case illustrates the limitations of fluorescent DNA probes and sampling errors.

Child, Preschool↗
PubMed1995

Association and linkage studies of the TAQI A1 allele at the dopamine D2 receptor gene in samples of female and male alcoholics.

To address the controversy surrounding DRD2 and alcoholism, we performed linkage and association studies utilizing alcoholic men from high-density families largely uncontaminated by other psychopathology and female alcoholics for whom secondary drug dependence (averaging 10 years later onset) was a prominent feature. The males and females were combined for a total of 52 alcoholics, and compared to 30 controls screened for the absence of alcoholism and other psychopathology, revealing a significant association between the frequency of the TaqI A1 allele and alcoholism. However, linkage and family-based association studies conducted on 20 families of male alcoholics found no evidence for association or linkage between Taq A and alcoholism. The results of our population-based association study, placed in the context of the literature, suggest that minimizing psychopathology in control groups is probably a more important explanation for divergent results than either sampling error or population stratification. When combined with the complete lack of within-family evidence, we concluded that the association, while not appearing to be artifactual, is not specific to the alcoholism phenotype, per se.

Alcoholism↗
PubMed1978

Population structure and genetic heterogeneity in the Upper Markham Valley of New Guinea.

An analysis is presented of the standardized Wahlund's variances (f) in gene frequencies of the ABO, Rh and MNS blood group systems among 19 villages of the Atsera isolate of the upper Markham Valley, Papua New Guinea. In the past, there has been some disagreement over the relative importance of population structure and natural selection in the determination of these variances. The Lewontin-Krakauer test is presented as a means of resolving this disagreement. According to this test, selectively neutral variation in gene frequencies should generate essentially homogeneous values of f for all loci, a homogeneity which can be tested by comparing the value of (formula: see text) to a theoretical (formula: see text) expected when variations in (formula: see text) are due solely to sampling error. The observed value of (formula: see text) for the Atsera isolate is 2.9 x 10(-5), which is not significantly different from the expected values that range from 1.23 x 10(-5) to 2.46 x 10(-5) depending on the constant used in calculating (formula: see text). Therefore it appears that nonselective aspects of population structure such as genetic drift and intervillage migration are responsible for the recorded genetic variation in this isolate.

ABO Blood-Group System↗
PubMed1985

A revised method of age determination using the os pubis, with a review and tests of accuracy of other current methods of pubic symphyseal aging.

All current standardized methods of age determination using the os pubis were tested by blind assessment of a skeletal sample with documented ages (from the Todd collection; N = 96). No demographic data (sex, age, race, age composition) were known to the assessors prior to completion of the test. Results showed the Todd method to be more reliable than more recent component techniques and that all systems tended to underage. Therefore, modifications were made of the Todd system to eliminate this and other deficiencies, and a second test using a new sample was conducted (N = 109). The age distribution determined by the revised Todd method did not significantly differ from the actual age distribution of the second sample. Error due to race was nonsignificant. Biological stages of pubic metamorphosis are described and possible evolutionary specializations of the hominid symphysis are discussed. Revised standards for age determination are presented.

Adult↗
PubMed2002

Trust, but verify: the necessity of empirical verification in quantitative neurobiology.

The preferred procedure for estimating neuron number has been the subject of intense discussion. Sampling error, systematic bias, and the physical properties of the tissue examined all contribute to the possibility that estimates may not reflect actual neuron number. Even when restricting analysis to a particular, well-defined structure such as dorsal root ganglia, these factors act in a manner that varies with maturity of the animal, species, fixation, processing, and neuron size. These considerations reinforce the necessity of comparing estimates with the actual number of neurons as determined by three-dimensional reconstructions.

Animals↗
PubMed1975

The place of frozen section in the practical management of melanoma.

A selective policy is proposed for the use of frozen section in suspected melanoma which provides maximal help while minimizing false frozen section diagnosis. It is based on the fact that suspected melanomas fall into two broad groups which present different problems in diagnosis and management. A raised lesion is likely to be a highly malignant melanoma or a lesion of non-naevoid cells. Differentiation is readily made on frozen section and allows immediate radical excision. A flat pigmented lesion is usually of obvious naevoid origin, and the problem is whether early malignant change has occurred. It is better managed by urgent paraffin section to avoid sampling error. Frozen section has a place in the management of a single doubtful node in a patient being managed by a 'watch' policy.

Biopsy↗
PubMed1981

Biochemical measurements of endomyocardial biopsies.

The purpose of this study is to investigate the validity of performing biochemical analyses on human endomyocardial biopsies. One problem of such analyses is the decay of metabolites between the time of biopsy and the analyses. This was addressed by varying the time delay from biopsy to submersion in liquid nitrogen (-200 degree C). Neither cyclic AMP or cyclic GMP changed significantly up to 90 seconds after biopsy. The reproducibility of the assays in human heart biopsies was determined by submitting paired samples from each procedure. The ATP content was determined by a fluorescent technique and was related to the protein and creatine content. The average ATP of 25 paired samples was 12.3 nm per mg protein; the average difference between the paired samples was -0.6, and the 95% confidence interval was 5.6 nm/mg protein. The average ATP-to-creatine ratio was 0.25; the 95% confidence interval was 0.12. The cyclic AMP and cyclic GMP were found to average 3.3 and 0.25 femtomoles/mcg protein, respectively. The 95% confidence intervals were 1.8 and 0.12 fmoles/mcg protein. The problems of sampling error and blood and connective tissue contamination decrease the reliability of the biochemical analyses. Reproducibility is adequate, however, to acquire meaningful biochemical information on the human heart.

Adenosine Triphosphate↗
PubMed1990

Myocarditis: unresolved issues in diagnosis and treatment.

Myocarditis is an enigmatic disease. Lymphocytic myocarditis is most commonly viral in origin. Considerable evidence suggests that myocardial damage is due to an immune-mediated mechanism rather than to direct effects of the virus itself. The presentation is variable, ranging from a clinically inapparent or relatively benign illness to acute progressive heart failure and death. Although examination of the endomyocardial biopsy specimen is the "gold standard" for the diagnosis of myocarditis there are problems with this technique, relating particularly to sampling error and histologic interpretation. Considerable evidence, both animal and human, suggests that a link between viral myocarditis and dilated cardiomyopathy does exist. There is a rational basis for the use of immunosuppressive therapy in myocarditis. Although many favorable responses have been reported with the use of these agents, the results of more definitive studies are awaited to determine the role of immunosuppressive therapy in myocarditis more clearly. Recommendations for the practical management of patients with myocarditis are made. Whenever possible, patients with this diagnosis should be entered into the ongoing NIH trial.

Animals↗
PubMed2002

Cervical smear interpretations in women with a histologic diagnosis of severe dysplasia: factors associated with discrepant interpretations.

BACKGROUND: Because most low-grade squamous intraepithelial lesions (LSIL) regress spontaneously, the appropriate follow-up of women with a cytologic diagnosis of LSIL has engendered discussion. This retrospective study was undertaken to assess the feasibility of limiting colposcopy to women with cytologic interpretations of high-grade squamous intraepithelial lesions (HSIL) in a high-risk population. METHODS: The pathology computer files (including files from January to December 1997) of The University Hospital, University of Oklahoma Health Sciences Center, revealed 197 women whose histologic samples were coded as severe dysplasia. Of these, 138 had a cervical smear interpreted in our laboratory before the colposcopic visit. On review, the tissue samples of 119 women met consensus criteria for severe dysplasia. RESULTS: Original cytologic diagnoses for 119 cytologic smears included 80 (62.7%) that were interpreted as HSIL. After retrospective review, 28 cases with LSIL or less were reclassified as HSIL and were considered to be discrepant for the purpose of this study. Major confounding factors in the original categorization include lack of consistency among the pathologists for the interpretation of metaplastic patterns and specimen adequacy, particularly air-drying artifact. Eleven cases (10.2%) did not have cells identifiable as HSIL because of sampling error and/or severe air-drying artifact. CONCLUSIONS: These results indicate that a substantial number of histologically verified cases of severe dysplasia can have a smear interpretation of LSIL or less. The factors that hampered recognition of the true severity of the lesion in this series were identified and tabulated.

Adolescent↗
PubMed2001

The spectrum of cytologic features in nonproliferative breast lesions.

BACKGROUND: The reliability of cytologic criteria to classify nonproliferative breast lesions (NPBL) is still debated. Sampling error and heterogeneity of breast lesions complicates the histologic correlation of fine-needle aspiration results further. METHODS: To provide optimal cytohistologic correlation, two smears (one that was stained with hematoxylin and eosin and one that was stained with Diff-Quik [American Scientific Products, McGraw Park, IL]) were prepared from specific tissue sections from breast biopsies without mass lesions. The 42 cases classified as NPBL histologically were included in the current study. The cytologic features of the smears were evaluated. RESULTS: Cellularity ranged from low (40% of cases) to moderate (50% of cases) to high (7% of cases). The cells were arranged in small clusters in 79% of cases, were mixed with large sheets in 17% of cases, and were in large sheets in 2% of cases. Intact lobules were noted in 31%. The configuration of the epithelial groups was complex in 62% of cases. Myoepithelial cells in the background and within the epithelial groups were noted in all the specimens. The percentage of single epithelial cells was < 10 in 38% of cases, 10-20 in 41%, and 20-30 in 19%. Mild nuclear enlargement and overlap, micronucleoli, and mild chromatin clumping were noted in a significant number of cases. CONCLUSIONS: NPBL have been found to have a wide spectrum of cytologic appearances. At one end of the spectrum, smears are cellular with up to 30% single cells and large sheets in a complex configuration and exhibit nuclear enlargement and overlap and prominent nucleoli, features that overlap with those described in proliferative breast lesions.

Adult↗
PubMed2001

DNA image analysis combined with routine cytology improves diagnostic sensitivity of common bile duct brushing.

BACKGROUND: Cytologic evaluation of common bile duct brushings has a low sensitivity for diagnosing malignancy because of scant cellularity, poor cellular preservation, or sampling errors occur. The aim of this study was to evaluate whether cytology combined with image analysis improves the diagnostic accuracy of bile duct brushing in comparison with cytology alone. METHODS: Forty-nine specimens of bile duct brushings obtained from 45 patients during endoscopic retrograde cholangiopancreatography were evaluated using cytology and image analysis. Specimens were classified as negative, atypical, suspicious, or malignant by using cytologic evaluation. DNA histograms were classified as diploid (D), broad diploid (BD), aneuploid (A), or tetraploid (T). Degree of hyperploidy (DH), representing cells with a DNA content > 5C was evaluated using a cutoff value of > or = 1%. Final diagnosis of cancer was based on tissue specimens that were obtained by fine-needle aspiration or surgical biopsy and clinical fol- low-up. RESULTS: Thirty-four patients ultimately proved to have a malignancy. Cytology revealed 19 negative cases, 15 atypical cases, 9 suspicious cases, and 6 malignant cases. Together, suspicious and malignant cytology cases yielded a sensitivity of 44% and a specificity of 100% for a cytologic diagnosis of cancer. The DNA histogram pattern was D in 24 cases, BD in 9 cases, and A in 16 cases. BD and A patterns were significantly associated with malignancy (P < 0.001). A DH > or = 1% was noted in 22 cases. DH alone had a sensitivity of 62% and a specificity of 91% and was significantly associated with malignancy (P < 0.004). Atypical cytology alone had a false-negative rate of 29%, but in combination with a DH > or = 1%, the false-negative rate decreased to 7%. Additionally, when the authors combined atypical, suspicious, and malignant cytology with a DH > or = 1%, the diagnostic sensitivity increased to 88%, but the specificity decreased to 73%. CONCLUSIONS: Combined cytology and image analysis of bile duct brushing increased diagnostic sensitivity compared with cytology alone. The findings suggest that image analysis may help select patients having atypical cytology who should undergo a more rigorous evaluation for malignancy. A larger prospective study of the usefulness of combined cytology and image analysis of bile duct brushing is warranted.

Adult↗