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The reliability of staging and grading of bladder tumours. Impact of misinformation on the pathologist's diagnosis.

The influence of misinformation on the reliability of the histopathological classification of bladder tumours was analysed. Four consultant pathologists assessed 40 biopsy specimens of bladder tumours staging invasion and grading the specimens according to the Bergkvist classification. A random sample of 20 specimens was accompanied by systematically distorted information ("bias"-unknown to the pathologists) about previous histological grading of the patient (bias group); the other 20 specimens were used as control group (non bias group). After 6 months a second round with the same specimens was arranged to assess the influence of bias on the intraobserver variation. Using kappa (kappa) statistics the chance corrected interobserver agreement rate was poor both in staging of invasion and grading according to the Bergkvist classification (kappa < 0.50). The kappa values in the intraobserver study ranged from poor to excellent with a tendency towards lower kappa when the observer had been biased. The kappa values in the assessment of malignancy were acceptable to excellent. False information did not affect the pathologists' diagnosis significantly.

Biopsy↗

Molecular biology primer for the pediatric pathologist.

Recent advances in the knowledge of molecular events of cell growth and differentiation have provided considerable gains to the understanding of neoplasia. Along with this understanding, molecular biology has yielded many new techniques of great potential for diagnostic use. This review illustrates, in general terms, current models of gene regulation, intracellular signal transduction, and the regulation of cell division that are relevant to pediatric pathologists. These concepts are used to examine the molecular pathology of three pediatric tumors: retinoblastoma, Wilms' tumor, and neuroblastoma. In addition, molecular biology techniques potentially useful to pediatric pathologists are discussed, with examples of some possible applications of these techniques. Hopefully, this review portrays the relevance of molecular biology to pediatric pathologists and serves as a useful guide to the interpretation of the molecular pathology literature.

Base Sequence↗

Diagnostic uncertainty expressed in prostate needle biopsies. A College of American Pathologists Q-probes Study of 15,753 prostate needle biopsies in 332 institutions.

OBJECTIVE: To determine the rate of diagnostic uncertainty in rendering diagnoses on prostate needle biopsies and to examine pathology practice variables that influence that rate. DESIGN: Anatomic pathology departments participating in the College of American Pathologists Q-Probes laboratory quality improvement program retrospectively reviewed their last 50 consecutive prostate needle biopsy diagnoses. For each diagnosis, participants provided information concerning patients' prostate-specific antigen levels; number, locations, and laterality of biopsy specimens; number of tissue levels examined; performance of high-molecular-weight cytokeratin immunoperoxidase staining; and acquisition of consultations from general pathologists or experts in prostate pathology. Characteristics of pathology practices included yearly surgical and prostate needle biopsy caseloads, number of pathologists rendering biopsy diagnoses, use of standard descriptive checklists, access to patients' prostate-specific antigen and digital rectal examination results, percentages of prostate needle biopsies routinely submitted for internal consultations, and presence of departmental experts in prostate pathology. SETTING AND PARTICIPANTS: Three hundred thirty-two public and private institutions located in the United States (n = 318), Canada (n = 6), Australia (n = 5), United Kingdom (n = 2), and Guam (n = 1). MAIN OUTCOME MEASURE: The rate of diagnostic uncertainty in prostate needle biopsy diagnoses. RESULTS: Participants submitted diagnoses on a total of 15 753 prostate needle biopsy cases, of which 33.4% were adenocarcinoma; 55.5% were benign; 3.9% were carcinoma in situ, prostatic intraepithelial neoplasia, or both; and 7.1% were diagnostically uncertain. The median rate of diagnostic uncertainty was 6%, ranging from 0 at the 10th percentile to 14% at the 90th percentile of all participating laboratories. Performing high-molecular-weight cytokeratin immunoperoxidase staining resolved diagnostic uncertainty in 68% of cases in which it was performed, and obtaining intradepartmental and extradepartmental consultations resolved diagnostic uncertainty in 70% to 87% of cases for which they were obtained. Knowledge of patients' prostate-specific antigen results and examining multiple biopsy cores had marginal effects on the rate of uncertainty. Thoroughness of prostate gland sampling and examination of multiple tissue block levels were not associated with the aggregate rate of diagnostic uncertainty. We found no particular pathology departmental practices or institutional demographic characteristics associated with institutional rates of diagnostic uncertainty. CONCLUSIONS: Use of high-molecular-weight cytokeratin immunoperoxidase staining and obtaining intradepartmental and extradepartmental consultations may be effective in reducing diagnostic uncertainty in prostate biopsies.

Adenocarcinoma↗

Practice guidelines for autopsy pathology: autopsy reporting. Autopsy Committee of the College of American Pathologists.

The Autopsy Committee of the College of American Pathologists has prepared this revised guideline to reflect changes that have occurred in the reporting of autopsies since the original guideline was published in February 1995. It is intended to be an instrument to assist pathologists in the reporting of autopsies. The guideline is to be regarded as being primarily an educational tool. Application of these recommendations on autopsy reporting is to be made on the basis of the judgment of the pathologist engaged in a specific case.

Autopsy↗

Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999.

BACKGROUND: Under the auspices of the College of American Pathologists, a multidisciplinary group of clinicians, pathologists, and statisticians considered prognostic and predictive factors in breast cancer and stratified them into categories reflecting the strength of published evidence. MATERIALS AND METHODS: Factors were ranked according to previously established College of American Pathologists categorical rankings: category I, factors proven to be of prognostic import and useful in clinical patient management; category II, factors that had been extensively studied biologically and clinically, but whose import remains to be validated in statistically robust studies; and category III, all other factors not sufficiently studied to demonstrate their prognostic value. Factors in categories I and II were considered with respect to variations in methods of analysis, interpretation of findings, reporting of data, and statistical evaluation. For each factor, detailed recommendations for improvement were made. Recommendations were based on the following aims: (1) increasing uniformity and completeness of pathologic evaluation of tumor specimens, (2) enhancing the quality of data collected about existing prognostic factors, and (3) improving patient care. RESULTS AND CONCLUSIONS: Factors ranked in category I included TNM staging information, histologic grade, histologic type, mitotic figure counts, and hormone receptor status. Category II factors included c-erbB-2 (Her2-neu), proliferation markers, lymphatic and vascular channel invasion, and p53. Factors in category III included DNA ploidy analysis, microvessel density, epidermal growth factor receptor, transforming growth factor-alpha, bcl-2, pS2, and cathepsin D. This report constitutes a detailed outline of the findings and recommendations of the consensus conference group, organized according to structural guidelines as defined.

Breast Neoplasms↗

Prognostic factors in prostate cancer. College of American Pathologists Consensus Statement 1999.

BACKGROUND: Under the auspices of the College of American Pathologists, a multidisciplinary group of clinicians, pathologists, and statisticians considered prognostic and predictive factors in prostate cancer and stratified them into categories reflecting the strength of published evidence and taking into account the expert opinions of the Prostate Working Group members. MATERIALS AND METHODS: Factors were ranked according to the previous College of American Pathologists categorical rankings: category I, factors proven to be of prognostic importance and useful in clinical patient management; category II, factors that have been extensively studied biologically and clinically but whose importance remains to be validated in statistically robust studies; and category III, all other factors not sufficiently studied to demonstrate their prognostic value. Factors in categories I and II were considered with respect to variations in methods of analysis, interpretation of findings, reporting of data, and statistical evaluation. For each factor, detailed recommendations for improvement were made. Recommendations were based on the following aims: (1) increasing uniformity and completeness of pathologic evaluation of tumor specimens, (2) enhancing the quality of data collected pertaining to existing prognostic factors, and (3) improving patient care. RESULTS AND CONCLUSIONS: Factors ranked in category I included preoperative serum prostate-specific antigen level, TNM stage grouping, histologic grade as Gleason score, and surgical margin status. Category II factors included tumor volume, histologic type, and DNA ploidy. Factors in category III included perineural invasion, neuroendocrine differentiation, microvessel density, nuclear roundness, chromatin texture, other karyometric factors, proliferation markers, prostate-specific antigen derivatives, and other factors (oncogenes, tumor suppressor genes, apoptosis genes, etc).

Biomarkers, Tumor↗

Surgical pathology-based outcomes assessment of breast cancer early diagnosis: a College of American Pathologists Q-Probes study in 199 institutions.

OBJECTIVE: To develop breast cancer outcomes data relating pathologic tumor variables at diagnosis with clinical method of detection. DESIGN: Anatomic pathologists assessed 30 consecutive breast cancers at each institution, resulting in an aggregate database of 4232 breast cancers. SETTING: Hospital-based laboratories from the United States (98%), Canada, Australia, and Belgium. PARTICIPANTS: One hundred ninety-nine laboratories in the 1999 College of American Pathologists Q-Probes voluntary quality improvement program. MAIN OUTCOME MEASURES: Pathologic variables indicative of favorable outcomes included percentage of carcinomas detected at the in situ stage, tumors < or = 1 cm in diameter, and invasive cancers with lymph nodes negative for metastases. RESULTS: All outcomes measures, including percent in situ carcinomas (26.9% vs 13.8%), tumor size < or = 1 cm (57.8% vs 36.5%), and lymph node-negative status (77.8% vs 64%), were more favorable when tumors were detected by screening mammography (P <.001) compared to all other detection methods. CONCLUSIONS: This study demonstrates an opportunity for pathologists to develop outcomes information of interest to health care organizations, providers, patients, and payers by integrating routine oncologic surgical pathology and clinical breast cancer detection data. Such readily obtained interim outcomes data trended and benchmarked over time can demonstrate the relative clinical efficacy of preventive breast care provided by health care systems long before mortality data are available.

Adult↗

Neck needle foreign bodies: an added risk for autopsy pathologists.

The risk to pathologists of contracting diseases due to cuts or needles punctures while performing autopsies is well known. An additional risk is an accidental needle puncture due to retained needle fragments within the subcutaneous tissues or internal organs of intravenous drug addicts. We report 4 cases of drug addicted patients infected with human immunodeficiency virus who came to autopsy and had retained needle fragments within their cervical-clavicular soft tissues. The presence of retained needle fragments increases the risk to the autopsy pathologist of accidental needle puncture and exposure to disease. Because of this phenomenon, the pathologist should take precautions in addition to those currently prescribed when performing autopsies on possible drug abusers.

Adult↗

Pathologists in a teaching institution assess the value of the autopsy.

CONTEXT: With the advent of modern diagnostic technology, use of the autopsy as a means of assessing diagnostic accuracy has declined precipitously. Interestingly, during the same period, the rate of misdiagnosis found at autopsy has not changed. OBJECTIVES: To ascertain why an autopsy was requested, whether or not questions asked by clinicians were specifically addressed, and what types of misdiagnoses were found. DESIGN: One hundred forty-two consecutive autopsy records from the University of Arkansas for Medical Sciences Hospital were reviewed. In the same period, 715 deaths occurred, giving an overall autopsy rate of 20.14%. RESULTS: Of the 125 autopsies in which the problem-oriented autopsy request was available for review, a reason for the autopsy was given in only 69 cases (55%). One hundred three clinical questions were asked, and of these, 81 were specifically addressed in the final anatomic diagnosis, 10 were addressed in some part of the autopsy report but not in the final anatomic diagnosis, 10 were not addressed at all, and 2 could not be answered by the autopsy. Sixty-one autopsies revealed 81 misdiagnoses: 47 class I (missed major diagnosis that, if detected before death, could have led to a change in management that might have resulted in cure or prolonged survival) and 34 class II misdiagnoses (missed major diagnosis in which antemortem detection would have not led to a change in management). CONCLUSIONS: The autopsy continues to be a vital part of medical education and quality assurance. It is important for the clinician to provide a clinical summary and specific clinical questions to be addressed or to speak directly with the pathologist and for the pathologist to provide answers that are easily accessible within the autopsy report. In this way, a problem-oriented autopsy can be performed based on questions raised by the clinician and the pathologist as a result of the gross dissection and microscopic evaluation.

Adolescent↗

Interpretation of skin biopsies by general pathologists: diagnostic discrepancy rate measured by blinded review.

CONTEXT: Slide review has been advocated as a means to reduce diagnostic error in surgical pathology and is considered an important component of a total quality assurance program. Blinded review is an unbiased method of error detection, and this approach may be used to determine the diagnostic discrepancy rates in surgical pathology. OBJECTIVE: To determine the diagnostic discrepancy rate for skin biopsies reported by general pathologists. DESIGN: Five hundred eighty-nine biopsies from 500 consecutive cases submitted by primary care physicians and reported by general pathologists were examined by rapid-screen, blinded review by 2 dermatopathologists, and the original diagnosis was compared with the review interpretation. RESULTS: Agreement was observed in 551 (93.5%) of 589 biopsies. Blinded review of these skin biopsies by experienced dermatopathologists had a sensitivity of 100% (all lesions originally reported were detected during review). False-negative errors were the most common discrepancy, but false positives, threshold discrepancies, and differences in type or grade were also observed. Only 1.4% of biopsies had discrepancies that were of potential clinical importance. CONCLUSIONS: Blinded review demonstrates that general pathologists reporting skin biopsies submitted by primary care physicians have a low diagnostic error rate. The method detects both false-negative and false-positive cases and identifies problematic areas that may be targeted in continuing education activities. Blinded review is a useful component of a dermatopathology quality improvement program.

Biopsy↗

Is there a way for pathologists to decrease interobserver variability in the diagnosis of dysplasia?

Many obstacles interfere with our efforts to screen patients with Barrett esophagus. Probably the largest is choosing the appropriate patient group for screening. Beyond this problem, sampling error on the part of endoscopists is probably more serious a problem than observer variation among pathologists reviewing patient samples. Pathologists agree well on lesions that merit close follow-up or other intervention (high-grade dysplasia and invasive carcinoma), although interobserver agreement between pathologists interpreting lesser lesions is not good. This lack of agreement is not likely to improve substantially, and many adjunct markers are being sought in an attempt to identify patients with lesions of lower grades that are most likely to progress, allowing doctors to identify patients who would benefit from upgraded surveillance.

Barrett Esophagus↗

Patients in the dark about pathologist functions.

Pathologists are little known to the public. In a day when each dollar for health care is so closely scrutinized, such a lack of understanding may lead to lack of support for our profession. Early this year, outpatients at the Milwaukee County Medical Complex in Wisconsin answered questions concerning laboratory tests, medical laboratories, and pathologists. The results revealed a severe lack of knowledge about pathologist functions, and, according to the authors, illustrates well the need for patient and public education about medical laboratory services. The results of the survey presented here were used in creating an educational videofilm, prepared within the Department of Pathology of the Medical College of Wisconsin, which was shown during the recent National Medical Laboratory Week in the same outpatient laboratory where the polling occurred.

Awareness↗

The pathologist and attending staff: working together for cost effective laboratory use.

To improve the cost effectiveness of the clinical laboratory the pathologist must be concerned not only about the accuracy of analytic procedures but also about the appropriateness of laboratory use. Though pathologists have little control over the amount and nature of the use of the clinical laboratory, the author explains how pathologists can teach attending staff to use clinical laboratory services appropriately.

Cost-Benefit Analysis↗

Australian speech pathologists' views of what professional practices lead to successful outcomes of therapy.

The relative importance attributed to factors perceived by speech pathologists as contributing to successful levels of therapeutic outcomes were addressed in a survey of 372 practicing therapists in Australia. The survey consisted of 42 items derived from interviews with a sample of ten speech pathologists in Sydney. Therapists were asked to rate the importance of each item on a seven-point scale ranging from "not at all important" to "critically important." The findings indicate that the most important ingredients of successful therapy incorporate a mix of support and therapeutic activity outside the clinic; the clinicians' organizational skills and involvement in conducting therapy and their use of techniques; the positive therapeutic relationship between clinician and client; and, finally, the client's attitude to therapy. These findings suggest that speech pathologists, like other allied health professionals, endorse a humanistic or holistic approach to health care. The results provide insights into the practices that should be addressed and fostered in undergraduate speech pathology programs.

Adult↗

[Autopsy and biopsy findings in disorders of mitochondrial beta-oxidation of fatty acids. Role of the pathologist in the diagnostic process].

Basic problems of the group of hereditary mitochondrial beta oxidation (BOX) disorders are presented with evaluation of the role of pathologists in the diagnostic process. The disorders manifest themselves clinically as usual by recurrent Reye-like episodes (acute hepatopathy and encephalopathy) typically in low age levels. Integral part of the clinical picture is often a myopathic symptomatology which at some cases may display even persisting character. The findings at the tissue level are dominated mostly by steatosis of the organ set with a high beta oxidation level (liver, heart, skeletal muscle, kidney) and toxic effects of the intermediate metabolic products of the derranged beta oxidation process. So far eighteen enzyme defects have been described affecting either transport of fatty acids across the mitochondrial membranes or their oxidative degradation at various levels, pointing to an absolute dependence of the final diagnosis on biochemical analysis. Pathologist's conclusion in cases dying without diagnosis is limited to suspicion of a BOX disorder only. However, pathologists can contribute significantly to unraveling and specification of the underlying BOX defect by collecting adequate samples of body fluids and of unfixed organs. Nevertheless, the validity of these samples, even if widely recognized, is limited. The best approach is to provide samples enabling to perform biochemical evaluation of the whole BOX process in integral mitochondrias. This requirement is fulfilled solely by establishing fibroblast tissue culture post mortem.

Child↗

A web-based tutorial improves practicing pathologists' Gleason grading of images of prostate carcinoma specimens obtained by needle biopsy: validation of a new medical education paradigm.

BACKGROUND: The Internet, although it is in widespread use in medicine, to the authors' knowledge has not been tested rigorously as an educational tool. The authors investigated, as a model to validate web-based education for physicians, the Gleason grading of images of prostate carcinoma tissue specimens that were obtained by needle biopsy, which provides critical information for patient management. METHODS: A free, web-based program (available at www. pathology.jhu.edu/prostate) was developed. It consisted of 20 pretutorial quiz images of prostate carcinoma specimens that were obtained by needle biopsy for grading, followed by 24 tutorial images with text describing the Gleason grading system. Subsequently, pathologists took a posttutorial quiz, which consisted of the same 20 images that were used in the pretutorial quiz. RESULTS: In 16 months, there were 2021 visits with 916 participants completing the entire web site; 643 participants (70.2%) were practicing pathologists and formed the basis of the current study. Only the location of practice within the United States compared with outside the United States (P < 0.0001) and < 5 years in practice (P = 0.003) were correlated independently with a higher pretutorial quiz score. Overall, the web-based tutorial significantly improved grading in 15 of 20 images. Of these, on average, there was an 11.9% increase (range, 6-25.3%) in assigning the correct Gleason score. Improvements were noted in images of tumors with the following grades: Gleason score, 2-4 (0 of 1 images); Gleason score, 5-6 (5 of 7 images); Gleason score, 7 (4 of 6 images); and Gleason score, 8-10 (6 of 6 images). Greater improvement after taking the tutorial was correlated with lower pretutorial scores (P < 0.0001). CONCLUSIONS: A web-based tutorial improves the accuracy of Gleason grading of practicing pathologists. To the authors' knowledge the current study is the first large scale, international study that has evaluated and validated the use of a web-based program to educate a population of widely dispersed physicians.

Biopsy, Needle↗

Interpretation of cutaneous biopsy specimens: choice of pathologist by primary care practitioners.

BACKGROUND: Primary care providers (PCPs) have limited training in recognizing common skin disorders, and additional emphasis may be placed on laboratory evaluation, including skin biopsies. METHODS: Primary care providers in Miami, Fla, were surveyed regarding skin biopsy and excision practices and histologic interpretation. They then participated in an examination, using 20 high-quality color photographs of common dermatologic disorders. RESULTS: Of the 80 PCPs who participated, 42% currently do skin biopsies and consult general pathologists for interpretation. Another 20% of PCPs intend to do biopsies within the next 5 years. Only 33% prefer to have a dermatopathologist interpret histopathology. We found no correlation between PCPs' scores on diagnostic testing and whether they do skin biopsies. CONCLUSION: Nearly all PCPs doing skin biopsies in our study sample use general pathologists to interpret histopathology. The limited training in clinical dermatology of both PCPs and general pathologists may result in compromised clinical-pathologic correlation.

Biopsy↗

[Challenges for pathologists in clinical laboratory medicine].

The number of pathologists in hospitals has been increasing and they are responsible for both surgical pathology and clinical laboratory medicine. In the future they will also play important roles in the modernized reform of the central laboratory as it establishes its own importance in improving the quality and safety of medical activities. As a pathologist, the author reports on challenges faced since assuming the present directorship of the department of laboratory medicine in 1995 including (a) establishing a decision-making system in collaboration with technologists, (b) improving expertise in the department through joining a variety of seminars, conferences and research activities, (c) publishing an annual department report, and (d) introducing both internal and external quality assessment. In the future, for young pathologists training in both pathology and laboratory medicine will be essential.

Clinical Laboratory Techniques↗