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PubMed2006

Interlaboratory comparison of immunohistochemical testing for HER2: results of the 2004 and 2005 College of American Pathologists HER2 Immunohistochemistry Tissue Microarray Survey.

CONTEXT: Correct assessment of human epidermal growth factor receptor 2 (HER2) status is essential in managing patients with invasive breast carcinoma, but few data are available on the accuracy of laboratories performing HER2 testing by immunohistochemistry (IHC). OBJECTIVE: To review the results of the 2004 and 2005 College of American Pathologists HER2 Immunohistochemistry Tissue Microarray Survey. DESIGN: The HER2 survey is designed for laboratories performing immunohistochemical staining and interpretation for HER2. The survey uses tissue microarrays, each consisting of ten 3-mm tissue cores obtained from different invasive breast carcinomas. All cases are also analyzed by fluorescence in situ hybridization. Participants receive 8 tissue microarrays (80 cases) with instructions to perform immunostaining for HER2 using the laboratory's standard procedures. The laboratory interprets the stained slides and returns results to the College of American Pathologists for analysis. In 2004 and 2005, a core was considered "graded" when at least 90% of laboratories agreed on the result--negative (0, 1+) versus positive (2+, 3+). This interlaboratory comparison survey included 102 laboratories in 2004 and 141 laboratories in 2005. RESULTS: Of the 160 cases in both surveys, 111 (69%) achieved 90% consensus (graded). All 43 graded cores scored as IHC-positive were fluorescence in situ hybridization-positive, whereas all but 3 of the 68 IHC-negative graded cores were fluorescence in situ hybridization-negative. Ninety-seven (95%) of 102 laboratories in 2004 and 129 (91%) of 141 laboratories in 2005 correctly scored at least 90% of the graded cores. CONCLUSION: Performance among laboratories performing HER2 IHC in this tissue microarray-based survey was excellent. Cores found to be IHC-positive or IHC-negative by participant consensus can be used as validated benchmarks for interlaboratory comparison, allowing laboratories to assess their performance and determine if improvements are needed.

Breast Neoplasms↗

PubMed2006

Hyperchromatic crowded groups in cervical cytology--differing appearances and interpretations in conventional and ThinPrep preparations: a study from the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology.

CONTEXT: The practice of gynecologic cytology requires that high-grade squamous intraepithelial lesion (HSIL) be precisely recognized. In this regard, hyperchromatic crowded groups are known to be difficult to classify in conventional gynecologic cytology, but whether this is true in ThinPrep specimens is uncertain. OBJECTIVE: To assess whether hyperchromatic crowded groups of cells in challenging HSIL cases are a problem in ThinPrep preparations, and whether these groups differ in appearance from those of conventional smears. DESIGN: Sixteen images were taken from both conventional smears and ThinPrep slides that had a reference diagnosis of HSIL in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology, but had performed poorly on subsequent participants' reviews. These 32 representative images were of hyperchromatic crowded groups and were classified by 20 Cytopathology Resource Committee members (17 pathologists and 3 cytotechnologists), who were masked to the reference diagnosis. A consensus classification was derived using the majority opinion of the individual reviewers. Finally, 5 cytologic features were assessed for those images that were interpreted as abnormal by the consensus classification. RESULTS: None of the 32 images was uniformly interpreted as either benign, squamous lesion, or glandular lesion on individual review. Only 27% of individual interpretations of conventional smear images and 15% of ThinPrep images were interpreted as HSIL/squamous cell carcinoma (P < .001). Individual interpretations of ThinPrep images as glandular lesions (60%) were more often made than those of conventional smears (44%, P < .001). The consensus interpretation of ThinPrep images was glandular lesion in 75% of cases, whereas fewer than 50% of the consensus interpretations of conventional smear images were in this category. Conventional smear images were characterized by elongate nuclei (43%) and large nuclei (71%), whereas ThinPrep images more often showed rounded smooth edges (53%) and small nuclei (80%), and were recognized as a glandular lesion. CONCLUSIONS: Hyperchromatic crowded groups of cells are a source of difficulty in challenging HSIL cases for both conventional smears and ThinPrep specimens. In conventional smears, these groups are more likely to be labeled as a squamous lesion, owing to their elongate and large nuclei. In ThinPrep specimens, however, these groups are more likely to be labeled as glandular lesions, owing to their smooth contoured borders and small nuclei.

Carcinoma, Squamous Cell↗

PubMed2002

The effects of the current World Health Organization/International Society of Urologic Pathologists bladder neoplasm classification system on urine cytology results.

BACKGROUND: Historically, the diagnostic accuracy of urine cytology for the detection of urothelial carcinoma has been low, particularly for low-grade lesions. In 1998, the World Health Organization and International Society of Urologic Pathologists (WHO/ISUP) established a new classification system for urothelial neoplasms. It has been postulated that the accuracy of urine cytology for the detection of low-grade carcinomas should improve, because the current WHO/ISUP system classifies bladder lesions that lack any significant cytologic atypia as papillary urothelial neoplasms of low malignant potential (PUNLMP). Also, the accuracy of urinary cytology for the detection of high-grade lesions is expected to decrease, because the criteria for high-grade lesions is lowered, placing most of the previous WHO Grade 2 tumors into the current high-grade carcinoma category. METHODS: One hundred bladder biopsies that were classified according to the previous WHO classification system were examined by one pathologist and were reclassified according to the new WHO/ISUP scheme. All biopsies had corresponding urine specimens that had been diagnosed previously by a different cytopathologists. The patients' previous WHO and current WHO/ISUP surgical diagnoses were compared with the corresponding urine cytology. In addition, cytospins obtained from 40 patients with a histologic diagnosis of low-grade urothelial carcinoma (n = 20 patients) and high-grade urothelial carcinoma (n = 20 patients) according to the WHO/ISUP classification system were reviewed to identify any outstanding cytologic features. RESULTS: According to the original WHO classification system, there were 26 patients with Grade 1 transitional cell carcinoma (TCC), 61 patients with Grade 2 TCC, and 13 patients with Grade 3 TCC. The corresponding cytology was positive in 11 of 26 Grade 1 tumors, 28 of 61 Grade 2 tumors, and 12 of 13 Grade 3 tumors. After the reclassification, there was 1 papilloma, 12 PUNLMP lesions, 50 low-grade urothelial carcinomas, and 37 high-grade carcinomas. The cytology was positive in 0 of 1 papillomas, 5 of 7 PUNLMP lesions, 18 of 50 low-grade carcinomas, and 28 of 37 high-grade carcinomas. In addition, morphologic uniformity and cytoplasmic homogeneity (50.0% and 45.0%, respectively) were seen more commonly in low-grade bladder tumors. CONCLUSIONS: The diagnostic accuracy of urine cytology for high-grade lesions decreased, as expected; however, cytologic detection of low-grade urothelial carcinomas was remarkably lower than expected. In addition, no outstanding cytologic features could be identified to make a definitive diagnosis.

Aged↗

PubMed2004

Incorporating pathologists' criteria of malignancy into the evolutionary model for cancer development.

A wide variety of alterations in cell and tissue structure still form the basis for cancer diagnosis by pathologists. Cancer development is recognized to be an evolutionary process [Foulds, 1954; Cairns, 1975; Nowell, 1976; Sager, 1982; Tomlinson et al., 1996; Cahill et al., 1999; Tomlinson and Bodmer, 1999], but the phenotypic changes diagnostic of cancer (pathologists' "criteria of malignancy") have not been integrated into the existing evolutionary framework. Since phenotypic changes bear an important relationship to the genetic and physiologic changes underlying Darwinian evolution, we propose that diagnostic structural alterations also bear an important and predictable relation to both the cancer genes and the functional alterations active at any particular step in the development of a cancer. Cancer genes are predicted to mediate the acquisition of cellular-level diagnostic criteria and the diagnostic cellular-level structural changes should reflect in a useful manner the altered cell physiology required for the cell to achieve increased "cellular fitness" at any particular step of colonal evolution. Tissue-level criteria of malignancy should relate less directly to specific cancer genes, but tissue-level criteria should still provide essential insight into the interplay of the altered cellular fitness with the constraints imposed by the cells' microenvironment. The evolutionary framework allows tissue-level criteria of malignancy to be expressed in terms of viable hypotheses for the mechanism of clonal expansion at any particular step in cancer development. This approach to conveying the tissue-level criteria of malignancy complements pattern recognition approaches to diagnosis, and establishes common ground between pathology and cell biology. When viewed from this perspective, the functions of cancer genes appear quite different from those predicted by the "Gatekeeper, Caretaker" or "Hallmarks of Cancer" models. Finally, a full evolutionary framework incorporating the criteria of malignancy restores congruity between the histogenetic classification and the emerging molecular classification of cancer.

Cell Transformation, Neoplastic↗

PubMedDate not supplied

Polyps: the pathologist's perspective.

Adenomas of the colon and rectum are perhaps the most commonly encountered of human benign epithelial neoplasms. Evidence of their relationship to the development of colorectal carcinoma has mounted over the years. They represent a phase present for significant duration in many fated to develop colon cancer. Because of this, and because of the technical advances in endoscopy, a great deal of effort has been expended on identifying and removing these lesions. Subsequent care of the patient is heavily dependent on the pathologic analysis of these lesions. they must be properly classified; the presence of cancer must be carefully sought. If present, the character and location of the cancer arising in the polyp must be carefully described. Communication between clinician and pathologist if of paramount importance. Attention must be paid to the precise meaning of such terms as dysplasia, carcinoma, and invasion. The pathologist's report needs to detail parameters important in determining prognosis and further therapy.

Adenomatous Polyps↗

PubMed1999

Consistency achieved by 23 European pathologists from 12 countries in diagnosing breast disease and reporting prognostic features of carcinomas. European Commission Working Group on Breast Screening Pathology.

A detailed analysis of the consistency with which pathologists from 12 different European countries diagnose and classify breast disease was undertaken as part of the quality assurance programme of the European Breast Screening Pilot Network funded by the Europe against Cancer Programme. Altogether 107 cases were examined by 23 pathologists in 4 rounds. Kappa statistics for major diagnostic categories were: benign (not otherwise specified) 0.74, atypical ductal hyperplasia (ADH) 0.27, ductal carcinoma in situ (DCIS) 0.87 and invasive carcinoma 0.94. ADH was the majority diagnosis in only 2 cases but was diagnosed by at least 2 participants in another 14, in 9 of which the majority diagnosis was benign (explaining the relatively low kappa for this category). DCIS in 4 (all low nuclear grade) and invasive carcinoma (a solitary 1-mm focus) in 1. The histological features of these cases were extremely variable; although one feature that nearly all shared was the presence of cells with small, uniform, hyperchromatic nuclei and a high nucleo-cytoplasmic ratio. The majority diagnosis was DCIS in 33 cases; kappa for classifying by nuclear grade was 0.38 using three categories and 0.46 when only two (high and other) were used. When ADH was included with low nuclear grade DCIS there was only a slight improvement in kappa. Size measurement of DCIS was less consistent than that of invasive carcinoma. The majority diagnosis was invasive carcinoma in 57 cases, the size of the majority being 100% in 49. The remainder were either special subtypes (adenoid cystic, tubular, colloid, secretory, ductal/medullary) or possible microinvasive carcinomas. Subtyping was most consistent for mucinous (kappa, 0.92) and least consistent for medullary carcinomas (kappa, 0.56). Consistency of grading using the Nottingham method was moderate (kappa=0.53) and consistency of diagnosing vascular invasion, fair (kappa=0.38). There was no tendency for consistency to improve from one round to the next, suggesting that further improvements are unlikely without changes in guidelines or methodology.

Breast Diseases↗

PubMed2004

Oropharyngeal dysphagia: surveying practice patterns of the speech-language pathologist.

The present study was designed to obtain a comprehensive view of the dysphagia assessment practice patterns of speech-language pathologists and their opinion on the importance of these practices using survey methods and taking into consideration clinician, patient, and practice-setting variables. A self-administered mail questionnaire was developed following established methodology to maximize response rates. Eight dysphagia experts independently rated the new survey for content validity. Test-retest reliability was assessed with a random sample of 23 participants. The survey was sent to 50 speech-language pathologists randomly selected from the Canadian professional association database of members who practice in dysphagia. Surveys were mailed according to the Dillman Total Design Method and included an incentive offer. High survey (64%) and item response (95%) rates were achieved and clinicians were reliable reporters of their practice behaviors (ICC>0.60). Of all the clinical assessment items, 36% were reported with high (>80%) utilization and 24% with low (<20%) utilization, the former pertaining to tongue motion and vocal quality after food/fluid intake and the latter to testing of oral sensation without food. One-third (33%) of instrumental assessment items were highly utilized and included assessment of bolus movement and laryngeal response to bolus misdirection. Overall, clinician experience and teaching institutions influenced greater utilization. Opinions of importance were similar to utilization behaviors (r = 0.947, p = 0.01). Of all patients referred for dysphagia assessment, full clinical assessments were administered to 71% of patients but instrumental assessments to only 36%. A hierarchical model of practice behavior is proposed to explain this pattern of progressively decreasing item utilization.

Attitude of Health Personnel↗

PubMedDate not supplied

Accidental childhood death and the role of the pathologist.

The following study provides an overview of accidental childhood death. This study is based on a review of 369 cases of fatal childhood accidents taken from the records of the Department of Histopathology, Women's and Children's Hospital, Adelaide, Australia, over a 34-year period from 1963 to 1996. Data provide information on deaths due to motor vehicle accidents, drownings, accidental asphyxia, burns, poisonings, electrocution, and miscellaneous trauma. In addition, certain categories have undergone further examination, including asphyxial deaths due to unsafe sleeping environments and unsafe eating practices, drowning deaths, and deaths on farms, following identification of significant child safety problems in these areas as part of the "Keeping Your Baby and Child Safe" program. Previously unrecognized dangers to children detected through this program include mesh-sided cots, V-shaped pillows, and certain types of stroller-prams. The production of information pamphlets and packages for parents and the recall of certain dangerous products following recommendations made by pathologists demonstrate that pediatric and forensic pathologists have an important role to play in preventive medicine issues and in formulating public health strategies.

Accident Prevention↗

PubMedDate not supplied

Intergroup Rhabdomyosarcoma Study: update for pathologists.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood, and 75% of such cases in the United States are reviewed at the Pathology Center for the Intergroup Rhabdomyosarcoma Study Group (IRSG). The first four generations of IRSG therapeutic trials (IRS I-IV) and supportive pathologic studies have generated a new International Classification of Rhabdomyosarcoma (ICR) that offers new morphologic concepts to the practicing pathologist. The objective of this report is to clearly define emerging histopathologic categories of RMS as defined by the ICR, and to emphasize correlative immunohistochemical or molecular studies. Emerging ICR variants of RMS place the patient in widely divergent prognostic categories (superior, botryoid or spindle cell variants; poor, solid alveolar or diffusely anaplastic variants). The cardinal histopathologic features of the ICR combined with results of studies of fusion genes seen with t(1;13) and t(2;13) will help delineate therapeutic subgroups of RMS for the fifth generation (IRS V) of IRSG studies. Consequently, it is imperative for the practicing pathologist to be familiar with the practical workup and diagnosis of RMS in childhood.

Biomarkers, Tumor↗

PubMed1979

Understanding death, dying, and the critically ill: a concern for speech-language pathologists.

The purpose of this article is to familiarize the speech-language pathologist with the behaviors that critically and terminally ill persons demonstrate. To work effectively with these groups of individuals, it appears essential that the clinician know the dynamics of the psychological stages associated with physical crisis, disability, death, and dying. This information is becoming more relevant to the speech-language pathologist, particularly as his/her role as a member of a rehabilitation team providing direct services to the aged expands.

Aged↗

PubMed1980

Sexual counseling--a new role for speech pathologists?

Sexual intercourse is discussed as a form of nonverbal human communication. During periods of good health, sexual intercourse contributes to the sense of personal worth and to the integrity of marriage. Following episodes of ill health, unresolved sexual difficulties contribute to loss of self-esteem, constitute barriers to clinical progress, and enhance marital discord. Speech pathologists are advised to give more attention to the sexuality of their patients, especially to those who are aphasic. With proper training, selected speech pathologists may find themselves ideally suited to incorporate sexual counseling in their clinical armamentarium.

Aphasia↗

PubMed1994

Are pathologists biased by clinical information?: A blinded cross-over study of the histopathological diagnosis of mesothelial tumours versus pulmonary adenocarcinoma.

In a blinded cross-over design, we studied whether three pathologists were biased by clinical information when making histopathological diagnoses of adenocarcinoma of the lung and benign and malignant mesothelial tumours. Furthermore, the interobserver variation of these diagnoses was assessed. Forty-one cases of adenocarcinoma of the lung and mesothelial tumours were assessed by three pathologists in four rounds. In the first two rounds, slides stained by H&E and clinical information were available. Slides and information were matched so that a specific slide in one round was given clinical information suggesting adenocarcinoma and in the other round, the clinical information suggested mesothelial tumour. In the third and fourth rounds, a panel of immunohistochemical stains was added. The clinical information was matched in the same way as in the first and second rounds. Bias by clinical information was observed when the diagnoses were made on slides stained by H&E, while no bias could be demonstrated when immunohistochemical reactions were included. The reproducibility also improved significantly when these slides were available.

Adenocarcinoma↗

PubMed2006

A pathologist's perspective of the somatoform disorders.

OBJECTIVE: The object of this study was to revisit the evidence that somatoform disorders should be classified as mental and not physical disorders, as viewed through the eyes of a pathologist rather than a psychiatrist. METHODS: An academic clinical pathologist was asked to review recent widening in the concepts of physical disease and to comment on whether these changes made the criteria for designating somatoform disorders as mental disorders more workable or less workable. RESULTS: The review showed that somatoform disorders share many characteristics with certain types of physical conditions, especially those with multiorgan manifestations and multifactor causes. The criteria used to separate somatoform disorders from physical diseases are now less clear than when this distinction was first proposed. CONCLUSION: Discussions for reviewing the status of the somatoform disorders for DSM-V need input from a wide range of medical disciplines besides psychiatry.

Humans↗

PubMed1989

A contemporary view of neoplasms in children. The pathologist's perspective.

The diagnosis of childhood malignancy is a complex endeavor that requires the cooperation of the clinician and pathologist. On occasion, potentially problematic situations arise when a biopsy cannot answer all of the questions or is nondiagnostic. Delays may occur before a final diagnosis is possible in an especially complicated case that requires several time-consuming studies. The pathologist should appreciate the pressure placed on the clinician to initiate treatment and, in turn, the clinician should realize that several steps are necessary before the pathologic examination can be completed.

Adolescent↗

PubMed1983

Morphometric grading of bladder tumors in comparison with histologic grading by pathologists.

The authors describe the results of the grading of bladder tumors using morphometry and then compare these with results of histologic grading of the same tumors by different pathologists. Nuclear sizes of cells obtained from superficial and deep cell layers of each carcinoma and from giant cells were measured in 27 cases in which histologic tumor grading by different pathologists was unequivocal. In cells from all three areas, nuclear area increased with higher tumor grade. However, tumors of grades I and II showed significant differences in the size only of the large cells. It is concluded that morphometry is a valuable tool in the objective grading of bladder tumors, with the exception of carcinoma in situ lining the bladder lumen.

Carcinoma↗

PubMed1995

The pathologist and the hydropic placenta, fetus, or infant.

Many anatomic and histologic abnormalities, in large variety, are associated with fetal and placental edema. It is the pathologist's responsibility first, to identify these abnormalities, and second, to propose or to establish a mechanism by which a candidate abnormality might have led to development of edema. The first process, of documentation, is often assisted by antenatal studies that have identified a candidate lesion. However, the pathologist must bear in mind that the presence of one disorder does not exclude others. The second process, of elucidating the abnormal physiologic mechanisms by which edema developed, can prove elusive and may verge on investigative rather than diagnostic work. An outline for pathologic examination of the hydropic placenta or fetus is presented.

Female↗

PubMed1988

Expert system for pathologists to generate an image analysis program for tumor grading.

The pathologist is usually not an expert in engineering or image analysis. We have, therefore, developed an expert system, entitled PARTICLE, to help pathologists producing image analysis programs by which to tackle problems in histological pathology, including tumor grading. The PARTICLE expert system is based on karyometric data, using the AMBA/R dialogue and programming system.

Diagnosis, Computer-Assisted↗

PubMed2004

[The pathologist and EGFR in 2004: I like you, nor do it].

Epithelial growth factor receptor (EGFR) appears as a key element in carcinogenesis. It displays high levels of expression in some tumor types. Its activation induces cell proliferation, angiogenesis, cell mobility and inhibition of apoptosis. EGFR inhibitors such as monoclonal antibodies or small molecules tyrosine kinase inhibitors have been developed. For EGFR, the diversity of the activation means (amplification, mutation, enhanced transcription, ligands...) leads to technical caveats. Immunohistochemistry appears to be the most appropriate test for clinical use, but standardized assays and scoring systems are mandatory. Pathologists are involved in the selection of patients for a monoclonal antibody based targeted treatment, Erbitux, and numerous standardization efforts are provided. No consensus has been reached, to date, for a scoring system. Whether the EGFR status has to be tested for the selection of patients is a non answered question. The selection of the "right patient for the right treatment" might be through the evaluation of other putative markers involved in resistance. EGFR testing may be required before targeted treatment. An exciting endpoint might be the functional and dynamic evaluation of EGFR and downstream proteins, for patients, before and during treatment. The exact role of the pathologist still have to be accurately determined.

Antibodies, Monoclonal↗