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PubMed1995

Will pathologists play as important a role in the future as they have in the past against the challenge of infectious diseases.

Since the recognition less than 120 years ago that organisms visible only microscopically are capable of causing human diseases, pathologists have played a major role in identifying and characterizing the etiologic infectious agents and in elucidating the pathogenic mechanisms. In face of the opportunities and challenges presented by molecular technology, AIDS and other emerging infections, and the evolution of health care systems, it is worthwhile to question whether the field of pathology will continue in the future to make major contributions in the field of infectious diseases. The AIDS epidemic has awakened pathologists to the need to reemphasize infectious diseases in diagnostic anatomic and clinical pathology, basic and applied research, and medical and scientific education. The knowledge and skills of pathologists are uniquely critical to the achievement of efficient advances in infectious diseases, and will remain so provided that pathologists embrace molecular science and apply it as a principal component in their methodologic and conceptual armamentarium.

Forecasting↗

PubMed1996

Consistencies and controversies in the application of the International Society for Heart and Lung Transplantation working formulation for heart transplant biopsy specimens. Rapamycin Cardiac Rejection Treatment Trial Pathologists.

BACKGROUND: The International Society for Heart and Lung Transplantation (ISHLT) working formulation was proposed in 1990 to promote standardization in the interpretation of endomyocardial biopsy specimens obtained after heart transplantation, especially in the setting of multicenter clinical trials and for publication purposes. METHODS: To assess uniformity in interpretation, 16 pathologists experienced in posttransplant endomyocardial biopsy specimen interpretation each read independently, in randomized order, an identical series of 23 biopsy specimens representing all ISHLT grades of rejection (n = 12) and other posttransplant biopsy findings (n = 11). The pathologists represented heart transplantation centers participating in the Rapamycin Treatment Trial for Grades 2 and 3A Rejection. The index diagnosis in each case was determined by two pathology consultants who had concurred blindly on 22 of 23 (96%) biopsy specimen evaluations on their first independent reading. Discrepancies that would not affect clinical response (for example grades 0 versus 1A, 1A versus 1B, 3A versus 3B, 3B versus 4) were considered minor; those that could alter therapy were considered major. RESULTS: The 16 trial pathologists were in exact agreement with the index diagnosis in 17 (mean) +/- 3 biopsy specimens (range 10 to 22) and 20 (mean) +/- 2 biopsy specimens (range 16 to 22) if minor discrepancies were excluded. Of 368 diagnoses rendered, 265 agreed exactly with the index diagnosis and 103 differed, of which 50 were minor discrepancies. The 53 major discrepancies included grades 1A/B versus 2, 22 discrepancies; 2 versus 3A, 11; Quilty B versus 2/3A, 10; biopsy site versus 3A, 2; ischemic injury versus 3A/B, 2; Toxoplasma versus 3A, 2; posttransplantation lymphoproliferative disorder versus 3B/4, 3; and Quilty B versus posttransplantation lymphoproliferative disorder, 1. Interobserver agreement assessed by weighted kappa values was 0.67. CONCLUSIONS: First, there was agreement among the trial pathologists and the index diagnosis (excluding minor discrepancies) in 85% of biopsy specimen interpretations. Second, of 53 major discrepancies, 43 (81%) involved grades 1A/B versus 2, 2 versus 3A, and Quilty B versus 2/3A. Third, in 54% of instances in which biopsy findings other than rejection were misdiagnosed as rejection grades, the grade was sufficiently high to have adverse treatment implications. Fourth, the ISHLT working formulation provides for a high degree of diagnostic consistency among experienced observers, and concordance could be further enhanced by clarification of criteria for grade 2 rejection and Quilty B lesions.

Biopsy↗

PubMed1998

"No pictures from summer vacation": portrayals of pathologists in the printed media.

Public perceptions of pathologists can be shaped by individuals' direct contacts with these medical specialists, as well as by portrayals of them in the media. Few lay people, whether healthy or ill, have direct professional interaction with pathologists. Accordingly, media portrayals can assume great importance in shaping public views of pathologists and their profession. This report discusses how pathologists and the specialty of pathology are depicted in newspaper articles.

Forensic Medicine↗

PubMed1998

Consistency achieved by 23 European pathologists in categorizing ductal carcinoma in situ of the breast using five classifications. European Commission Working Group on Breast Screening Pathology.

The increased detection of ductal carcinoma in situ (DCIS) by mammographic screening, the greater use of breast-conserving surgery, and the recognition that certain histological subtypes are associated with a greater risk of local recurrence has led to the formulation of several new classifications of DCIS in recent years. There are, however, no data concerning the degree of consistency with which these schemes can be applied by reasonable numbers of pathologists. Thirty-three cases of DCIS were thus examined by a working group of 23 European pathologists who categorized them using five recently published classifications: (1) that of the European Pathologists' Working Group based on differentiation (a combination of nuclear grade and cell polarization) with categories of poorly, intermediately, and well differentiated; (2) one based entirely on nuclear grade with categories of high, intermediate, and low, currently in use in the UK national and EC-funded breast screening programs; (3) the same classification in which only two categories, high nuclear grade and other, were used; (4) the Van Nuys system in which lesions are divided into high grade, non-high grade with necrosis and non-high grade without necrosis; and (5) a two-category classification based entirely on the presence or absence of comedo necrosis. Of the three systems with three categories, Van Nuys gave the highest overall kappa statistic of 0.42. Others gave similar values of 0.37 and 0.35 showing that assessing cell polarization in addition to nuclear grade neither improves nor worsens consistency. In all three systems, the middle category was associated with the lowest value for kappa. Of the two systems with two categories, that based on nuclear grade gave the highest overall kappa of 0.46 and that based on comedo necrosis the lowest of 0.34. The most robust histological features were thus high- and low-grade nuclei and necrosis as long as the latter did not involve the recognition of a comedo growth pattern. These values probably represent the maximum achievable, at least by reasonable numbers of pathologists in everyday practice. They are better than those previously reported for classification based entirely on architecture, but further improvement is needed.

Breast Neoplasms↗

PubMed2005

Altered recognition of reparative changes in ThinPrep specimens in the College of American Pathologists Gynecologic Cytology Program.

CONTEXT: Previous studies have shown that the diagnosis of reparative changes in conventional smears in the College of American Pathologists Interlaboratory Comparison Program in Gynecologic Cytology is one of the least reproducible diagnoses. Indeed, the diagnosis of reparative changes consistently yields the highest false-positive rate of any negative for intraepithelial lesions and malignancy (NILM) cytodiagnostic category. It is unknown whether cytologists recognize reparative changes in ThinPrep specimens as well, or less often, as in conventional smears. OBJECTIVE: To assess and compare the ability of cytologists to recognize reparative changes in conventional and ThinPrep preparations. DESIGN: We compiled performance data from the College of American Pathologists Interlaboratory Comparison Program in Gynecologic Cytology from the 2000-2003 program years. More than 400 slides with a reference diagnosis of reparative changes met our study criteria, representing a total of 11 200 individual responses for conventional cases and 1155 individual responses for ThinPrep specimens. We evaluated the results of both individual and laboratory participants using 2 performance criteria: the false-positive discordancy rate and the exact match error rate (any response that does not exactly match the reference diagnosis of 120 [reparative changes]). RESULTS: Cases with a reference diagnosis of reparative changes made up 1.2% of all ThinPrep slides and 3.7% of all conventional slides in circulation. The false-positive discordancy rate of individual responses on educational slides for conventional smears was significantly higher than the corresponding false-positive discordancy rate for ThinPrep specimens (15.7% for conventional vs 7.1% for ThinPrep specimens, P < .001). Laboratory responses on educational conventional smears and ThinPrep slides showed a similar trend (14.2% for conventional smears vs 2.4% for ThinPrep slides, P = .002). The exact match error rate on educational conventional slides was 41.4% for individual responses, while on educational ThinPrep slides, the overall error rate was 57.5% (P < .001). For laboratory responses, the exact match error rate was 40.5% for educational conventional smears versus 58.9% for educational ThinPrep smears (P < .001). Characteristic features of reparative changes were identified in ThinPrep specimens. CONCLUSIONS: In the College of American Pathologists Interlaboratory Comparison Program in Gynecologic Cytology, ThinPrep slides with a reference diagnosis of reparative changes have a lower false-positive discordancy rate than conventional slides. Responses to ThinPrep cases with a reference diagnosis of reparative change show a higher exact match error rate than conventional smears. Since reparative changes in gynecologic cytology are recognized as indicating an increased risk of significant lesions, the clinical significance of these altered patterns of recognition of reparative changes in ThinPrep specimens warrants further investigation.

Cervix Uteri↗

PubMed1992

Cutaneous T-cell lymphoma. Evaluation of pretreatment skin biopsy specimens by a panel of pathologists.

BACKGROUND AND DESIGN: Cutaneous T-cell lymphoma (CTCL) frequently presents a difficult diagnostic challenge for the clinician and pathologist. To assess the diagnostic validity of conventional histopathologic findings in CTCL, pretreatment skin biopsy specimens were scored prospectively and independently by a panel of five to seven dermatopathologists and pathologists. Scores were compared with disease outcome. Repeatability of these scores was examined among observers and for the same observer. The study population consisted of 165 subjects, initially referred for suspected mycosis fungoides or Sézary syndrome. Ninety-two patients determined to have CTCL have been followed up for 6.3 +/- 3.5 years (mean +/- SD) and are categorized according to disease outcome: 22 are in complete remission, 35 are in partial remission, three have progressive lymphoma, 15 died of disease, 13 died of other causes, and four were unavailable for follow-up. Seventy-three patients determined not to have CTCL have been followed up for 5.3 +/- 3.2 years without subsequent clinicopathologic evidence of CTCL. These longitudinal data allowed comparisons of the clinical course with the original histologic interpretations. RESULTS: Data showed that the histologic scores rendered by the pathology panel did not correlate with stage of disease and were not an accurate predictor of clinical outcome, because the histologic ratings did not discriminate between patients who eventually had complete remission and those with either progressive lymphoma or who have died of disease. The results also substantiate the low inherent reliability of histopathologic findings in CTCL. Large differences existed among pathologists in scoring the study populations and repeated reading of selected cases by the same panel member resulted in a change of diagnosis 15% of the time. Among the histologic features evaluated, only the presence of mitoses in the infiltrating cells showed a trend toward an unfavorable outcome. CONCLUSION: Pathologic diagnosis in the CTCL disease spectrum should be interpreted with caution and then only in conjunction with the clinical evaluation. As expected, the use of an average value from a panel of readers added a component of stability to the histologic interpretation.

Biopsy↗

PubMed1976

Common errors made by pathologists in the diagnosis of bone tumors.

The pathologist must obtain X-rays before attempting to make a diagnosis in a bone tumor. Errors are made with both benign and malignant lesions associated with calluses. Infection may stimulate a malignant bone tumor radiographically and pathologically. Secondary aneurysmal bone cyst may dominate the radiographic and pathologic findings and obscure the primary diagnosis. Osteoblastomas are becoming increasingly difficult to diagnose. The question of whether such an entity can become malignant has not been resolved. Cartilagenous tumors are often difficult to diagnose and the pathologist must not only rely on histologic findings, but in particular pay attention to the radiographic pattern which is often diagnostic. Accuracy of diagnosis in Ewing's sarcoma is essential because the treatment now can result in a cure rate of almost 40%. Certain lesions such as lymphoma or osteosarcoma can mimic this tumor. To re-emphasize the problem, the pathologist must have all the clinical information before attempting a diagnosis of a bone tumor and without the pertinent X-ray, errors are almost inevitable.

Adolescent↗

PubMed1982

Disagreement of histopathological diagnosis of different pathologists in ovarian tumors-with some theoretical considerations.

Microscopical sections of forty-nine ovarian tumors have been assessed as benign, borderline or malignant by four different pathologists, who were unaware of the FIGO stage and clinical follow-up of each patient and each others' diagnosis. There was absolute agreement in 37 cases (75.5%), and disagreement in 12 cases (24.5%). The majority of the disagreements involved borderline-malignant differences. If one of the pathologists did disagree with the other three (in 9 cases, or 18%), there is no correlation between disagreement and histopathological experience. In three cases (6.5%) two pathologists did disagree with the other two. It is concluded that in pathology, objective reproducible and if possible, quantitative techniques should be used instead of subjective grading methods. The probability of the diagnosis should be expressed in a numerical way.

Diagnosis, Differential↗

PubMed2004

Malpractice--role of the forensic pathologist in Germany.

Medicolegal malpractice assessments have been an important part of the work of forensic pathologists. Not only botchers are concerned but also physicians of all clinical subjects, especially malpractice charges claiming a malpractice leading to death. Single long articles and book chapters have been published about malpractice assessments since the end of the 17th century by forensic pathologists. After World War II systematic studies of malpractice charges first were published in the 1960s. Meanwhile the attention focuses more and more on the role of forensic pathologists to help in prevention of malpractice.

Forensic Pathology↗

PubMed2004

Research issues in forensic pathology: a survey of academic institutions employing forensic pathologists.

In an effort to characterize research efforts in forensic pathology, a questionnaire was sent to a representative of each of the 14 academic medical centers that employ full-time faculty forensic pathologists. Responses were received from all 14 (100%) of the institutions queried, representing a total of 39 forensic pathology faculty positions; 21 positions were tenure track and 18 positions were clinical or other tracks. Of the 39 positions, 25 positions (64%) at 10 institutions required some degree of research or scholarly output. Of the 25 forensic pathologists with a research imperative, only 3 (12%) were principal investigators or co-investigators on funded forensic pathology-based projects. The major limitation cited by respondents on the performance of forensic pathology research was the lack of protected time from service responsibilities. Fellowship training in forensic pathology was available at 6 of the 14 respondent institutions. Of these institutions, 4 (67%) had a research requirement for trainees, and 4 (67%) provided research training. In conclusion, very few US medical schools currently employ full-time faculty forensic pathologists. Of these, only a small number of institutions prioritize research by these faculty members. Scant federal funds are available to support research in forensic pathology. Few forensic pathology fellowship programs provide research training. To achieve a robust research agenda in forensic pathology that is sufficient to support the needs of the criminal justice and public health systems will require a paradigm shift in the medicolegal death investigative system and investment by federal agencies.

Academic Medical Centers↗

PubMed2006

Current practice of diagnosis and reporting of prostate cancer on needle biopsy among genitourinary pathologists.

As there is a lack of hard data in the literature about many of the issues relating to diagnosing and reporting prostate cancer, we sought to survey current practices. A questionnaire was sent to 93 genitourinary pathologists with a response rate of 69%. Almost all respondents (95%) used formalin as fixative for needle biopsies. Unstained intervening sections were retained by 47%. Three levels of needle biopsies were used routinely by 63%. For verification of a diagnosis of cancer, high-molecular-weight cytokeratin was still the most commonly used immunohistochemical marker (91%), followed by p63 (58%) and alpha-methylacyl-CoA-racemase (50%). Features considered pathognomonic for cancer were glomeruloid bodies (58%), collagenous micronodules (64%), circumferential perineural invasion (84%), and growth in fat (36%). With none of these present, 39% required a minimum of 2 to 10 glands (median, 3) to diagnose cancer, whereas the others had no lower limit. A Gleason score was always given to even minute cancer foci by 86% and typically a Gleason score 6 was assigned (77%). Perineural invasion was mentioned by 86%. The extent of cancer on needle biopsies was quantified by all respondents with number of involved cores (80%) being the most commonly used measure. Linear extent was estimated by almost all, either as a percentage (80%) or millimeters of cancer length (41%) or both (22%). Measuring cancer from end to end or subtracting intervening benign tissue were almost equally common. For those general pathologists who would like to be in the mainstream of most urological pathologists, our survey data provide a guideline on how to diagnose and report prostate cancer.

Biopsy, Needle↗

PubMed2006

Role of the pathologist in organ transplantation: the North Italy Transplant program experience.

The North Italy Transplant program (NITp) is one of the three organ exchange organizations in Italy together with AIRT and OCST, supervised by the Centro Nazionale Trapianti. It started its activity on June 18, 1972 and serves an area of about 18 million inhabitants in northern Italy. From June 18, 1972 to December 31, 2004, 5761 cadaveric donors have been used and 18,390 transplants performed in the NITp. At December 31, 2004, the NITp waiting list included 3407 patients (2261 kidney, 425 heart, 387 liver, 153 pancreas, 181 lung). From January 1 to August 31, 2005, 13 donors with cancer were used, namely, 4.2% of the overall number of procured donors. The yearly projection of this figure is more than twofold above that in the previous year. Pathologists play a crucial role in NITp activity, by assessing donor suitability and organ quality, by performing the autopsy control of donors, and by participating in transplant follow-up. In addition the pathologist responsible for the Veneto-centralized pathology unit plays the role of expert for second opinion for the NITp area. Pathologists are involved in expanding the pool of donors by analyzing organ biopsies in specific programs. Eight HBV(+) and/or HCV(+) liver biopsies have been evaluated during 2003 and 18 during 2004 and 12 livers, according to the protocol, were suitable for transplantation, and 14 double kidney transplantations were performed in 2003 and 35 in 2004.

Cadaver↗

PubMed2000

The pathologist's role in sentinel lymph node evaluation.

Patients with high-risk (thick, deeply invasive) primary melanoma were, in the past, managed by wide local excision and elective node dissection or wide local excision alone, with subsequent lymphadenectomy if the regional nodes developed clinically detectable metastases. We recently developed a more logical approach called selective lymph node dissection. To be effective, this requires close collaboration of surgeons, pathologists, and nuclear medicine physicians. The draining lymph node basin is identified preoperatively by lymphoscintigraphy. During surgery, a marker dye (isosulfan blue) and radioactive technetium labeled albumin are injected intradermally around the primary melanoma and the afferent lymphatics are followed up to the first lymph nodes of the ipsilateral regional nodal basin. The surgeon excises the blue-colored and maximally radioactive sentinel nodes and the pathologist critically evaluates these for the presence of a metastatic tumor. If the sentinel nodes are tumor free, no further nodal dissection is undertaken; if a tumor is present, a complete dissection of the nodal basin is performed. We have examined 1,119 sentinel lymph nodes from 669 patients treated by selective lymph node dissection. We identified melanoma cells in sentinel nodes from 126 patients (17.8%). A single node contained tumors in 67% of patients, 2 nodes were positive in 25%, and the remaining 12% of patients had three tumor-containing nodes. Melanoma cells were dispersed singly or in variably sized groups, usually in the peripheral nodal sinus. In around 40% of patients, immunohistochemistry is required to identify minute numbers of tumor cells. With experience, pathologists identify tumors in hematoxylin and eosin (H&E) preparations in an increasing proportion of lymph nodes. Tumor cells are more frequent in the sentinel nodes of patients with primary tumors of deeper Clark level and greater Breslow thickness. Tumor cells must be discriminated from capsular nevus cells, interdigitating dendritic leukocytes, macrophages, and intranodal neural tissues.

Humans↗

PubMed2000

Her Majesty's coroners and home office forensic pathologists perception of the nurses' role in the coroner's enquiry.

A study was performed to elicit the perceived role of the registered nurse in the coroner's enquiry from Her Majesty's coroners and Home Office forensic pathologists viewpoint. A qualitative small sample study of unstructured interviews was performed followed by a quantitative and qualitative survey of all 134 coroners and 44 forensic pathologists practising in England and Wales. 72 (53.5%) coroners and 26 (59.1%) forensic pathologists finally participated in the study of which 51% perceived that there was a role for the nurse in the coroner's enquiry. Roles identified included: actual i. e. keeping records, being conversant with nursing policies and "knowing" ("Knowing" means having knowledge about coroners' enquiries); potential i.e. resource provider, communicator, supporter, presencing, evidence giver and stewardship; and future i. e. certifying the fact of death and being an expert witness. Possible action by the registered nurse to embrace the outcome of this study is put forward.

Attitude of Health Personnel↗

PubMed1980

The general pathologist's role in forensic medicine: the Massachusetts scene.

The Commonwealth of Massachusetts medicolegal system is discussed. The current situation necessitates active participation by general pathologists. The rudimentary skills needed in forensic pathology are delineated. It is emphasized that since medicolegal cases are nationally increasing and since recent comprehensive studies confirm the present shortage of full time forensic pathologists, it is imperative that general pathologists become more involved.

Autopsy↗

PubMed1998

Arthur Purdy Stout (1885-1967), a pioneer of surgical pathology: a survey of his Notes on the Education of an "Oncological" Surgical Pathologist.

Arthur Purdy Stout (1885-1967) started his medical career as a surgical intern and house surgeon at institutions that were to join the Columbia-Presbyterian Medical Center. With virtualy no formal training in pathology and little supervision, he was given the opportunity to work in a laboratory of surgical pathology. He focused his attention on neoplasms and tumor-like conditions, and authored Human Cancer in 1932. This book was organized according to topography of lesions and set a model for the Atlas of Tumor Pathology project. In addition to his many articles and slide seminars, Stout embarked during his "postretirement" years, with the help of residents and fellows, on a systematic study of soft tissue tumors in children. In 1950, he also began his Notes on the Education of an "Oncological" Surgical Pathologist. This manuscript of 427 typewritten pages offers candid details on his development as a surgical pathologist from rather primitive and chaotic beginnings, and on the post-World War II rise of surgical pathology. Notes provides interesting glimpses of his rapidly changing world, particularly of New York, the College of Physicians and Surgeons of Columbia University, and other pathologists. It also portrays an individual absorbed by his work and intent on leaving behind the legacy of a pioneer in the field of surgical pathology.

Academic Medical Centers↗

PubMed2006

Current practice of diagnosis and reporting of prostatic intraepithelial neoplasia and glandular atypia among genitourinary pathologists.

The criteria for diagnosing prostatic intraepithelial neoplasia (PIN) and lesions suspicious for cancer are described in the literature. However, it is unknown how these are applied in practice by experts in genitourinary (GU) pathology. A questionnaire was sent to 93 GU pathologists in countries around the world with the purpose of surveying current practices. The response rate was 69% including 40 North American pathologists and 24 from other continents. For preneoplastic lesions, the term PIN was universally endorsed by the respondents. PIN was graded by 83%, usually as low/high-grade PIN (LGPIN/HGPIN) or as HGPIN only. Most respondents would usually not report lesions that may qualify for LGPIN. A majority (81%) did not specify architectural patterns of PIN. With both HGPIN and invasive cancer present, 69% would still mention HGPIN. Among the diagnostic criteria for HGPIN were any nucleoli visible (52%), or nucleoli seen in at least 10% of cells (33%). However, 56% would diagnose HGPIN in the absence of prominent nucleoli, most commonly based on prominent pleomorphism, marked hyperchromasia or mitotic figures. The number of cores involved with HGPIN was specified by 50%. Lesions suspicious for but not diagnostic of carcinoma were reported by 45% as atypia, atypical glands or suspicious for cancer and by 42% as atypical small acinar proliferation. The degree of suspicion was further defined by 41%. Our survey data may serve as a guideline to general pathologists on how to diagnose and report atypia and PIN in prostate biopsies.

Adult↗

PubMed2000

Ubiquitin immunochemistry as a diagnostic aid for community pathologists evaluating patients who have dementia.

Alzheimer's disease is the most common cause of dementia It is associated with genetic risk factors and at least three autosomal dominant mutations. Community pathologists are frequently asked by families to evaluate autopsy material for Alzheimer's disease. Neuropathologic diagnosis is based on technically difficult silver impregnation stains that may not be readily available to community-based pathologists. Because immunohistochemical techniques are more widely accessible, we evaluated the practical utility of using a single immunohistochemical stain for diagnosing Alzheimer's disease. The ubiquitin antigen was selected because of its presence in morphologically distinct deposits characteristic of several neurodegenerative diseases. Paraffin blocks were obtained from the Bryan Alzheimer's Disease Research Center Brain Bank, a repository of approximately 900 brains. Tissues from 16 individuals who exhibited the entire range of Alzheimer's-type neuropathology were selected. Ubiquitin immunostains, evaluated blindly and independently by four pathologists ranging from first-year resident trainee to experienced neuropathologist, reliably stained both neuritic plaques and neurofibrillary tangles essential for diagnosing and staging Alzheimer's disease. Nondemented controls with early Alzheimer's-type changes were easily distinguished from cases of definitive Alzheimer's disease. The stains also highlighted characteristic inclusions of Parkinson's disease or Lewy body dementia Ubiquitin immunohistochemistry is a reliable, reproducible, and readily available diagnostic aid for distinguishing Alzheimer's disease from other causes of dementia.

Aged↗