bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoplasia Without Dysplasia: Lessons From Barrett Esophagus and Other Tubal Gut Neoplasms
Authors: Odze Robert D. , Maley Carlo C. 
Published: February 2021

Abstract
Context.—Classic pathology teaching emphasizes that neoplastic lesions of the gastrointestinal tract are characterized by architectural and cytologic abnormalities that distinguish it from normal tissue. Recent studies suggest that many important—and in some cases clonal—molecular abnormalities that lead to dysregulation of cell proliferation and differentiation (neoplasia) occur before morphologic expression of dysplasia.
Objective.—To summarize the biologic and pathologic features of preneoplastic conditions of the tubal gut that reveal evidence of neoplastic alteration, but without the traditional morphologic features of dysplasia, in order to provide guidance on how to identify these lesions. Particular attention is given to Barrett esophagus, a chronic inflammatory condition in which early molecular and morphologic events that drive carcinogenesis are best understood.
Data Sources.—Selected references and abstracts were obtained by a PubMed (US National Library of Medicine) search by using the search headings neoplasia, preneoplasia, dysplasia, adenoma, serrated polyps, and Barrett's esophagus between the years 1980 and 2009.
Conclusions.—Many types of lesions throughout the tubal gut fulfill the most basic and classic principles of a neoplastic precursor lesion but lack conventional morphologic evidence of dysplasia and/or maintain the capacity for cell differentiation and maturation. All of these lesions, such as squamous dysplasia of the esophagus, dysplasia in Barrett esopahagus, and hyperplastic/serrated polyps of the colon, represent early neoplastic precursor lesions but without conventional histologic features of dysplasia. It is important for pathologists to be aware of these lesions, both for diagnostic and prognostic purposes, but also so that future studies can be performed with regard to risk stratification of patients.
Recommendations for Validating Estrogen and Progesterone Receptor Immunohistochemistry Assays
Authors: Fitzgibbons Patrick L. , Murphy Douglas A. , Hammond M. Elizabeth H. , Allred D. Craig , Valenstein Paul N. 
Published: February 2021

Abstract
Context.—Estrogen receptor and progesterone receptor status is assessed on all newly diagnosed, invasive breast carcinomas and in recurrences to determine patient eligibility for hormonal therapy, but 10% to 20% of estrogen receptor and progesterone receptor test results are discordant when tested in multiple laboratories.
Objective.—To define the analytic (technical) validation requirements for estrogen receptor and progesterone receptor immunohistochemistry assays used to select patients for hormonal therapy.
Data Sources.—Literature review and expert consensus.
Conclusions.—A standardized process for initial test validation is described. We believe adoption of this process will improve the accuracy of hormone-receptor testing, reduce interlaboratory variation, and minimize false-positive and false-negative results. Required ongoing assay assessment procedures are also described.
American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer (Unabridged Version)
Authors: Hammond M. Elizabeth H. , Hayes Daniel F. , Dowsett Mitch , Allred D. Craig , Hagerty Karen L. , Badve Sunil , Fitzgibbons Patrick L. , Francis Glenn , Goldstein Neil S. , Hayes Malcolm , Hicks David G. , Lester Susan , Love Richard , Mangu Pamela B. , McShane Lisa , Miller Keith , Osborne C. Kent , Paik Soonmyung , Perlmutter Jane , Rhodes Anthony , Sasano Hironobu , Schwartz Jared N. , Sweep Fred C. G. , Taube Sheila , Torlakovic Emina Emilia , Valenstein Paul , Viale Giuseppe , Visscher Daniel , Wheeler Thomas , Williams R. Bruce , Wittliff James L. , Wolff Antonio C. 
Published: February 2021

AbstractPurpose.—To develop a guideline to improve the accuracy of immunohistochemical (IHC) estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer and the utility of these receptors as predictive markers.Methods.—The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance.Results.—Up to 20% of current IHC determinations of ER and PgR testing worldwide may be inaccurate (false negative or false positive). Most of the issues with testing have occurred because of variation in pre-analytic variables, thresholds for positivity, and interpretation criteria.Recommendations.—The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences. A testing algorithm that relies on accurate, reproducible assay performance is proposed. Elements to reliably reduce assay variation are specified. It is recommended that ER and PgR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of randomized clinical trials.
Pathology Practice in a Resource-Poor Setting: Mwanza, Tanzania
Authors: Rambau Peter F 
Published: February 2021

AbstractPracticing pathology in a resource-poor setting presents many challenges that are unfamiliar to pathologists in developed countries. Typically, the number of pathologists in a resource-poor country is small, even as a percentage of the total medical workforce. Although pathology should play a central role in the delivery of appropriate health care to the patient, this role is often hidden and not well recognized by patients, clinical colleagues, or other stakeholders, such as administrators and politicians. The public tends to think of the pathologist as the “Doctor of the Dead.” The financial rewards are also small. Consequently, it is difficult to recruit physicians into pathology. The lack of human and material resources allocated to pathology leads inevitably to a large gap in health care for many patients, with an unmeasured negative effect, at both the individual and societal levels. Correct management of the patient, even when available, is not administered because of the lack of pathologic information. Surgery may be performed without the benefit of preoperative or postoperative pathologic confirmation of the diagnosis, let alone identification of important prognostic information. The pathologist plays a key role as an educator in developing countries to medical students, allied health professionals, and medical colleagues and is, therefore, called upon to provide many hours of teaching. The pathologist is uniquely qualified to provide knowledge and understanding regarding the diseases in the region where he or she practices. Although many of these challenges are universal, they are perhaps nowhere more acute than in resource-poor settings.
Cytopathology Including Fine-Needle Aspiration in Sub-Saharan Africa: A Cameroon Experience
Authors: Guggisberg Kelly , Okorie Chukwudi , Khalil Moosa 
Published: February 2021

Abstract
Context.—Surgical pathology is unavailable in most of sub-Saharan Africa because of equipment costs and lack of expertise. Cytopathology is an inexpensive and reliable alternative.
Objective.—To explore the utility of cytopathology in a rural hospital setting in Africa.
Design.—A cytopathologist and a pathology resident from Calgary, Alberta, Canada, went to Cameroon to provide a cytopathology service at the Banso Baptist Hospital. Both performed the fine-needle aspiration procedures. Direct smears were fixed in alcohol and stained with hematoxylin-eosin. Surgical specimens subsequently obtained from the patients were processed and reported at Calgary Laboratory Services, Canada. The histopathologic diagnoses were the gold standard for determining the accuracy of the cytologic diagnoses.
Results.—Fifty-nine patients were examined during a 5-week period, 33 females (56%) and 26 males (44%). Sixteen (27%) were known to be HIV positive. Forty-four fine-needle aspiration procedures were performed for 43 patients (73%). The cost of each procedure was approximately US $10. Head and neck and breast were the sites most frequently sampled for aspirates. Cervical smears from 5 patients were also assessed, as were 8 fluid specimens and 2 touch preparations of prostatic core biopsies. The most frequent diagnoses for malignancy were carcinoma and lymphoma. Tuberculous lymphadenitis was diagnosed in 6 patients, 4 of whom were HIV positive. Surgical specimens were received from 18 patients (30%). Cytohistologic and clinicopathologic correlation revealed 1 false-positive (1.6%) and 1 false-negative (1.6%) diagnosis.
Conclusion.—Cytopathology is a reliable alternative for tissue diagnosis in low-resource settings.
Malaria in Malawi: Inside a Research Autopsy Study of Pediatric Cerebral Malaria
Authors: White Valerie A 
Published: February 2021

Abstract
Context.—Malaria is still a major cause of death in sub-Saharan Africa.
Objectives.—To describe my participation as a pathologist in a research autopsy study in Malawi and to examine retinal pathologic findings in cerebral malaria and correlate them with those in the brain. To describe the challenges of conducting a research study in sub-Saharan Africa and the personal and scientific benefits resulting from this.
Design.—Children with coma are admitted to the pediatric research ward, classified according to the clinical definition of severe malaria or another cause of coma, evaluated, and treated systematically. The eyes are examined by indirect ophthalmoscopy after dilatation. If a child dies and permission is given, a standardized autopsy is carried out. The patients' condition is then reclassified pathologically.
Results.—Ninety autopsies have been completed, with the cause of death confirmed as cerebral malaria in 64 cases (71.1%). These patients showed heavy parasite sequestration and often extravascular pathologic findings in the brain, retina, gastrointestinal tract, and subcutaneous fat. Clinical and pathologic findings in the retina correlated with those in the brain, and ophthalmoscopy has become a useful tool in the diagnosis and prognosis of children with cerebral malaria. Twenty-eight percent of patients clinically classified as having cerebral malaria showed another cause of death and no malarial pathologic process or retinopathy.
Conclusions.—The human, financial, and transportation resources and organization required for this autopsy project are substantial. The scientific benefits are now becoming evident after sufficient autopsies have been completed for detailed comparisons. Personal benefits include the opportunity to work and travel in an African setting and to develop collaborations world-wide.
External Quality Assurance of Antithrombin, Protein C, and Protein S Assays: Results of the College of American Pathologists Proficiency Testing Program in Thrombophilia
Authors: Cunningham Mark T , Olson John D , Chandler Wayne L , Van Cott Elizabeth M , Eby Charles S , Teruya Jun , Hollensead Sandra C , Adcock Dorothy M , Allison Paul M , Kottke-Marchant Kandice K , Smith Marc D 
Published: February 2021

Abstract
Context.—Hereditary and acquired deficiencies of antithrombin (AT), protein C (PC), and protein S (PS) are risk factors for venous thromboembolism. Proper diagnosis requires high-quality assays for these proteins.
Objective.—To determine the accuracy and interlaboratory precision of AT, PC, and PS assays used by laboratories participating in the United States College of American Pathologists proficiency testing program in thrombophilia and to grade the performance of laboratories.
Design.—Standardized normal plasma with assigned analyte values was sent in 2 separate challenges to participating laboratories. Participants measured AT, PC, and PS levels using local methods.
Results.—When compared with the assigned values for the international standard, the order of assay accuracy from highest to lowest was AT activity, PC antigen, AT antigen, total PS antigen, PC activity, PS activity, and free PS antigen (range of assay bias, 2.6%–8.8%). The order of assay precision from highest to lowest was PC activity, AT activity, AT antigen, total PS antigen, PS activity, free PS antigen, and PC antigen (range of assay coefficient of variation, 6.1%–20.0%). Most testing events (87.8%) could be graded as pass or fail using a target range of ±3 standard deviations from the method-specific mean. The pass rate was 98.2% for all AT, PC, and PS testing events combined.
Conclusions.—Accuracy and precision were higher for AT assays and lower for PC and PS assays. It was feasible to grade individual laboratory performance.
The Movat Pentachrome Stain as a Means of Identifying Microcrystalline Cellulose Among Other Particulates Found in Lung Tissue
Authors: Sigdel Saroj , Gemind J. Todd , Tomashefski Joseph F 
Published: February 2021

AbstractContext.—Microcrystalline cellulose (MCC) is extensively used as a filler material in pharmaceutical tablets. When injected intravenously in aqueous tablet suspensions, MCC may contribute to embolic pulmonary hypertension and be identified histologically in lung tissue samples. In this study, we evaluated a modified Russell Movat pentachrome stain (MMPS) as a means of recognizing MCC and distinguishing it from other birefringent crystals in lung specimens.Objective.—To study the staining properties of MCC versus other crystalline materials using the MMPS stain.Design.—Archival, formalin-fixed, paraffin-embedded lung specimens that contained birefringent crystals, including MCC (3 cases of intravenous drug abuse), talc (2 cases of intravenous drug abuse, 1 talc pleurodesis), mixed silicates (1 case of silicate pneumoconiosis), and calcium oxalate (1 case of aspergillosis from Aspergillus niger infection), were evaluated with MMPS. Crystal identification was confirmed by morphology, other histochemical stains, infrared spectroscopy (1 case), and cellulose controls.Results.—The MMPS stained the MCC bright yellow in tissue and control specimens. Talc stained light greenish-blue; mixed silicates appeared either greenish-blue or unstained. Oxalate crystals stained sea-green. Crospovidone, a nonbirefringent tablet filler substance, stained yellow to dark green with MMPS and was easily distinguished from MCC. Starch granules were unstained by MMPS.Conclusions.—The MMPS is an excellent method for the histochemical identification of MCC in tissue and its separation from other birefringent crystals with which MCC might be confused. The MMPS is especially useful in the evaluation of pulmonary foreign body embolization in cases of suspected intravenous substance abuse.
Solitary Fibrous Tumor of the Orbit With Epithelioid Features
Authors: Warraich Irfan , Dunn Dale M. , Oliver Jeffrey W. 
Published: February 2021

Abstract
Extrapleural solitary fibrous tumors have often been confused with other mesenchymal tumors, such as hemangiopericytoma, fibrous histiocytoma, fibrous meningioma, and leiomyoma, because of morphologic similarity and underrecognition, especially if some unusual features are present. Recently, epithelioid solitary fibrous tumor has been reported in the mediastinum. We report a case of solitary fibrous tumor of the orbit with biphasic architecture, including spindle cell and epithelioid components. Both components demonstrated immunohistochemical features of a solitary fibrous tumor. A background of scattered vessels was present. No evidence of significant nuclear atypia or mitotic activity was noted. In this report, we discuss the differential diagnosis of solitary fibrous tumor with unusual epithelioid features. Extrapleural solitary fibrous tumor should be included in the differential diagnosis of tumors of the orbit with a spindle cell appearance even in the presence of some epithelioid morphology.
Update on Pancreatic Endocrine Tumors
Authors: Frankel Wendy L. 
Published: February 2021

Abstract
Endocrine tumors of the pancreas represent 1% to 2% of all pancreatic neoplasms. The tumors tend to have an indolent behavior, and long-term survival is common. There is no gender or age predilection. Patients can present with symptoms due to hormonal excess or a local mass effect or be asymptomatic. The tumors tend to be solid and well circumscribed. Typical microscopic findings include an organoid pattern of growth, with cells containing scant to moderate amounts of cytoplasm, and nuclei with dispersed chromatin and inconspicuous nucleoli. The morphologic spectrum of these tumors can be variable, and the differential diagnosis includes chronic pancreatitis with neuroendocrine hyperplasia, ductal adenocarcinoma, solid pseudopapillary tumor, acinar cell carcinoma, and pancreatoblastoma. The classification of these tumors remains controversial, and prognosis is difficult to predict, but important features include metastasis and invasion of adjacent structures. Resection remains the mainstay of surgical treatment. It is important to be aware that unusual morphologic variants of pancreatic endocrine tumors are common, and immunohistochemical stains can help avoid misdiagnosis.
Accuracy and Cost-Effectiveness of Core Needle Biopsy in the Evaluation of Suspected Lymphoma: A Study of 101 Cases
Authors: Lachar Whitney A. , Shahab Imran , Saad A. Joe 
Published: February 2021

Abstract
Context.—Lymphomas have traditionally been diagnosed on excisional biopsies of lymph nodes in order to evaluate tissue architecture and cytomorphology. Recent lymphoma classification schemes emphasize immunophenotypic, genetic, and molecular aspects in addition to morphology as diagnostic features. Core needle biopsies are increasingly being used to obtain tissue for diagnosis in patients with lymphadenopathy and a clinical suspicion of lymphoma. These procedures are rapid, minimally invasive, well tolerated, and may provide some architectural framework (unlike fine-needle aspirations), as well as material for ancillary studies.
Objective.—To explore the accuracy, utility, and cost-effectiveness of this technique.
Design.—Core needle biopsies of 101 consecutive patients from 2 large community hospitals who were suspected of having primary or recurrent lymphomas were retrospectively reviewed. All patients had hematoxylin-eosin–stained sections of needle cores. Specimens morphologically suspicious for lymphoma were subjected to ancillary studies, including immunohistochemistry, flow cytometry, and/or molecular studies. Core needle biopsy diagnoses were correlated with subsequent excisional biopsies, if performed.
Results.—Core needle biopsies established a definitive pathologic diagnosis for the vast majority of cases. A diagnosis was considered sufficient to begin treatment for primary and recurrent lymphomas in most cases. Compared with an open biopsy, there is a cost savings of greater than 75%.
Conclusion.—The accuracy of this technique, along with the cost savings and decreased morbidity, suggest that this method may be used safely and reliably as a first-line diagnostic technique.
The Contribution of Bifunctional SkipDewax Pretreatment Solution, Rabbit Monoclonal Antibodies, and Polymer Detection Systems in Immunohistochemistry
Authors: Wong Sze Chuen Cesar , Chan John K. C. , Lo Elena S. F. , Chan Amanda K. C. , Wong Manson C. K. , Chan Charles M. L. , Lam Money Y. Y. , Chan Anthony T. C. 
Published: February 2021

Abstract
Context.—In immunohistochemistry, nonstandardized antigen retrieval protocols and fluids, poor-quality antibodies, and the presence of endogenous biotin frequently lead to incorrect results. Recently, advanced reagents including bifunctional SkipDewax pretreatment solution (BSPS), rabbit monoclonal (RM) antibodies, and biotin-free polymer detection systems (PDSs) have been developed, which, it is claimed, resolve these problems.
Objectives.—To determine whether BSPS, RM antibodies, and biotin-free PDSs improve the accuracy of immunohistochemistry; to optimize a new protocol consisting of a combination of BSPS, RM antibodies, and PDSs; and to compare it with a conventional protocol.
Design.—The efficacies of BSPS, RM antibodies, and PDSs were compared with those of their respective conventional reagents using multitissue spring-roll sections. The new protocol was compared with a conventional protocol using Ki-67 immunostaining of 49 colorectal carcinoma specimens.
Results.—For antigen retrieval, BSPS resulted in similar or better tissue staining than an EDTA solution, but the efficacy of BSPS decreased when it was reused. Most RM antibodies resulted in a greater proportion of positive cells than the corresponding non-RM antibodies, which did not produce satisfactory results in the absence of antigen retrieval. The PDSs Bond, ChemMate, and SuperPicture resulted in a high percentage of positive cells, good staining intensities, and low backgrounds. Other PDSs, except that from Ventana, resulted in high backgrounds and false positivity. The new combined protocol resulted in better Ki-67 staining than the conventional assay.
Conclusions.—Bifunctional SkipDewax pretreatment solution, RM antibodies, and PDSs improve staining quality and diagnostic accuracy of immunohistochemistry assays and provide a foundation for standardization.
A Proposal on the Identification, Histologic Reporting, and Implications of Intraductal Prostatic Carcinoma
Authors: Cohen Ronald J. , Wheeler Thomas M. , Bonkhoff Helmut , Rubin Mark A. 
Published: February 2021

AbstractContext.—Prostatic adenocarcinoma growing within acinar-ductal spaces (intraductal carcinoma) in contrast to high-grade prostatic intraepithelial neoplasia (HG-PIN) impacts negatively on patient outcome. There is currently no generally accepted definition of this lesion nor is it classified in the current prostate cancer grading system (Gleason).Objective.—To define intraductal carcinoma of the prostate (IDC-P) with major and minor diagnostic criteria that clearly separate it from HG-PIN. The implications of such a lesion are discussed with proposals to incorporate this entity into the Gleason grading system.Data Sources.—We reviewed all published data referring to intraductal spread of prostate carcinoma. Articles discussing endometrial, endometrioid, and ductal carcinoma are included.Conclusions.—Intraductal carcinoma of the prostate as defined by major criteria that include enlarged gland structures, neoplastic cells spanning the gland lumen, central comedonecrosis, and further supported by minor diagnostic criteria including molecular biological markers, separate this entity from HG-PIN. Despite its perimeter basal cells, IDC-P should be interpreted as biologically equivalent to Gleason pattern 4 or 5 adenocarcinoma. Several hypotheses are proposed as to the evolution of IDC-P, which is almost always a late event in prostate carcinoma progression. Diagnosis of IDC-P on needle biopsy should prompt therapeutic intervention rather than surveillance or repeat biopsy, as is the case for HG-PIN.