bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presence of c-KIT–Positive Mast Cells in Obliterative Bronchiolitis From Diverse Causes
Authors: Fuehrer Neil E. , Marchevsky Alberto M. , Jagirdar Jaishree 
Published: February 2021

AbstractContext.—The mechanism of fibrosis is not clear in patients with obliterative bronchiolitis after a remote injury. Immune-mediated progression may be a reason. c-KIT (CD117)–positive mast cells have been associated with chronic fibrosing diseases and may potentially be treated with imatinib (Gleevec), a c-KIT blocker.Objective.—To evaluate the role of mast cells in fibrosis associated with obliterative bronchiolitis.Design.—Four cases of obliterative bronchiolitis (household cleaner exposure, ammonia exposure, idiopathic, and posttransplantation) were compared with asthma/emphysema. Small and large airways were stained for CD20, CD3, CD4, CD8, CD117, CD34, CD25, stem cell factor (c-KIT ligand) and with toluidine blue, hematoxylin-eosin, and trichrome. c-KIT (CD117)–stained slides were digitally scanned with Aperio ScanScope and stained cells within the epithelium and subepithelium of small and large airways were counted (per millimeter of basement membrane).Results.—Mast cells were concentrated within the involved subepithelium of small airways in obliterative bronchiolitis (122 cells/mm), unlike asthma/emphysema (25 cells/mm). Conversely, there were more mast cells in the epithelium in cases of asthma/emphysema than in obliterative bronchiolitis (7 cells/mm and 2 cells/mm, respectively). Mast cells were significantly increased around involved airways versus uninvolved airways (52 cells/mm vs 14 cells/mm). Large airways in either group had similar c-KIT (CD117) expression. Stem cell factor was not increased.Conclusions.—Mast cells appear to be concentrated in the lesional small-airway subepithelium in obliterative bronchiolitis. The possible role of c-KIT inhibitors such as imatinib (Gleevec) in the progression of fibrosis preceding the development of obliterative bronchiolitis is discussed.
Follow-up Findings for Women With Human Papillomavirus–Positive and Atypical Squamous Cells of Undetermined Significance Screening Test Results in a Large Women's Hospital Practice
Authors: Armah Henry , Austin R. Marshall , Dabbs David , Zhao Chengquan 
Published: February 2021

Abstract
Context.—Reflex human papillomavirus (HPV) testing has been designated in consensus guidelines as “preferred” for women with atypical squamous cells of undetermined significance (ASC-US) liquid-based cytology (LBC) results, and colposcopy is currently recommended for patients with HPV-positive ASC-US results. Data from large clinical practices using newer screening methods and current cytology terminology are limited.
Objectives.—We analyzed data from patients with ASC-US LBC and positive HPV test results. We also assessed the impact of the presence or absence of an endocervical cell/ transformation zone sample (EC/TZS) on biopsy diagnoses.
Design.—The information system of a large women's hospital serving an older-than-average population was searched over a 21-month period between July 1, 2005, and March 31, 2007, for HPV-positive cases interpreted as ASC-US (Bethesda System 2001) using computer-imaged LBC. Histologic diagnoses, patient ages, and presence or absence of an EC/TZS were analyzed. The average follow-up period was 7.5 months.
Results.—Among 4273 women with HPV-positive ASC-US results, the cumulative cervical intraepithelial neoplasia 2 or 3 (CIN 2/3) and CIN 1 rates for 2192 women with available biopsies were 5.1% and 43.6%, respectively. Cervical intraepithelial neoplasia 2/3 and CIN 1 rates for women with HPV-positive ASC-US results were not significantly different for women with and without an EC/TZS.
Conclusions.—The risk of CIN 2/3 in the study population was significantly lower than reported in widely cited trial data. Neither presence nor absence of an EC/TZS, nor the age of the patient, had a statistically significant impact on the likelihood of biopsy diagnoses of CIN 2/3 and CIN 1 for patients with HPV-positive ASC-US test results.
Circulating Tumor Cells From Well-Differentiated Lung Adenocarcinoma Retain Cytomorphologic Features of Primary Tumor Type
Authors: Marrinucci Dena , Bethel Kelly , Luttgen Madelyn , Bruce Richard H. , Nieva Jorge , Kuhn Peter 
Published: February 2021

Abstract
The detailed cytomorphologic appearance of circulating tumor cells (CTCs) in cancer patients is not well described, despite publication of multiple methods for enumerating these cells. In this case study, we present the cytomorphology of CTCs obtained from the blood of a woman with stage IIIB well-differentiated lung adenocarcinoma. Four years after she was diagnosed with her disease, 67 CTCs were identified in a blood sample using an immunofluorescent staining protocol and then subsequently stained with Wright-Giemsa. The cytomorphology of the CTCs was compared with the original tissue biopsy from 4 years prior. We found that CTCs and cells from the original biopsy had strikingly similar morphologic features, including large size in comparison to white blood cells and low nuclear to cytoplasmic ratios with voluminous cytoplasm. Careful cytomorphologic evaluation of CTCs will provide insights about the metastatic significance of these cells, which could yield widespread implications for the diagnosis, treatment, and management of cancer.
Basal-like Breast Carcinoma: A Phenotypically Distinct Entity
Authors: Haupt Bisong , Ro Jae Y. , Schwartz Mary R. 
Published: February 2021

AbstractGene microarray profiling of human breast carcinomas has recently categorized invasive breast carcinomas into 5 distinct subtypes; luminal A, luminal B, normal breastlike, human epithelial growth factor receptor 2 (HER2) overexpressing, and basal-like. Basal-like breast carcinomas are characterized by high expression of basal cytokeratins; low or absent expression of estrogen receptor, progesterone receptor, and HER2/neu; and expression of epidermal growth factor receptor (EGFR) and/or c-kit, and they are frequently associated with breast cancer 1 (BRCA1) mutations and poor clinical outcome. Recent studies have begun to provide insights into the molecular genetics, biology, morphology, and clinical outcome of this subtype of breast carcinoma. We reviewed the literature related to basal-like breast carcinomas to better understand this clinically significant subtype of breast carcinoma.
Diagnosis of Metastatic Neoplasms: Molecular Approaches for Identification of Tissue of Origin
Authors: Monzon Federico A. , Koen Tracie J. 
Published: February 2021

AbstractContextTumors of uncertain or unknown origin are estimated to constitute 3% to 5% of all metastatic cancer cases. Patients with these types of tumors show worse outcomes when compared to patients in which a primary tumor is identified. New molecular tests that identify molecular signatures of a tissue of origin have become available.ObjectiveTo review the literature on existing molecular approaches to the diagnosis of metastatic tumors of uncertain origin and discuss the current status and future developments in this area.Data SourcesPublished peer-reviewed literature, available information from medical organizations (National Comprehensive Cancer Network), and other publicly available information from tissue-of-origin test providers and/or manufacturers.ConclusionsMolecular tests for tissue-of-origin determination in metastatic tumors are available and have the potential to significantly impact patient management. However, available validation data indicate that not all tests have shown adequate performance characteristics for clinical use. Pathologists and oncologists should carefully evaluate claims for accuracy and clinical utility for tissue-of-origin tests before using test results in patient management. The personalized medicine revolution includes the use of molecular tools for identification/confirmation of the site of origin for metastatic tumors, and in the future, this strategy might also be used to determine specific therapeutic approaches.
Patient Misidentification in Laboratory Medicine: A Qualitative Analysis of 227 Root Cause Analysis Reports in the Veterans Health Administration
Authors: Dunn Edward J. , Moga Paul J. 
Published: February 2021

Abstract

Context
Mislabeled laboratory specimens are a common source of harm to patients, such as repeat phlebotomy; repeat diagnostic procedure, including tissue biopsy; delay in a necessary surgical procedure; and the execution of an unnecessary surgical procedure. Mislabeling has been estimated to occur at a rate of 0.1% of all laboratory and anatomic pathology specimens submitted.

Objective
To identify system vulnerabilities in specimen collection, processing, analysis, and reporting associated with patient misidentification involving the clinical laboratory, anatomic pathology, and blood transfusion services.

Design
A qualitative analysis was performed on 227 root cause analysis reports from the Veterans Health Administration. Content analysis of case reports from March 9, 2000, to March 1, 2008, was facilitated by a Natural Language Processing program. Data were categorized by the 3 stages of the laboratory test cycle.

Results
Patient misidentification accounted for 182 of 253 adverse events, which occurred in all 3 stages of the test cycle. Of 132 misidentification events occurring in the preanalytic phase, events included wrist bands labeled for the wrong patient were applied on admission (n  =  8), and laboratory tests were ordered for the wrong patient by selecting the wrong electronic medical record from a menu of similar names and Social Security numbers (n  =  31). Specimen mislabeling during collection was associated with “batching” of specimens and printed labels (n  =  35), misinformation from manual entry on laboratory forms (n  =  14), failure of 2-source patient identification for clinical laboratory specimens (n  =  24), and failure of 2-person verification of patient identity for blood bank specimens (n  =  20). Of 37 events in the analytic phase, relabeling all specimens with accession numbers was associated with mislabeled specimen containers, tissue cassettes, and microscopic slides (n  =  27). Misidentified microscopic slides were associated with a failure of 2-pathologist verification for cancer diagnosis (n  =  4), and wrong patient transfusions were associated with mislabeled blood products (n  =  3) and a failure of 2-person verification for blood products before release by the blood bank (n  =  3). There were 13 events in the postanalytic phase in which results were reported into the wrong patient medical record (n  =  8), and incompatible blood transfusions were associated with failed 2-person verification of blood products (n  =  5).

Conclusions
Patient misidentification in the clinical laboratory, anatomic pathology, and blood transfusion processes were due to a limited set of causal factors in all 3 phases of the test cycle. A focus on these factors will inform systemic mitigation and prevention strategies.
A Rare Case of Lipoprotein Glomerulopathy in a White Man: An Emerging Entity in Asia, Rare in the White Population
Authors: Boumendjel Redouane , Papari Mona , Gonzalez Miguel 
Published: February 2021

AbstractLipoprotein glomerulopathy is a rare entity that predominantly affects the Asian population, mainly the Japanese and Chinese. Lipoprotein glomerulopathy is clinically characterized by proteinuria and progression to renal failure and is caused by glomerular lipoprotein thrombi formation in association with increased levels of serum apolipoprotein E. The disease has a male predominance and can affect virtually any age group. We describe the third reported case, to our knowledge, of lipoprotein glomerulopathy to affect a white patient.
Activation-Induced Cytidine Deaminase Expression in Diffuse Large B-Cell Lymphoma With a Paracortical Growth Pattern: A Lymphoma of Possible Interfollicular Large B-Cell Origin
Authors: Aguilera Nadine S. , Auerbach Aaron , Barekman Carol L. , Lichy Jack , Abbondanzo Susan L. 
Published: February 2021

Abstract
Context.—Activation-induced cytidine deaminase, necessary for immunoglobulin somatic hypermutation and class switch recombination, is usually expressed within the follicular dendritic network but is also expressed in a population of interfollicular large B cells outside the germinal center.
Objective.—To report 7 cases of diffuse large B-cell lymphoma with a distinct paracortical distribution. Expression of activation-induced cytidine deaminase, previously described in interfollicular large B cells, was evaluated.
Design.—A panel of immunohistochemical markers, including double staining for activation-induced cytidine deaminase and CD20, was used to illustrate the cases. Molecular studies were performed by polymerase chain reaction in the paraffin-embedded tissue for t(14;18) chromosomal translocation and immunoglobulin heavy chain and T-cell receptor rearrangements.
Results.—Patients included 3 males and 4 females ranging in age from 11 to 59 years (mean, 39 years). All specimens were lymph nodes (4 from the groin, 2 from the neck, and 1 from the axilla). Malignant lymphocytes were positive for CD20 and negative for CD5 and CD10. Staining for CD30, CD43, and BCL-2 was variable. The malignant cells showed at least focal staining with activation-induced cytidine deaminase. All cases were found to be monoclonal by immunoglobulin heavy-chain gene rearrangement or showed light-chain restriction. None of the tested cases showed t(14;18).
Conclusions.—Diffuse large B-cell lymphoma with a paracortical distribution is unusual and may be a distinct morphologic variant. More study is necessary to determine the stage of B-cell development and the cell of origin of these tumors. However, activation-induced cytidine deaminase expression suggests they may arise from a putative interfollicular large B cell.
A Proposed Histopathologic Classification, Scoring, and Grading System for Renal Amyloidosis: Standardization of Renal Amyloid Biopsy Report
Authors: Şen Sait , Sarsık Banu 
Published: February 2021

Abstract
Context.—A disease associated with amyloid deposits, called amyloidosis, is associated with characteristic electron microscopic appearance, typical x-ray pattern, and specific staining. Renal involvement mainly occurs in AA amyloidosis and AL amyloidosis and usually progresses to renal failure.
Objective.—The renal histopathologic changes with amyloidosis comprise a spectrum. Clear relationships between the extent of amyloid deposition and the severity of clinical manifestations have not been demonstrated. Whether there is a lack of clinicopathologic correlation is not clear, but studies have revealed the need for standardization of the renal amyloid biopsy report. With these objectives in mind, we proposed a histopathologic classification, scoring, and grading system. Renal amyloidosis was divided into 6 classes, similar to the classification of systemic lupus erythematosus. Amyloid depositions and other histopathologic lesions were scored. The sum of these scores was termed the renal amyloid prognostic score and was divided into 3 grades.
Data Sources.—AA amyloidosis was detected in 90% of cases, mostly related to familial Mediterranean fever. Positive correlations between class I and grade I, class VI and grade III, and class III and grade II were observed. Also, a positive correlation was identified between severity of glomerular amyloid depositions, interstitial fibrosis, and inflammation. Because of the inadequacy of the patients' records and outcomes, different therapy regimes, and etiologies, clinical validation of this study has not been completed.
Conclusions.—Standardization of the renal amyloid pathology report might be critical for patients' medication and comparison of outcome and therapeutic trials between different clinics. Because of our AA to AL amyloidosis ratio and the predisposition of familial Mediterranean fever–related AA amyloidosis, there is a need for further international collaborative studies.
Cystic Diseases of the Kidney: Molecular Biology and Genetics
Authors: Deltas Constantinos , Papagregoriou Gregory 
Published: February 2021

AbstractContext.—Cystic diseases of the kidney are a very heterogeneous group of renal inherited conditions, with more than 33 genes involved and encompassing X-linked, autosomal dominant, and autosomal recessive inheritance. Although mostly monogenic with mendelian inheritance, there are clearly examples of oligogenic inheritance, such as 3 mutations in 2 genes, while the existence of genetic modifiers is perhaps the norm, based on the extent of variable expressivity and the broad spectrum of symptoms.Objectives.—To present in the form of a mini review the major known cystic diseases of the kidney for which genes have been mapped or cloned and characterized, with some information on their cellular and molecular biology and genetics, and to pay special attention to commenting on the issues of molecular diagnostics, in view of the genetic and allelic heterogeneity.Data Sources.—We used major reviews that make excellent detailed presentation of the various diseases, as well as original publications.Conclusions.—There is already extensive genetic heterogeneity in the group of cystic diseases of the kidney; however, there are still many more genes awaiting to be discovered that are implicated or mutated in these diseases. In addition, the synergism and interaction among this repertoire of gene products is largely unknown, while a common unifying aspect is the expression of nearly all of them at the primary cilium or the basal body. A major interplay of functions is anticipated, while mutations in all converge in the unifying phenotype of cyst formation.
Glomerulocystic Kidney: One Hundred–Year Perspective
Authors: Lennerz Jochen K. , Spence David C. , Iskandar Samy S. , Dehner Louis P. , Liapis Helen 
Published: February 2021

AbstractContext.—Glomerular cysts, defined as Bowman space dilatation greater than 2 to 3 times normal size, are found in disorders of diverse etiology and with a spectrum of clinical manifestations. The term glomerulocystic kidney (GCK) refers to a kidney with greater than 5% cystic glomeruli. Although usually a disease of the young, GCK also occurs in adults.Objective.—To assess the recent molecular genetics of GCK, review our files, revisit the literature, and perform in silico experiments.Data Sources.—We retrieved 20 cases from our files and identified more than 230 cases published in the literature under several designations.Conclusions.—Although GCK is at least in part a variant of autosomal dominant or recessive polycystic kidney disease (PKD), linkage analysis has excluded PKD-associated gene mutations in many cases of GCK. A subtype of familial GCK, presenting with cystic kidneys, hyperuricemia, and isosthenuria is due to uromodullin mutations. In addition, the familial hypoplastic variant of GCK that is associated with diabetes is caused by mutations in TCF2, the gene encoding hepatocyte nuclear factor–1β. The term GCK disease (GCKD) should be reserved for the latter molecularly recognized/inherited subtypes of GCK (not to include PKD). Review of our cases, the literature, and our in silico analysis of the overlapping genetic entities integrates established molecular-genetic functions into a proposed model of glomerulocystogenesis; a classification scheme emerged that (1) emphasizes the clinical significance of glomerular cysts, (2) provides a pertinent differential diagnosis, and (3) suggests screening for probable mutations.
Quantitative Evaluation of Protein Expression as a Function of Tissue Microarray Core Diameter: Is a Large (1.5 mm) Core Better Than a Small (0.6 mm) Core?
Authors: Anagnostou Valsamo K. , Lowery Frank J. , Syrigos Konstantinos N. , Cagle Philip T. , Rimm David L. 
Published: February 2021

Abstract
Context.—Tissue microarrays (TMAs) have emerged as a high-throughput technology for protein evaluation in large cohorts. This technique allows maximization of tissue resources by analysis of sections from 0.6-mm to 1.5-mm core “biopsies” of standard formalin-fixed, paraffin-embedded tissue blocks and by the processing of hundreds of cases arrayed on a single recipient block in an identical manner.
Objective.—To assess the expression of a series of biomarkers as a function of core size. Although pathologists frequently feel better if larger core sizes are used, there is no evidence in the literature showing that large cores are better (or worse) than small cores for assessment of TMAs.
Design.—Estrogen receptor, HER2/neu, epidermal growth factor receptor, STAT3, mTOR, and phospho-p70 S6 kinase were measured by immunofluorescence with automated quantitative analysis. One random 0.6-mm field (one 0.6-mm spot) was compared to 6 to 12 fields per spot, representing 1-mm and 1.5-mm cores, for 3 different tumor types.
Results.—We show that measurement of a single random 0.6-mm spot was comparable to analysis of the whole 1-mm or 1.5-mm spot (Pearson R coefficient varying from 0.87–0.98) for all markers tested.
Conclusions.—Since TMA technology is now being used in all phases of biomarker development, this work shows that TMAs with 0.6-mm cores are as representative as those with any common larger core size for optimization of standardized experimental conditions. Given that a greater number of 0.6-cores can be arrayed in a single master block, use of this core size allows increased throughput and decreased cost.
Surgical Pathology Case Reviews Before Sign-Out: A College of American Pathologists Q-Probes Study of 45 Laboratories
Authors: Nakhleh Raouf E. , Bekeris Leonas G. , Souers Rhona J. , Meier Frederick A. , Tworek Joseph A. 
Published: February 2021

Abstract
Context.—To avoid errors many surgical pathology services mandate review of a case by a second pathologist before reports are released (signed out).
Objective.—To study the extent and characteristics of such review.
Design.—Participants retrospectively examined up to 400 cases to identify a maximum of 30 cases reviewed by at least one additional pathologist before sign-out. For each case, participants documented the organ system, primary disease type, number of additional pathologists consulted, and the reason for case review. The main outcome measure was the fraction of surgical pathology cases that underwent second pathologist review before sign-out.
Results.—From 45 laboratories, examination of 18 032 surgical pathology cases yielded 1183 (6.6%) cases that had been reviewed before sign-out. The median laboratory reviewed 8.2% of cases. Three-fifths of reviews focused on 4 organ systems: gastrointestinal (20.5%), breast (16.0%), skin (12.7%), and female genital tract (10.0%). Malignant neoplasm far exceeded all other categories of disease in reviewed cases (45.3%). Cases were reviewed by one additional pathologist 78% of the time. Two dominant reasons for case review emerged: difficult diagnosis (46.2%) and audit required by departmental policy (43.0%). Most laboratories (71%) had departmental policies regarding review of cases. These laboratories reviewed cases about 33% more often than laboratories without policies (9.6% versus 6.5%).
Conclusions.—Review of selected surgical pathology cases before sign-out is widely accepted with 71% of participant laboratories following policies to this effect. About 1 case in 15 (6.6%) were reviewed with the median laboratory of participants reviewing about 1 in 12 (8.2%).