bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flow Cytometric Analysis of Acute Leukemias
Authors: Kaleem Zahid , Crawford Eric , Pathan M. Hanif , Jasper Leah , Covinsky Michael A. , Johnson Lawrence R. , White Glenda 
Published: January 2021

Abstract
Context.—Acute leukemia displays characteristic patterns of surface antigen expression (CD antigens), which facilitate their identification and proper classification and hence play an important role in instituting proper treatment plans. In addition to enzyme cytochemical analysis, multiparameter flow cytometric analysis has become commonplace in most laboratories for that purpose. The essential role and caveats of flow cytometry in that regard, however, have received little scrutiny.
Objective.—To evaluate the expression of commonly used immunomarkers and patterns in various acute leukemias to help define the best use and role of multiparameter flow cytometry in the diagnosis and proper classification of acute leukemias.
Design.—We have retrospectively analyzed the immunophenotypic data from 508 de novo adult and pediatric acute leukemia patients, as studied using multiparameter flow cytometry in addition to routine morphologic and enzyme cytochemical analysis. Cytogenetic and/or molecular data were correlated in all 41 cases of acute promyelocytic leukemia (APL) and in 203 other cases of acute leukemia where those data were available. We have also determined the positive and negative predictive values of a combined CD34 and HLA-DR expression pattern for the differentiation of APL from other myeloid leukemias.
Results.—In acute myeloid leukemia (AML) other than APL, expression of CD34 was seen in 62% and expression of HLA-DR in 86% of all cases. Twenty-six (10%) of 259 cases of non-APL AML were negative for both CD34 and HLA-DR as opposed to 33 (80%) of 41 cases of APL. None of the cases of APL were positive for both CD34 and HLA-DR in contrast to 149 (58%) of 259 cases of non-APL AML. Fifty-three cases were found to be examples of minimally differentiated AML (AML M0) based on the lack of expression of cytoplasmic CD3 and cytoplasmic CD79a and expression of one or more myelomonocytic-associated antigens and/or myeloperoxidase. Expression of CD20 was seen in 40 (24%) of 168 cases of precursor B-cell acute lymphoblastic leukemia (pB-ALL) and 52 (29%) lacked CD34 expression. Five of 180 cases of pB-ALL and 2 cases of precursor T-cell ALL (pT-ALL) were negative for terminal deoxynucleotidyl transferase (TdT). Aside from cytoplasmic CD3, CD5 and CD7 were the most sensitive antigens present in all 21 cases of pT-ALL. CD33 was more sensitive but less specific than CD13 for myeloid lineage.
Conclusion.—Aside from identification of blasts, flow cytometry was found to be especially useful in the correct identification of AML M0, differentiation of APL from AML M1/M2, and correct identification of TdT-negative ALL and unusual variants, such as transitional B-cell ALL and undifferentiated and biphenotypic acute leukemias.
Artifactual Hyperbilirubinemia Due to Paraprotein Interference
Authors: Pantanowitz Liron , Horowitz Gary L. , Upalakalin Jan N. , Beckwith Bruce A. 
Published: January 2021

Abstract
Context.—Paraprotein interference in automated chemistry is uncommon. We describe 2 patients with paraproteinemia and elevated total bilirubin levels measured erroneously using the Roche total bilirubin assay.
Objectives.—To explain the mechanism of this artifactual hyperbilirubinemia and to determine its frequency in patients with monoclonal or increased immunoglobulins.
Materials and Methods.—The assay was performed manually using serum from 2 index patients and from control patients (without M proteins). Total bilirubin was also determined using another manufacturer's assay. A prospective study was then undertaken using serum from 100 consecutive patients with various monoclonal gammopathies and from 13 patients with polyclonal hypergammaglobulinemia and cryoglobulins. For all patients, serum immunoglobulin (Ig) G, IgA, IgM, total and direct bilirubin, creatinine, and a direct spectrophotometric assessment of icterus were measured.
Results.—After the addition of assay reagents, a white precipitate formed in the reaction mixtures containing serum from the index patients, but not in other samples. This turbidity, rather than the expected color change to pink, increased the absorbance and falsely elevated the total bilirubin value. Serum from both index patients was anicteric, their direct bilirubin measurements were unaffected, and total bilirubin measured using an alternate assay was normal. Among the 113 patients studied, no additional spurious total bilirubin values were detected.
Conclusion.—Paraprotein interference with the Roche automated total bilirubin assay is caused by precipitate formation. This interference is rare and probably idiosyncratic. Spurious hyperbilirubinemia from paraprotein interference may cause clinical confusion. If artifactual elevation of total bilirubin is suspected, the laboratory should examine the specimen for icterus (manually or by spectrophotometry) or measure total bilirubin using a different method.
Interpretative Problems and Preparative Technique Influence Reliability of Intraoperative Parathyroid Touch Imprints
Authors: Yao Davis X. , Hoda Syed A. , Yin Diana Y. , Kuhel William I. , Harigopal Malini , Resetkova Erika , DeLellis Ronald A. 
Published: January 2021

Abstract
Context.—Identification of parathyroid tissue (PT) is crucial during parathyroid and thyroid surgery. Touch imprint preparation (TIP) examination is potentially a more time-effective and less labor-intensive approach than frozen section examination for identification of PT during intraoperative consultation. However, the reliability of PT-TIP remains controversial, and this fact has hindered its adoption as a replacement for frozen section examination.
Objective.—To assess the factors contributing to the relative lack of reliability of TIP in a retrospective study.
Methods.—Fifty randomly selected, alcohol-fixed, hematoxylin-eosin– and/or Diff-Quik–stained TIPs of specimens that had been submitted to confirm PT during intraoperative consultation were retrospectively reviewed by 5 observers. The observers were blinded to the final interpretation (based on hematoxylin-eosin–stained permanent sections), which included PT in 39 (78%) of the 50 specimens, thyroid in 9 (18%), lymph node in 1 (2%), and adipose tissue 1 (2%). Cases in which a unanimous diagnosis was not attained were re-reviewed by 3 observers.
Results.—Of 50 TIPs reviewed, a unanimous diagnosis was rendered in 33 cases (66%), including 27 (69%) of 39 PT cases, 5 (56%) of 9 thyroid cases, and the 1 lymph node case. Cytologic features observed in the TIPs that were unanimously accepted as being diagnostic of PT included the presence of small uniform cells in isolation or in small groups, round to oval nuclei, salt-and-pepper chromatin, occasional naked nuclei, and delicate vacuoles both within the cytoplasm and in the background. Re-review of the 17 remaining TIPs cases, in which diagnostic unanimity was not achieved, demonstrated that factors hindering assessment of the TIPs included hypocellularity (n = 5 cases), air-drying effect (n = 4), hemorrhagic background (n = 4), and presence of PT cells in follicular (thyroid-like) arrangements (n = 4).
Conclusions.—The major factors influencing reliability of TIP of PT during intraoperative consultation are related primarily to interpretative problems and preparative technique. Awareness of interpretative problems and attention to preparation of TIPs may further enhance the accuracy of TIP during intraoperative consultation.
Concept-Match Medical Data Scrubbing
Authors: Berman Jules J. 
Published: January 2021

Abstract
Context.—In the normal course of activity, pathologists create and archive immense data sets of scientifically valuable information. Researchers need pathology-based data sets, annotated with clinical information and linked to archived tissues, to discover and validate new diagnostic tests and therapies. Pathology records can be used for research purposes (without obtaining informed patient consent for each use of each record), provided the data are rendered harmless. Large data sets can be made harmless through 3 computational steps: (1) deidentification, the removal or modification of data fields that can be used to identify a patient (name, social security number, etc); (2) rendering the data ambiguous, ensuring that every data record in a public data set has a nonunique set of characterizing data; and (3) data scrubbing, the removal or transformation of words in free text that can be used to identify persons or that contain information that is incriminating or otherwise private. This article addresses the problem of data scrubbing.
Objective.—To design and implement a general algorithm that scrubs pathology free text, removing all identifying or private information.
Methods.—The Concept-Match algorithm steps through confidential text. When a medical term matching a standard nomenclature term is encountered, the term is replaced by a nomenclature code and a synonym for the original term. When a high-frequency “stop” word, such as a, an, the, or for, is encountered, it is left in place. When any other word is encountered, it is blocked and replaced by asterisks. This produces a scrubbed text. An open-source implementation of the algorithm is freely available.
Results.—The Concept-Match scrub method transformed pathology free text into scrubbed output that preserved the sense of the original sentences, while it blocked terms that did not match terms found in the Unified Medical Language System (UMLS). The scrubbed product is safe, in the restricted sense that the output retains only standard medical terms. The software implementation scrubbed more than half a million surgical pathology report phrases in less than an hour.
Conclusions.—Computerized scrubbing can render the textual portion of a pathology report harmless for research purposes. Scrubbing and deidentification methods allow pathologists to create and use large pathology databases to conduct medical research.
A Regional Centralized Microbiology Service in Calgary for the Rapid Diagnosis of Malaria
Authors: Church Deirdre L. , Lichtenfeld Angelika , Elsayed Sameer , Kuhn Susan , Gregson Daniel B. 
Published: January 2021

Abstract
Context.—A regional centralized laboratory service for the rapid diagnosis of malaria was implemented 3 years ago in May 1999 within the Division of Microbiology, Calgary Laboratory Services.
Objective.—To describe the design and performance of this unique microbiology laboratory service.
Design.—Blood specimens must arrive at the central laboratory within 2 hours of collection. Thin blood smears are read and reported from suspected acute cases within 1 hour of receipt, 24 hours per day, 7 days a week, by trained and experienced microbiology technologists. All positive malaria smears are reviewed by a medical microbiologist and confirmed by polymerase chain reaction at a reference laboratory.
Setting.—Calgary Laboratory Services provides integrated laboratory services to the Calgary Health Region, an urban area of more than 1 million people.
Main Outcome Measures.—Performance of the service has been continuously monitored by measuring preanalytic and analytic test turnaround times, test accuracy, clinical relevance, and the results of proficiency testing.
Results.—More than 90% of blood specimens for malaria from community locations have consistently arrived within 2 hours of collection, and hospitals have reached this target within the past year. Although polymerase chain reaction was more sensitive at detecting the presence of malaria, the expert microscopists were as accurate at determining the type of Plasmodium infection. More than 95% of all positive smear results are consistently reported within 2 hours of receipt of a blood specimen.
Conclusions.—Implementation of a regional centralized microbiology service has improved our ability to make a rapid and accurate diagnosis of malaria in this region.
Microsatellite Instability in Colorectal Carcinoma
Authors: Rigau Valérie , Sebbagh Nicole , Olschwang Sylviane , Paraf François , Mourra Najat , Parc Yann , Flejou Jean-François 
Published: January 2021

Abstract
Context.—Microsatellite instability (MSI) due to defective mismatch repair (MMR) genes has been reported in the majority of colorectal tumors from patients with hereditary nonpolyposis colorectal cancer syndrome and in 10% to 15% of sporadic colorectal cancers. The identification of cancers associated with MSI requires classical molecular testing as the gold standard.
Objective.—The aim of this study was to evaluate the role of immunohistochemistry with antibodies directed against 4 MMR proteins as a screening tool for carcinomas with MSI.
Methods.—In this study, 204 formalin-fixed, paraffin-embedded colorectal carcinomas were examined for MMR protein expression (hMLH1, hMSH2, hMSH6, and hPMS2) and analyzed for MSI (MSI-H indicates at least 2 of 6 markers affected). These results were correlated with histopathologic parameters.
Results.—Immunohistochemical analysis revealed that loss of expression of at least 1 protein was present in 17% of cases. One hundred percent of carcinomas that showed high instability (MSI-H) showed loss of expression of hMLH1, hMSH2, or hMSH6. Loss of expression of 2 proteins was present in 59.4% of MSI-H cases, with only 2 combinations, namely, hMLH1/hPMS2 and hMSH2/hMSH6. Isolated loss of hMSH6 expression was present in 2 MSI-H cases.
Conclusions.—These findings confirm that examination of MMR protein expression by immunohistochemistry is a simple method to diagnose colorectal cancer with MSI. Our data suggest that the study of hMSH6 may be useful, in addition to hMLH1 and hMSH2. Moreover, immunohistochemistry could represent a screening method with which to direct research on the mutations of MMR genes observed in hereditary nonpolyposis colorectal cancer syndrome.
Rapid Polymerase Chain Reaction–Based Confirmation of Cat Scratch Disease and Bartonella henselae Infection
Authors: Margolis Ben , Kuzu Isinsu , Herrmann Marille , Raible Michele D. , Hsi Eric , Alkan Serhan 
Published: January 2021

Abstract
Context.—Cat scratch disease (CSD) commonly occurs secondary to Bartonella henselae infection, and the diagnosis has traditionally been made by microscopic findings, the identification of organisms by cytochemistry, and clinical history. However, cytochemical analysis tends to be very difficult to interpret, and histology alone may be insufficient to establish a definitive diagnosis of CSD.
Objective.—To demonstrate the presence of B henselae in tissue suspected of involvement by CSD, using a novel polymerase chain reaction (PCR) assay.
Design.—Isolates of B henselae (American Tissue Culture Collection 49793) and Afipia felis (American Tissue Culture Collection 49714) were cultured on blood agar and buffered charcoal yeast extract agar, respectively. DNA was isolated from these organisms and from formalin-fixed, paraffin-embedded tissue sections with involvement by CSD (8 patients). Negative controls included water, human placental tissue, and lymph node specimens from 6 patients with reactive lymphoid hyperplasia and from 2 patients with granulomatous lymphadenitis. A primer complementary to B henselae citrate synthase gltA gene sequence was designed to perform a seminested PCR amplification. For restriction fragment length polymorphism analysis, PCR products were digested by TaqI restriction enzyme and analyzed by gel electrophoresis.
Results.—Seminested PCR analysis of the cultured isolates of B henselae, but not of A felis, showed specific amplification. However, nonnested PCR did not provide consistently positive results in tissue sections with CSD. Therefore, we used a seminested PCR, which revealed positivity in all of the cases with clinicopathologic diagnoses of CSD. None of the negative controls showed positivity. Restriction enzyme provided confirmation of the specific PCR amplification of the B henselae sequence.
Conclusions.—Since the amplification product has a low molecular size (&lt;200 base pairs), this assay is useful for detection of B henselae in formalin-fixed, paraffin-embedded tissues. The seminested PCR protocol described here can be used for rapid and reliable confirmation of B henselae in samples that are histologically suggestive of CSD.
Xanthomatous Pseudotumor
Authors: Tan Kong-Bing , Thamboo Thomas Paulraj , Raju Gangaraju C. 
Published: January 2021

Abstract
Neoadjuvant chemotherapy has become an integral part of the treatment for locally advanced breast cancer. It facilitates tumor resectability and also provides an opportunity for the assessment of therapeutic response and prognosis. We report a case in which a large primary breast carcinoma was significantly reduced in size clinically and replaced by a mass lesion that was composed almost entirely of foamy histiocytes. This peculiar phenomenon is described in detail, together with a brief review of the other known postchemotherapy histologic features that include tumor necrosis, tumor cell cytoplasmic vacuolation and marked nuclear atypia, accompanying chronic inflammatory cellular infiltrate, fibrosis, and ductal-lobular atrophy.
Indeterminate Cell Histiocytosis
Authors: Rodríguez-Jurado Rodolfo , Vidaurri-de la Cruz Helena , Durán-Mckinster Carola , Ruíz-Maldonado Ramón 
Published: January 2021

Abstract
Indeterminate cell histiocytosis is a rare disorder involving altered homing mechanisms of the cutaneous histiocytic/dendritic system. It has been described predominantly in adults, with less than a dozen cases in children. A 13-year-old adolescent girl presented with a 4-year history of asymptomatic erythematous nodules and plaques, measuring from 1 to 5 cm in diameter, that were located mainly on the trunk and proximal portions of her limbs. A skin biopsy showed dermal diffuse infiltration of histiocytic cells. Most of the histiocytic cells were strongly positive for S100 protein. No Birbeck granules were found. Treatment with topical steroid was ineffective. After 6 months of pure coal tar and 5% 5-fluorouracil cream, an almost total clearing of lesions was observed. An accurate diagnosis of this condition is mandatory in order to avoid unnecessary treatments. Conservative management is also discussed.
Electronic Medical Devices; A Primer for Pathologists
Authors: Weitzman James B. 
Published: January 2021

AbstractContext.—Electronic medical devices (EMDs) with downloadable memories, such as implantable cardiac pacemakers, defibrillators, drug pumps, insulin pumps, and glucose monitors, are now an integral part of routine medical practice in the United States, and functional organ replacements, such as the artificial heart, pancreas, and retina, will most likely become commonplace in the near future. Often, EMDs end up in the hands of the pathologist as a surgical specimen or at autopsy. No established guidelines for systematic examination and reporting or comprehensive reviews of EMDs currently exist for the pathologist.Objective.—To provide pathologists with a general overview of EMDs, including a brief history; epidemiology; essential technical aspects, indications, contraindications, and complications of selected devices; potential applications in pathology; relevant government regulations; and suggested examination and reporting guidelines.Data Sources.—Articles indexed on PubMed of the National Library of Medicine, various medical and history of medicine textbooks, US Food and Drug Administration publications and product information, and specifications provided by device manufacturers.Study Selection.—Studies were selected on the basis of relevance to the study objectives.Data Extraction.—Descriptive data were selected by the author.Data Synthesis.—Suggested examination and reporting guidelines for EMDs received as surgical specimens and retrieved at autopsy.Conclusions.—Electronic medical devices received as surgical specimens and retrieved at autopsy are increasing in number and level of sophistication. They should be systematically examined and reported, should have electronic memories downloaded when indicated, will help pathologists answer more questions with greater certainty, and should become an integral part of the formal knowledge base, research focus, training, and practice of pathology.
Survivin in Glioblastomas
Authors: Kleinschmidt-DeMasters B. K. , Heinz David , McCarthy Paul J. , Bobak Joanna B. , Lillehei Kevin O. , Shroyer A. Laurie W. , Shroyer Kenneth R. 
Published: January 2021

Abstract
Context.—Survivin is a novel inhibitor of apoptosis that acts via a pathway independent of bcl-2. Little is known about its distribution in brain tumors or how it correlates with other biomarkers of malignancy, such as telomerase, an enzyme that plays a critical role in cellular immortalization and cancer biology.
Objectives.—To assess survivin protein expression in gliomas and to compare expression with that of telomerase.
Design.—Immunohistochemical staining for survivin protein expression was performed using an antibody developed in our laboratory. Quantitative survivin messenger RNA (mRNA) levels were assessed by reverse transcriptase-polymerase chain reaction. In selected cases, survivin results were compared with quantitative telomerase values analyzed by polymerase chain reaction–based telomerase repeat amplification protocol (TRAP) assay. Twenty-five tumor tissue samples from 16 cases of glioblastoma multiforme (GBM; including multiple tissue samples in 6 patients), 2 grade II gliomas, 4 grade III gliomas, and 3 control temporal lobectomy specimens were studied.
Results.—Nuclear immunoreactivity for survivin protein and survivin mRNA were detectable in most glioma samples, regardless of grade. Glioblastoma multiforme demonstrated moderate protein expression and survivin mRNA levels compared to epithelial malignancies previously tested in our laboratory. Although the association of survivin mRNA with the levels of telomerase within the GBM cases did not reach statistical significance, most GBMs also expressed survivin. The quantitative score for survivin mRNA was higher in GBMs than in grade II and III gliomas (P = .02), after accounting for multiple specimens per patient.
Conclusions.—Quantitative survivin mRNA analysis, but not immunohistochemistry, distinguished GBMs from lower grade gliomas. Mechanisms that promote both cell proliferation (telomerase expression) and cell survival (survivin expression) are often activated in GBMs.