bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative Real-Time Polymerase Chain Reaction Detection of BK Virus Using Labeled Primers
Authors: Gu Zhengming , Pan Jianmin , Bankowski Matthew J. , Hayden Randall T. 
Published: February 2021

Abstract
Context.—BK virus infections among immunocompromised patients are associated with disease of the kidney or urinary bladder. High viral loads, determined by quantitative polymerase chain reaction (PCR), have been correlated with clinical disease.
Objective.—To develop and evaluate a novel method for real-time PCR detection and quantification of BK virus using labeled primers.
Design.—Patient specimens (n = 54) included 17 plasma, 12 whole blood, and 25 urine samples. DNA was extracted using the MagNA Pure LC Total Nucleic Acid Isolation Kit (Roche Applied Science, Indianapolis, Indiana); sample eluate was PCR-amplified using the labeled primer PCR method. Results were compared with those of a user-developed quantitative real-time PCR method (fluorescence resonance energy transfer probe hybridization).
Results.—Labeled primer PCR detected less than 10 copies per reaction and showed quantitative linearity from 101 to 107 copies per reaction. Analytical specificity of labeled primer PCR was 100%. With clinical samples, labeled primer PCR demonstrated a trend toward improved sensitivity compared with the reference method. Quantitative assay comparison showed an R2 value of 0.96 between the 2 assays.
Conclusions.—Real-time PCR using labeled primers is highly sensitive and specific for the quantitative detection of BK virus from a variety of clinical specimens. These data demonstrate the applicability of labeled primer PCR for quantitative viral detection and offer a simplified method that removes the need for separate oligonucleotide probes.
Asbestos Fiber Content of Lungs With Diffuse Interstitial Fibrosis: An Analytical Scanning Electron Microscopic Analysis of 249 Cases
Authors: Schneider Frank , Sporn Thomas A. , Roggli Victor L. 
Published: February 2021

Abstract
Context.—Asbestosis is one of many forms of diffuse interstitial pulmonary fibrosis. Its histologic diagnosis rests on the pattern of fibrosis and the presence of asbestos bodies by light microscopy in lung biopsies.
Objective.—To determine the asbestos fiber burden in patients with diffuse pulmonary fibrosis (DPF) who had a history of asbestos exposure, but whose biopsies did not meet established criteria for asbestosis, and compare it with the fiber burden in confirmed asbestosis cases.
Design.—Fiber burden analysis was performed using scanning electron microscopy and energy-dispersive x-ray analysis of lung parenchyma from 86 patients with DPF and 163 patients with asbestosis. The correlation of the number of asbestos fibers found for a quantitative degree of fibrosis was analyzed.
Results.—The fibrosis scores of the asbestosis cases correlated best with the number of uncoated commercial amphibole fibers. Seven DPF cases fell within the 95% interval of asbestos body count by light microscopy and 3 cases within that of the total commercial amphibole fiber count.
Conclusions.—Strict histologic criteria are useful for positive identification of asbestosis among cases of advanced pulmonary fibrosis. Few DPF patients with history of asbestos exposure whose biopsies did not meet the criteria for asbestosis may have asbestos fiber counts in the range seen in asbestosis, and fiber type identification by scanning electron microscopy with energy-dispersive x-ray analysis should be considered in these rare instances to avoid false-positive and false-negative diagnoses of asbestosis.
Variable Specimen Handling Affects Hormone Receptor Test Results in Women With Breast Cancer: A Large Multihospital Retrospective Study
Authors: Nkoy Flory L. , Hammond M. Elizabeth H. , Rees William , Belnap Tom , Rowley Braden , Catmull Steve , Sause William 
Published: February 2021

AbstractContext.—Intermountain Healthcare hospitals use a single, standardized laboratory and automated testing process for estrogen receptor/progesterone receptor (ER/PR) tests to minimize testing errors.Objectives.—To test the (1) variability in ER/PR negativity among hospitals and (2) association between specimen handling conditions and ER/PR negativity.Design.—Retrospective study of women who had breast cancer surgery at 7 Intermountain hospitals and ER/PR tests ordered between 1997 and 2003. Data were extracted from cancer registry. Frequency of ER/PR negativity was calculated for each surgery day and compared among hospitals and between 2 groups: regular (specimens obtained Sunday through Thursday, more likely to be tested within 24 hours of surgery) and prolonged (specimens obtained on Friday and Saturday, more likely to be tested more than 24 hours after surgery) specimen handling conditions.Results.—Five thousand seventy-seven women were tested for ER/PR. The frequency of ER and PR negativity was 20.9% and 27.9%, respectively. It increased with each day of the week for both ER (P  =  .03) and PR (P  =  .059) and tended to be higher for prolonged specimens for ER (23.6% versus 20.4%; P  =  .03) and for PR (30.1% versus 27.4%; P  =  .11) compared with regular specimens. After controlling for age and tumor size, both ER (P  =  .02) and PR (P  =  .02) negativity was significantly different among the hospitals and was associated with prolonged specimens for ER (P  =  .04) but not for PR (P  =  .09).Conclusions.—Estrogen receptor and PR negativity remained highly variable among hospitals despite use of a single laboratory and tended to be significantly associated with prolonged specimen handling. More studies are needed to confirm these findings.
Pathology of Small Airways Disease
Authors: Allen Timothy Craig 
Published: February 2021

AbstractContext.—The term small airways disease encompasses a generally poorly understood group of lung diseases that may arise primarily within the small airways or secondarily from diseases primarily affecting the bronchi or lung parenchyma. Their histology may be confusing; however, because treatments and prognoses vary, correct pathologic diagnosis is important.Objective.—To present a nonexhaustive review of the pathology of primary and secondary small airways diseases, including small airways disease related to tobacco; to various other exposures, including mineral dusts; to diseases involving other areas of the lung with secondary bronchiolar involvement; and to recently described bronchiolitic disorders.Data sources.—Current literature is reviewed.Conclusions.—Small airways diseases include a wide variety of diseases of which the pathologist must consider. Uncommon conditions such as diffuse idiopathic neuroendocrine cell hyperplasia and diffuse panbronchiolitis may show relatively specific diagnostic features histologically; however, most small airways diseases exhibit nonspecific histologic features. Conditions not considered primary pulmonary diseases, such as collagen vascular diseases, bone marrow transplantation, and inflammatory bowel disease, must also be considered in patients with small airways changes histologically. Clinical and radiologic correlation is important for obtaining the best possible diagnosis.
TNM Staging System of Colorectal Carcinoma: A Critical Appraisal of Challenging Issues
Authors: Puppa Giacomo , Sonzogni Angelica , Colombari Romano , Pelosi Giuseppe 
Published: February 2021

Abstract
Context.—Colorectal cancer is the leading cause of morbidity and death among gastrointestinal tumors and ranks fourth after lung, breast, and ovarian cancers. Despite a continuous refinement of the T (tumor), N (node), and M (metastasis) staging system to express disease extent and define prognosis, and eventually to guide treatment, the outcome of patients with colorectal cancer may vary considerably even within the same tumor stage. Therefore, the need for new factors, either morphologic or molecular, that could more precisely stratify patients into different risk categories is clearly warranted.
Objectives.—To present the state of the art with regard to the colorectal cancer staging system and to discuss confusing and/or challenging issues, including the assessment of peritoneal membrane involvement, vascular invasion, tumor deposits, and pathologic tumor response to neoadjuvant chemoradiotherapy.
Data Sources.—Literature review of relevant articles indexed in PubMed (US National Library of Medicine) and primary material from the authors' institutions.
Conclusions.—Two emerging needs exist for the TNM system, namely, further stratification of patients with the same tumor stage and incorporation of nonanatomic factors, the latter including molecular and treatment factors. The identification and classification of morphologic features encountered in the pathologic examination of colorectal cancer specimens may be difficult and a source of subjective variability. Enhanced pathologic analysis, agreed-upon standard protocols, and standardization should improve the completeness and accuracy of pathology reports.
Observer Variability in the Interpretation of HER2/neuImmunohistochemical Expression With Unaided and Computer-Aided Digital Microscopy
Authors: Gavrielides Marios A , Gallas Brandon D , Lenz Petra , Badano Aldo , Hewitt Stephen M 
Published: February 2021

AbstractContext.—Observer variability in digital microscopy and the effect of computer-aided digital microscopy are underexamined areas in need of further research, considering the increasing use and future role of digital imaging in pathology. A reduction in observer variability using computer aids could enhance the statistical power of studies designed to determine the utility of new biomarkers and accelerate their incorporation in clinical practice.Objectives.—To quantify interobserver and intraobserver variability in immunohistochemical analysis of HER2/neu with digital microscopy and computer-aided digital microscopy, and to test the hypothesis that observer agreement in the quantitative assessment of HER2/neu immunohistochemical expression is increased with the use of computer-aided microscopy.Design.—A set of 335 digital microscopy images extracted from 64 breast cancer tissue slides stained with a HER2 antibody, were read by 14 observers in 2 reading modes: the unaided mode and the computer-aided mode. In the unaided mode, HER2 images were displayed on a calibrated color monitor with no other information, whereas in the computer-aided mode, observers were shown a HER2 image along with a corresponding feature plot showing computer-extracted values of membrane staining intensity and membrane completeness for the particular image under examination and, at the same time, mean feature values of the different HER2 categories. In both modes, observers were asked to provide a continuous score of HER2 expression.Results.—Agreement analysis performed on the output of the study showed significant improvement in both interobserver and intraobserver agreement when the computer-aided reading mode was used to evaluate preselected image fields.Conclusion.—The role of computer-aided digital microscopy in reducing observer variability in immunohistochemistry is promising.
Cardiac Troponin T Measured With a Highly Sensitive Assay for Diagnosis and Monitoring of Heart Injury in Chronic Chagas Disease
Authors: Saravia Silvia Gilka Muñoz , Haberland Annekathrin , Bartel Sabine , Araujo Raul , Valda Gregorio , Reynaga Diana Duchen , Ramirez Ivan Diaz , Borges Adrian C , Wallukat Gerd , Schimke Ingolf 
Published: February 2021

Abstract
Context.—Chronic Chagas disease (15 million patients; annual incidence, 40 000 patients; annual mortality, 12 500 patients) is the most serious parasitic disease in Latin America. Between 10 and 30 years after infection, 30% of patients with Chagas disease develop heart injury, which is the main reason for its high mortality. Consequently, frequent cardiac diagnostics are required for patients with Chagas disease.
Objective.—To minimize time-intensive and cost-intensive diagnostics, such as electrocardiography, echocardiography, and radiologic imaging, we tested the effect of measuring serum cardiac troponin T (cTnT) with a highly sensitive assay. To indicate the pathophysiologic background for cTnT release in Chagas heart injury, inflammation markers, such as C-reactive protein and interleukin 6, were measured in parallel.
Design.—Serum cTnT was measured in 26 healthy subjects and in 179 patients with chronic Chagas disease who were asymptomatic (indeterminate stage, n  =  86), who were suffering from cardiomyopathy with or without megacolon (n  =  71), or who were suffering from megacolon exclusively (n  =  22).
Results.—Serum cTnT was significantly higher in patients with cardiomyopathy with or without megacolon than in healthy subjects, asymptomatic subjects, and patients with megacolon, and the cTnT value was correlated with the severity of the cardiomyopathy. The lower limit of detection for the highly sensitive assay (3 ng/L) was best at distinguishing patients with, and without, heart injury. C-reactive protein and interleukin 6 were found to parallel cTnT changes in both the different Chagas groups and the cardiomyopathy groups separated by disease severity.
Conclusions.—Highly sensitive cTnT measurement has the potential to contribute to diagnosis and monitoring of heart injury in patients with chronic Chagas disease. The highly sensitive assay of cTnT release seems to be related to Chagas heart disease–specific inflammation.
Pancreatic Mucinous Cystic Neoplasm of the Main Pancreatic Duct
Authors: Masia Ricard , Mino-Kenudson Mari , Warshaw Andrew L , Pitman Martha B , Misdraji Joseph 
Published: February 2021

Abstract
Mucinous cystic neoplasm and intraductal papillary mucinous neoplasm are 2 types of cystic pancreatic mucinous tumors, each with its own distinct clinicopathologic features and pathogenetic mechanisms. We report here an unusual pancreatic mucinous neoplasm with features of both a mucinous cystic neoplasm and an intraductal papillary mucinous neoplasm in a 40-year-old woman who underwent total pancreatectomy. The endoscopic retrograde cholangiopancreatogram and gross examination demonstrated a mucin-producing intraductal neoplasm involving the length of the main pancreatic duct, typical of main duct intraductal papillary mucinous neoplasm, but histology of the main duct showed involvement by a biphasic tumor composed of columnar epithelium overlying ovarian-type stroma, characteristic of a mucinous cystic neoplasm. Immunohistochemistry confirmed that the stromal cells expressed estrogen and progesterone receptors, inhibin, and calretinin. Pancreatic mucinous cystic neoplasm involving the entire main pancreatic duct has not, to our knowledge, been previously reported.
Immunohistochemical Characterization of p57Kip2 Expression in Tetraploid Hydropic Placentas
Authors: Fukunaga Masaharu 
Published: February 2021

Abstract
Context.—Because there are differences in the origin, morphology, and natural history of hydropic placental villous issues, it is important to identify and document rare specimens that deviate from the diploid complete hydatidiform mole (CM), triploid partial hydatidiform mole (PM), or diploid hydropic abortion (HA). Tetraploid hydropic placentas have rarely been studied.
Objectives.—To evaluate the frequency of p57Kip2 protein (p57) expression in tetraploid hydropic placentas and to determine its clinicopathologic significance.
Design.—Forty hydropic DNA tetraploid placental specimens were evaluated by immunohistochemistry of formalin-fixed tissues, using a monoclonal antibody against p57, a putative paternally imprinted inhibitor gene. DNA ploidy in all cases was analyzed by flow cytometry.
Results.—Thirty cases were histologically diagnosed as CMs, 10 were HAs, and none were PMs. In all HAs, nuclear p57 was strongly expressed in cytotrophoblasts, intermediate trophoblasts, and villous stromal cells. In contrast, in CMs, p57 expression in cytotrophoblasts and villous stromal cells was either absent (26 cases) or very low (4 cases). Assuming that the degree of molar change roughly correlates with the proportion of paternal chromosomes present, all chromosomes might be paternally derived in all tetraploid CMs and the 10 HAs, including 2 that were karyotyped as 92,XXYY or 90,XXYY,−13,−14, which were presumably due to 2 sets of chromosomes each from paternal and maternal origin.
Conclusions.—Expression of p57 is aberrant in tetraploid CMs. This finding is in line with the hypothesis that the loss of p57 is involved in the abnormal development of androgenetic CMs. For the evaluation of a patient with trophoblastic disease, p57 immunostaining is an ancillary diagnostic method that may be used in concert with flow cytometry.
Paneth Cell Carcinoma of the Ampulla of Vater
Authors: Mora Jorge I. , Barroeta Julieta E. , Bernstein David A. , Lechago Juan 
Published: February 2021

Abstract
We describe a Paneth cell carcinoma arising within the ampulla of Vater in a 64-year-old man. The phenotype of virtually all neoplastic cells was consistent with that of Paneth cells, based on routine morphology and their strong positive immunostaining for lysozyme. Additional widespread positive immunostaining for carcinoembryonic antigen and CA 19.9 supports a totipotential cell as the origin of such neoplastic cells. This case, therefore, represents a true Paneth cell carcinoma, as opposed to inclusion of occasional neoplastic Paneth cells into a poorly differentiated adenocarcinoma. This pattern of differentiation is rare, and predictions regarding its ultimate biological behavior and malignant potential must be guarded.
Challenge in Diagnosis of CD56+ Lymphoproliferative Disorders: Two Cases of CD56+CD33+ Lymphoma/Leukemia
Authors: Yang Xu , Wasserman Patricia G. , Bhargava Archana , Iqbal Uzma , Ragnauth Shrutikant , Fuchs Alexander 
Published: February 2021

Abstract
Two cases of CD56+CD33+ leukemia/lymphoma are reported. The patient in case 1 presented with skin rash, diffuse lymphadenopathy, and hepatosplenomegaly. Blasts with monocytoid and lymphoid features were present in the peripheral blood. The tumor cells expressed HLA-DR, CD4, CD33, CD38, and CD56. Cytogenetic analysis revealed del(2)(p13),del(9)(q22),add(6)(q25),add(12)(p12),−13,−18, and −20. The clinicopathologic features were similar to those of blastic natural killer cell leukemia/lymphoma or type 2 dentritic cell leukemia. The patient in case 2 presented with generalized weakness and skin erythema not responding to antibiotics. Circulating blasts with monocytoid features were seen in the peripheral blood. The tumor cells expressed CD7, CD13, CD33, CD38, and CD56, and cytogenetic analysis revealed −5,add(7)(p22),−8, del(10)(p11.2),−12,der(13; 14)(p10;p10),+14,−16,−18,−19, and del(20)(q13.1). The clinicopathologic features were consistent with a myeloid/ natural killer cell precursor acute leukemia. Both disorders are aggressive hematopoietic malignancies that have similar clinical presentation and morphology but differ in immunophenotype and cytogenetic features.
Posttransplant Primary Cutaneous Ki-1 (CD30)+/CD56+ Anaplastic Large Cell Lymphoma
Authors: Kim Hee Kyung , Jin So-Young , Lee Nam Su , Won Jong Ho , Park Hee Sook , Yang Woo Ick 
Published: February 2021

Abstract
An anaplastic large cell lymphoma that was negative for Epstein-Barr virus and positive for Ki-1 (CD30) presented as a polypoid scalp mass in a 56-year-old man 16 years after renal transplantation. The lymphoma was of the CD4+ cytotoxic T-cell lineage, and the tumor cells also expressed CD56. Despite reduction in the dose of immunosuppression and localized radiotherapy, the tumor had rapidly progressed to involve the soft tissue of the right hand. Systemic chemotherapy induced complete regression of the soft tissue lesion. This case illustrates that posttransplant primary cutaneous CD30+ anaplastic large cell lymphomas may assume an aggressive clinical course but can still be controlled by systemic chemotherapy.
Measuring the Significance of Field Validation in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology: How Good Are the Experts?
Authors: Renshaw Andrew A. , Wang Edward , Mody Dina R. , Wilbur David C. , Davey Diane D. , Colgan Terence J. 
Published: February 2021

Abstract
Context.—Expert opinion is often used as a gold standard for gynecologic cytology in the evaluation of new technologies, in the legal setting, and in the validation of cases for use in educational programs and proficiency testing. However, the reliability of expert opinion alone in selecting slides of a specific cytodiagnosis that can be reproducibly and reliably identified by subsequent reviewers has not been determined.
Objective.—To assess the ability of expert opinion to select slides that are validated in subsequent reviews.
Design.—In the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology, each case in every cytodiagnostic category is accepted for circulation only after review by 3 expert cytopathologists. The percentage of these cases that could not be reliably and reproducibly identified by program participants for each cytodiagnostic category (“failed field validation”) was determined during the duration of the program from 1989 to 2004.
Results.—More than 10 000 conventional smears and ThinPrep cases were selected by the expert panel for circulation. Of these selected slides, 19% of conventional smears and 15% of ThinPrep specimens failed field validation. Compared with the overall slide performance, significantly higher percentages (P &lt; .001) of conventional smears with reference diagnoses of unsatisfactory (51.7%), repair (58%), or low-grade intraepithelial lesion (31.8%) and of ThinPrep specimens with reference diagnoses of unsatisfactory (54.5%) and repair (76.9%) failed field validation. In contrast, significantly lower percentages of conventional smears with reference diagnoses of squamous cell carcinoma (4.5%), high-grade squamous intraepithelial lesion (9%), Trichomonas vaginalis infection (11.7%), or herpes (9.9%) and of ThinPrep specimens with reference diagnoses of adenocarcinoma (5.1%), herpes (2.1%), and fungal organism consistent with Candida (8.4%) failed field validation (P &lt; .001 for all).
Conclusions.—Between 15% and 19% of gynecologic cytologic cases that have been selected by expert cytopathologists as good examples of cytodiagnostic abnormalities fail field validation. The proportion of cases failing field validation varies with cytodiagnostic category, but it occurs in all cytodiagnostic entities.