bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Detection of Transfusion Transmitted Virus Coinfection With Some Hepatotropic Viruses
Authors: Zaki Maysaa El-Sayed , Hady, MD Nagy Abd El 
Published: February 2021

Abstract
Context.—A novel human DNA virus was isolated from the serum of a patient with posttransfusion hepatitis; it was named transfusion transmitted virus (TTV).
Objective.—To ascertain the influence of TTV (detected by polymerase chain reaction amplification of a conserved region of the viral genome) coinfection in individuals infected with hepatitis viruses (A, B, and C) and to investigate the putative role played by TTV in hepatic dysfunction in individuals with acute non-A-E hepatitis.
Design.—Sixty-two patients with viral hepatitis were included in the study in addition to 18 blood donors. Viral study of 4 hepatotropic viruses (A, B, C, and E) was carried out. Study for TTV DNA was performed by nested polymerase chain reaction.
Results.—The prevalence of TTV was not statistically different between hepatitis patients and blood donors, and it was not correlated to the levels of the hepatic aspartate aminotransferase and alanine aminotransferase between individuals evidencing dual infection with hepatitis B and C viruses and healthy blood donors. However, in the group of patients with viral hepatitis of unknown etiology (non-A-E), those evidencing TTV viremia had statistically significant lower levels of alanine aminotransferase (P = .03) and aspartate aminotransferase (P = .04) than those who were TTV negative.
Conclusions.—We can conclude that TTV is a frequent virus isolated from patients with various types of viral hepatitis, from cases of hepatitis without obvious viral agent, and from the healthy population. TTV has no effect on biochemical markers of associated viral hepatitis. It may be associated with a mild form of non-A-E hepatitis.
Nucleophosmin Gene Mutations in Acute Myeloid Leukemia
Authors: Chen Weina , Rassidakis Georgios Z. , Medeiros L. Jeffrey 
Published: February 2021

Abstract
Context.—Heterozygous mutation of the nucleophosmin gene (NPM1) has recently been described as one of the most frequent genetic lesions in acute myeloid leukemia (AML).
Objective.—(1) To discuss the clinical, morphologic, immunophenotypic, and genetic features of AML with NPM1 gene mutations, along with various detection methods, (2) To explore the mechanisms by which NPM1 gene mutations contribute to leukemogenesis.
Data sources/extraction.—Data were analyzed from 7 recently published papers.
Results.—NPM1 gene mutations tend to occur more frequently in women, and also tend to be associated with a higher white blood cell count. There is no significant age difference. NPM1-mutated AML is preferentially associated with AML with monocytic differentiation (in particular FAB M5b), lack of CD34, normal cytogenetics, FLT3 gene mutations, and a trend toward favorable clinical outcome, especially in patients without FLT3 gene mutation. NPM1 gene mutations cause a frame shift in the C-terminus of exon 12, disrupting the NPM nucleolar-localization signal or generating a leucine-rich nuclear export motif, resulting in abnormal cytoplasmic accumulation of NPM. Several methods are suitable for detecting NPM1 gene mutation, including molecular and immunohistochemical studies. These mutations may contribute to leukemogenesis, at least in part, through disruption of the p14ARF (alternative reading frame) MDM2-p53 pathway and centrosomal duplication.
Conclusions.—Detection of NPM1 gene mutations may allow dissection of the heterogeneous group of AML with normal karyotype into prognostically different subgroups. Exploring the mechanisms may lead to a better understanding of how mutant NPM protein becomes leukemogenic, thereby providing insights for the development of new chemotherapeutic agents.
Follicular Dendritic Cell Sarcoma Arising in the Dura Mater of the Spine
Authors: Choi Jung Woo , Lee Ju-Han , Kim Aeree , Kim Chul Hwan , Chae Yang Seok , Kim Insun 
Published: February 2021

Abstract
There have been some individual case reports and a few large series of reports describing the clinicopathologic features of follicular dendritic cell sarcoma. This tumor originates from the dendritic cells of lymphoid follicles and is extremely rare in the extranodal location. We report the case of a 68-year-old man who presented with low back pain. A mass was found in the lumbar dura mater and extended to the right epidural space. The tumor was composed of nodules, sheets, and interlacing fascicles of oval-to-spindle cells intermingled with the dense infiltrates of small lymphocytes. Immunohistochemical staining revealed that the tumor cells were positive for CD21, CD23, CD35, and clusterin, and focally positive for CD68, CD20, and CD79a. To our knowledge, this is the first case of follicular dendritic cell sarcoma occurring in the dura mater of the spine.
Vascular Adrenal Cysts: A Brief Review of the Literature
Authors: Carvounis Eleni , Marinis Athanasios , Arkadopoulos Nikolaos , Theodosopoulos Theodosios , Smyrniotis Vassilios 
Published: February 2021

AbstractAdrenal cysts are rare and form a heterogeneous group of lesions that includes (a) parasitic cysts, (b) epithelial cysts, (c) pseudocysts, and (d) endothelial cysts. There is evidence (immunohistochemical and ultrastructural) that both pseudocysts and endothelial cysts are variants of vascular cysts. Adrenal vascular cysts account for 84% of adrenal cysts. They are more common in women and present clinically with abdominal pain or are incidental findings. Their imaging features are not specific. Grossly, both types of adrenal vascular cysts are encapsulated. Pseudocysts are unilocular, thick-walled, and devoid of endothelial lining, whereas endothelial cysts are thin-walled, multilocular, and lined by endothelium. Adrenal vascular cysts probably originate from a preexisting vascular hamartoma. The treatment of choice is surgical excision. The prognosis is excellent.
Leukemia/Lymphoma in Cerebrospinal Fluid: Distinguishing Between Cases That Performed Well and Poorly in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology
Authors: Renshaw Andrew A. , Hughes Jonathan H. , Wang Edward , Haja Jennifer , Wilbur David , Henry Michael R. , Moriarty Ann T. 
Published: February 2021

Abstract
Context.—Although the cytologic features of leukemia/ lymphoma in cerebrospinal fluid specimens are well known, the correlation of these features with the ability of cytologists to identify this tumor have not been well studied.
Objective.—To identify the morphologic features of leukemia/lymphoma in cerebrospinal fluid that are associated with good performance and poor performance in an educational interlaboratory comparison program; and to identify the morphologic features associated with how well a slide performs with regard to its reference diagnosis.
Design.—The performance of 147 cases of leukemia/ lymphoma in the College of American Pathologists Interlaboratory Comparison Program in Non-gynecologic Cytology was analyzed. The cytologic features of a subset of 31 cases composed of relatively equal numbers of Romanowsky-stained and Papanicolaou-stained specimens were further evaluated, and those that performed poorly (n = 12) were compared with those that performed extremely well (n = 19).
Results.—For all cases of leukemia/lymphoma in the program, the rate of misclassification as benign for cases with Papanicolaou stain was significantly higher than for those with Romanowsky stain (9.5% vs 2.6%, P &lt; .001). Compared with cases that performed well, slides that performed poorly were more likely to have less than 200 abnormal cells (42% vs 5%, P = .02). The size of the tumor cells and preservation were not significant.
Conclusion.—Cases of specimens of leukemia/lymphoma in cerebrospinal fluid are more likely to be misdiagnosed as benign if they are Papanicolaou-stained or have 200 abnormal cells.
Determination of Ultrafilterable Prolactin: Elimination of Macroprolactin Interference With a Monomeric Prolactin-Selective Sample Pretreatment
Authors: Quinn Adam M. , Rubinas Tara C. , Garbincius C. Jean , Holmes Earle W. 
Published: February 2021

Abstract
Context.—Macroprolactin (macroPRL), present in as many as 25% of serum specimens with elevated serum prolactin concentrations, can cause apparent hyperprolactinemia in the absence of clinical features and lead to unnecessary clinical, laboratory, and neuroradiological workups.
Objective.—To develop an ultrafiltration method that eliminates macroPRL interference from PRL immunoassays.
Design.—The method involves centrifugation of undiluted serum in a Centricon-100 filter device followed by a PRL assay of the serum ultrafiltrate.
Results.—Ultrafiltrates prepared by this technique are devoid of gamma globulins and contain (mean ± SE) 19% ± 7% of the albumin concentration of the original serum. These ultrafiltrates contain 85% ± 7% of the total PRL immunoreactivity of serum spiked with 23 kd recombinant human prolactin (rHuPRL) and less than 2% of the 50 kd big PRL (bPRL) of whole serum. The fractional recovery of ultrafilterable PRL (uPRL) from serum samples of 54 female patients was 0.78 (confidence interval 0.73–0.83) of the total. The run-to-run coefficient of variation of the uPRL assay was 4.3%. The uPRL concentration (mean ± SD) in a group of healthy female controls was 8.0 ± 3.1 ng/mL.
Conclusions.—Ultrafiltration is a rapid and simple method for eliminating analytical interference by macroPRL. Ultrafiltrates can be analyzed by most, if not all, currently available PRL immunoassays and represent a practical and precise alternative to gel filtration chromatography for the estimation of the monomeric prolactin concentration of serum.
Blood Transfusions Leading to Apparent Hemoglobin C, S, and O-Arab Hemoglobinopathies
Authors: Kozarski Tzvetan B. , Howanitz Peter J. , Howanitz Joan H. , Lilic Nenad , Chauhan Yeshpal S. 
Published: February 2021

Abstract
Context.—Apparent hemoglobinopathies caused by blood transfusions rarely have been reported in the scientific literature.
Objective.—To interpret the abnormal hemoglobins appearing as small peaks on hemoglobin chromatograms or electrophoresis membranes.
Design.—In the clinical laboratories of a university hospital and a metropolitan hospital affiliated with a medical school, we interpreted hemoglobin chromatograms and electrophoresis membranes; correlated them with patients' medical, laboratory, and transfusion records; and when possible, identified the abnormal hemoglobin in the donors' transfusion segments.
Results.—We detected 52 incidences of apparent hemoglobinopathies in 32 recipients caused by blood transfusion, of which 46 were hemoglobin C, 4 were hemoglobin S, and 2 were hemoglobin O-Arab. When first detected, the abnormal hemoglobins in recipients ranged from 0.8% to 14% (median, 5.6%). Multiple transfusions with abnormal hemoglobins occurred in 11 patients with 2 patients receiving hemoglobin C blood 5 separate times. One patient received hemoglobin C and later S, and another patient received C and later O-Arab.
Conclusions.—Apparent hemoglobinopathies caused by blood transfusions are far more common than previously reported and represent diagnostic challenges. Misdiagnosis could lead to unnecessary testing, treatment, and counseling. If a hemoglobinopathy from a unit of transfused blood is identified in a recipient, we recommend notifying the donor of that abnormality.
Reduced Interference by Phenothiazines in Amphetamine Drug of Abuse Immunoassays
Authors: Melanson Stacy E. F. , Lee-Lewandrowski Elizabeth , Griggs David A. , Long William H. , Flood James G. 
Published: February 2021

Abstract
Context.—Emergency department physicians frequently request urine drug screens, but many are unaware of their limitations, including the potential for false-positive results. Promethazine, a phenothiazine derivative, is used for the treatment of allergies, agitation, nausea, and vomiting. Many patients taking promethazine are subject to urine drug screens and any potential interferences are important to recognize.
Design.—During an 11-month period, all patients presenting to the Massachusetts General Hospital emergency department who had a finding of promethazine in their serum drug screen, and who also had a urine drug screen performed, were selected for inclusion in the study. The urine drug screen results (n = 22 patients/samples) were then studied.
Objective.—To determine if promethazine use can cause false-positive urine amphetamine results in widely used drug of abuse immunoassays.
Results.—Thirty-six percent of patients taking promethazine had false-positive test results for urine amphetamines using the EMIT II Plus Monoclonal Amphetamine/Methamphetamine Immunoassay. Sixty-four percent of patients showed cross-reactivity greater than 20% higher than the blank calibrator rate. In a separate, related study, no promethazine-induced false-positive results were seen with the EMIT II Plus, Triage, and TesTcard 9 amphetamine assays, or the Triage methamphetamine assay. Reduced chlorpromazine interference was also seen with these other assays.
Conclusions.—False-positive urine amphetamine results can be obtained in patients taking promethazine. Promethazine metabolite(s), and not the parent compound, are the likely cause of these urine false-positive results obtained with EMIT II Plus Monoclonal Amphetamine/Methamphetamine Immunoassay. Immunoassays from different manufacturers can have very different “interference” profiles, which the pathologist and laboratory scientist must understand and relay to clinicians.
Pseudallescheriasis: A Summary of Patients From 1980–2003 in a Tertiary Care Center
Authors: Jayamohan Yasodah , Ribes Julie A. 
Published: February 2021

AbstractContext.—Pseudallescheria boydii is being increasingly isolated in immunocompromised patients.Objective.—To present 24 years of data on patients from whom P boydii was isolated.Design.—Retrospective review of archival laboratory data and patient charts at a tertiary care hospital with a full service mycology laboratory. All patients evaluated from whom P boydii was isolated between 1980 and 2003 were included in this study.Results.—Twenty-four patients from whom P boydii had been isolated were identified. The majority of cases represented pulmonary involvement, particularly in cystic fibrosis patients. Three additional patients had infections in surgical or traumatic lesions of the head and 4 had disseminated disease. Invasive disease was associated with underlying malignancy or transplantation and resulted in death secondary to the fungal infection in the majority of cases.Conclusions.—Pseudallescheria boydii may cause significant disease in humans. Invasive infections with P boydii are often misdiagnosed and inadequately treated. Aggressive treatment of locally invasive disease may be of value in preventing rapid and fatal dissemination with this organism.
Fine-Needle Aspirates of Hepatocellular Carcinoma That Are Misclassified as Adenocarcinoma: Correlating Cytologic Features and Performance in the College of American Pathologists Nongynecologic Cytology Program
Authors: Renshaw Andrew A. , Haja Jennifer , Wilbur David C. , Miller Theodore R. 
Published: February 2021

Abstract
Context.—The cytologic features of hepatocellular carcinoma in fine-needle aspirates are well described. While some cases are easily distinguished from adenocarcinoma, poorly differentiated tumors can be difficult to differentiate. We reviewed the cytologic findings for 9 aspirates from cases of hepatocellular carcinoma that were frequently misclassified as adenocarcinoma and compared them with another 10 cases of hepatocellular carcinoma that were rarely misclassified.
Objective.—To compare the cytologic features of cases of hepatocellular carcinoma in fine-needle aspirates that were both rarely and frequently misclassified as adenocarcinoma.
Design.—We reviewed a total of 762 interpretations from 19 different cases of hepatocellular carcinoma in liver fine-needle aspiration specimens in the College of American Pathologists Nongynecologic Cytology Program and correlated the cytologic features with performance in the program.
Results.—Overall, cases that were frequently misclassified as adenocarcinoma were misclassified 39% of the time (range, 18%–70%), while cases that were rarely misclassified were classified as adenocarcinoma 2% of the time (range, 0%–8%). The difference was statistically significant (P &lt; .001). On review, 4 cytologic patterns were found. The most common pattern for cases that were rarely misclassified was prominent trabeculae of cells and endothelial cells wrapping the trabeculae (6/10 cases vs 2/9 cases that were frequently misclassified). The most common pattern among cases that were frequently misclassified was clusters of cells with granular cytoplasm and associated stripped nuclei (5/9 cases vs 2/10 cases that were rarely misclassified). However, the distribution of neither pattern was significantly different (P = .16 for both). One case with large atypical granular cells, as seen in the fibrolamellar variant, was rarely misclassified. The remaining 3 cases (2 frequently misclassified, 1 rarely misclassified) had a nonspecific a pattern of cells with granular cytoplasm without obvious trabeculae or stripped nuclei.
Conclusion.—Correctly classifying hepatocellular carcinoma by cytology alone remains a significant challenge. While some patterns are more common in cases that performed well and other patterns are more common in cases that performed poorly, there was no significant difference in the distribution of these patterns. These results suggest that people should support their interpretations of aspirations with either immunologic evidence, biopsy evidence, or review by an experienced cytopathologist. Continued educational efforts in this area may be of value.
Changes and Problematic Areas in Interpretation of the AJCC Cancer Staging Manual, 6th Edition, for Breast Cancer
Authors: Connolly James L. 
Published: February 2021

Abstract
Context.—Tumor stage is an important prognostic factor and guides therapy for patients with breast cancer. The American Joint Committee on Cancer (AJCC) periodically updates the staging standards. This article describes changes and problematic areas in interpretation of the AJCC Cancer Staging Manual, 6th edition, for breast cancer and provides practical advice.
Objectives.—This article reviews the variety of practical problems that can arise during assessment of the pathologic stage and other prognostic/predictive factors included in the College of American Pathologists Checklist for Evaluation of Resected Breast Cancers. Potential practical difficulties that can arise include the classification of lymph nodes, for example, isolated tumor cells, micrometastases, metastases, and the combination of locations. Another difficult area is assignment of a correct size. The use of clinical and imaging studies for optimal pathologic staging is discussed. Finally, the proper use of the TNM descriptors is described.
Conclusions.—The various practical problems that can arise during the assessment of important prognostic and predictive features included in the College of American Pathologists Checklist for Evaluation of Resected Breast Cancers are discussed, and specific recommendations are given.
Problems in Pathologic Staging of Lung Cancer
Authors: Marchevsky Alberto M. 
Published: February 2021

Abstract
Context.—Tumor stage is the most important prognostic and predictive factor for patients with lung cancer, the most lethal neoplasm in the United States. It is used by thoracic surgeons, radiation therapists, and oncologists to determine whether patients with these neoplasms will be treated surgically with curative intent or with palliative radiation therapy and/or chemotherapy.
Objective.—To review the variety of practical problems that can arise during the assessment of the pathologic stage and other prognostic/predictive factors included in the College of American Pathologist checklist for evaluation of resected lung neoplasms.
Data Sources.—Potential practical difficulties that can arise during the pathologic staging of lung cancer patients include the distinction between pT1, pT2, and pT3 lesions based on their location and the presence of visceral pleura and/or parietal pleura invasion; the differential diagnosis between multiple synchronous or metachronous primary lung neoplasms (pT1m) and intrapulmonary metastasis of non-small cell carcinoma of the lung (pT4 or pM1 according to their location); and the role of the recent American Joint Committee on Cancer terminology for the classification of lymph nodes (isolated tumor cells, micrometastases, and metastases).
Conclusions.—The variety of practical problems that can arise during the assessment of important prognostic and predictive features such as resection margin status and evaluation of lymphovascular invasion are reviewed. A brief discussion of the assessment of the effects of neoadjuvant therapy on resected lung neoplasms is also included.
HER-2 Fluorescence In Situ Hybridization: Results From the Survey Program of the College of American Pathologists
Authors: Persons Diane L. , Tubbs Raymond R. , Cooley Linda D. , Dewald Gordon W. , Dowling Patricia K. , Du Emma , Mascarello James T. , Rao Kathleen W. , Wilson Kathleen S. , Wolff Daynna J. , Habegger-Vance Gail 
Published: February 2021

Abstract
Context.—Fluorescence in situ hybridization (FISH) is a common method used to determine HER-2 status in breast cancer. Limited information is available concerning reproducibility of FISH in determining HER-2 gene amplification.
Objective.—To present proficiency testing results of FISH for HER-2 conducted by the Cytogenetics Resource Committee of the College of American Pathologists/American College of Medical Genetics.
Design.—During the past 5 years, unstained sections from 9 invasive breast carcinomas were used for HER-2 FISH proficiency testing, allowing for comparison of FISH results among a large number of laboratories. Additional data were collected using an educational (ungraded) challenge and supplemental questions in the surveys.
Results.—The number of laboratories participating in HER-2 FISH proficiency testing has increased steadily during the past 5 years (from 35 in 2000 to 139 in 2004). Reproducibility of test results among laboratories was excellent for breast tumors with low copy number (no HER-2 amplification) and for breast tumors with high copy number (HER-2 amplification). However, there was considerable variation in interpretation of results for a tumor with low-level HER-2 amplification that was tested on 2 separate occasions. Responses to supplemental questions indicated that there was a need for consensus on the use of a separate equivocal/borderline interpretative category and the need for standardization of cutoff values used to define interpretative categories.
Conclusions.—The College of American Pathologists proficiency survey programs provide useful information concerning the reproducibility of clinical testing for HER-2 by FISH and reflect clinical interpretation of HER-2 FISH analyses from laboratories across the country.