bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification Errors Involving Clinical Laboratories: A College of American Pathologists Q-Probes Study of Patient and Specimen Identification Errors at 120 Institutions
Authors: Valenstein Paul N. , Raab Stephen S. , Walsh Molly K. 
Published: February 2021

Abstract
Context.—Misidentified laboratory specimens may cause patient injury, but their frequency in general laboratory practice is unknown.
Objectives.—To determine (1) the frequency of identification errors detected before and after result verification, (2) the frequency of adverse patient events due to specimen misidentification, and (3) factors associated with lower error rates and better detection of errors.
Design.—One hundred twenty clinical laboratories provided information about identification errors during 5 weeks.
Results.—In aggregate, 85% of errors were detected before results were released; one quarter of laboratories identified more than 95% of errors before result verification. The overall rate of patient identification errors involving released results was 55 errors per 1 000 000 billable tests. A total of 345 adverse events were reported. Most of the adverse events caused material inconvenience to the patients but did not result in any permanent harm. On average, adverse events resulted from 1 of every 18 identification errors. Extrapolating the adverse event rate observed in this study to all United States hospital-based laboratories suggests that more than 160 000 adverse events per year result from misidentification of patients' laboratory specimens.
Conclusions.—Identification errors are common in laboratory medicine, but most are detected before results are released, and only a fraction are associated with adverse patient events. Even when taking into consideration the design of this study, which used imperfect case finding, institutions that did a better job of detecting errors within the laboratory released a smaller proportion of results that involved specimen misidentification.
The Potential for Failure in Gynecologic Regulatory Proficiency Testing With Current Slide Validation Criteria: Results From the College of American Pathologists Interlaboratory Comparison in Gynecologic Cytology Program
Authors: Young Nancy A. , Moriarty Ann T. , Walsh Molly K. , Wang Edward , Wilbur David C. 
Published: February 2021

Abstract
Context.—Current regulatory proficiency testing scoring results in an automatic failure for identifying high-grade squamous intraepithelial lesion (HSIL) as negative.
Objective.—The College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology data from January 2004 to April 2005 were analyzed to estimate the percentage of failure based on negative responses for HSIL and validation criteria.
Design.—More than 15 000 participants received field-validated and educational slide sets for conventional, ThinPrep, and SurePath modules. Educational sets fulfilled the validation criteria of the Center for Medicare and Medicaid Services, which required the consensus diagnosis of biopsy-proven HSIL (not field-validated) after review by 3 pathologists. The College of American Pathologists field validation required at least 20 responses to the HSIL+ series, with 70% matched to HSIL+ (standard error ≤ 0.05). Minimum regulatory proficiency testing failure estimates were based on incorrect negative responses for the reference category of HSIL.
Results.—For both cytotechnologists and pathologists, there was a statistically significant higher failure rate for slides that were not field-validated versus those that were field-validated. In conventional modules, 5.3% of the slides that were not field-validated were called negative, versus 1.2% of the field-validated slides. In all liquid-based preparations, 4.0% of the non–field-validated versus 2.2% field-validated slides were called negative. Pathologists would have failed more often than cytotechnologists for the slides that were not field-validated, whereas there was no statistical difference in failure performance with field-validated slides.
Conclusions.—Failures were significantly greater with the slides that were not field-validated for both conventional and liquid-based preparations (ThinPrep only) and have implications for both regulatory proficiency testing and expert legal review. Poor performance of pathologists relative to that of cytotechnologists may reflect a lack of prescreening of slides or scope of practice issues.
Essential Thrombocythemia: A Review of Diagnostic and Pathologic Features
Authors: Sanchez Steven , Ewton April 
Published: February 2021

Abstract
Context.—Essential thrombocythemia (ET) is a chronic myeloproliferative disorder (CMPD) characterized predominately by thrombocytosis and abnormal megakaryocyte proliferation.
The current diagnostic criteria require a combination of clinical, histologic, and cytogenetic data. The diagnosis relies largely on exclusion of other causes of thrombocytosis.
Objective.—Describe historical, clinical, and laboratory features of ET in order to understand, clarify, and more accurately diagnose this entity.
Data Sources.—Review contemporary and historical literature on ET and other causes of thrombocytosis.
Conclusions.—ET is a relatively indolent and often asymptomatic CMPD that is characterized primarily by a sustained elevation in platelets ≥600 × 103/μL (≥600 × 109/L), proliferating enlarged and hyperlobated megakaryocytes, and minimal to absent bone marrow fibrosis. Significant changes and revisions to the diagnostic requirements and criteria for ET have occurred during the last 30 years. Recently, a mutation in the Janus kinase 2 (JAK2) gene has been found in a significant number of cases of ET and other CMPDs. In up to 57% of ET cases, a mutation in the JAK2 gene can be detected. In the absence of a JAK2 mutation and features of another CMPD, the diagnosis of ET remains a diagnosis of exclusion after other causes of thrombocytosis have been excluded.
Health Care Fraud and Abuse Laws
Authors: Klein Roger D. , Campbell Sheldon 
Published: February 2021

Abstract
Context.—Health care fraud and abuse enforcement actions have significantly expanded in number and scope during the past several years. The Department of Health and Human Services Office of Inspector General named review of in-office pathology services a critical priority in its 2005 Work Plan. As providers of pathology and laboratory medicine services, pathologists need to be aware of the potential impact of these laws on their practices.
Objectives.—To review the major statutes and regulations underlying most federal investigations and prosecutions of health care fraud, with a special emphasis on their relationships to pathology practice.
Design.—The authors reviewed pertinent federal statutes, regulations, and other documents, along with relevant legal literature.
Results.—The health care fraud and abuse laws are complicated and potentially impact pathology practice in unforeseen ways.
Conclusions.—The health care fraud and abuse laws are complex and often counterintuitive. The penalties for violation of these laws are severe. Because they may impact many areas of pathology and laboratory medicine practice, pathologists are advised to consult experienced legal counsel prior to embarking on potentially suspect health care arrangements.
Molecular Diagnosis of Sarcomas: Chromosomal Translocations in Sarcomas
Authors: Lazar Alexander , Abruzzo Lynne V. , Pollock Raphael E. , Lee Sangkyou , Czerniak Bogdan 
Published: February 2021

AbstractContext.—Sarcomas are rare, numerous in type, and often difficult to definitively classify. Work in the last 2 decades has revealed that a significant subset of sarcomas are associated with specific chromosomal translocations producing chimeric (fusion) genes that play a role in the sarcomas' biology and are helpful in their differential diagnosis.Objective.—To briefly review the sarcomas associated with specific translocations presenting Ewing sarcoma and synovial sarcoma as archetypes and to further explain how cytogenetic and molecular biologic approaches are being used in the diagnosis of sarcomas.Data Sources.—This work is based on a selected review of the relevant medical and scientific literature and our extensive experience with molecular testing in sarcomas.Conclusions.—In addition to, and complementing, the traditional diagnostic methods of examination of hematoxylin-eosin stained slides, immunohistochemistry, and sound clinical-pathologic correlation, additional cytogenetic and molecular biologic methods are being increasingly utilized and relied on in sarcoma pathology. These methods include chromosomal karyotyping, fluorescence in-situ hybridization, spectral karyotyping, and polymerase chain reaction– based methods for demonstrating specific chromosomal translocations and fusion genes. Understanding the basis of these methods and their application is critical to better provide accurate and validated specific diagnoses of sarcomas.
Mre11 Expression in Atypical Adenomatous Hyperplasia and Adenocarcinoma of the Lung
Authors: Nakanishi Kuniaki , Kumaki Fumiyuki , Hiroi Sadayuki , Mukai Makio , Ikeda Eiji , Kawai Toshiaki 
Published: February 2021

AbstractContext.—The Mre11-Rad50-NBS1 complex plays an important role in telomere maintenance. Recently, it has been proposed that alterations in Mre11 function may be contributing factors in the development of some tumors. Moreover, mutations of Mre11 have been demonstrated to cause reduced Mre11 immunostaining.Objective.—To investigate Mre11 in atypical adenomatous hyperplasia (AAH) and nonmucinous bronchioloalveolar carcinoma (NMBAC), an issue not previously explored.Design.—We examined (1) the expression of Mre11 protein in 27 AAHs (9 lesions interpreted as low-grade AAH and 18 as high-grade AAH) and 40 NMBACs (using immunohistochemistry) and (2) Mre11 mRNA expression in 1 high-grade AAH and 6 NMBACs (using reverse transcription polymerase chain reaction). For the analysis of immunoreactivity, the intensity and extent of staining were each scored from 0 to 3. These 2 scores were summed to give in each case a final score of 0 to 6.Results.—Scores for Mre11 expression were 5.0 ± 2.1 for low-grade AAH, 5.4 ± 1.2 for high-grade AAH, and 5.5 ± 0.9 for NMBAC, and there was no statistically significant difference among these 3 types of lesions. In the reverse transcription polymerase chain reaction for Mre11 mRNA, polymerase chain reaction products were detected in all samples.Conclusions.—On this basis, we suggest that the part played by Mre11 in telomere maintenance may not be important for the progression of the adenoma–carcinoma (AAH–NMBAC) sequence in the lung, although some role for it in carcinogenesis cannot be completely ruled out.
Phyllodes Tumor: A Clinicopathologic and Immunohistochemical Study of 30 Cases
Authors: Esposito Nicole Nicosia , Mohan Deepak , Brufsky Adam , Lin Yan , Kapali Malathy , Dabbs David J. 
Published: February 2021

AbstractContext.—Phyllodes tumors (PTs) of the breast are biphasic neoplasms composed of epithelium and a spindle-cell stroma. Currently, PTs are classified as benign, borderline, or malignant based on histopathologic features. However, histologic classification does not always predict outcome.Objective.—To determine the prognostic value of a variety of clinicopathologic features and immunoreactivities in PTs.Design.—Sixteen benign, 8 borderline, and 6 malignant PTs with follow-up were examined for reactivity across a panel of immunohistochemical stains, including c-Kit, endothelin 1, p16, p21, p53, and Ki-67. Clinicopathologic features, including stromal cellularity, mitotic rate, and margin status, were also assessed. Tumor variables were compared among tumor subgroups and between tumors that did and did not recur.Results.—Of the 30 PTs, 4 recurred (1 benign, 2 borderline, 1 malignant). One patient with a malignant tumor died of metastatic disease 34 months after initial diagnosis. The overall positive rate of c-Kit immunoreactivity was 13% in benign, 63% in borderline, and 67% in malignant PTs. Endothelin 1 epithelial cytoplasmic staining was seen in 100% of benign, 50% of borderline, and 17% of malignant PTs. Additionally, p16, p21, p53, and Ki-67 were differentially expressed among benign, borderline, and malignant tumors. Positive surgical resection margins was the only variable that significantly predicted recurrent disease (P = .02).Conclusions.—Stromal c-Kit positivity and epithelial endothelin 1 negativity are more often associated with malignant PTs; however, only positive margin status is significantly associated with tumor behavior.
Immunoreactivity of MIC2 (CD99) and Terminal Deoxynucleotidyl Transferase in Bone Marrow Clot and Core Specimens of Acute Myeloid Leukemias and Myelodysplastic Syndromes
Authors: Kang Loveleen C. , Dunphy Cherie H. 
Published: February 2021

AbstractContext.—MIC2 (“thymus leukemia”) antigen has been shown to be expressed by T cells and monocytes, as well as B cells and granulocyte-lineage cells. It is most intensely expressed by the most immature thymus T-lineage cells and is more intensely expressed by CD34-positive/CD33-positive myeloid cells (compared to more mature myeloid cells) and the earliest CD34-positive/CD10-positive B-cell precursor cells (compared to cells of later B-cell precursor stages). CD99 (MIC2) is characteristically expressed in precursor B- and T-cell lymphoblastic lymphomas/leukemias, as well as in Ewing sarcoma/primitive neuroectodermal tumors (ES/PNET). It has also been shown to be expressed in a few terminal deoxynucleotidyl transferase (TdT)–positive myeloid processes, but has been uniformly negative in TdT-negative myeloid processes. A more recent study showed that 43% of acute myeloid leukemias (AMLs) and 55% of chloromas express CD99, concluding that CD99 is commonly expressed in AML and rarely seen in myeloproliferative disorders, myelodysplastic syndromes, or normal bone marrow. Although this study speculated that MIC2 expression was probably not limited to TdT-positive AML, there was no comparison with TdT reactivity in this study.Objective.—Since AML and high-grade myelodysplastic syndrome may occasionally be difficult to distinguish morphologically from acute lymphoblastic leukemia and ES/ PNET, we undertook a study to analyze MIC2 expression in conjunction with TdT reactivity in distinguishing AML or high-grade myelodysplastic syndrome from acute lymphoblastic leukemia and ES/PNET.Design.—We studied bone marrow core and clot paraffin specimens from AML (classified according to criteria of the World Health Organization; n = 49), myelodysplastic syndromes (n = 4), precursor B-cell acute lymphoblastic leukemia (n = 4), ES/PNET (n = 1), and normal bone marrow (n = 3) with MIC2 (CD99) and TdT immunohistochemistry.Results.—Overall, CD99 was expressed in 24 (49%) of 49 AML cases, including all (11/11) TdT-positive cases. CD99 was expressed in all subtypes of AML except M5. Myelodysplastic syndromes and normal bone marrow specimens were uniformly CD99 negative. Expression of TdT was limited to a subset of AML-M0, -M1, -M2, and -M4, and AML with multilineage dysplasia.Conclusions.—In contrast to a previous study, CD99 expression was not restricted to TdT-positive hematologic proliferations. In particular, the CD99-positive M3 and M7 AMLs were TdT negative. An M5 AML may likely be excluded based on a uniform TdT-negative/CD99-negative immunophenotype. In addition, in our experience, CD99 should be routinely evaluated on bone marrow clots, owing to decreased reactivity or loss of reactivity in rapid decalcifying (RDO) solution–decalcified specimens.
Inflammatory Myofibroblastic Tumor of the Liver
Authors: Solomon Garron J. , Kinkhabwala Milan M. , Akhtar Mohammed 
Published: February 2021

Abstract
We report a case of hepatic inflammatory myofibroblastic tumor in a 26-year-old African American man who presented with right upper quadrant pain, weight loss, and fatigue during the previous year. Hepatomegaly was found on physical examination. Laboratory findings were significant for mild normocytic, normochromic anemia and elevated erythrocyte sedimentation rate. Imaging studies showed 2 contiguous masses suspicious for malignancy. A left partial hepatectomy was performed; the preoperative differential diagnosis was for angiosarcoma and hepatocellular carcinoma. The resected liver specimen showed 2 contiguous, firm, tan-white nodules that microscopically represented a proliferation of spindled myofibroblast cells set in an inflammatory and collagenized background. The spindle cells were strongly reactive for smooth muscle actin but negative for ALK-1. The morphologic and immunophenotypic findings, coupled with the clinical presentation, were consistent with an inflammatory myofibroblastic tumor of the liver.
Fatal Adenoviral Hepatitis After Rituximab Therapy
Authors: Iyer Anita , Mathur Radhika , Deepak Banglore V. , Sinard John 
Published: February 2021

Abstract
Rituximab is an anti-CD20 monoclonal antibody used in the treatment of B-cell proliferative disorders. Although it is very effective in many cases, a number of case reports in the literature have described fatal viral reactivations associated with rituximab therapy. We report what is to our knowledge the first case of fatal adenoviral hepatitis in a patient with Waldenstrom macroglobulinemia treated with rituximab. This case is a new example of an emerging pattern of association between rituximab therapy and fatal viral reactivations, and it urges increased vigilance when using rituximab-based treatment regimens.
Effect of Fondaparinux on Coagulation Assays: Results of College of American Pathologists Proficiency Testing
Authors: Smogorzewska Agata , Brandt John T. , Chandler Wayne L. , Cunningham Mark T. , Hayes Timothy E. , Olson John D. , Kottke-Marchant Kandice , Van Cott Elizabeth M. 
Published: February 2021

Abstract
Context.—Fondaparinux, a factor Xa inhibitor, is approved for thromboprophylaxis after orthopedic surgery and for treatment of venous thromboembolism. It may also be efficacious, safe, and cost-effective for other patients; thus, more widespread use of fondaparinux is likely. The effect of fondaparinux on coagulation testing needs to be thoroughly examined.
Objective.—To report the effects of fondaparinux on coagulation tests (prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin, factor VIII, thrombin time, anti–factor Xa) across diverse methodologies.
Design.—Samples with different concentrations of fondaparinux (0, 0.4, 0.8, and 2.0 μg/mL) were sent to laboratories participating in the College of American Pathologists Comprehensive Coagulation proficiency survey (N = 898). Laboratory-specific methods were used to assay coagulation parameters.
Results.—Prophylactic or therapeutic fondaparinux prolonged the prothrombin time by approximately 1 second and the activated partial thromboplastin time by 4 to 5 seconds, and reduced factor VIII from 119% to 107% and 102%, respectively. Supratherapeutic fondaparinux reduced factor VIII to 85%. The activated partial thromboplastin time was prolonged in 19%, 29%, and 52% of laboratories with prophylactic, therapeutic, and supratherapeutic fondaparinux levels, respectively. Fibrinogen, antithrombin, and thrombin time assays did not show clinically significant changes. When measuring fondaparinux concentration using an anti–factor Xa assay, the most accurate results were obtained when fondaparinux was used as the calibrator.
Conclusions.—Fondaparinux, even in prophylactic doses, slightly prolongs the prothrombin time and activated partial thromboplastin time and can interfere with factor VIII assays, but it has no clinically relevant effect on fibrinogen, antithrombin, or thrombin time. A fondaparinux standard curve should be used for reporting fondaparinux levels using an anti–factor Xa assay.
Specificity and Sensitivity of Hemosiderin-Laden Macrophages in Routine Bronchoalveolar Lavage in Children
Authors: Salih Zeynep N. , Akhter Afreen , Akhter Javeed 
Published: February 2021

Abstract
Context.—The presence of iron or hemosiderin in macrophages obtained in routine bronchoalveolar lavage is considered crucial in the diagnosis of the clinical syndrome of hemosiderosis. However, there do not appear to be any data on the sensitivity and specificity of the finding of hemosiderin-laden macrophages (HLMs) in bronchoalveolar lavage in children.
Objective.—To review data from bronchoalveolar lavage studies done in children to correlate the presence of HLMs with pneumonia and hemosiderosis and to determine what proportion of HLMs has the optimal sensitivity and specificity for the diagnosis of hemosiderosis.
Design.—One hundred ten bronchoalveolar lavage specimens obtained via flexible bronchoscopy were reviewed retrospectively. The data collected for demographics, indication for the bronchoscopy, diagnosis of pneumonia, anemia, and bronchoscopy and bronchoalveolar lavage findings were compared between patients diagnosed with hemosiderosis and those diagnosed with other diseases.
Results.—Six patients were diagnosed with hemosiderosis by clinical findings, lung biopsy, or autopsy. There were no statistical differences in pneumonia (P &gt; .99), anemia (P &gt; .99), or coughing (P = .08) between patients with hemosiderosis and other patients. Hemoptysis was the only symptom that was significantly different between the 2 groups (P = .04). The mean HLM index for patients with hemosiderosis was 56% ± 16.17% and for other patients, 7.5% ± 10.74% (P &lt; .001). A HLM index of 35% gave a sensitivity of 1% and a specificity of .96%.
Conclusions.—These results confirm a strong association between HLM index and diagnosis of hemosiderosis in a pediatric population. Availability of this HLM index will result in accurate and timely diagnosis of pulmonary hemosiderosis, which may influence treatment and long-term prognosis.
Angioimmunoblastic T-Cell Lymphoma With Supervening Epstein-Barr Virus–Associated Large B-Cell Lymphoma
Authors: Hawley Robert C. , Cankovic Milena , Zarbo Richard J. 
Published: February 2021

Abstract
Patients with angioimmunoblastic T-cell lymphoma can have profound immune dysfunction and immunodeficiency. Epstein-Barr virus–driven B-cell lymphoid proliferation can occur in angioimmunoblastic T-cell lymphoma, as in other immunodeficiency states. However, few cases of Epstein-Barr virus–positive B-cell lymphoma arising in patients with preexisting angioimmunoblastic T-cell lymphoma have been reported. We report a case of angioimmunoblastic T-cell lymphoma in which diffuse large B-cell lymphoma developed 56 months after the diagnosis of angioimmunoblastic T-cell lymphoma. The patient survived for 9 years after the initial diagnosis of angioimmunoblastic T-cell lymphoma, and molecular studies performed on multiple biopsy specimens during this period revealed the dynamic nature of clonal lymphoid expansion. Epstein-Barr virus latent membrane protein 1 and Epstein-Barr virus– encoded RNA were detected in the diffuse large B-cell lymphoma, suggesting that Epstein-Barr virus may have played a role in the pathogenesis of the diffuse large B-cell lymphoma.