bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA Technology in the Clinical Laboratory
Authors: Kiechle Frederick L. 
Published: January 2021

Abstract
Objectives.—To review the advances in clinically useful molecular biological techniques and to identify their applications in clinical practice, as presented at the Eighth Annual William Beaumont Hospital Symposium.
Data Sources.—The 10 manuscripts submitted were reviewed, and their major findings were compared with literature on the same topic.
Study Selection.—Two manuscripts addressed specimen (nucleic acid) stability, 2 described novel analytic approaches, 3 discussed detection of B- or T-cell clonality in lymphoproliferative disorders, and 3 reported the frequency of a variety of genetic polymorphisms found in cardiac disorders.
Data Synthesis.—DNA from dried blood spots is stable and may be purified rapidly for amplification and mutation analysis. RNA is much less stable, and a variety of methods may be used to reduce ribonuclease degradation of enteroviral RNA. False-negative reactions may be reduced by genomic amplification of ligated padlock probes by cascade rolling circle or polymerase chain reaction. A multiplex polymerase chain method using fluorescence-labeled products that separate both the wild-type and mutant hemochromatosis gene alleles by capillary gel electrophoresis represents another approach for detecting the 2 major missense mutations (C282Y and H63D) in hemochromatosis. Southern blotting and polymerase chain reaction have been used to detect B- and T-cell clonality in lymphoproliferative diseases, including mantle cell lymphoma and lymphoma of the breast. Genetic polymorphisms in a variety of coagulation factors and platelet glycoprotein IIIa are associated with ischemic heart disease.
Conclusions.—As the Human Genome Project continues to define disease-associated mutations, the number of clinically useful molecular pathologic techniques and assays will expand. Clinical outcome analysis is still required to document a decrease in the patient's length of stay to offset the cost of introducing molecular biological assays in the routine clinical pathology laboratory.
Reverse-Transcription Polymerase Chain Reaction Detection of the Enteroviruses
Authors: Romero JoséR. 
Published: January 2021

AbstractObjective.—This review focuses on commercial and in-house–developed reverse-transcription polymerase chain reaction (RT-PCR) assays used for the detection of enteroviral infections. In addition to providing details on the performance of RT-PCR, its specificity, and sensitivity, the clinical utility of this diagnostic method with specific reference to its impact on hospitalization and cost savings is addressed.Data Sources.—MEDLINE was searched for reports relating to RT-PCR detection of the enteroviruses in adults and children. The search was restricted to studies reported in English language journals.Study Selection.—Reports documenting detailed information regarding the RT-PCR conditions, primers, sensitivity, specificity and, if relevant, clinical impact were selected for analysis.Data Extraction.—Details regarding method of extraction of the enteroviral genome, the primers used, RT-PCR conditions, and sensitivity and specificity of the assay were extracted from the literature. For reports detailing the use of RT-PCR in the clinical management of enteroviral infections in children, the reduction in duration of hospitalization and health care cost savings were recorded.Data Synthesis.—Reverse-transcription PCR can increase the yield of detection of enteroviruses from cerebrospinal fluid by a mean of approximately 20% over tissue culture. Reverse-transcription PCR of cerebrospinal fluid has been shown to exhibit sensitivity and specificity values of 86% to 100% and 92% to 100%, respectively. Reductions of 1 to 3 days of hospitalization per patient are predicted if RT-PCR is used to diagnose enteroviral meningitis in children.Conclusions.—Reverse-transcription PCR detection of enteroviral infections is an extremely rapid, sensitive, and specific diagnostic modality. Both commercial assays and assays developed in-house appear to be equivalent with regard to sensitivity and specificity. Reverse-transcription PCR diagnosis of enteroviral infections in children could reduce the length of hospitalization and result in significant health care cost savings.
Overview of the Role of Molecular Methods in the Diagnosis of Malignant Lymphomas
Authors: Medeiros L. Jeffrey , Carr Jeanne 
Published: January 2021

Abstract
Objective.—To review the role of molecular genetics in the diagnosis of malignant lymphomas.
Data Sources and Study Selection.—Primary research studies and reviews published in the English literature that focus on molecular genetics and malignant lymphoma, in particular, clonality, chromosomal translocations, tumor suppressor genes, and Hodgkin disease.
Data Extraction and Synthesis.—Molecular genetics has an important role in the assessment of malignant lymphomas. Clonality, detected by Southern blot analysis or the polymerase chain reaction, is helpful for establishing the diagnosis of lymphoma in lesions with ambiguous morphologic and immunophenotypic findings. Southern blot analysis is the “gold standard” for clonality assessment, but the process is labor-intensive and time-consuming. Polymerase chain reaction analysis is more convenient, but a potentially significant false-negative rate exists in the analysis of some antigen receptor genes as a result of using consensus primers and the process of somatic hypermutation. Chromosomal translocations, which result in oncogene activation, occur in many types of B- and T-cell lymphomas, and their detection is helpful in classification as well as in establishing a diagnosis of malignancy. Gene rearrangements and chromosomal translocations also can be used to monitor minimal residual disease. Tumor suppressor genes, although their analysis is relatively less useful for diagnosis, are involved in both pathogenesis and tumor progression and will be more important diagnostically as this field continues to expand. Molecular genetic analysis has played a major role in improving our understanding of Hodgkin disease.
Conclusions.—Molecular genetic tests are currently important ancillary tools for the diagnosis and classification of malignant lymphomas, and their role is likely to increase in the future.
An Overview of Genetic Factors Influencing Plasma Lipid Levels and Coronary Artery Disease Risk
Authors: Ozturk I. Cetin , Killeen Anthony A. 
Published: January 2021

Abstract
Background.—Coronary artery disease (CAD) is a major cause of morbidity and mortality in most Western countries and its origin involves a significant genetic component.
Methods.—Genetic and epidemiologic studies have been performed to identify factors that influence the CAD risk in the population.
Results.—The primary loci that have been demonstrated to be associated with increased CAD risk owing to genetic mutations include the low-density lipoprotein receptor, apolipoprotein B-100, and lipoprotein(a). Additional implicated loci include lipoprotein lipase, apolipoprotein CII, cholesteryl ester transfer protein, apolipoprotein AI, and lecithin–cholesterol acyl transferase.
Conclusions.—Numerous mutations in known genes exert a major effect on CAD risk in some patients. However, in most patients with CAD, the genetic component is believed to be attributable to the aggregate effect of loci that, individually, exert only a minor influence on lipoprotein levels.
Higher Prevalence of GPIIIa PlA2 Polymorphism in Siblings of Patients With Premature Coronary Heart Disease
Authors: Goldschmidt-Clermont Pascal J. , Coleman Lindsay D. , Pham Youm M. , Cooke Glen E. , Shear William S. , Weiss Ethan J. , Kral Brian G. , Moy Taryn F. , Yook Raphael M. , Blumenthal Roger S. , Becker Diane M. , Becker Lewis C. , Bray Paul F. 
Published: January 2021

Abstract
Background.—The PlA2 polymorphism of GPIIIa has been associated with unstable coronary syndromes in some studies, but the association has remained debated. None of the previous studies have focused on families at high risk. Risk factors tend to cluster within kindreds with high prevalence of premature coronary heart disease (CHD). Therefore, a heightened prevalence of the PlA2 polymorphism among siblings of patients with CHD would support the hypothesis that PlA2 is linked, directly or indirectly, to CHD.
Objectives.—To measure the prevalence of the PlA2 polymorphism among siblings of patients with CHD before the age of 60 years and to seek an association between the PlA2 polymorphism and established atherosclerotic and thrombogenic risk factors.
Methods.—From January 1994 to April 1996, we genotyped 116 asymptomatic siblings (60 Caucasians, 56 Afro-Caribbeans) of patients with CHD manifestations before the age of 60 years for the PlA polymorphism (also called HPA-1). A control cohort was used for comparison, consisting of individuals that were matched for race and geographic area but were free of CHD (n = 268, 168 Caucasians and 100 Afro-Caribbeans). In addition, we have characterized the sibling cohort for other atherogenic and thrombogenic risk factors.
Results.—The prevalence of PlA2-positive individuals (PlA2[+], PlA1/A2 heterozygotes plus PlA2/A2 homozygotes) in the sibling cohort was high: 41.4%. When analyzed separately, the prevalence of PlA2(+) siblings was 53.3% among Caucasians and 28.6% among Afro-Caribbeans. There was no association between PlA2 and other established atherogenic or thrombogenic risk factors. Interestingly, the clustering of other risk factors was lesser among PlA2(+) siblings than their PlA1 counterparts.
Conclusions.—This study supports the hypothesis that the prevalence of PlA2(+) individuals is high in kindreds with premature CHD. Hence, like the established risk factors that tend to cluster in families with premature CHD and contribute strongly to the accelerated atherosclerotic process affecting these individuals, the PlA2 polymorphism of GPIIIa may represent an inherited risk that promotes the thromboembolic complications of CHD. That these asymptomatic PlA2(+) siblings had overall less established risk factors than their PlA1 counterparts might represent an explanation for why they remained asymptomatic despite their PlA2 positivity.
Molecular Pathology of Soft Tissue and Bone Tumors
Authors: Slominski Andrzej , Wortsman Jacobo , Carlson Andrew , Mihm Martin , Nickoloff Brian , McClatchey Kenneth 
Published: January 2021

Abstract
Objective.—To present recent concepts on the molecular pathogenesis of tumors of soft tissue and bone, and on the use of molecular genetic methods, including their significance as diagnostic markers and prognostic indicators.
Data Sources and Study Selection.—Reports on tumors of bone and/or soft tissue published in the English language literature and observations made using specimens available at the Departments of Pathology at Albany Medical College and Loyola University Medical Center.
Data Extraction and Synthesis.—Studies on bone and soft tissue tumors containing chromosomal or genetic evaluation were selected for further analysis. Specific chromosomal abnormalities, such as numerical aberrations or translocations with production of fusion genes, were classified according to the tumor of origin. Data were also collected on mutations in tumor suppressor genes, genes coding for growth factors or their receptors, and genes coding for tyrosine kinases. Also noted were mutations of uncertain significance, for which the pathogenic connection between tumor production and mutated gene function is still unclear.
Conclusions.—In general, the mutations reported interfere with the action of peptide growth factors coordinating mesenchyme proliferation and differentiation, although membrane-bound receptors expressing the intracellular signaling modifier, tyrosine kinase activity, have also been involved. Functional types of genes most commonly affected include tumor suppressors, oncogenes, and nuclear transcription factors. Thus, the mutations involved in the pathogenesis of soft tissue and bone tumors have affected multiple genes. Moreover, aberrant fusion gene products may be formed in tumoral tissue and may then act as transcription regulators stimulating cellular proliferation. Cytogenetic studies help at the clinical level by demonstrating aneuploidy and increased ploidy, which may correlate with malignant behavior. Diagnostic tumor-specific chromosomal translocations may be detected with Southern hybridization analysis, polymerase chain reaction, reverse-transcription polymerase chain reaction, or with the fluorescence in situ hybridization technique. Notably, early metastatic disease may be detectable in blood specimens using polymerase chain reaction or reverse-transcription polymerase chain reaction techniques.
Presence of Human Herpesvirus 8 DNA Sequences in Renal Transplantation-Associated Pleural Kaposi Sarcoma
Authors: Gómez-Román J. Javier , Ocejo-Vinyals J. Gonzalo , Sánchez-Velasco Pablo , Leyva-Cobián Francisco , Val-Bernal J. Fernando 
Published: January 2021

Abstract
Objective.—To describe one case of symptomatic skin and pleural Kaposi sarcoma (KS) associated with kidney transplantation. Diagnosis was supported by morphologic study and human herpesvirus 8 (HHV-8) detection in both tissues. Pulmonary involvement was not present.
Design.—The presence of HHV-8 DNA sequences was proved using polymerase chain reaction (PCR), Southern blot hybridization, and in situ hybridization.
Setting.—Human herpesvirus 8 is found in most KS from patients with and without the acquired immunodeficiency syndrome. Clinically significant pulmonary infiltration by KS is diagnosed uncommonly antemortem, and pleural disease is exceptional.
Patient.—A 49-year-old man who had renal transplant with immunosuppressive therapy (tacrolimus and prednisone) and developed a cutaneous KS. A pleural effusion appeared without pulmonary involvement. Both lesions disappeared when immunosuppressive drugs were suspended. Later, the pleural effusion and the cutaneous lesions reappeared. Pleural biopsy specimens showed KS infiltration.
Outcome.—The patient refused treatment and was lost to follow-up.
Results.—The skin and pleural biopsies showed a proliferation of spindle-shaped cells positive for CD34. The HHV-8 sequences were detected by nested PCR. No amplification was detected in uninvolved skin from the patient or in peripheral blood mononuclear cells from 10 healthy individuals used as controls. The Southern blot hybridization confirmed these results.
Conclusions.—To our knowledge, this is the first report of HHV-8 in symptomatic pleural KS, which was probably associated with immunosuppression after kidney transplantation. The demonstration of HHV-8 DNA in biopsy material in the appropriate cells could be diagnostic when the morphologic setting is consistent with KS.
Guidelines for Clinical Use of the Antinuclear Antibody Test and Tests for Specific Autoantibodies to Nuclear Antigens
Authors: Kavanaugh Arthur , Tomar Russell , Reveille John , Solomon Daniel H. , Homburger Henry A. 
Published: January 2021

AbstractThe following guideline presents a series of recommendations based on published medical literature for use of the antinuclear antibody (ANA) test and tests for specific autoantibodies to nuclear antigens in the diagnostic evaluation, prognostic assessment, and monitoring of patients with systemic rheumatic diseases. The guideline emphasizes the need for clinical evaluation to improve the usefulness of test results in patient management. Consideration is given to appropriate use of the generic ANA test in the initial evaluation of patients with signs and symptoms of a systemic rheumatic disease, the evaluation of patients suspected of having lupus erythematosus, use in clinical situations in which the ANA test is required to establish a disease diagnosis, and identification of clinical situations in which the ANA test has little value. Sections are also devoted to recommendations aimed at improving the analytic methods used to detect and measure ANA and specific autoantibodies to nuclear antigens and to the appropriate use of tests for specific autoantibodies in several disease situations that commonly occur in patients with suspected or documented systemic rheumatic diseases. Emphasis is placed on the use of these tests only in situations in which the test results can be expected to provide information necessary for clinical decision making. Those tests of limited medical usefulness and situations in which test results are likely to be misleading are also identified.
Worrisome Histologic Alterations Following Fine-Needle Aspiration of Benign Parotid Lesions
Authors: Li Shiyong , Baloch Zubair W. , Tomaszewski John E. , LiVolsi Virginia A. 
Published: January 2021

Abstract
Objective.—To describe the histologic changes associated with preoperative fine-needle aspiration biopsies of benign parotid lesions and the features that distinguish these changes from malignant neoplasms.
Materials and Methods.—Ten benign parotid lesions with a recent history of preoperative fine-needle aspiration were selected, including pleomorphic adenoma (4 cases), oncocytic adenoma (3 cases), myoepithelioma (1 case), Warthin tumor (1 case), and lymphoepithelial cyst (1 case).
Results.—A spectrum of histologic alterations were observed. Alterations included squamous cell metaplasia (8 cases), infarction and necrosis (4 cases), subepithelial stromal hyalinization (3 cases), acute and chronic hemorrhage and inflammation with multinucleated giant cells (all cases), granulation tissue with subsequent fibrosis (all cases), cholesterol cleft formation (1 case), pseudoxanthomatous reaction (1 case), pseudocapsular invasion (1 case), and microcystic degeneration (2 cases). In cases with exuberant squamous metaplasia, necrosis, or subepithelial stromal hyalinization, a diagnosis of squamous cell carcinoma or low-grade mucoepidermoid carcinoma was seriously considered.
Conclusions.—Knowledge of a previous fine-needle aspiration procedure and awareness of its effects on histology of the subsequent parotidectomy specimens are necessary to avoid potential misdiagnosis.
Peripheral Nerve Amyloidosis in Sural Nerve Biopsies
Authors: Rajani Bijal , Rajani Vakesh , Prayson Richard A. 
Published: January 2021

Abstract
Objective.—Amyloidosis is a well-recognized but uncommon cause of peripheral neuropathy. Our objectives were to determine the overall prevalence of peripheral nerve amyloidosis in sural nerve biopsies and to evaluate the clinical and pathologic features of these lesions.
Methods.—All available histologic and ultrastructural materials on biopsy tissue from 13 cases of peripheral nerve amyloidosis were examined. Muscle biopsies performed at the same time as the nerve biopsy were reviewed when available. Clinical data were collected on all patients.
Results.—The prevalence of amyloidosis in sural nerve biopsies at our institution was 13 (1.2%) of 1098 cases over a 15.8-year period. These patients ranged in age from 41 to 82 years (median, 61 years) at initial presentation and included 10 men and 3 women. Presenting neuropathy symptoms were sensory in 6 of the 13 patients, motor in 2 cases, and mixed in 5 cases. Cardiac, renal, or gastrointestinal involvement was present in 7 of 13 cases. Two patients had myeloma and 7 had systemic autonomic symptoms. Two patients had probable familial amyloid polyneuropathy, and 1 patient demonstrated an alanine 60 point mutation. Amyloid, identified as amorphous eosinophilic extracellular deposits demonstrating apple green birefringence on Congo red stain or recognized by its characteristic fibrillar ultrastructure by electron microscopy, was identified in the endoneurium in 12 nerves, perineurium in 2 nerves, and epineurium in 9 nerves. Chronic inflammation was identified in 5 nerves. Axonal loss was recorded as mild (&lt;25%) in 1 nerve, moderate (25% to 75%) in 8 nerves, and severe (&gt;75%) in 4 nerves. Axonal degeneration predominated over demyelination in 8 of 10 cases that could be evaluated. Concomitant muscle biopsies contained amyloid deposits in 8 of 9 cases.
Conclusions.—Amyloidosis is a rare (1.2% in our series) cause of peripheral neuropathy with a distinct microscopic and ultrastructural appearance. Just over half the patients in our study had visceral organ involvement and systemic autonomic symptoms. The peripheral neuropathy was associated with axonal degeneration and a moderate to severe axonal loss in the majority of cases. Amyloid deposition was present in 8 out of 9 muscle biopsies performed at the same time.
Malignant Melanoma Presenting as an Intrathymic Tumor
Authors: Alli P. M. , Crain B. J. , Heitmiller R. , Argani P. 
Published: January 2021

Abstract
The identification of malignant melanoma in a visceral organ of nonepidermal origin is not an uncommon occurrence. Frequently, these cases are solitary metastases that present years after a thin epidermal melanoma has been diagnosed (and sometimes forgotten). However, primary visceral melanomas have been reported that have not been preceded by an epidermal lesion. We describe herein a unique case of melanoma presenting as a primary intrathymic tumor. The patient had no previous history of epidermal melanoma, and extensive workup did not reveal evidence for an alternative primary site. The tumor exhibited histologic features characteristic of melanoma, including an abundance of large pleomorphic cells with eosinophilic cytoplasm, prominent nucleoli, and occasional intranuclear inclusions. Tumor cells stained for HMB-45 and S-100 protein and ultrastructural analysis revealed stage II and stage III melanosomes. The patient remained free of disease until intrathoracic recurrence was detected on a computed tomographic scan 14 months later. The lack of clinical history and physical findings of melanoma at presentation, the intrathymic location of the tumor, and the pattern of recurrence suggest that this case likely represents a primary thymic melanoma, a previously unreported entity.
Pleomorphic Giant Cell Carcinoma of the Esophagus With Coexpression of Cytokeratin and Vimentin and Neuroendocrine Differentiation
Authors: Mosnier Jean-Francois , Balique Jean-Gabriel 
Published: January 2021

Abstract
A pleomorphic (giant cell) carcinoma of the esophagus is reported in a 52-year-old man who had dysphagia and weakness. The 8-cm-high vegetating tumor consisted of solid sheets of poorly cohesive epithelioid cells broken into clusters by strands of stroma. Numerous giant cells showing phagocytic phenomenon were present. Immunochemical analyses demonstrated the epithelial origin of the neoplasm, although most of the tumor cells strongly expressed vimentin. Numerous tumor cells expressed synaptophysin. Neurosecretory granules were detected in some tumor cells on electron microscopic examination. The patient died 4 months after he became symptomatic. As far as we can ascertain, this is the first case report describing a pleomorphic carcinoma arising in the esophagus. This poorly differentiated carcinoma might be of neuroendocrine differentiation. In the esophagus, pleomorphic carcinoma must be distinguished from polypoid tumors such as carcinosarcoma and malignant melanoma.
Diagnosis of Papillary Carcinoma in a Thyroglossal Duct Cyst by Fine-Needle Aspiration Biopsy
Authors: Yang Yi Jun , Haghir Shahandeh , Wanamaker John R. , Powers Celeste N. 
Published: January 2021

Abstract
The incidence of papillary thyroid carcinoma arising in a thyroglossal duct cyst is rare and occurs in about 1% of thyroglossal duct cysts. Only 17 such cases diagnosed with fine-needle aspiration biopsy have been previously reported in the English-language literature, with a diagnostic rate of 53%. In this article, the cytologic features of the current case are emphasized and those of the previous reported cases are briefly reviewed. Diagnostic pitfalls of papillary carcinoma arising in thyroglossal duct cysts diagnosed by fine-needle aspiration biopsy are also discussed.