bluuebunny/crossref_metadata_2025 huggingface dataset:
Autopsy Result Utilization
Authors: Nakhleh Raouf E. , Baker Peter B. , Zarbo Richard J.
Published: January 2021

Objectives.—To document the level of involvement and communication with nonpathology clinical personnel regarding autopsies and to document the destination of autopsy reports.

Design.—The College of American Pathologists Q-Probes format was used to collect information on 15 consecutively performed autopsies per institution or for 6 months, whichever occurred first. The following information was recorded for each autopsy: decedent’s age, hospital service, length of hospital stay, whether organs were donated, who was present at autopsy, methods of communicating preliminary and final autopsy results, special techniques used to arrive at a preliminary diagnosis, activities for which the autopsy was used, and destination of final report.

Participants.—Two hundred fifty-six laboratories collected information on 2755 autopsies.

Results.—The aggregate autopsy rate was 12.4% (median 8.5%). Nonpathology clinical personnel attended 35.8% of all autopsies. A clinical physician was more likely to attend an autopsy if the patient was from a surgical service. Three primary methods were used to communicate preliminary autopsy results, namely, written reports (82.5%), telephone calls (50.6%), and meetings (11.5%). The primary care physician was sent the autopsy report in 91.1% of cases. Approximately half of the autopsy cases were used in both pathology departmental and extradepartmental activities. Aggregate autopsy data were distributed in the majority of cases to various departmental chairpersons and institutional quality assurance committees.

Conclusions.—This study provides a comparative multi-institutional database for the utilization of autopsy results by clinicians and clinical departments. Although autopsy rates are low, autopsy results are routinely being used for hospital quality assurance activities and for educational purposes.
Intrasellar Paraganglioma Presenting as Nonfunctioning Pituitary Adenoma
Authors: Sambaziotis Demetrios , Kontogeorgos George , Kovacs Kalman , Horvath Eva , Levedis Athanassios
Published: January 2021

Paragangliomas arising in the sellar region are rare. We report a case of intrasellar paraganglioma of a 54-year-old man who presented with gradually decreasing visual acuity. Physical examination revealed bitemporal hemianopsia with no apparent signs of endocrinologic dysfunction. Magnetic resonance imaging revealed a large sellar mass believed to be a nonfunctioning pituitary adenoma. The tumor was removed transsphenoidally and submitted for histologic examination. The morphologic features, based on histologic, immunocytochemical, and electron microscopic analyses, were consistent with the diagnosis of paraganglioma. The diagnostic morphologic features and the immunocytochemical profile of the tumor are reported.
Recurrent Intranodal Palisaded Myofibroblastoma With Metaplastic Bone Formation
Authors: Creager Andrew J. , Garwacki Christopher P.
Published: January 2021

Intranodal palisaded myofibroblastoma (IPM) is a rare primary nonlymphoid tumor of the lymph node, which can easily be mistaken for other spindle cell tumors. Intranodal palisaded myofibroblastoma is thought to arise from intranodal myofibroblasts, a finding that is supported by its immunophenotype, positive immunostaining for actin and vimentin, and negative immunostaining for desmin. Characterized by a benign clinical course, IPM is treated by simple surgical excision. We describe a 49-year-woman, who had cadaveric renal transplantation in 1992 and recurrent IPM 4½ years after its original excision. To our knowledge, this case represents only the second known case of recurrent IPM. The histologic feature of metaplastic bone formation in this case has not been previously described in IPM.
An Examination of Ethical Issues Raised in the Pretreatment of Normal Volunteer Granulocyte Donors With Granulocyte Colony-Stimulating Factor
Authors: Volk Emily E. , Domen Ronald E. , Smith Martin L.
Published: January 2021

Objective.—To explore some of the ethical issues surrounding the administration of granulocyte colony-stimulating factor (G-CSF) to healthy individuals for the purpose of retrieval of granulocytes.

Design.—Review of the historical precedent of drug administration to normal blood donors and review of the literature concerning the side effects of G-CSF administration to healthy individuals, particularly as related to granulocyte collection. We identify and discuss some of the ethical questions regarding this issue.

Results.—Although the short-term side effects of G-CSF use in normal donors are generally felt to be benign, little is known about the long-term side effects. Ethical questions regarding the administration of this drug to normal donors for the purpose of collecting large numbers of granulocytes include the following: Does the potential benefit to a patient/recipient justify the unknown risks to the medicated granulocyte donor? Who should act as an advocate for donors so that their best interests are protected? What is the role and quality of informed consent for donors undergoing G-CSF administration? Is monetary compensation appropriate for donors administered G-CSF as part of a research protocol?

Conclusions.—We recommend the establishment of a donor registry to collect the needed data on the side effects of G-CSF on normal donors. Until adequate data are collected, the use of G-CSF and similar agents in normal donors should be regarded as experimental and subject to review by institutional review boards.
Using Outlier Events to Monitor Test Turnaround Time
Authors: Steindel Steven J. , Novis David A.
Published: January 2021

Objectives.—To determine the causes of excessive test turnaround time (TAT) and to identify methods of improvement by studying reasons for those tests reported in excess of 70 minutes from the time the test was ordered (ie, outliers).

Design.—Self-directed data-gathering of stat outlier TAT events from intensive care units and emergency departments, with descriptive parameters associated with each event and additional descriptive parameters associated with the participant.

Participants.—Laboratories enrolled in the 1996 College of American Pathologists Q-Probes program.

Main Outcome Measures.—Components associated with outlier TAT events and outlier TAT rates.

Results.—Four hundred ninety-six hospital laboratories returned data on 218 551 stat tests, of which 10.6% had TATs in excess of 70 minutes. Ten percent of stat emergency department tests and 14.7% of stat intensive care unit tests were outliers. Major areas in which delays occurred were test ordering, 29.9%; within-laboratory (analytic) phase, 28.2%; collection of the specimen, 27.4%; postanalytic phase, 1.9%; and undetermined, 12.5%. The type of test performed was a significant factor and was independent of location: Chemistry–Multiple Test appeared most frequently (∼40%), followed closely by Hematology–Complete Blood Count (∼20%) and Chemistry–Single Test (∼18%). Factors of outlier TAT components for intensive care unit specimens were identified using statistical modeling and included hour of day, type of health care personnel collecting specimen, performing the test in a stat laboratory, and reason for delay. Outlier rates were not associated with any identified factors. The practice parameters of laboratories with outlier rates in the lowest 10th percentile significantly differed from those with rates in the top 10th percentile in test request computerization, report methods, and ordering methods.

Conclusions.—We observed that outlier analysis yields new information, such as type of test and reason for delay, concerning test delays when compared with TAT determination alone. Laboratories experiencing stat test TAT problems should use this tool as an adjunct to routine TAT monitoring for identifying unique causes of delay.
Primary Hepatic B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue
Authors: Kirk Cheryl M. , Lewin David , Lazarchick John
Published: January 2021

Mucosa-associated lymphoid tissue (MALT) lymphomas are low-grade B-cell lymphomas that occur in a variety of extranodal sites but rarely as a primary hepatic lymphoma. We describe the histological findings, immunophenotype, and immunohistochemistry of one such lymphoma found incidentally in a 69-year-old woman. The lymphoid infiltrate invaded the liver in a serpiginous configuration with entrapment of nodules of normal liver. Reactive follicles were surrounded by intermediate-sized lymphoid cells with slightly irregular nuclei and pale cytoplasm. Only a few scattered lymphoepithelial lesions were identified since most of the bile ducts were destroyed. The immunophenotype determined by flow cytometry identified the lymphoid cells as being CD19, CD20 positive and exhibiting λ light chain restriction. CD5, CD10, and CD23 were negative. Immunohistochemistry showed the neoplastic cells to be positive for CD20 (L-26) and bcl-2. The reactive follicles were negative for bcl-2. CD3 showed only a few scattered T cells. Cyclin D1 did not stain the neoplastic cells. Cytokeratin (AE1/AE3) highlighted the lymphoepithelial lesions and residual bile ducts. MALT lymphomas need to be recognized and distinguished from other B-cell lymphomas, particularly mantle cell lymphomas, because of the difference in behavior and treatment.
Munchausen Syndrome Presenting as Pulmonary Talcosis
Authors: Egan A. J. Matthew , Tazelaar Henry D. , Myers Jeffrey L. , Abell-Aleff Patrice C.
Published: January 2021

We describe a patient with self-induced inhalational pulmonary talcosis originally diagnosed as asthma. A 35-year-old female respiratory technologist developed severe asthma that was refractory to steroids and methotrexate. An open lung biopsy specimen showed scattered aggregates of refractile golden crystals within membranous and respiratory bronchioles. The particles ranged in size from 30 to 100 μm and were birefringent when viewed with polarized light. Following review of the lung biopsy specimen, the patient admitted to regularly inhaling large amounts of hospital baby powder. Analysis of the lung biopsy specimen and a sample of the hospital baby powder by x-ray energy dispersion showed identical spectroscopic peaks, including elemental peaks for magnesium silicate. Many patients with self-induced illness lack the picturesque symptomatology classically attributed to Munchausen syndrome. Awareness of these more subtle and varied patterns of presentation may aid in earlier recognition.
Evaluation of a Fully Automated High-Performance Liquid Chromatography Assay for Hemoglobin A1c
Authors: Khuu Hanh M. , Robinson C. Andrew , Goolsby Kathy , Hardy Robert W. , Konrad Robert J.
Published: January 2021

Introduction.—Measurement of hemoglobin A1c (HbA1c) is used as an objective measure of long-term blood glucose control in diabetic patients. Recent improvements in automation combined with new recommendations for precision and accuracy have caused us to reevaluate our methods for measuring HbA1c.

Objective.—We evaluated a newly automated high-performance liquid chromatography (HPLC) instrument for measurement of HbA1c (Tosoh A1c 2.2 Plus Glycohemoglobin Analyzer, Tosoh Medics, Foster City, Calif) and compared the results obtained by HPLC to those obtained with an immunoassay (Hitachi 911, Boehringer Mannheim Corporation, Indianapolis, Ind).

Results.—The Tosoh analyzer was found to be linear in a range of 5.3% to 17% and had a throughput of 20 samples per hour. HbA1c results for 102 patient samples by the 2 techniques showed good correlation, with a slope of 0.87 and an intercept at 1.27% ± 0.15%. Both the total and within-run coefficients of variation were consistently lower for the HPLC method compared with the immunoassay method. The HPLC method produces a chromatogram that shows the different hemoglobin fractions, allowing identification of abnormal hemoglobin variants. In heterozygous individuals, HbA1c measurements are made with no interference from the hemoglobin variant. In the case of homozygous or doubly heterozygous hemoglobin variants, the Tosoh HPLC identifies the hemoglobin variants as such and correctly does not report a HbA1c value in the presence of a markedly decreased amount of hemoglobin A.

Conclusions.—The Tosoh HPLC provides adequate throughput and improved precision, and the method is traceable to the Diabetes Control and Complications Trial.
Intrathecal Methotrexate–Induced Megaloblastic Anemia in Patients With Acute Leukemia
Authors: Sallah Sabah , Hanrahan L. Robert , Phillips Debra L.
Published: January 2021

Objective.—To evaluate the occurrence of megaloblastic anemia induced by the infusion of therapeutic or prophylactic methotrexate in patients with acute leukemia.

Design.—Data on 3 patients with acute leukemia receiving intrathecal methotrexate were prospectively analyzed.

Setting.—Large tertiary-care center.

Results.—All 3 patients with acute leukemia developed megaloblastic anemia confirmed by examination of the bone marrow aspirate and biopsy. Two of the 3 patients had low folic acid levels, while all patients had normal serum B12 levels. All patients responded favorably to a therapeutic trial of folic acid. The median time for recovery of the hematologic parameters in these patients was 7 days.

Conclusions.—Intrathecally administered methotrexate may result in megaloblastic changes in the bone marrow of leukemic patients. The morphologic clues suggestive of folate deficiency in patients with acute leukemia may be masked by coexisting factors, such as the effects of cytotoxic treatment, prior transfusions, or persistent changes from the leukemic clone itself. Caution should be exercised to avoid attributing these changes to the neoplastic process, since the prognosis and treatment for the conditions involved are totally different. Repeat examination of the bone marrow, obtaining folic acid and vitamin B12 levels, and a therapeutic trial of folic acid may help identify and reverse these changes.
The Myoepithelial Immunophenotype in 135 Benign and Malignant Salivary Gland Tumors Other Than Pleomorphic Adenoma
Authors: Prasad Anil R. , Savera Adnan T. , Gown Allen M. , Zarbo Richard J.
Published: January 2021

Background.—We have previously studied the immunoreactivity of 3 novel smooth muscle–specific proteins, α-smooth muscle actin, smooth muscle myosin heavy chains, and calponin, to assess myoepithelial differentiation in pleomorphic adenomas.

Objective.—To further expand our knowledge of myoepithelial differentiation in other benign and malignant salivary gland tumors.

Design.—Formalin-fixed paraffin sections of 135 salivary gland tumors with associated normal glands were stained with monoclonal antibodies using the avidin-biotin complex immunoperoxidase method and enzymatic and microwave heat–induced epitope retrieval.

Results.—In adenoid cystic carcinomas and epithelial-myoepithelial carcinomas, all 3 markers exclusively highlighted the myoepithelial cell components and the epithelial cells were entirely negative. No immunostaining was detected in canalicular adenomas, oncocytomas, Warthin tumors, acinic cell carcinomas, mucoepidermoid carcinomas, squamous cell carcinomas, and polymorphous low-grade adenocarcinomas. Salivary duct carcinomas and adenocarcinomas, not otherwise specified had a distinctive pattern of uniform periductal staining of reactive myofibroblastic cells, and in salivary duct carcinomas some ducts retained a peripheral immunoreactive myoepithelial cell layer.

Conclusion.—Immunoreactivity for these 3 smooth muscle–specific proteins confirms the known neoplastic myoepithelial component of adenoid cystic carcinomas and epithelial-myoepithelial carcinomas. The consistently positive staining pattern in adenoid cystic carcinomas may be diagnostically useful in discriminating histologically similar but consistently negative polymorphous low-grade adenocarcinomas. Periductal linear staining in adenocarcinoma, not otherwise specified and salivary duct carcinomas is distinctive and appears to represent a tight cuff of myofibroblasts associated with the infiltrating glands.
Myiasis Secondary to Dermatobia hominis (Human Botfly) Presenting as a Long-standing Breast Mass
Authors: Kahn Douglas G.
Published: January 2021

A case of a 54-year-old woman who presented with a breast mass is reported. Histologically, a chronic granulomatous inflammatory response was observed. The response was associated with an organism diagnosed as a fly larva, Dermatobia hominis (human botfly). The incidence of myiasis, infestation by fly larvae, presenting as a long-standing breast mass and mimicking a neoplasm is extremely rare, especially in the United States.
Osteosarcoma Arising in a Solitary Osteochondroma of the Fibula
Authors: Lamovec Janez , Špiler Marko , Jevtić Vladimir
Published: January 2021

We present a case of osteosarcoma arising in an osteochondroma of the right fibula in a 30-year-old woman. The available radiographic studies of the lesion were not suggestive of malignant transformation. The lesion and underlying bone were excised. Histologic examination showed a conventional high-grade osteoblastic osteosarcoma that focally eroded the fibrocartilaginous cap. The patient received postoperative chemotherapy and shows no evidence of disease 27 months following operation. The occurrence of osteosarcoma in an osteochondroma is an extremely rare event, and only a few cases are on record in the literature.
Epithelioid Hemangioendothelioma, Multiple Focal Nodular Hyperplasias, and Cavernous Hemangiomas of the Liver
Authors: Bralet Marie-Pierre , Terris Benoit , Vilgrain Valérie , Brégeaud Laurence , Molas Georges , Corbic Michèle , Belghiti Jacques , Fléjou Jean-François , Degott Claude
Published: January 2021

Malignant vascular neoplasms of the liver are uncommon. We report the case of a young woman who developed an epithelioid hemangioendothelioma of the liver associated with multiple focal nodular hyperplasias and hepatic cavernous hemangiomas. Such an unusual association is probably not fortuitous and could support the theory that focal nodular hyperplasia is a reaction to an abnormal vascular supply rather than a true neoplasm.
Platelets
Authors: Silberman Simone
Published: January 2021

Objective.—To summarize current knowledge and recent progress pertaining to platelet concentrate preparations, modifications, and future prospects for platelet substitutes.

Methods.—Current publications identified through a search of an electronic literature database were evaluated and reviewed. Relevant data were abstracted into this article. Abstractions of the data were made depending on their relevance. This review starts with standard methods of platelet preparation and goes on to describe different modifications intended to optimize the product and increase its safety. The article concludes with a discussion of the use of hematopoietic growth factors and novel kinds of platelet components for future use.

Conclusions.—Many modifications in the preparation of platelet transfusions have occurred in recent years. Platelets prepared by standard techniques contain significant numbers of donor leukocytes, which are responsible for several adverse effects. Awareness of this problem has lead to the development of effective means for their removal. Several methods to reduce the risk of viral and bacterial transmission through platelet transfusions are emerging. New technologies in the use of platelet substitutes have attempted to prolong the platelet storage potential and prevent the development of recipient alloimmunization. As the biological activities of growth factors become better understood, the clinical applications of novel recombinant products may redefine the concept of future platelet transfusions. It is important that research continues into the optimal methods for the preparation and use of platelet transfusions to provide maximal clinical benefits with minimal risk of complications.
Neuroendocrine Carcinoma of the Posterior Mediastinum
Authors: Horie Yasushi , Kato Masako
Published: January 2021

A paravertebral mass was noted in the posterior mediastinum in a 47-year-old man. Microscopically, the tumor showed solid and trabecular patterns and consisted of poorly differentiated atypical cells that often formed Flexner-Wintersteiner rosettelike glands. Immunohistochemically, the tumor cells expressed both epithelial and neuroendocrine markers, including cytokeratin (AE1/3), carcinoembryonic antigen, epithelial membrane antigen, neuron-specific enolase, chromogranin A, and synaptophysin, but were negative for CD99 (MIC2). Ultrastructurally, numerous desmosomes and neurosecretory granules were identified in the tumor cells. The present lesion was a primary neuroendocrine carcinoma of the posterior mediastinum—an unusual site for such a lesion.
A Case of Familial Angiolipomatosis With Lisch Nodules
Authors: Cina Stephen J. , Radentz Stephen S. , Smialek John E.
Published: January 2021

Familial angiolipomatosis is a rare syndrome that may be confused clinically with neurofibromatosis type 1. This condition is most often inherited in an autosomal recessive manner; however, several reports have been published suggesting an autosomal dominant mode of inheritance. Angiolipomatosis, although somewhat disfiguring, is a benign condition with no known association with malignant neoplasms. This is in contradistinction to neurofibromatosis, an autosomal dominant syndrome associated with a myriad of benign and malignant neoplasms. It is, therefore, important to discriminate this entity from neurofibromatosis when a patient presents with multiple subcutaneous tumors and a family history of similar lesions. Described is a case of a prison inmate with a history of seizures and “neurofibromatosis” without clinical documentation. Lisch nodules were noted on the irides. Postmortem examination showed multiple subcutaneous yellow tumors on the chest and arms. Fine-needle aspiration of 1 mass yielded adipose tissue with prominent vessels; histologic sections of another mass showed angiolipoma. The remainder of the autopsy showed significant coronary artery disease and a remote cerebral infarction of the temporal lobe but no signs of neurofibromatosis. We feel that the presence of multiple angiolipomas in combination with Lisch nodules lends credence to the proposed relationship between fatty tumors and neurofibromatosis suggested by other authors.
Practice Guidelines for Autopsy Pathology
Authors: Hutchins Grover M. , Berman Jules J. , Moore G. William , Hanzlick Randy
Published: January 2021

The Autopsy Committee of the College of American Pathologists has prepared this revised guideline to reflect changes that have occurred in the reporting of autopsies since the original guideline was published in February 1995. It is intended to be an instrument to assist pathologists in the reporting of autopsies. The guideline is to be regarded as being primarily an educational tool. Application of these recommendations on autopsy reporting is to be made on the basis of the judgment of the pathologist engaged in a specific case.
Lack of Epstein-Barr Virus Infection in Cervical Carcinomas
Authors: de Oliveira Deilson Elgui , Monteiro Talita Antônia Furtado , de Melo Wyller Alencar , Moreira Marise Amaral Rebouças , Alvarenga Marcelo , Bacchi Carlos E.
Published: January 2021

Context.—The Epstein-Barr virus (EBV) is a ubiquitous microorganism strongly associated with lymphoproliferative disorders and a large number of human neoplasms, mainly undifferentiated nasopharyngeal carcinoma and Burkitt lymphoma. The viral DNA has been detected in other tumors, such as carcinomas from tonsil, salivary glands, and thymus, and malignancies of the female genital tract. Some authors have proposed that EBV could play a role in the carcinogenesis of cervical tumors; however, other studies do not support this hypothesis.

Objective.—To assess whether EBV is associated with female genital tract neoplasms.

Design.—Sixty-five biopsy specimens (5 in situ carcinomas, 24 invasive squamous cell carcinomas, 6 lymphoepithelioma-like carcinomas, and 30 endocervical adenocarcinomas) were used to perform EBV detection through RNA in situ hybridization.

Results.—None of the cervical carcinoma cases studied was positive for EBV infection.

Conclusions.—The results suggest that it is still premature to incriminate EBV in the carcinogenesis of cervical carcinoma.
Invasive Cystic Hypersecretory Ductal Carcinoma of Breast
Authors: Herrmann Marille E. , McClatchey Kenneth D. , Siziopikou Kalliopi P.
Published: January 2021

Few individual cases of invasive cystic hypersecretory ductal carcinoma of the breast have been described. Review of 33 cases of cystic hypersecretory carcinoma, including the current case, indicate that only 6 cases presented with invasive disease. Two of these cases had positive nodes and 2 had distal metastases. The case presented here is unique in an additional aspect: the contralateral breast harbored lobular breast carcinoma 10 years after mastectomy of the first malignancy. Bilateral breast disease resulting in bilateral mastectomies over long-term follow-up, as in the case presented here, was reported in 3 of 33 cases.
Squamous Cell Carcinoma Arising in a Ciliated Hepatic Foregut Cyst
Authors: Vick Dan J. , Goodman Zachary D. , Ishak Kamal G.
Published: January 2021

Ciliated hepatic foregut cysts are rare congenital lesions derived from the embryologic foregut. They are considered benign, and a review of 64 published cases revealed no instances of malignant transformation. We report a case of squamous cell carcinoma arising in a ciliated hepatic foregut cyst in a 51-year-old man. The tumor was found during a routine cholecystectomy and involved the adjacent mesentery and duodenal wall. There was histologic evidence of perineural and perivascular involvement. Despite an en bloc resection of the tumor and contiguous areas of gross involvement, the patient died 2 months later. Although aspiration of cyst contents is an accepted treatment for asymptomatic lesions, this case suggests that most ciliated hepatic foregut cysts should be excised, especially when radiologic studies yield equivocal results.
DNA Technology in the Clinical Laboratory
Authors: Kiechle Frederick L.
Published: January 2021

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

Objective.—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

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

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

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

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

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.
Protocol for the Examination of Specimens From Patients With Carcinomas of the Extrahepatic Bile Ducts, Exclusive of Sarcomas and Carcinoid Tumors
Authors: Henson Donald E. , Albores-Saavedra Jorge , Compton Carolyn C.
Published: January 2021

No Abstract Available
Protocol for the Examination of Specimens From Patients With Carcinomas of the Gallbladder, Including Those Showing Focal Endocrine Differentiation
Authors: Henson Donald E. , Albores-Saavedra Jorge , Compton Carolyn C.
Published: January 2021

No Abstract Available
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

The 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

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

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 (<25%) in 1 nerve, moderate (25% to 75%) in 8 nerves, and severe (>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.