bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of Factor V Leiden and Prothrombin Gene Mutations in Patients Who Died With Thrombotic Events
Authors: Ranguelov Rostislav D. , Rosenthal Nancy , Bromley Christine , Vasef Mohammad A. 
Published: January 2021

Abstract
Context.—Individuals with factor V or prothrombin gene mutations are at increased risk for thrombotic events. Furthermore, the risk of recurrent deep venous thrombosis in heterozygous carriers of both factor V Leiden and prothrombin gene mutations is high enough that some investigators suggest lifelong warfarin prophylaxis for these individuals, even with a single spontaneous thrombotic event.
Objectives.—To assess the incidence of factor V Leiden and prothrombin gene mutations in an autopsy population and to determine if these tests can prove useful in identification of at-risk family members.
Design.—We analyzed factor V Leiden and prothrombin gene mutations in 45 patients who died with or of thrombotic events, using archival tissue and multiplex allele-specific polymerase chain reaction amplification. The wild-type factor V gene was amplified in all 45 patients, whereas the wild-type prothrombin gene was amplified in 29 patients.
Results.—Two patients (4.4%) who died with thrombotic events at the ages of 35 and 92 years were heterozygous for factor V gene mutation. Two additional patients (6.7%), who died with thrombotic events at the ages of 26 and 39 years, were heterozygous for prothrombin gene mutation. Patients homozygous for either factor V or prothrombin gene or simultaneously heterozygous for both genes were not detected in our study.
Conclusions.—Our findings suggest that screening the relatives of elderly patients who die with thrombotic events would not be cost-effective because of the low incidence of these mutations in the autopsy population. However, because the incidence of these mutations appeared significantly more frequently among individuals who died at 39 years or younger, testing the relatives of this subset of patients may prove useful for detection of at-risk individuals who would benefit from preventive anticoagulation therapy.
Nonseminomatous Germ Cell Tumor Arising in Splenogonadal Fusion
Authors: Imperial Sandy L. , Sidhu Jagmohan S. 
Published: January 2021

Abstract
Splenogonadal fusion is a rare congenital malformation in which the spleen is abnormally connected to the gonads or to the mesonephric derivatives. A few more than 150 cases have been described in the world literature. We report an additional case of splenogonadal fusion. A nonseminomatous germ cell tumor was found in the testicle involved in this splenogonadal fusion. To our knowledge, this is the third reported case of a testicular neoplasm associated with splenogonadal fusion and the first reported case of intra-abdominal nonseminomatous germ cell testicular tumor arising in this rare anomaly. The literature pertaining to splenogonadal fusion and the testicular tumor arising in this anomaly is briefly reviewed.
Plasminogen and Tissue-Type Plasminogen Activator Deficiency as Risk Factors for Thromboembolic Disease
Authors: Brandt John T. 
Published: January 2021

Abstract
Objective.—To review the published evidence for an association between a deficiency of plasminogen or tissue-type plasminogen activator (tPA) and the risk of thrombosis.
Data Sources.—Review of the medical literature, with an emphasis on the last 10 years.
Data Extraction and Synthesis.—After an initial assessment of the literature, including review of clinical study design and laboratory methods, a draft manuscript summarizing the findings was prepared and circulated to participants in the College of American Pathologists Conference on Diagnostic Issues in Thrombophilia. The key findings and each recommendation were presented for discussion at the conference. Recommendations were accepted if a consensus of the 27 experts attending the conference was reached. The results of the discussion were used to revise the manuscript into its final form.
Conclusions.—The consensus of the conference was that routine laboratory assessment of plasminogen and tPA concentration in patients with thrombophilia is not warranted at this time. Analysis of plasminogen and tPA gene alterations in patients with thrombophilia is also not warranted at this time. Determination of plasminogen concentration should be performed in patients suspected of having ligneous conjunctivitis.
Plasminogen Activator Inhibitor-1 Levels and Polymorphisms
Authors: Francis Charles W. 
Published: January 2021

Abstract
Objective.—To review the published evidence of a relationship between levels of plasminogen activator inhibitor-1 (PAI-1) or the 4G/5G polymorphism of the PAI-1 gene and the occurrence of venous thromboembolic disease.
Methods.—Review of the medical literature using computerized databases and a review of secondary sources identified through bibliographies.
Data Synthesis.—Plasminogen activator inhibitor-1 is an important inhibitor of the fibrinolytic system, so it is biologically plausible that elevated levels could suppress fibrinolysis and result in an increased risk of thrombosis. Several small studies reported associations between PAI-1 levels and venous thromboembolism, some of which appear to be familial. Problems with these studies include variations in PAI-1 plasma levels due to circadian changes and the acute phase response, as well as alterations due to common comorbid disease states. More recent investigations have focused on genetic polymorphisms, particularly the 4G/5G insertion/deletion in the promoter region, affecting transcription rates. The relation of 4G/5G to venous thrombosis has been investigated primarily in case-control studies, which have produced inconsistent findings. Most studies, however, have reported higher PAI-1 plasma levels in individuals with 4G/4G.
Conclusions.—The evidence regarding the relationship between an elevated PAI-1 plasma level or PAI-1 genetic polymorphism and the risk of venous thromboembolism is conflicting. There is insufficient information to recommend use of PAI-1 levels or genotype in evaluating thrombophilia.
Adrenal Cortical Adenoma With Adrenalin-Type Neurosecretory Granules Clinically Mimicking a Pheochromocytoma
Authors: Ivsic Tomislav , Komorowski Richard A. , Sudakoff Gary S. , Wilson Stuart D. , Datta Milton W. 
Published: January 2021

Abstract
Adrenal tumors often present with clinical features that are specific and unique to their endocrine metabolism. When these features are in conflict with the pathologic appearance of the tumor, there can be great consternation for both the pathologist and the surgeon. In the case reported herein, an adrenalectomy was performed for clinical features of pheochromocytoma that on gross and histologic examination had the pathologic features of an adrenal cortical adenoma. Electron microscopy subsequently revealed that the tumor cells contained adrenalin-type granules, explaining the clinical outcome. It is crucial for both the surgeon and the surgical pathologist to be aware of this possibility when the clinical and pathologic features of an adrenal tumor are not congruent.
Ectopic Parathyroid Adenoma Initially Suspected to Be a Thyroid Lesion
Authors: Pitsilos S. A. , Weber R. , Baloch Z. , LiVolsi V. A. 
Published: January 2021

Abstract
Considering the variety of aberrant locations in which ectopic parathyroid adenomas may be found, these neoplasms can be difficult to identify and treat surgically. The results of radiographic and cytologic studies may lead to confusion of these neoplasms with lesions of thyroid origin. We present a case of an ectopic parathyroid adenoma for which misleading localization prompted cytologic misdiagnosis and intraoperative suspicion of thyroid carcinoma.
Mature B-Cell Leukemias With More Than 55% Prolymphocytes
Authors: Merchant Shakil , Schlette Ellen , Sanger Warren , Lai Raymond , Medeiros L. Jeffrey 
Published: January 2021

Abstract
Context.—The molecular genetic events involved in the pathogenesis of mature B-cell leukemias with more than 55% prolymphocytes are not well characterized. We have encountered 2 such cases in which conventional cytogenetic analysis identified Burkitt lymphoma–type chromosomal translocations involving 8q24.
Objective.—To assess these 2 cases for involvement of the c-myc gene using fluorescence in situ hybridization analysis with probes specific for the c-myc and immunoglobulin heavy-chain (IgH) genes.
Results.—In both cases, conventional cytogenetic analysis demonstrated complex karyotypes, including chromosomal translocations involving 8q24. In case 1, a case of de novo prolymphocytic leukemia, the t(8;14)(q24;q32) was detected. In case 2, a case of chronic lymphocytic leukemia in prolymphocytoid transformation, the t(8;22)(q24;q11) was identified. Fluorescence in situ hybridization studies showed c-myc/IgH fusion signals in case 1, proving the presence of the t(8;14). Split c-myc signals without fusion to IgH were observed in case 2, proving c-myc gene rearrangement and consistent with the t(8;22).
Conclusion.—These results suggest that c-myc gene alterations may be involved in the pathogenesis of a subset of mature B-cell leukemias with more than 55% prolymphocytes.
Management of Patients Refractory to Platelet Transfusion
Authors: Sacher Ronald A. , Kickler Thomas S. , Schiffer Charles A. , Sherman Laurence A. , Bracey Arthur W. , Shulman Ira A. 
Published: January 2021

AbstractObjective.—To present a current assessment and practical approach to the diagnosis and management of patients who are refractory to platelet transfusions.Design.—A task force was convened by the College of American Pathologists under the auspices of the Transfusion Medicine Resource Committee for the purposes of outlining current concepts in the definition and diagnosis of this difficult clinical management problem and selection of the optimal platelet component for these patients.Results.—This article represents a contemporary approach to the diagnosis and management of patients who are refractory to platelet transfusions. This document is based on a current literature review and dialog among members of the task force convened to address the subject.Conclusions.—It is hoped that this document will represent a resource and practical approach to the issue of diagnosis and management of patients who are refractory to platelet transfusions.
Mature B-Cell Acute Lymphoblastic Leukemia With Associated Translocations (14;18)(q32;q21) and (8;9)(q24;p13)
Authors: Dunphy Cherie H. , van Deventer Hendrik W. , Carder Kathryn J. , Rao Kathleen W. , Dent Georgette A. 
Published: January 2021

Abstract
The translocation t(14;18)(q32;q21) is most commonly associated with follicular lymphoma but has also been described in acute lymphoblastic leukemia (ALL) of B-cell origin. Although these ALL cases have had a pre-pre-B, pre-B, or mature B-cell immunophenotype and L2 or L3 morphology, all have been associated with an abnormality of 8q24. In fact, 91% (10 of 11) have been associated with t(8;22) or t(8;14), marker chromosomes for Burkitt-type ALL. The other case was associated with del(8)(q24). Thus, Burkitt-type ALL may have various immunophenotypes and morphology when associated with t(14;18). We describe a case of mature B-cell ALL associated with t(14;18) and t(8;9)(q24;p13). The morphology was suggestive but not entirely characteristic of the L3 subtype. However, on the basis of the cytogenetic findings and the review of the literature, perhaps this case represents a variant of Burkitt-type ALL, which would be important to recognize for prognostic and therapeutic purposes. We describe our findings and review the literature to heighten awareness of this group of ALLs associated with t(14;18). Additional cases need to be accrued and documented to determine the significance of an associated abnormality of 8q24 in this setting.
Multilaboratory Evaluation of Serum Analysis for HLA Antibody and Crossmatch Reactivity by Lymphocytotoxicity Methods
Authors: Duquesnoy RenéJ. , Marrari Marilyn 
Published: January 2021

Abstract
Context.—This report presents results of the serum antibody analysis and crossmatch challenges in the proficiency testing program for histocompatibility testing jointly sponsored by the American Society for Histocompatibility and Immunogenetics and the College of American Pathologists.
Objective.—To obtain information about consensus rates among participating laboratories that reported antibody screening and crossmatch results by direct complement-dependent lymphocytotoxicity (CDC) and/or anti-human globulin (AHG)–augmentation methods.
Design.—We analyzed responses from approximately 165 laboratories participating in 32 surveys during 1993–2000. Most of the testing was done by CDC methods, but increasing proportions of laboratories are using AHG augmentation of these techniques; almost one half of the serum screenings and crossmatches were done by AHG.
Results.—A total of 40 serum specimens were screened to determine the percent panel-reactive antibody (PRA) and identify HLA-specific antibodies. Participants often reported very wide ranges of PRA values. Panel-reactive antibody ranges exceeded 60 percentage points for 16 (40%) of the serum screening results by CDC and for 31 (77%) of the results by AHG. The interlaboratory variability of PRA values suggests that in many laboratories, the CDC or AHG procedures were often too insensitive or overly sensitive. The antibody identification results revealed inconsistent patterns among the participants performing CDC or AHG screening. Most participants reported the same primary antibody specificities by both methods. The consensus levels were generally high for the monospecific sera. On the other hand, there was much less agreement among the participants if the sera reacted with 2 or more HLA antigens. Participants using the more sensitive AHG method reported additional antibody specificities in many specimens, but invariably the consensus levels were rather low. A total of 192 serum-cell combinations were used for the crossmatch challenges. There was considerable interlaboratory variability; 21% of the CDC crossmatches and 36% of AHG crossmatches failed to reach the 90% consensus threshold.
Conclusions.—This experience demonstrates considerable inconsistencies in serum screening and crossmatching among laboratories participating in the American Society for Histocompatibility and Immunogenetics/College of American Pathologists surveys. A lack of uniformity in test results may limit the efficient application of these methods in a clinical setting. Standardization of crossmatch and antibody screening techniques is highly desirable.
Low Nuclear Proliferative Activity Is Associated With Nonmetastatic Islet Cell Tumors
Authors: Jorda Merce , Ghorab Zeina , Fernandez Gustavo , Nassiri Mehdi , Hanly Andrew , Nadji Mehrdad 
Published: January 2021

Abstract
Context.—Traditional morphologic features of tumor aggression are of limited value in predicting the malignant behavior of endocrine neoplasms. We explored the potential value of nuclear proliferative activity (using Ki-67 immunostaining with semiquantitative scoring) in predicting the clinical behavior of pancreatic islet cell tumors (ICTs), and we correlated this characteristic with hormone expression.
Objective.—To evaluate whether Ki-67 immunostaining using a semiquantitative scoring system has value in predicting the clinical behavior of pancreatic ICTs.
Design.—We studied 39 pancreatic ICTs from 39 patients. Twenty-two ICTs did not metastasize in a median follow-up period of 91 months. The remaining 17 neoplasms did produce metastases (8 in liver, 7 in regional lymph nodes, and 2 in peritoneum). Immunohistochemistry was performed using antibodies to Ki-67 and pancreatic hormones (insulin, glucagon, gastrin, somatostatin, pancreatic polypeptide, vasoactive intestinal polypeptide, and corticotropin). A semiquantitative Ki-67 grading system was followed. The nuclear proliferative activity, as determined by a positive reaction for Ki-67, was considered low (&lt;5% of cells staining positively), intermediate (5%–25% of cells staining positively), or high (&gt;25% of cells staining positively).
Results.—The majority of the nonmetastatic ICTs (16 cases, 73%) demonstrated either negative or low staining for Ki-67 (P &lt; .001). Conversely, all metastatic ICTs expressed at least an intermediate-grade reaction. High nuclear proliferative activity was only seen in metastatic neoplasms (3 cases, 17%). There was no relationship between immunoexpression of pancreatic hormones and nuclear proliferative activity by either group of tumors.
Conclusion.—An ICT with low nuclear proliferative activity is unlikely to metastasize, whereas high proliferative activity is associated with a metastatic phenotype. Immunohistochemical assessment of Ki-67 using a semiquantitative scoring system is a simple and reliable detection method of cellular proliferative activity in ICTs of the pancreas.
Herpes Simplex Pancreatitis
Authors: Shintaku Masayuki , Umehara Yasushi , Iwaisako Keiko , Tahara Masao , Adachi Yasushi 
Published: January 2021

Abstract
Lesions of the pancreas induced by viral infection have drawn relatively little attention because of their low incidence, and the histopathologic features of viral pancreatitis have not been fully elucidated. We report the autopsy findings of 2 patients, a 59-year-old woman with allergic granulomatous angiitis and a 73-year-old man with invasive pulmonary aspergillosis who had a disseminated visceral herpes simplex virus (HSV) infection. In both cases, the liver was the organ most severely affected by the viral infection. The pancreas showed multiple small foci of hemorrhagic necrosis, which were not accompanied by fat necrosis of the surrounding adipose tissue. Histopathologically, Cowdry type A intranuclear inclusions and a ground-glass appearance of the nuclei were found in many degenerated acinar cells around the necrotic foci. The gross appearance and histopathologic features of HSV pancreatitis were characteristic and, in particular, distinct from those of the more common acute hemorrhagic pancreatitis. Immunohistochemistry using an anti-HSV antibody revealed immunoreactivity in the intranuclear inclusions and ground-glass nuclei, and polymerase chain reaction analysis disclosed that the causative virus in these 2 cases was HSV-1. Herpes simplex virus pancreatitis constitutes a rare, but distinct pathologic entity among a group of acute pancreatitis diseases with diverse etiopathogenesis.
Male Versus Female Breast Cancers
Authors: Muir D. , Kanthan R. , Kanthan S. C. 
Published: January 2021

AbstractContext.—The rate of male breast cancer is a small fraction of that observed in females, thus severely limiting our understanding of the pathogenesis of this condition. It remains unclear whether the biological behavior and tumor progression associated with male breast cancer parallel that of the female form.Objectives.—To evaluate the immunohistochemical profile of male breast carcinomas and to compare this profile with that of stage-matched female breast cancers.Design.—Seventy-five cases of primary male breast cancer were identified using the records of the Saskatchewan Cancer Foundation over a period of 26 years (1970–1996). Fifty-nine of these cases had formalin-fixed, paraffin-embedded tissue blocks available for the purposes of this study. All cases were reviewed and a standardized modified Bloom-Richardson grading criterion was applied. Estrogen receptor status, progesterone receptor status, c-Erb-B2 expression, p53 expression, and Bcl-2 expression were evaluated by immunohistochemistry. Results from 240 consecutive cases of stage-matched female breast cancers analyzed in the same laboratory were used as a standard set for comparison.Results.—Male breast cancers tended to be high grade (85% grade 3) in comparison with the female breast cancers (50% grade 3). In descriptive analysis across all stages of disease, male carcinomas were more frequently estrogen receptor positive (81% vs 69%) than their female counterparts. Despite their high grade, they were less likely to overexpress p53 (9% vs 28%) and Erb-B2 (5% vs 17%) than the female counterparts. There was no significant difference in either progesterone receptor (63% vs 56%) or Bcl-2 (79% vs 76%) overexpression. Stratified analysis by stage-matched controls showed no statistically significant differences among the men and women with stage I disease. However, in stage II–matched samples, statistically significant differences were observed between the 2 groups. The male cancers were more likely to overexpress estrogen receptor (81.6% vs 64.4%, P = .04), progesterone receptor (71.1% vs 47.5%, P = .01), and Bcl-2 (78.9% vs 69.4%, P = .20). They also showed statistically significant lower expression of p53 (7.9% vs 36.3%, P = .001) and Erb-B2 (5.3% vs 23.8% P = .01).Conclusion.—Male breast cancers display distinct immunophenotypic differences from those occurring in women, implying a different pathogenesis in the evolution and progression of this disease. Such differences may play key roles in therapeutic management, warranting different treatment strategies in comparison to female breast cancers.
Personnel Standards and Quality Assurance Practices of Biochemical Genetic Testing Laboratories in the United States
Authors: McGovern Margaret M. , Benach Marta , Wallenstein Sylvan , Boone Joe , Lubin Ira M. 
Published: January 2021

Abstract
Context.—It has been suggested that specific regulation of laboratories performing genetic testing may be needed to ensure standards and quality assurance, and to safeguard the rights of patients with regard to confidentiality and providing informed consent. Previously, a comprehensive analysis of current practices of molecular genetic testing laboratories was conducted, the results of which have assisted in the assessment of the need for regulation and its impact on access to testing. However, a study designed to determine clinical laboratory practices with regard to biochemical genetic testing has not been carried out.
Objective.—To collect and analyze data regarding availability of clinical biochemical genetic testing, personnel standards, and laboratory quality assurance practices.
Design.—A mail survey of biochemical genetic testing laboratory directors and assignment of a quality assurance score based on responses to genetic testing process items.
Setting.—Hospital-based, independent, and research-based biochemical genetic testing laboratories in the United States.
Participants.—Directors of biochemical genetic testing laboratories (n = 133; response rate 68.5%).
Main Outcome Measure.—Laboratory process quality assurance score based on the standards defined by the American College of Medical Genetics Laboratory Practice Committee.
Results.—Personnel qualifications varied, although all directors had doctoral degrees. The mean quality assurance score was 77% (range 28%–100%). Higher scores were associated with the following variables: test director having an MD degree versus PhD degree (P = .002), director board certification in biochemical genetics (P = .002), research and hospital laboratory versus independent laboratory setting (P &lt; .001), and participation in a proficiency testing program (P = .03). Twelve percent of participants had a confidentiality policy, and 19% required informed consent before testing.
Conclusion.—The finding that a number of laboratories had quality assurance scores that may reflect suboptimal laboratory practices, particularly with regard to reporting practices, suggests that personnel qualification and laboratory practice standards may be in need of improvement to ensure quality in clinical biochemical genetic testing laboratories, as well as the appropriate clinical use of the test results.