bluuebunny/crossref_metadata_2025_split huggingface dataset:
Congenital Macroglossal Angiodysplasia (“Lymphangioendotheliomatosis”)
Authors: Bakaeen Ghazi , Winkler Sheldon , Bakaeen Lara , Rehani Lina A. , Katsetos Christos D. 
Published: January 2021

Abstract
A case of congenital lingual angiodysplasia with macroglossia in a 5-year-old girl is presented. A diffusely enlarged tongue was present at birth and continued to grow as the child aged. It was accompanied by impaired speech, difficulty in eating and breathing, and sleep apnea, necessitating surgical intervention. The fundamental lesion represents a complex vascular malformation of the lymphangioma-hemangioma type, involving extensively the deep musculature of the tongue. Multifocal and multicentric cavernous lymphangioma-like and hemangioma-like areas merge with benign angioendotheliomatous-like foci in a background of variable muscle degeneration and marked fibrosis. Neither a borderline nor an overtly malignant vasoformative neoplasm was present. Because of its distinctively widespread, multicentric intramuscular distribution, this lesion may be construed as a diffuse variant of lingual lymphangioma-hemangioma malformation, closely resembling a previously described case of macroglossal lymphangioendotheliomatosis.
Recurrent Umbilical Cord Torsion Leading to Fetal Death in 3 Subsequent Pregnancies
Authors: Bakotic Bradley W. , Boyd Theonia , Poppiti Robert , Pflueger Solveig 
Published: January 2021

Abstract
During a span of 3.5 years, a 30-year-old, gravida 9, para 3 woman experienced 3 pregnancies complicated by umbilical cord torsion and constriction. In each case, the complication resulted in acute vascular compromise and intrauterine fetal demise. Gross examination disclosed cord constriction and torsion at the fetal end of the cord in each instance. Histologic sections from the cord torsion sites demonstrated fibrosis and deficiencies in Wharton's jelly in each case. Cytogenetic studies prepared using fetal villous tissue demonstrated normal karyotypes in fetal cells from the first 2 pregnancies (46,XX and 46,XY, respectively). The karyotype from the third pregnancy showed a 46,XX,del(X)(q24) mutation in 3 of 15 cultured cells, while 12 of 15 cells possessed a normal 46,XX karyotype. This cytogenetic abnormality was not believed to represent the cause of fetal demise in this case. To our knowledge, this is the first report of umbilical cord torsion in 3 pregnancies within one family. The familial clustering observed in this report suggests that a genetic predisposition for umbilical cord torsion may exist in some cases.
An Unusual Variant of Composite Lymphoma
Authors: Thirumala Seshadri , Esposito Michael , Fuchs Alexander 
Published: January 2021

Abstract
We recently encountered an unusual case of composite lymphoma arising in a 73-year-old man with a history of follicular small cleaved cell lymphoma. The neoplasm was composed of follicular small cleaved cell lymphoma and nodular sclerosing Hodgkin disease within a single groin lymph node. In addition to morphologic evidence, the immunologic studies performed in this case demonstrated the simultaneous occurrence of 2 separate lymphocytic proliferations. To the best of our knowledge, only one such histologic type has been reported in the literature.1 Hodgkin lymphoma can develop in patients with non-Hodgkin disease and vice versa, especially after treatment. The simultaneous occurrence of Hodgkin disease and non-Hodgkin lymphoma in a single lymph node is extremely rare. In this article, the relationship between Hodgkin disease and non-Hodgkin lymphoma is explored, possible explanations for the occurrence of composite lymphoma are discussed, and the literature is reviewed.
Cellular Origin of Gastrointestinal Stromal Tumors
Authors: Wang Lina , Vargas Hernan , French Samuel W. 
Published: January 2021

Abstract
Context.—Interstitial cells of Cajal (ICCs), also known as pacemaker cells, are cells in the gastrointestinal tract that play a role in the control of gut motility. The ICCs express the c-kit proto-oncogene encoding a type III tyrosine kinase (KIT) receptor, a ligand that is known as stem cell factor (SCF). The maturation of ICCs is dependent on SCF-KIT interaction. The cellular origin, differentiation, nomenclature, and prognosis of gastrointestinal stromal tumors (GISTs) are controversial.
Objective.—To test the hypothesis that GISTs originate from CD34-positive stem cells and differentiate toward an ICC phenotype.
Materials and Methods.—We studied 27 cases of smooth muscle differentiated GISTs collected for 14 years (1985–1999), including 8 benign (leiomyoma), 15 malignant primary (leiomyosarcoma), and 4 metastatic to the liver. Immunohistochemical studies of selected lineage-directed monoclonal antibodies of c-kit (CD117), CD34, vimentin, desmin, α-actin, S100, and MIB-1 were performed on both normal and tumor tissues.
Results.—Immunoperoxidase stains of normal gastrointestinal tract showed both c-kit and CD34-positive cells surrounding the Auerbach ganglia plexus in the gastrointestinal tract. Twenty-seven of 27 tumors strongly expressed c-kit. Fourteen of 27 tumors were positive for CD34. Of the malignant GISTs, 14 of 19 were positive for CD34; of the benign tumors, 0 of 8 were positive for CD34. Thus, CD34 was the best indicator of malignant phenotype.
Conclusion.—This is the first description of benign smooth muscle GISTs negative for CD34. The results of this study suggest that GISTs originate from CD34-positive stem cells and differentiate toward pacemaker cell phenotype. The lack of expression of CD34 in the benign GIST may indicate that benign GISTs are composed of more mature ICCs, whereas malignant GISTs are composed of dedifferentiated ICCs that express CD34-positive stem cells.
Effect of a New International Reference Preparation for Proteins in Human Serum (Certified Reference Material 470) on Results of the College of American Pathologists Surveys for Plasma Proteins
Authors: Johnson A. Myron , Whicher John T. , Ledue Thomas B. , Carlström Anders , Itoh Yoshihisa , Petersen Per Hyltoff 
Published: January 2021

Abstract
Objective.—To examine the impact of a new international reference preparation for serum proteins on the among-manufacturer variance in the College of American Pathologists Surveys.
Data Source.—The results of the Surveys for the years 1993–1998, supplied by the College of American Pathologists.
Data Extraction and Synthesis.—Mean values for manufacturers' assays were compared for each protein in the quality control samples. Results were separated by the reported reference material from which values for calibrators had been transferred. Standard statistical parameters (means, standard deviations, and coefficients of variation) were calculated from the reported means.
Conclusions.—Among-manufacturer coefficients of variation have dropped significantly for most serum proteins since the introduction of the new reference material. Possible reasons for continued differences are discussed.
Kaposiform Hemangioendothelioma of the Thymus
Authors: Wilken Jennifer J. , Meier Frederick A. , Kornstein Michael J. 
Published: January 2021

Abstract
Kaposiform hemangioendothelioma is a rare pediatric neoplasm that presents most commonly in the soft tissues. We report the case of a 1-month-old infant who presented with stridor and was found to have a diffusely infiltrating tumor in the thymus that extended into the pericardium and up the carotid sheaths. Histologic examination revealed a vascular tumor infiltrating among the lobules of the lymphocyte-depleted thymus. The lesion had features of both a capillary hemangioma and Kaposi sarcoma. Immunoperoxidase studies on formalin-fixed, paraffin-embedded tissue demonstrated the neoplastic endothelial cells to be positive for vascular markers CD31 and CD34. Antibody to factor VIII-related antigen labeled feeding vessels, but failed to stain the lobules of tumor. Although these tumors have been treated in a fashion similar to capillary hemangiomas in the past, it may be important to differentiate Kaposiform hemangioendotheliomas because of their association with Kasabach-Merritt syndrome and recent success with more aggressive chemotherapy regimens.
Mixed Mucus-Secreting and Oncocytic Carcinoma of the Thyroid
Authors: Uccella Silvia , La Rosa Stefano , Finzi Giovanna , Erba Silvia , Sessa Fausto 
Published: January 2021

AbstractWe report a carcinoma that is, to the best of our knowledge, the first case of a mixed mucus-secreting and oncocytic carcinoma of the thyroid. We also describe the histochemical, immunohistochemical, and ultrastructural features of this tumor. A 59-year-old man complaining of severe bone pain and weight loss underwent clinical and radiologic investigations. The studies revealed a nodule in the left thyroid lobe that was “cold” by 131I scintiscan and multiple lytic lesions of the skeleton that showed increased uptake by 99mTc-Sestamibi scintiscan. Left hemithyroidectomy was performed and the surgical specimen contained a well-circumscribed nodule of 3 cm in the greatest diameter. Light microscopy showed an oncocytic carcinoma with an area of glandular and papillary proliferation of mucin-producing cells. A double histochemical approach (Alcian blue–periodic acid–Schiff and Alcian blue–high-iron diamine) combined with ultrastructural investigation confirmed the presence of true mucus, ruling out the presence of breakdown products of thyroglobulin. Ultrastructural and immunohistochemical studies, together with clinical findings, excluded a possible metastatic origin of the mucin-producing component.
Hyperplasia of Type II Pneumocytes in Pulmonary Lymphangioleiomyomatosis
Authors: Matsui Kazuhiro , Riemenschneider William K. , Hilbert Stephen L. , Yu Zu-Xi , Takeda Kazuyo , Travis William D. , Moss Joel , Ferrans Victor J. 
Published: January 2021

AbstractBackground.—Little is known of the morphology of the pneumocytes lining the parenchymal cysts in lymphangioleiomyomatosis (LAM).Objective.—To evaluate the structural characteristics of the alveolar epithelial cells in LAM.Methods.—Immunohistochemical and electron microscopic studies were performed on lung tissue from 22 women with pulmonary LAM.Results.—Epithelial cells that reacted with PE-10 (a mouse monoclonal antibody that recognizes the surfactant apoprotein A in type II pneumocytes) and TTF-1 (an antibody that identifies nuclear transcription factor found in type II pneumocytes) were the predominant cell type lining the surfaces of lesions of LAM and normal areas of lung. Scanning and transmission electron microscopic studies confirmed that these cells were type II pneumocytes as demonstrated by (1) apical microvilli, (2) electron-dense lamellar bodies, and (3) cytoplasmic projections that extended from the basal surfaces into the underlying connective tissue, where they made extensive contact with interstitial connective tissue cells. A few cells had morphologic characteristics of type I pneumocytes, including large flat surfaces lacking microvilli. Cells that appeared intermediate between type I and type II pneumocytes were observed occasionally.Conclusions.—These observations and the reactivity of these cells with antibody to proliferating cell nuclear antigen demonstrate that extensive hyperplasia of type II pneumocytes is a major characteristic of LAM.
Pathophysiology of Heparin-Induced Thrombocytopenia
Authors: Fabris Fabrizio , Ahmad Sarfraz , Cella Giuseppe , Jeske Walter P. , Walenga Jeanine M. , Fareed Jawed 
Published: January 2021

AbstractObjective.—This review of heparin-induced thrombocytopenia (HIT), the most frequent and dangerous side effect of heparin exposure, covers the epidemiology, pathophysiology, clinical presentation, diagnosis, and treatment of this disease syndrome.Data Sources and Study Selection.—Current consensus of opinion is given based on literature reports, as well as new information where available. A comprehensive analysis of the reasons for discrepancies in incidence numbers is given. The currently known mechanism is that HIT is mediated by an antibody to the complex of heparin–platelet factor 4, which binds to the Fc receptor on platelets. New evidence suggests a functional heterogeneity in the anti-heparin-platelet factor 4 antibodies generated to heparin, and a “superactive” heparin-platelet factor 4 antibody that does not require the presence of heparin to promote platelet activation or aggregation has been identified. Up-regulation of cell adhesion molecules and inflammatory markers, as well as preactivation of platelets/endothelial cells/leukocytes, are also considered to be related to the pathophysiology of HIT. Issues related to the specificity of currently available and new laboratory assays that support a clinical diagnosis are addressed in relation to the serotonin-release assay. Past experience with various anticoagulant treatments is reviewed with a focus on the recent successes of thrombin inhibitors and platelet GPIIb/IIIa inhibitors to combat the platelet activation and severe thrombotic episodes associated with HIT.Conclusions.—The pathophysiology of HIT is multifactorial. However, the primary factor in the mediation of the cellular activation is due to the generation of an antibody to the heparin-platelet factor 4 complex. This review is written as a reference for HIT research.
Smooth Muscle Tumor of the Pleura
Authors: Proca Daniela M. , Ross Patrick , Pratt Jerry , Frankel Wendy L. 
Published: January 2021

Abstract
Smooth muscle tumors of the serosal membranes are extremely rare and have received little attention in the literature. To the best of our knowledge, only 1 published series of 5 pleural smooth muscle neoplasms has been published to date. We describe a primary pleural neoplasm with smooth muscle differentiation documented by light microscopy, immunohistochemistry, and electron microscopy. This tumor originated in the parietal pleura in a 32-year-old white man and was diagnosed incidentally by chest radiography; the diagnosis was confirmed by magnetic resonance imaging and biopsy. Four years later, the tumor was noted to have increased in size and disseminated into the chest wall as a separate circumscribed mass located in the pectoral muscle. Both masses were resected and diagnosed as smooth muscle tumors. We conclude that smooth muscle tumor of the pleura is a well-defined entity with a low, but definite malignant potential; therefore, we recommend complete resection and long-term follow-up for all patients.
Malakoplakia of the Appendix
Authors: Jain Mona , Arora Vinod K. , Singh Navjeevan , Bhatia Arati 
Published: January 2021

Abstract
Malakoplakia of the appendix is an unusual condition that has been reported to occur in association with tumors, infections, and immunocompromised states. We describe a case of appendicular malakoplakia associated with eggs of Taenia species. The diagnosis was made on histopathologic examination of surgically resected tissue from an appendicular mass. To the best of our knowledge, this is the first time that helminths have been documented to be associated with malakoplakia. We also discuss the implications of helminthic infestation in the pathogenesis of the lesion.
Fat Replacement of the Glycogen in the Liver as a Cause of Death: Seventy-five Years Later
Authors: Chejfec Gregorio 
Published: January 2021

Abstract
Seventy-five years ago, E. R. LeCount and H. A. Singer published a report in the first issue of the Archives of Pathology & Laboratory Medicine entitled “Fat Replacement of the Glycogen in the Liver as a Cause of Death.” The report described 11 patients with chronic alcoholism who died suddenly. Markedly enlarged fatty livers were the only abnormality noted at postmortem examination in each of the subjects. Groups in this country and abroad subsequently repeated the authors' observation. The mechanism of sudden death in patients with fatty livers due to chronic alcoholism is currently understood to be an abnormality in the conduction system of the heart, manifested as a prolonged QT interval. The triggering event leading to the conduction defect has been suggested to be hypoglycemia complicated by hypopotassemia and hypomagnesemia. In this review we will summarize the changes that have taken place in this field since the initial publication by LeCount and Singer.
Hereditary Cancer Syndromes
Authors: Frank Thomas S. 
Published: January 2021

Abstract
Objective.—To summarize the biological basis, clinical implications, identification, and medical management of syndromes associated with increased risk of common adult cancers.
Data Sources.—Recent studies and data available from molecular and clinical analysis of genes responsible for autosomal-dominant inheritance of cancer risk.
Data Synthesis.—Several hereditary cancer syndromes have been identified for which there are increasingly effective diagnostic and management options. Specific hereditary susceptibility syndromes have been characterized that increase the risk of malignancies of the breast, ovary, colon, endometrium, and endocrine organs. Following a summary of the biological basis of hereditary cancer risk in adults, the identification of such syndromes by clinical and laboratory means is reviewed. Finally, management options for individuals with these syndromes are summarized.
Conclusions.—Advances in gene discovery have allowed the diagnosis of recently characterized hereditary cancer syndromes to enhance medical management for individuals with inherited susceptibility to common cancers.
Expression of c-Kit (CD117) in Benign and Malignant Human Endometrial Epithelium
Authors: Elmore Lynne W. , Domson Kelly , Moore Jonathan R. , Kornstein Michael , Burks R. Tucker 
Published: January 2021

Abstract
Background.—The proto-oncogene c-kit encodes a tyrosine kinase receptor (CD117) with a molecular weight of 145 kd. Previous studies, predominantly utilizing immunohistochemistry, have led to contradictory findings regarding the expression of CD117 in the endometrium. To help resolve this issue, we analyzed a series of benign and malignant endometrial tissues using both immunohistochemistry and Western blot analysis.
Objective.—To examine the expression of CD117 in benign and malignant human endometrial tissues.
Methods.—The expression of CD117 in 35 benign endometrial tissues (7 hyperplastic, 14 proliferative, 14 secretory) and 10 endometrioid carcinomas was investigated by immunohistochemistry (clone K45 monoclonal antibody). Immunoprecipitation (clone K69 monoclonal antibody) followed by Western blotting (clone K45 monoclonal antibody and clone 1.D9.3D6 monoclonal antibody) was performed to confirm CD117 expression.
Results.—Fifty-seven percent of the hyperplasias, 93% of proliferative endometria, and 79% of secretory endometria immunostained positively for CD117. In benign endometria, epithelial staining tended to be more intense in the hyperplastic and proliferative endometria as compared to the secretory endometria, whereas endometrial stromal cells were not immunoreactive. Of the 10 frozen endometrial tissues analyzed by immunohistochemistry, 4 of 9 endometrioid carcinomas and a single case of an endometrioid polyp developing in association with a carcinoma expressed CD117. Immunoprecipitation followed by Western blot analysis confirmed expression of full-length CD117 in an endometrial polyp and carcinoma, and revealed a correlation between levels of immunoprecipitated CD117 and immunohistochemical staining intensity.
Conclusions.—Benign and malignant endometrial tissues express CD117. Our data suggest (a) a possible relationship between estrogen and CD117 expression in benign endometrium and (b) potential involvement of this growth factor receptor in endometrial carcinogenesis.
Sources of Variability
Authors: Steele Bernard W. , Wang Edward , Palomaki Glenn , Klee George G. , Elin Ronald J. , Witte David L. 
Published: January 2021

Abstract
Objective.—To determine the magnitudes and sources of analytic variation in testing for therapeutic drugs. Specifically, among laboratories using the same analytic method, to compare the within-laboratory variation (including both short- and long-term variation) with the between-laboratory variation.
Design.—Four identical challenges were prepared from a lyophilized pool of spiked sera and were sent in pairs 4 months apart to laboratories participating in a nationwide proficiency-testing program. For each of 25 drugs, the variability in reported results from laboratories using the same method was investigated using nested analysis of variance.
Setting.—The first 2 mailings of the College of American Pathologists Therapeutic Drug Monitoring Survey, 1996, sets Z and ZM.
Main Outcome Measures.—For each drug, total variance was partitioned into within- and between-laboratory components for common methods. The within-laboratory component was further partitioned into short- and long-term components.
Participants.—The approximately 5000 laboratories enrolled in the survey.
Results.—For the 25 drugs, the average percentages of the total variance due to short-term, within-laboratory variance; long-term, within-laboratory variance; between-laboratory variance; and total laboratory variance were 25.0% (range, 8.8–50.6%), 57.8% (35.3–73.7%), 17.3% (5.0–35.4%), and 82.7% (64.6–95.0%), respectively.
Conclusion.—For all drugs tested, the within-laboratory component of variance was greater than the between-laboratory component of variance. Within laboratories, the magnitude of the long-term component was generally greater than the magnitude of the short-term component. This information will be helpful in determining the clinical utility of various drug assays and in evaluating the appropriateness of regulations involving therapeutic drug testing.
Detection of T-Cell Receptor-γ Gene Rearrangement in Lymphoproliferative Disorders by Temperature Gradient Gel Electrophoresis
Authors: Alkan Serhan , Cosar Ediz , Ergin Melek , Hsi Eric 
Published: January 2021

Abstract
Objective.—Polymerase chain reaction amplification of DNA for T-cell receptor (TCR) gene rearrangement analysis is helpful in the evaluation of T-cell lymphoproliferative disorders. Detection of polymerase chain reaction products is limited by the poor resolution of bands analyzed by agarose or polyacrylamide gel electrophoresis. To improve the detection of a clonal T-cell population, we used temperature gradient gel electrophoresis (TGGE) as an alternative method for analysis of TCR gene rearrangement.
Design.—One hundred eighteen archival DNA samples were randomly selected based on previous Southern blot analysis results. Samples included 58 T-cell neoplasms with positivity for TCRβ gene rearrangement, 22 cases of reactive hyperplasia with germline pattern for both TCRβ and JH, and 38 patients with B-cell lymphoma. MOLT-16, a T-cell lymphoblastic cell line, was used for the sensitivity assay. Polymerase chain reaction was performed using GC;chclamped multiplex primers to amplify the TCRγ locus and was analyzed by TGGE. The range of temperature gradients was empirically determined for optimal resolution of bands.
Results.—The sensitivity of TGGE was 0.1% when DNA from the MOLT-16 cell line was serially diluted with DNA from reactive lymphoid tissue. Fifty-four (93%) of 58 T-cell neoplasms with TCRβ gene rearrangements showed rearrangement patterns by TCRγ TGGE, and only 1 of 60 samples (reactive or B-cell lymphomas) showed evidence of gene rearrangement by TGGE. Patients with T-cell neoplasm and involvement of multiple sites showed an identical migration pattern by TGGE analysis.
Conclusion.—We demonstrate that TGGE is an effective method for analysis of TCR gene rearrangement in the evaluation of nodal and extranodal lymphoid lesions.