bluuebunny/crossref_metadata_2025 huggingface dataset:
Herausforderungen und Gefahren der Integration von Genomdaten in die Erforschung der frühmittelalterlichen Geschichte
Authors: geary Patrick J.
Published: January 2021

Die Chancen und ideologischen Gefahren der Arbeit mit rezentem und altem Genommaterial am Beispiel der Völkerwanderung.

Spektakulär sind die Fortschritte, die die Genomik in jüngster Zeit erreicht hat. Populationsgenetische Studien verwenden die Daten aus der heutigen Bevölkerung und beziehen diese auf vergangene demografische Vorgänge; doch auch altes Skelettmaterial wird für Deutungen der Vergangenheit herangezogen. Nicht nur die Fachwelt, sondern auch eine breite Öffentlichkeit erhofft sich dadurch neue Aufschlüsse über die Identität von Menschen in Gegenwart und Vergangenheit. Doch einige dieser Arbeiten laufen Gefahr, die Fehler eines Reduktionismus zu wiederholen, der in der Geschichtsschreibung des 20. Jahrhunderts dem Rassismus Vorschub geleistet hat.

Der amerikanische Mittelalterhistoriker Patrick J. Geary sucht für seine Auswertung von Genomdaten der Völkerwanderung die Zusammenarbeit mit Archäogenetikern und stellt in seinem Essay grundlegende Fragen zur historischen Nutzung dieses Materials: Wie können Genomdaten so mit der bekannten schriftlichen Überlieferung verbunden werden, dass sich grundlegende historische Prozesse wie Migration und sozialer Wandel neu interpretieren lassen? Und kann auf dieser Grundlage unser Verständnis der jüngeren Vergangenheit vertieft werden?

Patrick J. Geary erhielt 2019 mit seinem Team den höchstdotierten Zuschuss des European Research Council, um das frühe Mittelalter mithilfe interdisziplinärer Methoden zu erforschen. Wer sich über die Chancen, aber auch die Probleme der Historischen Genetik im Mittelalter informieren will, kann zur Zeit nichts Besseres als diese Schrift konsultieren.
Longitudinal development of clast shape characteristics from different material sources in Hrbye River, Central Svalbard
Authors: Ondráčková Lenka
Published: January 2021

The sediment transport in polar regions is highly changeable and it is getting faster in connection with a climate change. This study describes the Hrbye River catchment located in the northern Billefjorden, Central Svalbard. The Czech Arctic Station and AMUPS - Adam Mickiewicz University Polish Polar Station are located in near this locality Petunia Bay. The material for this study was sampled in August 2016, during the summer research campaign of Czech Arctic Station together with a cooperation between Masaryk University in Brno and the University of Oslo via Norway Grants. The catchment area is 60 km2. The area of interest lies around the 10 km long Hrbye River in its braidplain, which is 2.3 km wide and 4.5 km long. In the Hrbye Glacier forefield, 27 sediment sampling localities were selected and defined into seven groups: (i) esker complex; (ii) debris stripes; (iii) till plain; (iv) hummocky moraine; (v) post-LIA braidplain; (vi) LIA moraine; (vii) LIA braidplain. Three main petrological types of rocks were studied (SVP – sandstone, VAP – limestone, ORT – orthogneiss). Lithology and roundness of the clasts were evaluated in order to study clast shape properties from various glacial sediments. The results show the dominant role of lithology on the clast shape modification in the Hrbye Glacier forefield.
Lichens, bryophytes and terrestrial algae of the Lake Untersee Oasis (Wohlthat Massiv, Dronning Maud Land, Antarctica)
Authors: Andreev Mikhail , Andersen Dale , Kurbatova Lyubov , Smirnova Svetlana , Chaplygina Olga
Published: January 2021

Lake Untersee is the largest ice-covered freshwater lake in the interior of East Antarctica. The mountain oasis is situated around it in the Gruber Mts. of the Wohlthat Massif. For approximately 7,000 years the area has been free of ice and the local climate relatively stable. It is very severe, cold, and windy and dominated by intense evaporation and sublimation but with little melt. Relative humidity averages only 37%. Vegetation is sparse in the oasis and previously only poorly investigated. Two lichen species and no bryophytes were known from the area. In November-December 2018, a survey of terrestrial flora and vegetation was made. The list of lichens was completed for the area, bryophytes were found for the first time, and some terrestrial algae were collected. In total, 23 lichen species, 1 lichenicolous fungus, 1 moss, and 18 terrestrial algae were discovered for the locality. The abundance of each species within their habitats was also evaluated. The lichen flora of the Untersee Oasis is typical for continental oases and similar to other previously investigated internal territories of Dronning Maud Land, except for the very rich lichen flora of the Schirmacher Oasis.
Differential Expression of Cyclin D1 in Breast Papillary Carcinomas and Benign Papillomas
Authors: Saddik M. , Lai R. , Medeiros L. J. , McCourty A. , Brynes R. K.
Published: January 2021

Objectives.—Distinguishing intraductal papilloma from papillary carcinoma of the breast can be difficult using histologic criteria. Since cyclin D1, a G1 cell-cycle regulatory protein, is detectable immunohistochemically in a subset of breast carcinomas but not in benign breast tissues, we hypothesized that cyclin D1 immunoreactivity may be a marker for identifying papillary carcinoma.

Methods.—Using an immunohistochemical method, we assessed for cyclin D1 expression in 8 breast papillomas and 6 papillary carcinomas, all of which were formalin fixed, routinely processed, and paraffin embedded. Cyclin D1 positivity also was compared with the overall proliferation rate, which was assessed by using the proliferation marker Ki-67. In each case, a 200-cell count was performed to obtain the percentage of cells positive for these 2 markers.

Results.—The percentage of cyclin D1–positive cells was significantly higher in papillary carcinomas (89% ± 18%; range, 53%–98%) than in papillomas (8% ± 7%; range, 0%–19%). This difference was highly statistically significant (P < .0001). Although the difference in Ki-67 positivity between these 2 groups was also statistically significant (P = .01), separation of papillary carcinomas and papillomas by Ki-67 immunoreactivity was less clear because of overlapping values between groups: 13% ± 6%; range, 9% to 23% for papillary carcinomas versus 8% ± 2%; range, 6% to 12% for papillomas.

Conclusions.—These results support the notion that cyclin D1 is a useful marker for distinguishing breast papillomas from papillary carcinomas. The marker Ki-67 is also helpful, but is less useful than cyclin D1, owing to the overlap in Ki-67 results in papillomas and papillary carcinomas.
Progressive Multifocal Leukoencephalopathy and JC Virus Genotypes in West African Patients With Acquired Immunodeficiency Syndrome
Authors: Chima Sylvester C. , Agostini Hansjürgen T. , Ryschkewitsch Caroline F. , Lucas Sebastian B. , Stoner Gerald L.
Published: January 2021

Objective—Progressive multifocal leukoencephalopathy is caused by polyomavirus JC in immunosuppressed patients. JC virus genotypes are identified by sequence analysis of the viral genome. Despite the prevalence of acquired immunodeficiency syndrome in sub-Saharan Africa, few cases of progressive multifocal leukoencephalopathy have been reported from this region. Here we describe 4 African cases and provide an analysis of viral genotypes.

Methods.—Immunohistochemical staining by labeled streptavidin-biotin for capsid protein antigen was performed on all cases. Polymerase chain reaction amplification of viral genomic DNA was followed by direct cycle sequencing.

Results.—JC virus type 3 was identified in 2 cases, and type 6 was isolated in 1 case. The viral regulatory region from 1 case showed an uncommon rearrangement pattern.

Conclusions.—Progressive multifocal leukoencephalopathy in West African patients with acquired immunodeficiency syndrome is caused by African genotypes of JC virus (types 3 and 6). The prevalence of disease in this autopsy series from sub-Saharan Africa (1.5%) was less than has been reported from Europe and the United States (4% to 10%) and may be partly due to biological differences in JC virus genotypes. Further studies will be needed to confirm this observation.
p53 Immunolocalization in Cell Block Preparations of Squamous Lesions of the Neck: An Adjunct to Fine-Needle Aspiration Diagnosis of Malignancy
Authors: Khurana Kamal K. , Ramzy Ibrahim , Truong Luan D.
Published: January 2021

Objective.—Mutations of the p53 tumor suppressor gene, with consequent nuclear p53 protein accumulation, are among the most common genetic abnormalities in human cancers. The purpose of this study was to determine the utility of p53 immunostaining as an adjunct to the diagnosis of malignancy in fine-needle aspirations of squamous lesions of the neck.

Materials and Methods.—Using a monoclonal antibody to the p53 protein and a standard avidin-biotin complex technique, immunostaining was performed on paraffin-embedded cell blocks of 20 cases with the following cytologic diagnoses: (1) metastatic squamous cell carcinoma (SCC) (7 cases); (2) atypical squamous cells, SCC cannot be excluded (7 cases); and (3) cytologic findings consistent with branchial cleft cyst (6 cases). Tissue or clinical follow-up was available in all cases.

Results.—Five (71%) of 7 cases with an unequivocal cytologic diagnosis of metastatic SCC were positive for p53 protein. Tissue follow-up confirmed metastatic SCC in all of these 7 cases. Of the 7 cases with cytologic diagnosis of atypical squamous cells, 2 were negative and 5 (71%) were positive for p53 protein. Subsequent excisional biopsies in these cases revealed metastatic SCC (6 cases) and branchial cleft cyst (1 case). The squamous cells in all 5 cases with cytologic findings consistent with branchial cleft cyst were negative for p53 protein; tissue follow-up confirmed the diagnoses of branchial cleft cyst in 4 cases. In the remaining 2 cases excision was not performed, as the cystic lesion was completely decompressed and, clinically, no recurrences were identified at 14 and 8 months of follow-up.

Conclusions.—Our findings suggest that p53 immunostaining is helpful in differentiating benign and malignant squamous lesions. While negative staining for p53 does not exclude malignancy, positive immunostaining may aid in accurate fine-needle aspiration diagnosis of malignancy in cytomorphologically equivocal squamous lesions of the neck.
Joint Commission on Accreditation of Healthcare Organizations' Expectations for Transfusion Medicine in Health Care Organizations
Authors: Belanger Anne C.
Published: January 2021

This article provides an overview of the Joint Commission on Accreditation of Healthcare Organizations' standards related to transfusion medicine found in its hospital, laboratory, and home care accreditation manuals. Hospital standards focus on the review and evaluation of the entire transfusion process from the order through the outcome to the patient, with special attention to the blood use review process. Laboratory standards provide the structure for the detailed review of the technical procedures and practices for collecting, processing, storing, testing, and transporting blood products. Home care standards relate to policies and procedures, infection control practices, education of the patient and family, and monitoring of adverse events and complications for transfusions of blood products performed in the home.
Blood Safety: The Food and Drug Administration's Role
Authors: Gustafson Mary
Published: January 2021

The federal government has a role in protecting consumers from threats to the blood supply. These threats range from the residual risks of known infection, to emerging infections that may contaminate the blood supply, to complacency in the area of adherence to product standards and Current Good Manufacturing Practices. The Food and Drug Administration is tasked with oversight of the safety of the nation's blood supply. The Food and Drug Administration's regulation of blood and blood components includes preapproval for products entering interstate commerce and adherence to Current Good Manufacturing Practices for all blood components. Oversight for Current Good Manufacturing Practices compliance includes inspection and reporting requirements. These regulatory programs are coupled with the Public Health Service's ongoing research and epidemiological surveillance. The goals of these programs are to prevent another infectious disease epidemic from infecting the blood supply as did the acquired immunodeficiency syndrome in the early 1980s and to further improve blood safety.
Neuropathology of Human Immunodeficiency Virus 1 Infection
Authors: Kibayashi Kazuhiko , Ng’walali Paul M. , Mbonde Martin P. , Makata Ahmed M. , Mwakagile Davis , Harada Shinji , Kitinya James N. , Tsunenari Shigeyuki
Published: January 2021

Objective.—In sub-Saharan Africa, only a few studies of neurologic complications of human immunodeficiency virus 1 (HIV-1) infection have been done. The authors studied neuropathology of HIV-1 infection in Tanzania.

Design.—Forensic autopsy study at Dar es Salaam, Tanzania.

Setting.—A joint research project between Dar es Salaam, Tanzania, and Kumamoto, Japan.

Patients.—Thirty patients with risk factors for HIV-1 infection.

Main Outcome Measures.—Human immunodeficiency virus 1 infection was evaluated by HIV-1 antibody test on postmortem serum samples. The brains of HIV-1–infected persons were studied histopathologically.

Results.—Infection with HIV-1 was identified on postmortem serum samples in 10 of 30 forensic autopsy cases. Neuropathologic changes of the brain were observed in 8 of the 10 HIV-1–infected persons; these changes consisted of lymphocytic meningitis, bacterial meningoencephalitis, cryptococcal meningoencephalitis, tuberculous meningitis with brain abscesses, and intracerebral hemorrhage.

Conclusions.—Because none of the persons studied was suspected to have had brain diseases before autopsy, the results suggest that brain diseases of HIV-1–infected patients are likely to go unrecognized in Tanzania. In addition, the high incidence of neuropathologic findings in HIV-1–infected persons indicates that HIV-1–related brain diseases are common in Tanzania, as they are in developed countries. Further forensic autopsy study will determine the range and prevalence of brain complications and have immediate impact on the management of HIV-1–infected patients in Tanzania and other developing countries.
Morphology and Other Prognostic Factors of Hepatocellular Carcinoma
Authors: Chedid Antonio , Ryan Louise M. , Dayal Yogeshwar , Wolf Barbara C. , Falkson Geoffrey
Published: January 2021

Objective.—Hepatocellular carcinoma is a malignancy found worldwide that has typically poor prognosis despite treatment. Although several studies have dealt with prognostic factors, just a few detailed analyses of large series correlating the pathology of hepatocellular carcinoma with prognosis are available. The present study was undertaken to address this limitation.

Patients and Methods.—Our prior clinical study described 432 patients, but sufficient tissue was available for evaluation in only 299 patients. Of these, 224 samples contained primary hepatocellular carcinoma, while the remainder contained only metastatic tumor. Characteristics evaluated included degree of tumor differentiation, associated cirrhosis or hepatitis, presence of cytoplasmic inclusion bodies, and blood vessel invasion by the neoplasm.

Results.—Of the 224 patients, 71% were male, 65% white, and 73% over the age of 45 years. Ninety-one percent were from North America. A total of 42 patients were found to have cirrhosis. Thirty-five percent had cytoplasmic inclusion bodies, and 25% showed evidence of blood vessel invasion. Tumor response rates (tumor shrinkage) were low (8%) regardless of treatment. Presence of cytoplasmic eosinophilic inclusion bodies and blood vessel invasion were not associated with increased survival. Some histopathologies (pelioid, spindle cell, fibrolamellar) were associated with a better prognosis. Patients with a predominant trabecular pattern (43%) did particularly poorly. Although sex was significantly associated with survival using a univariate analysis, this effect disappeared in a multivariate Cox model that adjusted simultaneously for other factors.

Conclusion.—This investigation suggests that histologic subtype and clinical features may provide useful prognostic information in hepatocellular carcinoma. Poorer survival was observed in males, older patients with poorly differentiated tumors, or when associated with cirrhosis. Age younger than 45 years was a good prognostic factor, and presence of cirrhosis had an adverse effect on survival.
Errors in Transfusion Medicine: Scope of the Problem
Authors: Linden Jeanne V.
Published: January 2021

Error is ubiquitous whenever humans are involved in a process. Fortunately, most transfusion-related errors are benign. However, the risk of death due to acute hemolytic transfusion reaction rivals that of human immunodeficiency virus transmission and administration of the wrong blood or of blood to the wrong recipient has occurred at many facilities. Most blood misadministration errors are caused by failure to identify the recipient and blood unit adequately, although phlebotomy errors and blood bank errors also contribute. Many errors are multifactorial and may reflect underlying systems defects. Noncompliant specimen labels may be a cue to an increased risk of phlebotomy error. Autologous blood is not immune from error and poses infectious disease risks as well as the risk of hemolytic transfusion reaction; also, perioperatively recovered blood may pose a risk of air embolism if improperly handled.
The Quality Systems Approach
Authors: Nevalainen David E.
Published: January 2021

Health care as an industry is going through an evolution similar to that experienced by manufacturing and other service sectors of the world economy. When competition threatens, the traditional management approach is slash-and-burn to manage costs. This approach affects people, services, and facilities. When the slash-and-burn method runs out of fuel, organizations start to merge, thinking that bigger is better. Just getting bigger only looks like change, with a new cast of fewer people and organizational structure. The root cause for existing problems has not been fixed. The only real solution, as manufacturing and services learned, is to understand and improve work processes to ensure that the right work is being done in a high-quality manner and at a competitive price. The era of quality systems is just dawning in health care. The focus must remain on quality patient outcomes at a competitive price by improving supporting systems and processes to accomplish these goals.
Process Improvement in Transfusion Medicine: One Blood Center's Approach
Authors: Kopko Patricia M. , Holland Paul V.
Published: January 2021

Ongoing efforts to decrease costs in the clinical laboratory make continuous process improvement especially important in difficult economic times. Process improvement can result in decreased workload, cost savings, and increased customer satisfaction but is an abstract concept in and of itself. To illustrate the steps of process improvement, we applied them to our blood component retrieval policy. By identifying the problems with the current system, proposing and implementing solutions, and measuring the effects before and after revamping the process, we have been able to show impressive reductions in the number of component retrievals initiated, the number acted on, wasted components, and customer complaints, all of which translate into cost savings. Once the cycle is completed, it begins anew. There must always be continuous process improvement.
Handling Sentinel Lymph Node Biopsy Specimens
Authors: Cibull Michael L.
Published: January 2021

This article reviews the “state of practice” with regard to sentinel lymph node biopsy, a new and evolving technique currently used most commonly for staging of malignant melanoma and adenocarcinoma of the breast. Sentinel lymph node biopsy has the potential to both increase the accuracy of lymph node sampling as a prognostic tool and to decrease the need for unnecessary and morbid extensive lymph node dissection in such patients. The need for close cooperation and planning involving the surgeon and pathologist is stressed, and gross room tissue handling, radiation safety, microscopic examination, and the use of ancillary diagnostic techniques are discussed.
Spherulosis of the Breast
Authors: Mooney Eoghan E. , Kayani Naila , Tavassoli Fattaneh A.
Published: January 2021

Objective.—Collagenous spherulosis of the breast is an uncommon localized pattern of basement membrane material deposition that may be mistaken for atypical proliferations or carcinoma. This report describes 9 cases in which the predominant or exclusive appearance of the spherules was basophilic instead of eosinophilic.

Design.—The files of all cases of collagenous spherulosis diagnosed at the Armed Forces Institute of Pathology were reviewed to ascertain the frequency of diagnosis.

Results.—Spherulosis with a predominantly basophilic pattern had a histochemical and immunohistochemical profile similar to collagenous spherulosis and was associated with more collagenous-appearing forms in 7 of 9 cases. Review of 81 cases showed that collagenous spherulosis was correctly diagnosed in 15% of referrals and was mistaken for intraductal or invasive carcinoma in 11% of cases.

Conclusions.—Mucinous and collagenous patterns appear to be related forms of spherulosis. They are underrecognized by pathologists and maybe mistaken for atypia or malignancy.
The Role of Transfusion Medicine Physicians
Authors: AuBuchon James P.
Published: January 2021

Physicians with interest or expertise in transfusion medicine must apply their clinical consultation and laboratory management skills to be accorded support for their activities. To establish credibility, efforts must initially be directed where patient benefit and financial gain can be documented. Focusing efforts on practice improvements and sharing the results of those efforts with physician colleagues and administrators can help ensure continued support. Transfusion medicine continues to play an important role in health care, particularly in an era of managed care and reduced resources. Investment in the activities of this discipline will pay off for patients, clinicians, and hospitals.
Endoscopic Biopsy Pathology of Helicobacter pylori Gastritis
Authors: Toulaymat Maher , Marconi Sharon , Garb Jane , Otis Christopher , Nash Shirin
Published: January 2021

Objectives.—To describe the endoscopic biopsy pathology of Helicobacter pylori gastritis, compare bacterial detection by immunohistochemistry using a specific antibody with the Genta stain, and to compare the relative costs of the 2 techniques.

Design.—One hundred cases of gastritis identified as positive for H pylori by Genta stain and 100 cases considered negative by the same technique were stained using an anti-H pylori–specific polyclonal antibody. Laboratory reagent and labor costs for the 2 methods were compared.

Results.—Chronic active gastritis with lymphoid follicles was significantly associated with H pylori infection (P < .0001). The immunohistochemical method had a sensitivity of 97% and a specificity of 98% compared with the Genta stain, with strong agreement for grading density of organisms (κ = 0.85; P < .001). Reagent costs were similar for both methods, but immunohistochemistry using an autoimmunostainer required less dedicated technical time and hence was less expensive than the Genta stain.

Conclusions.—Immunohistochemistry using a specific antibody is an accurate and cost-effective method for H pylori detection in gastric biopsies.
Epithelioid and Spindle-Celled Leiomyosarcoma of the Heart
Authors: Pins Michael R. , Ferrell Margaret A. , Madsen Joren C. , Piubello Quirino , Dickersin G. Richard , Fletcher Christopher D. M.
Published: January 2021

Background.—Primary cardiac leiomyosarcomas are rare. Isolated reported cases and small series generally describe spindle-celled, high-grade tumors with poor short-term survival; however, the pathologic features of many of these tumors are incompletely documented. The authors report in detail the clinicopathologic features of 2 relatively low-grade epithelioid and spindle-celled primary cardiac leiomyosarcomas.

Methods.—Cases 1 and 2 were studied using standard histochemical and immunohistochemical techniques, and case 1 was examined by electron microscopy. The literature was reviewed with regard to primary cardiac leiomyosarcomas.

Results.—Both tumors showed epithelioid and spindle-celled areas. The tumor in case 1 was low grade, and the tumor in case 2 was predominately low grade with a high-grade focus. A review of 28 reported cases revealed a wide age range (mean, 43 years), equal male-to-female ratio, and a predilection for the left atrium (48%). Follow-up of reported cases with fewer than 5 mitoses per 10 high-power fields showed a mean survival of 22 months compared with a 9-month mean survival for all others.

Conclusions.—Short-term follow-up of reported cases of high-grade cardiac leiomyosarcoma suggests a poor prognosis. Long-term follow-up in our case 2, along with follow-up of reported cases that were histologically similar to our cases, suggests that cardiac leiomyosarcomas with low-grade features or mixed low- and high-grade features also have a poor overall long-term survival, with a high rate of local recurrence and systemic spread.
Immunoexpression of Villin in Neuroendocrine Tumors and Its Diagnostic Implications
Authors: Zhang Paul J. , Harris Kenneth R. , Alobeid Bachir , Brooks John J.
Published: January 2021

Background.—Villin, a 95-kd cytoskeletal protein associated with axial microfilament bundles of brush border microvilli, is mostly restricted to intestinal glandular tumors. Villin immunoexpression was recently observed in a small number of carcinoids of the intestinal tract and lung, but its significance in a broad category of neuroendocrine tumors has not been evaluated.

Design.—A total of 114 neuroendocrine tumors of different origins were tested for villin expression. They included gastrointestinal carcinoids (n = 30), lung carcinoids (n = 15), small cell carcinomas of the lung (n = 24), small cell carcinomas of other sites (n = 15), islet cell tumors (n = 8), Merkel cell carcinomas (n = 6), paragangliomas (n = 6), and others (n = 10). Nine round cell sarcomas were tested as well.

Results.—Villin immunoreactivity was present in 85% of gastrointestinal carcinoids and small cell carcinomas, but was found in only 40% of lung carcinoids. Other tumors tested were virtually negative for villin. In general, while cytoplasmic reactivity was most common, a characteristic apical membranous pattern simulating brush border was seen in 76% of the gastrointestinal carcinoids and in 50% of the lung carcinoids.

Conclusions.—We found that villin was predominantly restricted to gastrointestinal neuroendocrine tumors (excluding islet cell tumors), although a small number of bronchial carcinoids may be positive as well. These results suggest a role for villin in the differential diagnosis of neuroendocrine tumors.
Congenital Gastrointestinal Pacemaker Cell Tumor
Authors: Wu Sandy S. , Buchmiller Terry L. , Close Pamelyn , Gershman George B. , Peng Shi-Kaung , French Samuel W.
Published: January 2021

The interstitial cells of Cajal complex within the gut wall function as a pacemaker to direct peristalsis. Their neoplastic counterpart is the gastrointestinal pacemaker cell tumor, a spindle and/or epithelioid cell mesenchymal tumor previously known as gastrointestinal stromal tumor or incorrectly called leiomyosarcoma in some cases of older reports. Although numerous cases of gastrointestinal leiomyosarcomas have been documented in the English-language literature, no pediatric case of gastrointestinal stromal tumor or gastrointestinal pacemaker cell tumor has, to our knowledge, been recorded. Herein, we report a case of congenital gastrointestinal pacemaker cell tumor confirmed by immunohistochemistry and electron microscopy in a full-term male newborn.
Evaluation of Epithelial and Keratin Markers in Glioblastoma Multiforme
Authors: Oh David , Prayson Richard A.
Published: January 2021

Objective.—Poorly differentiated metastatic carcinoma may be difficult to distinguish histologically from high-grade astrocytic malignant neoplasms, particularly on small open or stereotactic biopsy specimens. Previous authors have reported that a subset of glioblastoma multiforme (GBM) variably stains with cytokeratin immunomarkers. The authors examined a panel of epithelial and keratin antibodies by paraffin immunohistochemistry to evaluate the immunophenotype of GBM for these markers and to determine what combination of immunostains would be optimal in distinguishing GBM from metastatic carcinoma.

Methods.—Twenty-three patients with GBM (age range, 19–86 years; mean, 63.4 years; 14 men and 9 women) and 22 patients with metastatic carcinoma (age range, 26–77 years; mean, 58.1 years; 7 men and 15 women) to the brain were studied with a panel of immunostains, including glial fibrillary acid protein (GFAP), Ber-EP4, antikeratin monoclonal antibodies AE1/3, and antibodies to CAM 5.2 and cytokeratins 7 (CK7) and 20 (CK20). Sites of origin for the metastatic tumors included lung (n = 11), breast (n = 5), endometrium (n = 1), prostate (n = 1), colon (n = 1), presumed kidney (n = 1), and unknown (n = 2).

Results.—All GBMs stained positive for GFAP (100%), and all but 1 (95.7%) stained positive for cytokeratins AE1/3. Only rare focal immunoreactivity was observed in a single case of GBM with CAM 5.2 (4.3%), CK7 (4.3%), and CK20 (4.3%). Immunoreactivity with Ber-EP4 was not observed in any of the GBMs (0.0%). All cases of metastatic carcinoma stained positive with cytokeratins AE1/3 (100%) and CAM 5.2 (100%). Variable staining was observed in carcinomas with CK7 (17 of 22, 77.3%), Ber-EP4 (11 of 22, 50.0%), and CK20 (9 of 22, 40.9%). Three metastatic carcinomas showed rare GFAP-positive staining cells (13.6%).

Conclusions.—Based on the aforementioned results, a combination of immunostains, including GFAP and cytokeratin CAM5.2, may be the most useful in differentiating poorly differentiated metastatic carcinoma from GBM. A significant number of GBMs stain with some cytokeratin markers, in particular cytokeratins AE1/3. Because of the poor specificity of cytokeratins AE1/3 in distinguishing metastatic carcinoma from GBM, it should not be used to differentiate the 2 entities.
Intravascular Lymphomatosis With Bone Marrow Involvement
Authors: Tucker Tammy J. , Bardales Ricardo H. , Miranda Roberto N.
Published: January 2021

We describe the case of a 56-year-old man who presented with numbness and tingling of the extremities, weakness, and fatigue. Laboratory findings included anemia and thrombocytopenia. A diagnosis of intravascular lymphomatosis was established when liver, omentum, and bone marrow samples were examined. A review of the literature reveals that most cases of intravascular lymphomatosis have cytopenias, mainly anemia and thrombocytopenia, but bone marrow involvement is rare. In our case, a subtle neoplastic infiltrate in the marrow sinusoids was highlighted with a B-cell marker. While immunohistochemical analysis was not performed in most reported cases in the literature, our studies suggest that a systematic search in bone marrow of cases of intravascular lymphomatosis may reveal unsuspected neoplastic cells. We conclude that bone marrow involvement in intravascular lymphomatosis appears to be rare, has subtle features, and is difficult to diagnose if unsuspected and not searched for.
Laboratory Recognition of a Rare Hemoglobinopathy
Authors: Kirk Cheryl M. , Papadea Christine N. , Lazarchick John
Published: January 2021

This article describes the laboratory investigation of an unusual hemoglobinopathy involving hemoglobin (Hb) S, HbSGPhiladelphia, and α-thalassemia-2 in a patient whose phenotype was HbSC by alkaline electrophoresis. Findings of a mean corpuscular volume of 62 fL and microcytes on the blood smear were inconsistent with HbSC disease. The patient's clinical course over several years had been mildly symptomatic. Testing in our hospital laboratory using isoelectric focusing and cation-exchange high-performance liquid chromatography to separate hemoglobins showed an unknown variant. Additional studies, including globin chain electrophoresis, reverse-phase high-performance liquid chromatography, and polymerase chain reaction–based DNA analysis were performed at reference laboratories, which reported the following findings: HbGPhiladelphia associated with α-thalassemia-2, HbS and HbGPhiladelphia, and the alpha-globin deletions defining the −α3.7/−α3.7 genotype. The hemoglobin molecular defects, α-thalassemia-2, and the pattern of inheritance are discussed.
Patient Outcomes and Pathology Practice
Authors: Bachner Paul
Published: January 2021

This article provides an abbreviated conceptual framework for viewing general issues of outcomes research and management and consideration of the emerging interest in patient-referenced outcomes in medicine and pathology. Specific issues addressed are the reasons for increased interest in outcomes research within the past decade; a review of the current language of outcomes management and research; a critique of the advantages and weaknesses of contemporary outcomes analysis and research methods; a summary of the responses of government, regulatory and accreditation organizations, medical societies, and the College of American Pathologists to the outcomes movement; and, in conclusion, a discussion of opportunities provided through outcomes management for enhanced involvement by pathologists in the care of patients.
Molecular Methods in the Detection and Identification of Mycobacterial Infections
Authors: Woods Gail L.
Published: January 2021

Nucleic acid amplification (NAA) tests for direct detection of Mycobacterium tuberculosis complex in respiratory specimens have the potential to provide a more rapid diagnosis of pulmonary tuberculosis (TB) than is currently possible by conventional stain, culture, and identification tests. Currently, 2 NAA tests—enhanced Amplified Mycobacterium Tuberculosis Direct (MTD) Test (Gen-Probe, Inc) and Amplicor Mycobacterium tuberculosis Test (Roche Molecular Systems, Inc)—have been approved by the Food and Drug Administration for testing respiratory specimens that are smear positive for acid-fast bacilli (AFB). This restriction to AFB smear–positive specimens was based on data from the initial clinical trials conducted to evaluate these products that showed low sensitivity (ie, 48%–53%) and less-than-optimal specificity (ie, 96%–99%) in AFB smear–negative specimens. Data from the clinical trial for the enhanced MTD test and from 2 subsequent studies, however, suggest that this version of the MTD test is a reliable tool for rapid diagnosis of pulmonary TB, regardless of the AFB smear result. Both NAA tests have been evaluated for diagnosis of extrapulmonary TB, and results were comparable to the results of tests performed with respiratory specimens. The NAA tests also appear to be reliable for rapid identification of M tuberculosis complex in positive broth cultures of all specimen types except blood. The impact of the NAA tests on patient outcome varies based on the AFB smear result. With smear-positive results, public health and hospital infection control resources are predominantly affected. With smear-negative results, however, the potential for affecting patient outcome is much greater. In patients with smear-negative results, the NAA test can result in earlier diagnosis of TB and subsequent initiation of therapy. Use of these tests also may eliminate the need for invasive diagnostic procedures, which are costly and pose an added risk to the patient, and they may allow earlier discharge of hospitalized patients.
Molecular Epidemiology in the Care of Patients
Authors: Pfaller Michael A.
Published: January 2021

Several different epidemiologic typing methods have been applied in studies of microbial pathogens. These methods include the more traditional nonmolecular approaches as well as the more sophisticated molecular typing methods. Application of traditional epidemiologic typing methods, such as antibiogram, serotyping, biotyping, and phage typing, have occasionally been useful in describing the epidemiology of infectious diseases. However, these methods have generally been considered to be too variable, labor intensive, and slow to be of practical value in epidemiologic investigations. In response to these limitations, several techniques have been adopted from the molecular biology field for use as epidemiologic typing methods and have been applied in studies of bacteria, fungi, viruses, and protozoa. The most widely used molecular typing methods are the DNA-based methods, such as plasmid profiling, restriction endonuclease analysis of plasmid and genomic DNA, Southern hybridization analysis using specific DNA probes, and chromosomal DNA profiling using either pulsed-field gel electrophoresis or polymerase chain reaction–based methods. The various molecular typing methods may be applied to the investigation of outbreaks of infections or may be used in the context of epidemiologic surveillance. For outbreak investigation, typing methods are used to compare isolates from a suspected outbreak to delineate clonally related and unrelated strains with the goal of short-term control of transmission. In the context of epidemiologic surveillance, molecular typing methods may be used to monitor geographic spread and prevalence shifts of epidemic and endemic clones with the goal of long-term evaluation of preventive strategies or for the detection and monitoring of emerging and reemerging infections. The specific typing method selected may vary with the task at hand; however, the typing studies must always be used to supplement, rather than replace, careful epidemiologic investigation.
Spurious Elevation of Automated Platelet Counts in Secondary Acute Monocytic Leukemia Associated With Tumor Lysis Syndrome
Authors: Li Shiyong , Salhany Kevin E.
Published: January 2021

The intent of this article is to describe the effect of tumor lysis on automated platelet counts in therapy-related, secondary acute monocytic leukemia. The first patient was a 69-year-old man with large cell carcinoma of the lung who developed acute monocytic leukemia 1½ years after initiation of radiation and chemotherapy for his carcinoma. The second patient was a 72-year-old female with peripheral T-cell lymphoma who developed acute monocytic leukemia 1 year after initiation of chemotherapy for her lymphoma. Platelet counts were determined by the automated Coulter (STKS) counter. Both patients had clinical and laboratory evidences of tumor lysis syndrome and disseminated intravascular coagulation. The peripheral blood smears revealed numerous fragments of leukemic cells and apoptotic cells with pyknotic nuclei. The Coulter machine enumerated these cellular fragments as platelets, resulting in falsely elevated platelet counts. Awareness of this laboratory artifact in secondary acute monocytic leukemia with tumor lysis syndrome is important so that potential life-threatening thrombocytopenia is not overlooked.
Mantle Cell Lymphoma
Authors: Hankin Rebecca C. , Hunter Susan V.
Published: January 2021

Objective.—This article summarizes the most useful ancillary immunohistochemical and molecular assays for use in the diagnosis of mantle cell lymphoma.

Data Sources.—The English language literature was surveyed, with an emphasis on recent publications, for articles presenting key advances in the molecular characterization of mantle cell lymphomas and for series of cases testing the utility of molecular diagnostic tests. The authors' series of 26 small B-cell lymphomas, analyzed for the cyclin D1 protein by paraffin immunohistochemistry and for t(11;14) by polymerase chain reaction, is included.

Conclusions.—Mantle cell lymphoma, a B-cell lymphoma now recognized in the 1994 Revised European-American Classification of Lymphoid Neoplasms (REAL) classification, is a relatively aggressive lymphoma with a poor prognosis. Its characteristic t(11;14)(q13;q32) translocation has a role in oncogenesis and has been exploited for molecular diagnostic tests, but these tests vary in sensitivity, specificity, and ease of use. Improved immunohistochemical tests are sufficient to confirm the diagnosis in most cases. Conventional cytogenetics and molecular diagnostic tests for t(11;14)—Southern blot and polymerase chain reaction analysis—may be helpful in selected cases, but are laborious or of limited sensitivity. Other methods, such as fluorescence in situ hybridization, need further development to provide faster, more sensitive diagnosis.
Polymorphisms in the Genes for Coagulation Factors II, V, and VII in Patients With Ischemic Heart Disease
Authors: Feng Yue Jin , Draghi Andrew , Linfert Douglas R. , Wu Alan H. B. , Tsongalis Gregory J.
Published: January 2021

Background.—Cardiovascular disease remains the leading cause of mortality in the United States, accounting for approximately 33% of all deaths in this country. Of these deaths, most are due to acute myocardial infarctions (AMIs), which are associated with thrombotic coronary artery obstruction and/or occlusion. These events could potentially be due to alterations in genes coding for coagulation factors. Several polymorphisms have been described in the factor II, V, and VII genes, which may predispose one to increased risk for ischemic heart disease (IHD).

Objective.—To determine if mutations in 3 coagulation factor genes could predispose an individual to increased risk for arterial thrombosis as a mechanism for developing unstable angina (UA) or AMI.

Methods.—We examined 125 hospitalized patients (mean age, 53 ± 6 years, 79 men and 46 women), including 32 with AMI, 68 with UA, and 25 noncardiac controls, for a genetic predisposition for increased risk of IHD. EDTA-anticoagulated whole blood was collected at the time of hospital admission. DNA was extracted, and the polymorphisms were detected by polymerase chain reaction amplification of these genes with subsequent restriction enzyme digestion and gel electrophoresis.

Results.—Our results showed that 3 (9.4%), 3 (4.4%), and 1 (4%) individuals were heterozygous for prothrombin G20210A and 3 (9.4%), 5 (7.4%), and 1 (4%) individuals were heterozygous for factor V Leiden in the AMI, UA, and control groups, respectively. The following genotype frequencies for the factor VII R353Q polymorphism were identified: 25 (78.1%), 56 (82.4%), and 18 (72%) with RR and 7 (21.9%), 12 (17.6%), and 7 (28%) with RQ in the AMI, UA, and control groups, respectively. No QQ homozygotes were identified. For the HVR4 size polymorphism, the following genotypes were identified: 3 (9.4%), 4 (5.9%), and 5 (20%) individuals with H7H7; 11 (34.4%), 33 (48.5%), and 12 (48%) with H6H7; and 18 (56.2%), 31 (45.6%), and 8 (32%) with H6H6 genotypes in the AMI, UA, and control groups, respectively. There were no H7H5 and H6H5 genotypes found in this study.

Conclusions.—Although the frequency differences of these polymorphisms in patients with AMI and UA were not statistically significant from those in controls, several trends are consistent with what has been reported in the literature. Although any of these or other undefined genetic abnormalities may result in IHD, it is possible that phenotypic predisposition to IHD initially presents as UA. A larger population study addressing the significance of these polymorphisms in the sequence of events that lead to IHD, including cases of UA, is warranted.
Mucinous Tumor of the Gallbladder With a Separate Nodule of Anaplastic Carcinoma
Authors: Mizuno Tsutomu , Eimoto Tadaaki , Tada Toyohiro , Tateyama Hisashi , Inagaki Hiroshi , Murase Takayuki
Published: January 2021

A case of mucinous tumor of the gallbladder with a separate nodule of anaplastic carcinoma is reported. The patient was an 83-year-old Japanese man who underwent cholecystectomy under the preoperative diagnosis of a mucus-producing gallbladder tumor. A mucinous tumor was found in the neck and distal body of the gallbladder, associated with a separate nodule in the fundus. The latter nodule was initially diagnosed as a benign xanthogranulomatous lesion. However, the immunohistochemical study revealed that the atypical cells in the superficial part of the nodule were positive for cytokeratin and epithelial membrane antigen, confirming the diagnosis of anaplastic carcinoma. Although the occurrence of mural nodules in mucinous cystic tumors of the ovary and pancreas is well reported, to our knowledge, this is the first report on the occurrence of a mucinous tumor with a nodule of anaplastic carcinoma in the gallbladder.
Protocol for the Examination of Specimens From Patients With Malignant Adrenal Cortical Tumors and Pheochromocytomas, Exclusive of Neuroblastoma and Other Adrenal Medullary Tumors of Childhood
Authors: Page David L. , Ruby Stephen G.
Published: January 2021

No Abstract Available
External Quality Assessment in the Examination of Blood Films for Malarial Parasites Within Ontario, Canada
Authors: Thomson Sam , Lohmann Reinhard C. , Crawford Linda , Dubash Ruby , Richardson Harold
Published: January 2021

Objective.—To assess laboratory practice in the examination of blood films for malarial parasites.

Method.—Ontario medical laboratories, licensed by the Ministry of Health, are required to participate in external quality assessment by the Laboratory Proficiency Testing Program, which assesses performance of laboratory assays and also examines the total testing process. Educational strategies are used to improve performance.

Results.—A 1995 survey indicated shortcomings in detection and identification of malarial parasites in blood films. Consequently, recommendations for the investigation of malarial parasites in blood were issued. In 1996 and 1997, 16 workshops were conducted. A 1997 follow-up external quality assessment survey indicated that problems persist as 27% of laboratories failed to correctly speciate Plasmodium falciparum. Good Practice Guidelines were issued in 1998.

Conclusion.—Further education and assessment are required. Laboratories lacking expertise must establish referral arrangements with more proficient laboratories.
Point-of-Care Glucose Testing
Authors: Louie Richard F. , Tang Zuping , Sutton Demetria V. , Lee Judith H. , Kost Gerald J.
Published: January 2021

Objective.—To assess the clinical performance of glucose meter systems when used with critically ill patients.

Design.—Two glucose meter systems (SureStepPro and Precision G) and a modular adaptation (Immediate Response Mobile Analysis-SureStepPro) were assessed clinically using arterial samples from critically ill patients. A biosensor-based analyzer (YSI 2700) and a hospital chemistry analyzer (Synchron CX-7) were the primary and secondary reference instruments, respectively.

Patients and Setting.—Two hundred forty-seven critical care patients at the University of California, Davis, Medical Center participated in this study.

Outcome Measures.—Error tolerances of ±15 mg/dL for glucose levels ≤100 mg/dL and ±15% for glucose levels >100 mg/dL were used to evaluate glucose meter performance; 95% of glucose meter measurements should fall within these tolerances.

Results.—Compared to the primary reference method, 98% to 100% of SureStepPro and 91% to 95% of Precision G measurements fell within the error tolerances. Paired differences of glucose measurements versus critical care variables (Po2, pH, Pco2, and hematocrit) were analyzed to determine the effects of these variables on meter measurements. Po2 and Pco2 decreased Precision G and SureStepPro measurements, respectively, but not enough to be clinically significant based on the error tolerance criteria. Hematocrit levels affected glucose measurements on both meter systems. Modular adaptation did not affect test strip performance.

Conclusions.—Glucose meter measurements correlated best with primary reference instrument measurements. Overall, both glucose meter systems showed acceptable performance for point-of-care testing. However, the effects of some critical care variables, especially low and high hematocrit values, could cause overestimated or underestimated glucose measurements.