bluuebunny/crossref_metadata_2025 huggingface dataset:
Stable and vulnerable domains in Germanic heritage languages
Authors: Westergaard Marit , Kupisch Tanja
Published: February 2021

This paper provides an overview of Germanic languages as heritage languages, i.e. languages acquired naturalistically by children in parts of the world where these languages are not the majority language. Summarizing research on different types of heritage speakers of Danish, German, Icelandic, Norwegian, and Swedish, we identify certain stable and vulnerable domains. We focus on the so far best studied areas, word order and grammatical gender, adding evidence from other lesser studied domains, such as definiteness and phonology. We propose that in addition to the linguistic make-up of the phenomena in question, the size of the heritage community and, relatedly, opportunities to use the language need to be taken into account. The latter may explain, for example, why moribund varieties of German and the Scandinavian languages in North America appear to be less stable than the language of second-generation heritage speakers in Europe.
Methodology for the Evaluation of the Electrical Energy Potential of Residual Biomass from the Wood Industry: A Case Study in Brazil
Authors: César de Mendonça Brasil Augusto
Published: February 2021

This chapter presents in a consolidated manner the step-by-step methodology to estimate the electrical energy potential of industrial wood residues considering the dependency of the efficiency of the power plants with their size. A function of the overall efficiency with power was obtained from a best curve fit of real data both taken from the literature and from Brazilian biomass-fired power plants. The methodology was applied to the determination of the electrical energy potential of wood industry residues in the State of Pará (data collected in 2004). Two cases were analyzed: one where a constant electrical efficiency of 25% was considered (independently of the amount of residues generated) and another where the proposed function of efficiency with power was used. Results show that in the State of Pará, the existent 675 sawmills generated 2.95 × 106 t in dry basis. When the dependency of efficiency with plant size is not considered, the electrical energy potential and average installed power (3140.4 GWh and 2 MWe) are overestimated in comparison to the herein proposed methodology (1868.8 GWh and 1 MWe). The present methodology, considering the efficiency as a function of the power, results in an average efficiency of 12.3% (lower than 25%).
Management of Wine Aroma Compounds: Principal Basis and Future Perspectives
Authors: G. Pereira Antia , Fraga Maria , Garcia-Oliveira Paula , Carpena Maria , Jimenez-Lopez Cecilia , Lourenço-Lopes Catarina , Barros Lillian , C.F.R. Ferreira Isabel , Angel Prieto Miguel , Simal-Gandara Jesus
Published: February 2021

Wine’s aroma is defined by volatile and non-volatile compounds that contribute to its make-up. The complex variety of volatile compounds, coming from grapes, interact with other non-volatile substances of the wine as precursors of wine’s aroma, known as primary aromas, which give the aroma of the young wine. The volatile compounds present in the skin and in the grape juice change according to the grape variety. Most of wine volatile compounds responsible for aroma are linked to sugars and they initially form odorless glycosides. Through the process of hydrolysis, they are reverted into an aromatic form. Chemical reactions among these compounds occur during the fermentation and in the first months of a wine’s existence, triggering fast and multiple modifications in wine’s aroma at this point. As wine ages and matures, changes and development in aroma will continue to take place but at a slower and more gradual pace. The study of the compounds responsible for aroma and flavor, as well as their correlation with the wine quality, is ongoing. Improving the knowledge of wine aromatic compounds could increase the risk of its potential adulteration; however, consumers prefer wine for its natural origin, so this scenario is unlikely in the future.
Case Study: Pathways from Forest to Energy in a Circular Economy at Lafões
Authors: d’Espiney Ana , Paula Marques Isabel , Maria Pinheiro Helena
Published: February 2021

The present case study deals with new pathways in demand for forest residues disposal in the Lafões region (Portugal), since this biomass is presently regarded as a residue and eliminated through open air burning. Different biomass-to-energy conversion systems have a high sustainability value and, thus, the energy potential of the biomass supplied by the forest of Lafões was assessed, using GIS-based methods and assumptions from the literature. The Lafões region produces large amounts of chicken manure from which energy can be recovered through anaerobic digestion. The energy potential held by the effluent of the several classes of the poultry industry of Lafões was assessed, using IPCC 2006 guidelines to estimate their biomass and methane production potential. Furthermore, integrated solutions were pursued. The present challenge is to explore complementarities between effluents for anaerobic digestion to achieve improved energy and waste management system performances. The complementarity between the residues from maritime pine forest management and from broiler production was assessed through bench-scale anaerobic co-digestion assays, leading to increased methane production when compared to those achieved with single substrate anaerobic digestion. This result highlights the interest of further research concerning complementarities between other effluents in the Lafões region.
Biodiversity and Environmental Integrity of Some Rivers in Derived Savannah Belt in Edo-North, Southern Nigeria
Authors: Dirisu Abdul-Rahman , Ovie Olomukoro John
Published: February 2021

Investigative study on macroinvertebrates and pollution tolerance index of four rivers in the derived savannah belt of Edo-North in Southern Nigeria was carried out from January to December, 2010. The study involved monthly field sampling and laboratory analysis of macrofauna. The objectives of the study were to evaluate the biodiversity status and importantly, the environmental integrity of the four selected rivers. Two dominant macroinvertebrate families were recorded; Baetidae and Chironomidae while, 53 macroinvertebrate taxa were identified across the rivers. The highest number of species (12) was recorded for Diptera, while, Hirudinea, Nematoda and Arachnida each had 1 species in the population. General diversity indices ranged from 2.02 to 2.78 with the least and highest recorded in Edion and Etuno Rivers, respectively. The fauna evenness index indicated that the water bodies had values less than 1.0. Meanwhile, Pollution tolerance index revealed spatial and seasonal variations in water quality conditions but only Edion River exhibited poor water quality in all the months of study.
Biomass Estimation Using Satellite-Based Data
Authors: Lourenço Patrícia
Published: February 2021

Comprehensive measurements of global forest aboveground biomass (AGB) are crucial information to promote the sustainable management of forests to mitigate climate change and preserve the multiple ecosystem services provided by forests. Optical and radar sensors are available at different spatial, spectral, and temporal scales. The integration of multi-sources sensor data with field measurements, using appropriated algorithms to identify the relationship between remote sensing predictors and reference measurements, is important to improve forest AGB estimation. This chapter aims to present different types of predicted variables derived from multi-sources sensors, such as original spectral bands, transformed images, vegetation indices, textural features, and different regression algorithms used (parametric and non-parametric) that contribute to a more robust, practical, and cost-effective approach for forest AGB estimation at different levels.
Distant Poverty, Human Vulnerability, and the African Ethics of Character
Authors: Badru Ronald Olufemi ,   DePaul University
Published: February 2021

This African moral framework discusses distant poverty as human vulnerability. Contextually, if vulnerability means human frailty, relative to some opposing facts of life, and that poverty makes the human person frail, relative to some largely unrealized/unrealizable desirables without assistance, then distant poverty as human vulnerability invariably connects, significantly, with poor dependency: poor people are vulnerable as dependent on the assisting other. Some fundamental questions arise: 1) What is the ontology of distant poverty as human vulnerability? 2) In what ways does the idea of poverty as human vulnerability essentially and morally connect with the idea of dependency? 3) Is the issue of addressing the problem of distant poverty as human vulnerability a question of perfect or imperfect moral duty or both? 4) In what ways do the perfect or imperfect moral duty (or both) connect to positive and negative moral duties? 5) What moral framework best accommodates, all things considered, moral duties? Considering these questions, this work advances that African ethics (AE) as character ethics, fundamentally serves as a better moral framework, compared to the Western ethics (WE) that has dominated the debates on addressing the questions for years.
Primary Nodal Gastrinomas
Authors: Herrmann Marille E. , Ciesla Marlyn C. , Chejfec Gregorio , DeJong Steven A. , Yong Sherri L.
Published: February 2021

Background.—The term primary lymph node gastrinoma was first used to describe a group of patients with gastrin-producing tumors present in lymph nodes located in a well-defined anatomic region. The patients had no known primary tumors in the pancreas or gastrointestinal tract and had disease-free survival for up to 18 years. The anatomic region in question has a triangular shape that extends from the cystic and common bile ducts to the second and third portion of the duodenum and the neck and body of the pancreas. The term gastrinoma triangle was coined to identify the area; in addition, it was postulated that lymph nodes located in the gastrinoma triangle normally contained neuroendocrine cells capable of secreting gastrin and other neuropeptides. From its inception, the postulate became the subject of controversy.

Design.—To extend previous observations, we examined the lymph nodes located in the gastrinoma triangle of 20 autopsy cases for the presence of neuroendocrine cells, as determined by immunohistochemistry, using antibodies to a panneuroendocrine substance (eg, synaptophysin) and a specific neuropeptide (eg, gastrin). Scanning for positive cells was performed by 2 observers (M.E.H. and M.C.C.). We compared the findings in these lymph nodes with lymph nodes obtained from axillary and inguinal dissections during surgical procedures.

Results.—In all, 417 lymph nodes were studied. Five of the 20 gastrinoma triangle cases contained synaptophysin reactive cells, whereas 3 had gastrin reactive cells. None of the axillary and inguinal lymph nodes contained neuroendocrine cells.

Conclusion.—Our findings support the hypothesis of entrapment of neuroendocrine cells during development and the presence of primary nodal gastrinomas.
Comparison of the Effectiveness of Polymerase Chain Reaction and Enzyme Immunoassay in Detecting Chlamydia trachomatis in Different Female Genitourinary Specimens
Authors: Chan Edward L. , Brandt Ken , Stoneham Heather , Antonishyn Nick , Horsman Greg B.
Published: February 2021

Background.—In high-volume laboratories, enzyme immunoassay (EIA) is the most commonly used method of detecting Chlamydia trachomatis. The optimal specimen for detecting C trachomatis is a combined urethral and cervical swab.

Objective.—To compare EIA with the combined urethral and cervical swab with polymerase chain reaction (PCR) on urine alone and urine mixed with cervical cells.

Patients and Methods.—Phase 1 of the study included 752 sets of specimens used for comparison. In phase 2, another 212 samples of urine and urine plus cervical cells were added to the study for comparison of the 2 specimen types using PCR.

Results.—In phase 1, 648 samples were negative and 76 were positive by all 3 methods and specimen combinations. Enzyme immunoassay was able to detect 81 positive samples (10.8%), whereas PCR on urine alone detected 97 positive samples (12.9%) and PCR on urine plus cervical cells detected 102 positive samples (13.6%), giving a sensitivity of 75%, 93.3%, and 98.1% respectively. In phase 2, PCR on urine alone detected 119 positive samples (12.3%) and PCR on urine plus cervical cells detected 127 positive samples (13.1%), with a sensitivity of 92.2% and 98.5%, respectively.

Conclusion.—Polymerase chain reaction on urine alone or urine plus cervical cells is superior to EIA on combined cervical and urethral swabs. There is a slight advantage of adding cervical cells to the urine compared with the urine specimen alone when PCR is used as the assay for detection. The total inhibition rate in our female population is only 3.1% when PCR is used.
Increased Midkine Expression in Hepatocellular Carcinoma
Authors: Kato Masako , Shinozawa Takao , Kato Shinsuke , Awaya Akira , Terada Tadashi
Published: February 2021

Context.—Midkine (MK) is a novel heparin-binding growth factor whose gene was identified in embryonal carcinoma cells in early stages of retinoic acid–induced differentiation.

Objective.—To examine the overexpression of MK in hepatocellular carcinoma (HCC).

Methods.—Seventy-seven primary HCC specimens from patients aged 17 to 72 years (63 men and 14 women) were examined. Histologically, 16 cases of HCC were classified as the well-differentiated type, 50 cases as the moderately differentiated type, and 11 cases as the poorly differentiated type. Immunohistochemical analysis was performed using a rat immunoglobulin G2a monoclonal antibody against the carboxyl terminal region of human MK. In situ hybridization was also performed on 20 HCC samples.

Results.—We successfully applied this monoclonal antibody against MK to analyze archival paraffin sections. The cancer tissues showed a positive reaction to this antibody, in which there was an intense reaction in their cytoplasm. Approximately one third of the individuals with HCC (26/77) had tumor cells that expressed MK, and these were classified into the following types: moderately differentiated (20/50), well differentiated (3/16), and poorly differentiated (3/11). The in situ hybridization analysis revealed that the signals of MK transcripts were found in the cytoplasm of the cancer cells; the distribution and localization of the MK transcripts' signals determined by in situ hybridization analysis were similar to those obtained by immunohistochemical analysis.

Conclusions.—Hepatocellular carcinoma expressed increased MK at the messenger RNA and protein level.
Low-Grade Intraosseous Osteosarcoma With Prominent Lymphoid Infiltrate
Authors: Ostrowski Mary L. , Johnson Mark E. , Smith Paula D. , Chevez-Barrios Patricia , Spjut Harlan J.
Published: February 2021

Low-grade intraosseous osteosarcoma is an uncommon and well-differentiated osteosarcoma with a good prognosis. We report a proximal tibial low-grade intraosseous osteosarcoma with a prominent intratumoral lymphoid infiltrate, which led to an initial diagnosis of probable malignant lymphoma. The importance of this infiltrate, which exhibited reactive features on flow cytometric studies, is not known. Our patient is free of tumor 1 year after limb salvage surgery, without hematologic or lymphoid abnormalities.
Identification of the Asexual State of Rhizopus Species on Histologic Tissue Sections in a Patient With Rhinocerebral Mucormycosis
Authors: Ciesla Marlyn C. , Kammeyer Patricia L. , Yeldandi Vijay , Petruzzelli Guy J. , Yong Sherri L.
Published: February 2021

Mucormycosis is an infection caused by a group of fungi in the order Mucorales in the phylum Zygomycota. The most well-known form of this disease is rhinocerebral mucormycosis, which usually develops in diabetic or immunocompromised patients. The fungal hyphal elements are easily detected in biopsy specimens by direct or histologic examination. However, the confirmatory identification of the genus or species requires culture of the specimen. This article presents a case of rhinocerebral mucormycosis in which presumptive identification of the genus was made without microbiologic cultures and was based on the extraordinarily rare appearance of fungal sporangia and sporangiospores in histologic tissue sections. Identification of these structures allowed an early and accurate diagnosis of rhinocerebral invasive mucormycosis.
Transfusion-Related Acute Lung Injury Secondary to Biologically Active Mediators
Authors: Lenahan Susan E. , Domen Ronald E. , Silliman Christopher C. , Kingsley Charles P. , Romano Paula J.
Published: February 2021

Transfusion-related acute lung injury is seen following the transfusion of blood components. The reported incidence is approximately 1 in 2000 transfusions. Clinically, it is similar to adult respiratory distress syndrome. The pathophysiology is unclear but has been attributed to HLA antibodies, granulocyte antibodies, and more recently to biologically active mediators in stored blood components. We report a case with laboratory evidence that supports the role of biologically active mediators in the pathogenesis of transfusion-related acute lung injury. To our knowledge, the case reported here is the first to use lipid extractions of patient samples to determine that lipid-priming activity was present at the time transfusion-related acute lung injury was identified clinically.
A Case of Fibrillary Glomerulonephritis With Linear Immunoglobulin G Staining of the Glomerular Capillary Walls
Authors: Sethi Sanjeev , Adeyi Oyedele A. , Rennke Helmut G.
Published: February 2021

We report a case of crescentic glomerulonephritis that presented with extensive crescent formation and fibrinoid necrosis in the glomeruli. Immunofluorescence staining was strongly positive for linear and pseudolinear staining of the capillary walls for immunoglobulin G (IgG) in the absence of significant mesangial staining. Histologic examination and immunofluorescence staining suggested a diagnosis of anti–glomerular basement membrane disease. However, electron microscopy showed the presence of numerous fibrillary deposits in the subepithelial areas of the glomerular capillary walls, supporting the diagnosis of fibrillary glomerulonephritis. Test results for circulating anti–glomerular basement membrane antibodies were negative. We report this interesting case to illustrate the point that fibrillary glomerulonephritis should be considered in the differential diagnosis of crescentic glomerulonephritis with linear and pseudolinear IgG deposits within the capillary walls. In such cases, electron microscopy is critical in differentiating the cause of crescentic glomerulonephritis.
Combined Tall Cell Carcinoma and Hürthle Cell Carcinoma (Collision Tumor) of the Thyroid
Authors: Baloch Zubair W. , Mandel Susan , LiVolsi Virginia A.
Published: February 2021

Tall cell carcinoma and Hürthle cell carcinoma are 2 aggressive forms of differentiated follicular-derived thyroid carcinomas. We present a case where these malignant tumors of thyroid coexisted. The tumor originated in the thyroid as a mixed tumor and metastasized as a tall cell tumor to the lymph nodes and as a Hürthle cell carcinoma to lungs. The coexistence of these tumor types is rare and sheds light on the histogenesis of Hürthle cell tumors and the metastatic behavior of combined tumors.
Urinary β2-Microglobulin Masquerading as a Bence Jones Protein
Authors: Handy Beverly C.
Published: February 2021

Bence Jones proteinuria, a common clinical manifestation of multiple myeloma, can also be seen in patients with other B-cell–derived neoplasms. Measurement of pretreatment levels is a useful adjunct in the diagnosis and staging of multiple myeloma, whereas serial levels reflect response to therapy. Serum concentrations of β2-microglobulin, a small-molecular-weight protein associated with the major histocompatibility complex class I antigens, are often elevated in hematopoietic neoplasms and are also commonly measured at baseline, before treatment, and serially throughout therapy in patients with multiple myeloma and other lymphoproliferative disorders as a marker of tumor burden. Urinary concentrations, however, are considered an indicator of renal tubular function. High urinary levels are found in tubular proteinuria, a frequent sequela of long-standing multiple myeloma. A case is described in which a high urinary concentration of β2-microglobulin interfered with Bence Jones protein quantification by electrophoresis studies.
Recurrent Breast Carcinoma Arising in a Transverse Rectus Abdominis Myocutaneous Flap
Authors: Chung Sun M. , Shin Sandra J. , Chen Xia , Rosen Paul Peter
Published: February 2021

Reconstruction after mastectomy for breast carcinoma with implants or myocutaneous flaps is a widely used surgical technique. Recurrence of breast carcinoma after these procedures is uncommon. Most recurrences occur in the skin or scar site of the mastectomy and are readily detectable by physical examination. There are rare reported cases of recurrent carcinoma occurring within the flaps that are usually diagnosed with the aid of imaging and subsequent pathologic examination. In most cases, these recurrences represent invasive or in situ ductal carcinoma. We report an additional 2 cases of breast carcinoma recurring within the myocutaneous flap, both of which exhibited uncommon histologic features not previously reported.
Hyperhomocysteinemia Measured by Immunoassay: A Valid Measure of Coronary Artery Atherosclerosis
Authors: Stauffenberg Michele T. , Lange Richard A. , David Hillis L. , Cigarroa Joaquin , Hsu Rebecca M. , Devaraj Sridevi , Jialal Ishwarlal
Published: February 2021

Context.—Homocysteine is emerging as a novel marker of atherothrombosis. Its role as an independent risk factor for cardiovascular disease is generally accepted. There is scanty data correlating homocysteine levels measured by immunoassay with cardiovascular disease. We previously validated a fluorescence polarization immunoassay for measuring homocysteine, which compared favorably with high performance liquid chromatography.

Objective.—To determine if homocysteine levels measured by immunoassay correlate with extent of atherosclerotic burden, as represented by degree of coronary artery stenosis determined by coronary angiography.

Design.—Fasting plasma samples were obtained from patients undergoing coronary angiography (N = 165). Homocysteine levels were measured by immunoassay and coronary artery stenosis was determined by coronary angiography.

Results.—Median coronary artery stenosis for the 3 homocysteine subgroups, less than 1.35, 1.35 to 6.75, and greater than 6.75 mg/L (<10, 10–15, and >15 μmol/L), was 75%, 90%, and 99%, respectively (P = .01 for trend). Also, folate and vitamin B12 levels decreased with increasing homocysteine levels (P = .01 and .04, respectively, for trend). Spearman's correlation showed a significant association between homocysteine level and coronary artery stenosis (r = 0.20; P = .009). When men and women were examined separately, the correlation was significant only for women (r = 0.30; P = .01).

Conclusion.—Homocysteine levels, as measured by immunoassay, show a positive correlation with cardiovascular disease in women. Thus, this is a valid measure of atherosclerotic burden and, therefore, a reliable addition to the established laboratory repertoire for the assessment of cardiovascular disease.
Molecular Diagnostics on Lymphoid Malignancies
Authors: Chan Wing C. , Fu Kai
Published: February 2021

Context.—Molecular diagnostics for lymphoid malignancies traditionally has focused on helping to provide a diagnosis on a tissue sample. The field has undergone substantial technical and conceptual evolution during the past 2 decades, and its role has expanded to new arenas, such as monitoring disease activities and detecting alterations in genes that are known to have a significant impact on disease outcome.

Objective.—To review the advances in molecular diagnostics on lymphoid malignancies, including recent developments that may facilitate the development of mechanism-based diagnosis for individualized therapy.

Design.—The development of molecular diagnostics in lymphoid malignancies is briefly reviewed with emphasis on the recent use of gene expression profiling for identifying important diagnostic and prognostic signatures.

Results.—Genome-scale investigations are becoming technically feasible and have provided promising results in the identification of new disease entities and new, molecularly defined prognosticators. This development can potentially revolutionize diagnostic medicine in the near future. As new genes or genetic pathways that affect the clinical and biologic behavior of tumors are defined and can be readily assayed, molecular diagnostics will be expected to provide this relevant information. Ideally, therapy will be based on this information, delivering the most appropriate treatment with the least toxicity.

Conclusions.—Molecular diagnostics in the future will be moving toward a mechanism-based diagnosis for individualized therapy.
The Value of Fluorescence In Situ Hybridization and Polymerase Chain Reaction in the Diagnosis of B-Cell Non-Hodgkin Lymphoma by Fine-Needle Aspiration
Authors: Safley Anne M. , Buckley Patrick J. , Creager Andrew J. , Dash Rajesh C. , Dodd Leslie G. , Goodman Barbara K. , Jones Claudia K. , Lagoo Anand S. , Stenzel Timothy T. , Wang Weihua , Xie Bill , Gong Jerald Z.
Published: February 2021

Context.—Molecular genetic analyses have been predicted to improve the diagnostic accuracy of fine-needle aspiration of B-cell non-Hodgkin lymphoma.

Objective.—To determine the value of routine molecular genetic assays, polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH), in the diagnosis of B-cell non-Hodgkin lymphoma by fine-needle aspiration (FNA).

Design.—A multiparametric method, including cytology, flow cytometry, PCR, and FISH, was prospectively evaluated in the diagnosis of B-cell non-Hodgkin lymphoma by FNA. Aspirates from 30 consecutive patients with suspected hematolymphoid malignancies were collected. All aspirates were triaged through a uniform program including cell-size analysis, B- and T-cell clonality studies, flow cytometric immunophenotyping, and bcl-1 and bcl-2 gene rearrangements by PCR and FISH. After completion of FNA evaluations, FNA results were compared with diagnoses from prior or subsequent surgical biopsies.

Results.—Monoclonal B-cell populations were detected in 18 of 20 B-cell non-Hodgkin lymphomas by flow cytometry and PCR. bcl-1 gene rearrangement was detected in 2 of 2 cases of mantle cell lymphoma. bcl-2 rearrangement was detected in 5 cases including 4 of 4 low-grade follicular lymphomas and 1 transformed follicular lymphoma. By incorporating the results of molecular genetic and ancillary diagnostics, a definitive classification was reached in 12 cases of B-cell non-Hodgkin lymphoma by FNA, including all cases of low-grade follicular lymphoma (4/4) and mantle cell lymphoma (2/2) and approximately 50% of small lymphocytic lymphoma (2/4) and large B-cell lymphoma (4/8). Ten of the 12 cases with a final classification reached by FNA had either prior or follow-up surgical biopsies, and all 10 cases showed agreement between the diagnoses rendered on FNA and surgical biopsies.

Conclusions.—With proper handling and management of specimens, FNA can routinely provide samples adequate for molecular genetic studies, in addition to cytomorphology and flow cytometry, making it possible to consistently render accurate and definitive diagnoses in a subset of B-cell non-Hodgkin lymphomas. By incorporating FISH and PCR methods, FNA may assume an expanded role for the primary diagnosis of B-cell non-Hodgkin lymphoma.
Radiographically Occult, Diffuse Intrasinusoidal Hepatic Metastases From Primary Breast Carcinomas: A Clinicopathologic Study of 3 Autopsy Cases
Authors: Allison Kimberly H. , Fligner Corinne L. , Tony Parks W.
Published: February 2021

Context.—Liver metastases usually present as radiographically detectable mass lesions that do not significantly compromise liver function. Rarely, metastatic carcinoma can diffusely infiltrate hepatic sinusoids, a pattern of metastasis that may be missed on imaging studies, and can result in liver failure.

Objective.—To describe the clinicopathologic features of 3 cases of diffuse intrasinusoidal hepatic metastases from primary breast carcinomas identified at autopsy.

Design.—Clinical histories and radiographic, macroscopic, and microscopic appearances of the livers were compared. Sampled liver tissue was stained with antibodies to E-cadherin, smooth muscle actin, and CD44.

Results.—Two of 3 cases had a history of infiltrating ductal carcinoma of the breast and presented with new-onset liver failure, but no hepatic metastases were identified on radiologic imaging. An additional case had no history of carcinoma, presented with a severe thrombocytopenic thrombotic purpura–like syndrome, and metastatic carcinoma of the breast was diagnosed only at autopsy. The livers in all 3 cases at autopsy were homogeneous, firm, and tan-yellow, and contained no large metastatic lesions. Microscopically, poorly differentiated carcinoma diffusely infiltrated hepatic sinusoids. Antibodies to smooth muscle actin stained activated hepatic stellate cells lining involved sinusoids. Cell surface adhesion molecules, E-cadherin or CD44, were not detected in any hepatic metastases.

Conclusion.—Diffuse intrasinusoidal hepatic metastases of breast carcinoma can occupy a large percentage of the hepatic volume, yet remain occult both radiographically and macroscopically. This type of metastatic spread can present as cryptogenic liver failure. The 3 cases we studied were associated with an absence of E-cadherin and CD44 expression.
Detection of Adenocarcinoma In Situ of the Cervix in Papanicolaou Tests: Comparison of Diagnostic Accuracy With Other High-Grade Lesions
Authors: Renshaw Andrew A. , Mody Dina R. , Lozano Richard L. , Volk Emily E. , Walsh Molly K. , Davey Diane D. , Birdsong George G.
Published: February 2021

Context.—Adenocarcinoma in situ of the cervix is a recently recognized interpretation in the Bethesda 2001 system. Although specific morphologic criteria have been published, recognizing this entity is still difficult.

Objective.—To compare pathologists' ability to correctly identify and categorize adenocarcinoma in situ with their ability to identify and categorize adenocarcinoma, high-grade squamous intraepithelial lesion, and squamous cell carcinoma.

Design.—Pathologists' reviews in the 2001 and 2002 College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology Program, an interlaboratory comparison program for gynecologic cytology, were examined. Cases were usually reviewed by multiple pathologists. False-negative rates, the percentage of reviews with exact agreement with reference interpretations, and the percentage of cases in which all reviews were in exact agreement with the reference interpretation for adenocarcinoma in situ, adenocarcinoma, high-grade squamous intraepithelial lesion, and squamous cell carcinoma were compared.

Results.—A total of 213 reviews of cases categorized as adenocarcinoma in situ were compared with 2821 reviews of adenocarcinoma, 7535 reviews of high-grade squamous intraepithelial lesion, and 1886 reviews of squamous cell carcinoma. The false-negative rate for adenocarcinoma in situ (11.7%) was significantly higher than that for high-grade squamous intraepithelial lesion (4.6%, P < .001) and squamous cell carcinoma (3.3%, P < .001) but not for adenocarcinoma (8.9%, P = .16). Of all the reviews of adenocarcinoma in situ cases, 46.5% were interpreted specifically as adenocarcinoma in situ, compared to 72.2% of reviews of adenocarcinoma, 73.2% of high-grade squamous intraepithelial lesion, and 75.1% of squamous cell carcinoma. No individual case of adenocarcinoma in situ was always specifically recognized as adenocarcinoma in situ; 26.5% of cases of adenocarcinoma were specifically recognized as such in all reviews. Findings were similar with and without the inclusion of high-grade squamous intraepithelial lesion/carcinoma, not otherwise specified, as an acceptable review interpretation for cases of adenocarcinoma, squamous cell carcinoma, and high-grade squamous intraepithelial lesion.

Conclusion.—These data from expert-referenced and biopsy-proven cases suggest that adenocarcinoma in situ is not as easily recognized or categorized as other serious diagnoses.
Current Applications of Flow Cytometry in the Diagnosis of Primary Immunodeficiency Diseases
Authors: Illoh Orieji C.
Published: February 2021

Context.—To review the applications of flow cytometry in the diagnosis and management of primary immunodeficiency disease.

Data Sources.—Articles describing the use of flow cytometry in the diagnosis of several primary immunodeficiency diseases were obtained through the National Library of Medicine database.

Study Selection.—Publications that described novel and known applications of flow cytometry in primary immunodeficiency disease were selected. Review articles were included. Articles describing the different immunodeficiency diseases and methods of diagnosis were also selected.

Data Extraction.—Approximately 100 data sources were analyzed, and those with the most relevant information were selected.

Data Synthesis.—The diagnosis of many primary immunodeficiency diseases requires the use of several laboratory tests. Flow cytometry has become an important part of the workup of individuals suspected to have such a disorder. Knowledge of the pathogenesis of many of these diseases continues to increase, hence we acquire a better understanding of the laboratory tests that may be helpful in diagnosis.

Conclusions.—Flow cytometry is applicable in the initial workup and subsequent management of several primary immunodeficiency diseases. As our understanding of the pathogenesis and management of these diseases increases, the use of many of these assays may become routine in hospitals.
Stability of JC Virus Coding Sequences in a Case of Progressive Multifocal Leukoencephalopathy in Which the Viral Control Region Was Rearranged Markedly
Authors: Zheng Huai-Ying , Yasuda Yukiharu , Kato Shunichi , Kitamura Tadaichi , Yogo Yoshiaki
Published: February 2021

Context.—It is generally accepted that JC virus variants in the brains of patients with progressive multifocal leukoencephalopathy are generated from archetypal strains through sequence rearrangement (deletion and duplication, or deletion alone) in the control region. This change is thought to occur during persistence of JC virus in patients.

Objective.—The present study was performed to ascertain whether amino acid substitution in the viral proteins is involved in the generation and propagation of JCV variants with rearranged control regions.

Design.—Many complete JC DNA clones were established from brain tissues (cerebellum, occipital lobe, and brainstem) autopsied in a case of progressive multifocal leukoencephalopathy in which multiple distinct control sequences were detected. Control and coding sequences were determined and compared among the JC DNA clones.

Results.—Twenty-eight control-region and 20 coding sequences of JC virus were compared. Five rearranged control sequences were detected, but they could be classified into 3 groups that shared common structural features. Viral coding sequences were identical among clones with different control regions and among clones derived from different brain regions.

Conclusion.—In the present case, nucleotide substitution in the viral coding regions (and resultant amino acid change in the viral proteins) was involved neither in the genesis of rearranged JC virus variants nor in the proliferation of demyelinated lesions in the brain.
Bacterial Contamination of Platelet Units: A Case Report and Literature Survey With Review of Upcoming American Association of Blood Banks Requirements
Authors: Burns Kathleen H. , Werch Jochewed B.
Published: February 2021

The most common transfusion-associated infectious risk in the United States today is bacterial contamination of platelet components. Bacterial contamination is estimated to occur at an incidence of 1:1000 to 1:3000 in platelet units, with severe episodes estimated to occur in about one sixth of contaminated products. Increased awareness and prompt reaction of the medical team can greatly affect the outcome and save a patient's life. The following case history illustrates this issue. A young woman developed chills and rigors while receiving 1 unit of leuko-reduced apheresis platelets for severe thrombocytopenia. The transfusion was stopped, blood cultures were drawn, and the patient developed clinical signs of sepsis. Cultures of both the platelet unit and the patient's blood revealed coagulase-negative Staphylococcus. Microbial susceptibilities in both samples were identical. Pretransfusion blood cultures taken from the patient earlier that day were negative. The platelet unit had been stored for 5 days. We review this case and the literature describing the persistent problem of platelet unit contamination and at the same time highlight the efforts now directed by the American Association of Blood Banks and College of American Pathologists to address this issue. Although there is no uniform approach to dealing with bacterial contamination of platelets, the American Association of Blood Banks and the College of American Pathologists have promulgated new accreditation requirements in an effort to prevent bacterial sepsis associated with platelet transfusion. A new American Association of Blood Banks standard, which will be effective March 1, 2004, requires a combination of strategies both to limit the initial inoculation of bacteria into the blood component and to detect subsequent growth at room temperature (American Association of Blood Banks Association Bulletin #03-12). The new College of American Pathologists Checklist question, which became effective in December 2003, is a Phase 1 requirement that calls for inspected facilities to have a platelet bacteria detection method in place.
Evidence for Involvement of Transforming Growth Factor β1 Signaling Pathway in Activation of JC Virus in Human Immunodeficiency Virus 1–Associated Progressive Multifocal Leukoencephalopathy
Authors: Enam Sahnila , Sweet Thersa M. , Amini Shohreh , Khalili Kamel , Del Valle Luis
Published: February 2021

Context.—Progressive multifocal leukoencephalopathy is a fatal demyelinating disease of the central nervous system frequently seen in patients with impaired immune systems, particularly acquired immunodeficiency syndrome. JC virus (JCV), a human neurotropic polyomavirus, is the etiologic infectious agent of this disease.

Objective.—The significantly higher incidence of progressive multifocal leukoencephalopathy in patients with acquired immunodeficiency syndrome than in patients with other immunosuppressive conditions suggests that molecular interactions between human immunodeficiency virus 1 and JCV, via the Tat protein, are responsible for the activation of the JCV enhancer/promoter and the development of progressive multifocal leukoencephalopathy. An indirect mechanism through activation of cytokines, such as transforming growth factor β1 and Smads 3 and 4, may also be responsible for the enhancement of JCV gene expression.

Design.—Immunohistochemical analysis in progressive multifocal leukoencephalopathy samples and chloramphenicol acetyl transferase assays on cell cultures were performed to corroborate this hypothesis.

Results.—The JCV capsid protein VP-1 was found in the nuclei of oligodendrocytes and in the nuclei and cytoplasm of bizarre astrocytes. Human immunodeficiency virus proteins, including p24 and Tat, were detected in the cytoplasm of astrocytes. Tat, but not p24, was detected in oligodendrocytes, suggesting that extracellular Tat accumulates in the nuclei of oligodendrocytes, where JCV gene transcription takes place. High levels of transforming growth factor β1 and Smads 3 and 4 were detected in JCV-infected oligodendrocytes. Results from in vitro studies confirm activation of the JCV early and late promoters by Smads 3 and 4.

Conclusions.—These observations support our model, suggesting that the induction of transforming growth factor β1 by human immunodeficiency virus 1 Tat can stimulate its downstream factors, including Smads 3 and 4, which in turn augment transcription of the JCV promoter in glial cells.
Quality Indices in a Cervicovaginal Cytology Service: Before and After Laboratory Accreditation
Authors: Tan Kong-Bing , Chang Satina A. E. , Soh Vanessa C. H. , Thamboo Thomas Paulraj , Nilsson Barbro , Chan Norman H. L.
Published: February 2021

Context.—Quality assurance practices contribute to the effectiveness of cervical screening and are formalized by participation in a laboratory accreditation program.

Objective.—To identify changes in the quality indices of our cervicovaginal cytology service preceding and following laboratory accreditation by the College of American Pathologists in 2000.

Design.—Cervicovaginal cytology quality indices for 2001 (postaccreditation) were compared with those of 1997 (preaccreditation). Performances in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology (PAP) for the years 1999–2002 were analyzed.

Results.—A comparison between data for 1997 and 2001 shows the following: (a) a higher inadequacy rate (1.3% vs 0.7%; P < .001) in 2001; (b) maintenance of a low atypical squamous cells of undetermined significance–squamous intraepithelial lesion ratio (0.79 and 0.76, respectively); (c) overall positive predictive values of positive cytology of 82% and 87%, respectively; (d) relatively few changes to the original cytologic diagnoses following review of significant cytohistologic discrepancies (4 cases and 2 cases, respectively); and (e) a higher subsequent positive yield of squamous intraepithelial lesions following atypical squamous cells of undetermined significance diagnoses in 2001 (41% vs 19%; P = .02). The performance of the laboratory and cytotechnologists in the PAP program showed maintenance of a high standard with almost no major discrepancies recorded.

Conclusions.—An increased awareness of quality-related issues and participation in intradepartmental consultation/diagnostic seminars, all part of the accreditation process, have very likely contributed to the modest improvements identified in the cytology service. Future challenges include increases in workload with the anticipated launch of Singapore's national cervical screening program and adaptation to the emerging cervical screening technologies.
Survivin and Bcl-2 Expression in Prostatic Adenocarcinomas
Authors: Kaur Prabhjot , Kallakury Bhaskar S. V. , Sheehan Christine E. , Fisher Hugh A. G. , Kaufman Ronald P. , Ross Jeffrey S.
Published: February 2021

Context.—Dysregulated cell proliferation caused by inhibitors of programmed cell death (apoptosis) contributes to tumor progression and spread. Aberrant expression of Bcl-2, the most notable inhibitor of apoptosis, has been well characterized in several human malignancies. Recent studies have described a novel apoptosis inhibitor, survivin, in human carcinomas, although its exact role remains to be characterized.

Objective.—The purpose of this study was to evaluate the immunohistochemical expression of Bcl-2 and survivin proteins in prostate cancer and to correlate the results with clinicopathologic variables.

Design.—Formalin-fixed, paraffin-embedded tissue sections from 138 cases of prostatic adenocarcinomas (PACs) were immunostained by an automated method using specific antibodies against survivin and Bcl-2. Staining was semiquantitatively scored based on both intensity and distribution, and results were correlated with morphologic and prognostic variables.

Results.—Of the 138 PACs tested, 113 (82%) expressed survivin. We found no correlation between survivin expression and prognostic variables, including grade, stage, DNA content (ploidy), and recurrence. Bcl-2 expression was positive in 95 (69%) of these 138 cases and correlated with nondiploid DNA content. Fourteen (50%) of 28 nondiploid PACs expressed Bcl-2, compared to 17 (25%) of 68 diploid tumors (P = .02). A trend for association of Bcl-2 expression with tumor stage was noted as follows: 21 (39%) of 54 advanced-stage PACs expressed Bcl-2, in comparison with 20 (24%) of 84 low-stage tumors (P = .07). On univariate analysis, 25 (48%) of the 52 PACs that recurred expressed Bcl-2, as compared with 16 (19%) of the 86 nonrecurrent PACs (P < .001). No correlation was noted between survivin and Bcl-2 expression.

Conclusion.—Survivin is expressed in a majority of PACs and is not a prognosis-related marker, but may be a potential target for apoptosis-based therapy. Overexpression of Bcl-2 correlates with other prognostic variables and predicts disease recurrence of PACs. These data also suggest that survivin and Bcl-2 may regulate cell proliferation and cell death through different mechanisms.
Heparin Monitoring and Patient Safety: A College of American Pathologists Q-Probes Study of 3431 Patients at 140 Institutions
Authors: Valenstein Paul N. , Walsh Molly K. , Meier Frederick
Published: February 2021

Context.—Appropriate laboratory monitoring of unfractionated heparin therapy promotes effective anticoagulation while minimizing hemorrhagic complications.

Objectives.—To measure heparin therapy monitoring in a “real-world” setting and to assess the degree of anticoagulation achieved.

Design.—One hundred forty institutions abstracted laboratory and pharmacy data from up to 30 inpatients receiving standard-dose unfractionated heparin therapy for 72 hours. Institutions also reported their therapeutic ranges and described heparin prescribing and monitoring policies.

Results.—Activated partial thromboplastin times or anti–factor Xa levels were measured at least once within the first 12 hours of administration for 95% of 3431 heparinized inpatients. Eighty-seven percent of patients had a platelet count performed within 72 hours of heparin administration. Seventy-eight percent of heparinized inpatients achieved therapeutic anticoagulation within 24 hours, but more than one third of patients entered the supratherapeutic range on at least 2 occasions during the first 72 hours. We found moderate variation in performance among the 140 institutions participating in the study, with more consistency in monitoring patients but less consistency in achieving therapeutic levels of anticoagulation. In one fourth of hospitals, more than half of the heparinized patients entered the supratherapeutic range on 2 or more occasions during the first 72 hours of therapy. None of 20 institutional practices we examined were meaningfully associated with more thorough monitoring of patients or with a higher percentage of patients achieving therapeutic anticoagulation. There was moderately wide variation in therapeutic ranges among the 140 sites.

Conclusions.—The prevention of heparin over-anticoagulation represents an important opportunity for improving patient safety in a significant number of institutions.
Giant Cell Tumor of Rib Masquerading as Thymoma: A Diagnostic Pitfall in Needle Core Biopsy of the Mediastinum
Authors: Volmar Keith E. , Sporn Thomas A. , Toloza Eric M. , Martinez Salutario , Dodd Leslie G. , Xie H. Bill
Published: February 2021

Giant cell tumor of bone is rarely seen in the rib, where it may present as a mediastinal mass. The diagnosis of giant cell tumor of bone is generally straightforward by fine-needle aspiration or needle core biopsy, but sampling problems may lead to confusion with other neoplasms or inflammatory processes. Here, we report a case of giant cell tumor of rib presenting as a mediastinal mass in a 36-year-old man. Because of inadequate sampling and inaccurate clinical information, the tumor was initially mistaken for thymoma. When the mass failed to respond to conventional chemotherapy, additional tissue was obtained and a giant cell tumor was diagnosed. Consequently, definitive therapy was delayed. The case illustrates an important diagnostic pitfall in the biopsy of mediastinal masses.