bluuebunny/crossref_metadata_2025 huggingface dataset:
Negligencia auditiva en pacientes con enfermedad de Alzheimer
Authors: Herrero Romero Marta , Thuissard Israel J. , Sanz-Rosa David , Ruiz Escudero Carlos , Vidal López Joaquin , Domínguez Ovejas Silvia Verónica
Published: February 2021

Introducción. La negligencia auditiva es una disfunción del sistema nervioso central que provoca dificultades para responder a un estímulo situado en el lado opuesto de la lesión, cuando se presentan sonidos o palabras por ambos oídos a la vez.El objetivo principal de este trabajo es valorar la existencia de negligencia auditiva en pacientes con enfermedad de Alzheimer grado I.Material y métodos. En este trabajo se han analizado 32 individuos, divididos en dos grupos. 16 pacientes diagnosticados con enfermedad de Alzheimer grado I. y 16 individuos control (sin enfermedad de Alzheimer u otras patologías neurológicas). Las edades de los sujetos estaban comprendidas entre los 60 y los 95 años. Para la valoración de la negligencia auditiva se les aplicó la prueba Auditory y el Test de Dígitos Dicóticos.Resultados. La prueba Auditory detectó que cuando se presentaban dos estímulos simultáneos por ambos oídos, los pacientes con enfermedad de Alzheimer grado I percibían el 72,5% de los tonos por el oído izquierdo, así mismo, los resultados del Test de Dígitos Dicóticos mostraron un menor número de aciertos en el oído derecho de estos pacientes. Los resultados de ambas pruebas Auditory y Test de Dígitos Dicóticos realizadas al grupo control no manifestaron diferencias estadísticamente significativas entre los dos oídos.Conclusión. Los resultados obtenidos sugieren que los pacientes con enfermedad de Alzheimer grado I presentan una negligencia auditiva izquierda.
Evolución cuantitativa y cualitativa de la presbiacusia en pacientes portadores de audífonos
Authors: Vicente García Ana María , Bartolomé Pascual María Visitación
Published: February 2021

Introducción. La presbiacusia es una enfermedad de origen multifactorial que afecta al oído y por tanto a la vida del paciente que la sufre, generándole alteraciones en la comunicación oral y aislamiento social, depresión e incluso demencia.
Objetivo. El objetivo de este estudio es analizar la influencia del uso o no de audífonos en la evolución de los umbrales auditivos así como en la conservación de la inteligibilidad en una muestra de pacientes presbiacúsicos en la Comarca de Tarazona y el Moncayo.
Material y métodos. La muestra está formada por 75 pacientes (44 hombres y 31 mujeres) de edades comprendidas entre 50 y 92 años, a los que se han realizado una revisión inicial y al menos otra de seguimiento en un plazo de más de 2 años y menos de 4 años. En cada revisión se ha realizado: anamnesis (en la revisión inicial), audiometría tonal y logoaudiometría. Todas las pruebas son realizadas en el mismo centro por un único examinador.
Resultados. En la muestra de pacientes presbiacúsicos analizada no se puede afirmar que el uso de audífonos prevenga el deterioro de los umbrales auditivos. Sin embargo su uso tiene un efecto positivo sobre la conservación de las habilidades de comprensión del lenguaje oral, más acentuado en los usuarios con pérdidas auditivas simétricas y adaptación binaural.
Discusión. Se trata de una muestra poblacional circunscrita en una zona geográfica rural. El tratamiento para la presbiacusia es aconsejable que se haga una adaptación binaural desde los primeros sistemas y diagnostico de la alteración auditiva para mantener la comunicación oral e impedir las consecuencias del asilamiento social.
Design of beam-column joints
Authors: Blakeley R. W. G.
Published: February 2021

This paper is the result of deliberations of the Society's discussion group on seismic design of ductile moment resisting reinforced concrete frames.
Rechte Orientierungen als Herausforderung professionellen Handelns
Authors: Görtler Michael
Published: February 2021

Mitarbeitende in sämtlichen Feldern der Sozialen Arbeit sehen sich zunehmend mit rechtspopulistischen und auch rechtsextremen Einstellungen konfrontiert, mit denen angemessen umzugehen eine enorme Herausforderung ist. Das gilt in besonderem Maße auch für die Kinder- und Jugendhilfe.
Jurastudium 4.0 – Im Wandel der Effektivitätssteigerung durch die Digitalisierung
Authors: Kock Kira
Published: February 2021

Als Dachverband der juristischen Fachschaften in Deutschland setzt sich der Bundesverband rechtswissenschaftlicher Fachschaften e.V. (BRF) aus 42 Fachschaften der bundesweit 44 juristischen Fachbereiche und Fakultäten zusammen und vertritt so mehr als 110.000 Studierende. Mit der jährlichen Hauptversammlung, der Bundesfachschaftentagung (BuFaTa), die dieses Jahr vom 05. bis 07. Juni 2020 erstmals digital unter dem Thema „Jurastudium 4.0 - Im Wandel der Effektivitätssteigerung durch die Digitalisierung“ stattfand, wird die inhaltliche Ausrichtung des BRF neu kalibriert. 120 Studierendenvertreterinnen und Studierendenvertreter diskutierten zu folgenden Themenschwerpunkten: „Zusammenarbeit mit externen Akteurinnen und Akteuren“1, „Digitales Examen“, „Datenbanken im Jurastudium“ und „Effektive Beschlussfassung“. Anhand von vorbereiteten Gutachten2 wurden die verschiedenen Themen in den Workshops aufbereitet und vertieft. Weiter wurden zur inhaltlichen Ausgestaltung der Themenkomplexe Beschlussvorlagen auf Basis jener Gutachten erarbeitet und anschließend den Teilnehmerinnen und Teilnehmern zur Abstimmung präsentiert. Die Ergebnisse3 der diesjährigen Bundesfachschaftentagung werden im Folgenden näher ausgeführt und der rechtsdidaktische Hintergrund debattiert.
Climate as the Major Factor Controlling Phenology
Authors: Guesmi Boubakeur
Published: February 2021

The witnessed aberrance and irregularities in the timing of pheno-phases is an undeniable evidence of the reality of the climate change and hence proves the complete control of climate over phenology. In fact, some researchers mentioned the advance of blooming and the delay of defoliation to the mid of winter as well as the disappearance of many animal and vegetal species. This would visibly illustrates the impact of climate changes which became a factual reality. These facts a long with the rhythmicity of life under the climate control and seasonality makes the importance of this chapter unequivocal, and a backbone for this very book of “Agrometeorology”. Accordingly, this chapter treats each phenophase from dormancy to fructification to cover all the plant life cycle. For each of which we focus on how climate is intimately controlling the biological processes of each life phase and how climatic elements are the strongest and first factor which induces plant to starts the appropriate phenophase according to the fitting season. Plant is indeed very sensitive to seasonal variation in climate elements which induces the transcription of specific genes to produce specific enzymes which to their turn are with specific act on specific cells and tissues. Hence there is a high harmony between plant physiological response and climate seasonality endorsed by the circadian clock which is merely created by the historical subjection of plants to the impact of climate. Nonetheless, the recent climate changes are seemingly to be against this natural harmony between phenology and climate. This should due to their erraticism which may cause damages to the ecosystem and available resources. Thence, this chapter within this book would be inspiring for some strategies of adaptation to the climate changes to avoid such a prejudice against crops by adjusting the agricultural calendar and planting dates to avoid coincidence of fragile phenophases (germination, flowering, and fructification) with climatic hazards.
Exploring the Histogenesis of Ovarian Mucinous and Transitional Cell (Brenner) Neoplasms and Their Relationship With Walthard Cell Nests: A Study of 120 Tumors
Authors: Seidman Jeffrey D. , Khedmati Fatemeh
Published: February 2021

Context.—The origin of and relationship between ovarian mucinous and transitional cell (Brenner) neoplasms are enigmatic. The reported association ranges from 1% to 16%, and whether there is an association with Walthard cell nests is unknown.

Objective.—To clarify the histologic relationship between mucinous and Brenner tumors.

Design.—A total of 40 mucinous cystadenomas, 67 Brenner tumors, and 13 combined tumors were studied. Peritoneal surfaces were examined for Walthard nests in 83 patients compared with 272 controls.

Results.—A total of 25% of tumors with a mucinous component contained a Brenner component, and 16% of tumors with a Brenner component contained a mucinous component. Most calcifications were spiculated (nonpsammomatous). In 6 combined tumors, the relative volume of the 2 components was less than 1:3000 (transitional-mucinous). Walthard nests were found in 50% of patients with Brenner tumors and 59% of patients with mucinous tumors. This was significantly higher than the 28% found in controls (P = .002 and P < .001, respectively). The number of fallopian tube blocks examined was correlated with the likelihood of finding Walthard nests, and accordingly, sampling accounted for 39% of the increase with Brenner tumors but strengthened the association with mucinous tumors.

Conclusions.—The strong association of mucinous and transitional cell components, similar type of calcification, complementary size distributions, and frequent identification of a transitional component in the face of an exceedingly small estimated proportion of that component suggest that this association has been underestimated. The association of Brenner tumors with Walthard nests, although significant, appears weak and not strongly supportive of a histogenetic relationship. The stronger association of Walthard nests with mucinous tumors remains unexplained.
Histopathologic and Clinical Features of Medullary Microcarcinoma and C-Cell Hyperplasia in Prophylactic Thyroidectomies for Medullary Carcinoma: A Study of 42 Cases
Authors: Etit Demet , Faquin William C. , Gaz Randall , Randolph Gregory , DeLellis Ronald A. , Pilch Ben Z.
Published: February 2021

Context.—Prophylactic thyroidectomies are increasingly performed on patients at risk for developing medullary thyroid carcinoma (MTC); consequently, pathologists are more commonly encountering these specimens in routine practice.

Objective.—To describe the detailed clinicopathologic features of prophylactic thyroidectomies for medullary carcinoma.

Design.—We present a retrospective series of 42 prophylactic thyroidectomies for MTC performed for one or more of the following: family history of multiple endocrine neoplasia (MEN) or MTC, elevated serum calcitonin level, or detection of a RET proto-oncogene mutation.

Results.—Patients included 22 men and 20 women (mean age, 26.2 years). Among those with known RET proto-oncogene mutations, affected sites included exons 10, 11, 14, and 16. In 93% (n = 39) of cases, either C-cell hyperplasia (n = 36), medullary microcarcinoma (MMC; n = 29), or medullary macrocarcinoma (n = 1) was found. C-cell hyperplasia was often multifocal (n = 30) and bilateral (n = 23) and included both nonnodular and nodular patterns. A total of 94% of C-cell hyperplasia cases and all MMC cases were microscopically detectable using hematoxylin-eosin stains. The MMCs were characterized by a complex microarchitectural pattern with a desmoplastic stromal response (n = 29) and focal amyloid deposition (n = 12). Most MMCs exhibited a solid pattern (n = 24) of round, polygonal, spindled, or plasmacytoid-shaped cells. Only 1 case of MMC showed evidence of metastatic disease to a pretracheal lymph node.

Conclusions.—Based upon our clinicopathologic findings and review of the literature, we conclude that thyroidectomies in at-risk patients are very frequently associated with C-cell hyperplasia and/or MMC; however, the clinical prognosis for these patients is very good.
Angiosarcoma, Radiation-Associated Angiosarcoma, and Atypical Vascular Lesion
Authors: Lucas David R.
Published: February 2021

Angiosarcoma, one of the least common sarcomas, has become increasingly important because of its association with radiation therapy, especially for breast cancer. Most are sporadic, presenting as cutaneous tumors in the scalp/face of elderly patients. However, angiosarcoma has a wide anatomic distribution including soft tissue, visceral organ, and osseous locations. Predisposing conditions include environmental exposures to chemical or radioactive sources. Radiation-associated angiosarcoma typically presents as a cutaneous tumor several years posttherapy. The latency for radiation-associated mammary angiosarcoma is relatively short, sometimes less than 3 years. Atypical vascular lesion refers to a small, usually lymphatic-type vascular proliferation in radiated skin. Although most atypical vascular lesions pursue a benign course, they recur and very rarely progress to angiosarcoma. Distinguishing this lesion from well-differentiated angiosarcoma in a biopsy can be challenging, especially because areas indistinguishable from atypical vascular lesion are found adjacent to angiosarcoma. Recently, vascular-type atypical vascular lesion, which resembles hemangioma, has been described, thus expanding the definition of this entity.
CD10 Is Expressed in Most Epithelioid Hemangioendotheliomas: A Potential Diagnostic Pitfall
Authors: Weinreb Ilan , Cunningham Kristopher S. , Perez-Ordoñez Bayardo , Hwang David M.
Published: February 2021

Context.—Epithelioid hemangioendothelioma (EHE) is a vascular neoplasm that occasionally is difficult to distinguish from primary/metastatic carcinomas, particularly when EHEs express keratins. We recently encountered an EHE with strong CD10 positivity mimicking renal cell carcinoma.

Objective.—To examine sensitivity and specificity of CD10 in EHE.

Design.—Nine EHEs were stained with keratins, factor VIII, CD31, CD34, and CD10. Mimics of EHE were also retrieved and stained with CD10.

Results.—The EHE patients included 5 men and 4 women. Patients ranged in age from 24 to 74 years. Tumors were located in liver (3), skin (2), lung/pleura (2), and sternomastoid and mediastinum (1 each). Two had skin metastases. All EHEs were positive for vascular markers. A total of 7 of 9 primary tumors expressed cytoplasmic and intracytoplasmic luminal CD10. The 2 skin metastases were positive, whereas 2 primary skin EHEs were negative. Of the mimics, CD10 showed staining in 7 of 23 cases: 3 of 3 renal cell carcinomas, 1 of 7 other carcinomas, 2 of 3 epithelioid angiosarcomas, 1 of 3 melanomas, 0 of 3 mesotheliomas, and 0 of 4 epithelioid hemangiomas.

Conclusions.—CD10 has a sensitivity of 78% (confidence interval, 63.6%–92.4%) and specificity of 70% (confidence interval, 54%–85.9%) for EHE. There is a growing list of tumors that show expression of CD10. Pathologists should be aware of this diagnostic pitfall.
Document Control Practices in 120 Clinical Laboratories
Authors: Valenstein Paul N. , Stankovic Ana K. , Souers Rhona J. , Schneider Frank , Wagar Elizabeth A.
Published: February 2021

Context.—A variety of document control practices are required of clinical laboratories by US regulation, laboratory accreditors, and standard-setting organizations.

Objective.—To determine how faithfully document control is being implemented in practice and whether particular approaches to document control result in better levels of compliance.

Design.—Contemporaneous, structured audit of 8814 documents used in 120 laboratories for conformance with 6 generally accepted document control requirements: available, authorized, current, reviewed by management, reviewed by staff, and archived.

Results.—Of the 8814 documents, 3113 (35%) fulfilled all 6 document control requirements. The requirement fulfilled most frequently was availability of the document at all shifts and locations (8564 documents; 97%). Only 4407 (50%) of documents fulfilled Clinical Laboratory Improvement Amendment requirements for being properly archived after updating or discontinuation. Policies and procedures were more likely to fulfill document control requirements than forms and work aids. Documents tended to be better controlled in some laboratory sections (eg, transfusion service) than in others (eg, microbiology and client services). We could not identify document control practices significantly associated with higher compliance rates.

Conclusions.—Most laboratories are not meeting regulatory and accreditation requirements related to control of documents. It is not clear whether control failures have any impact on the quality of laboratory results or patient outcomes.
New Variants of Epithelial-Myoepithelial Carcinoma: Oncocytic-Sebaceous and Apocrine
Authors: Seethala Raja R. , Richmond Jeffrey A. , Hoschar Aaron P. , Barnes E. Leon
Published: February 2021

Context.—Recently described variants of epithelial-myoepithelial carcinoma have not been well characterized but raise a distinct set of differential diagnostic considerations than the classic type.

Objective.—To report a detailed analysis of oncocytic-sebaceous epithelial-myoepithelial carcinoma (OEMCa) and a similar, but novel, variant, apocrine epithelial-myoepithelial carcinoma (ApEMCa).

Design.—Clinical, histologic, and immunophenotypic features of 5 OEMCas and 5 ApEMCas were analyzed. Ultrastructural examination was also performed on 3 OEMCa and 1 ApEMCa tumors.

Results.—The mean age for OEMCa (74.4 years; range, 58–82 years) was slightly higher than for ApEMCa (61.6; range, 46–79 years). All tumors arose in the parotid glands and demonstrated a multinodular pattern of growth with an average size of 3.3 cm (range, 2.3–6.5 cm). Available follow-up (n = 6; 3 OEMCas, 3 ApEMCas) shows a favorable course (no evidence of disease; mean, 17.4 months). Both were morphologically similar, but only OEMCa had sebaceous elements. Phosphotungstic acid hematoxylin staining, antimitochondrial antibody immunohistochemistry, and ultrastructural examination confirm the abundance of mitochondria in OEMCa but not in ApEMCa. The ductal component in ApEMCa was distinguished from that of OEMCa by apical snouts, intracytoplasmic vacuoles, nuclear pleomorphism, prominent nucleoli, and androgen receptor immunoreactivity.

Conclusions.—Oncocytic-sebaceous epithelial-myoepithelial carcinoma and ApEMCa should be considered in the differential diagnosis of oncocytic/oncocytoid salivary gland tumors. Oncocytic-sebaceous epithelial-myoepithelial carcinoma morphology may reflect a senescent phenotype, similar to other oncocytic lesions. The ductal component of ApEMCa shares some similarities with salivary duct carcinoma and supports the notion that epithelial-myoepithelial carcinoma can serve as the progenitor tumor for hybrid tumors.
Update in Nonneoplastic Lung Diseases
Authors: Gordon Ilyssa O. , Cipriani Nicole , Arif Qudsia , Mackinnon A. Craig , Husain Aliya N.
Published: February 2021

Context.—Nonneoplastic lung diseases include a wide range of pathologic disorders from asthma to interstitial lung disease to pulmonary hypertension. Recent advances in our understanding of the pathophysiology of many of these disorders may ultimately impact diagnosis, therapy, and prognosis. It is important for the practicing pathologist to be aware of this new information and to understand how it impacts the diagnosis, treatment, and outcome of these diseases.

Objective.—To update current progress toward elucidating the pathophysiology of pulmonary alveolar proteinosis, idiopathic pulmonary hemosiderosis, and pulmonary arterial hypertension, as well as to present classification systems for pulmonary hypertension, asthma, and interstitial lung disease and describe how these advances relate to the current practice of pulmonary pathology.

Data Sources.—Published literature from PubMed (National Library of Medicine) and primary material from the authors' institution.

Conclusions.—Improved understanding of the pathophysiology of pulmonary alveolar proteinosis, pulmonary hypertension, and idiopathic hemosiderosis may impact the role of the surgical pathologist. New markers of disease may need to be assessed by immunohistochemistry or molecular techniques. The classification systems for interstitial lung disease, asthma, and pulmonary hypertension are evolving, and surgical pathologists should consider the clinicopathologic context of their diagnoses of these entities.
Epstein-Barr Virus–Associated Smooth Muscle Tumor of the Iris in a Patient With Transplant: A Case Report and Review of the Literature
Authors: Yu Le , Aldave Anthony J. , Glasgow Ben J.
Published: February 2021

Epstein-Barr virus infection has been linked to the development of smooth muscle tumors in immunocompromised patients with organ transplants and acquired immunodeficiency syndrome. A 52-year-old female recipient of a renal transplant presented with enlarging masses of the left iris. Incisional biopsy of the mass revealed a smooth muscle tumor of the iris. Epstein-Barr virus infection was confirmed by in situ hybridization for Epstein-Barr virus–encoded, small RNA in tumor cells. Eight months after total iridectomy the patient was free of disease. Although the prognosis and classification of Epstein-Barr virus–associated smooth muscle tumors are controversial, mortalities caused by these tumors are rare.
KRas and BRaf Mutational Status Analysis From Formalin-Fixed, Paraffin-Embedded Tissues Using Multiplex Polymerase Chain Reaction–Based Assay
Authors: Jakubauskas Arturas , Griskevicius Laimonas
Published: February 2021

Context.—Monoclonal anti–epidermal growth factor receptor antibodies bind to the epidermal growth factor receptor and inhibit receptor kinase activity. Clinical trials have indicated that evaluation of the mutational status of KRas and BRaf is necessary to exclude patients who are resistant to the clinical benefit of anti–epidermal growth factor receptor therapy.

Objective.—To develop a multiplex polymerase chain reaction–based assay for the evaluation of KRas and BRaf mutational status.

Design.—A sample-saving and cost-effective, multiplex polymerase chain reaction–based assay to detect somatic mutations in KRAS exon 2 and exon 3 as well as in BRAF exon 15 was developed. The same primer pairs could be successfully used in amplification of a single DNA fragment under the same conditions.

Results.—DNA isolated from 20 retrospective formalin-fixed, paraffin-embedded samples of colorectal cancer was screened for mutations using the multiplex polymerase chain reaction assay followed by dideoxy-termination sequencing. Five samples bearing mutations—p.G12D (identified twice), p.G12V, p.G12S, and p.G13D, all encoded in KRAS exon 2—were identified. Three samples were found bearing amino acid substitution p.V600E of BRaf. The detected KRas and BRaf mutations were found to be mutually exclusive.

Conclusions.—A multiplex polymerase chain reaction–based amplification followed by dideoxy-termination sequencing may be used advantageously for the evaluation of KRas and BRaf mutational status from formalin-fixed, paraffin-embedded samples.
Multiple Patient Samples of an Analyte Improve Detection of Changes in Clinical Status
Authors: Kroll Martin H.
Published: February 2021

Context.

When comparing results over time, biologic variation must be statistically incorporated into the evaluation of laboratory results to identify a physiologic change. Traditional methods compare the difference in 2 values with the standard deviation (SD) of the biologic variation to indicate whether a “true” physiologic change has occurred.

Objective.

To develop methodology to reduce the effect of biologic variation on the difference necessary to detect changes in clinical status in the presence of biologic variation.

Design.

The standard test for change compares the difference between 2 points with the 95% confidence limit, given as . We examined the effect of multiple data pairs on the confidence limit.

Results.

Increasing the number of data pairs using the formula , where n  =  number of data pairs, significantly reduces the difference between values necessary to achieve a 95% confidence limit.

Conclusions.

Evaluating multiple paired sets of patient data rather than a single pair results in a substantial decrease in the difference between values necessary to achieve a given confidence interval, thereby improving the sensitivity of the evaluation. A practice of using multiple patient samples results in enhanced power to detect true changes in patient physiology. Such a testing protocol is warranted when small changes in the analyte precede serious clinical events or when the SD of the biologic variation is large.
Reducing the Variation in Performance of Antibody Titrations
Authors: AuBuchon J. P. , de Wildt-Eggen J. , Dumont L. J.
Published: February 2021

Background.—Antibody titration is difficult to standardize. We investigated whether a detailed, uniform procedure for antibody titration would reduce variation in both tube-based and gel card titres in an international study.

Methods.—Laboratories (n = 35) tested proficiency testing material provided by the College of American Pathologists each according to (i) their routine method; (ii) a detailed, uniform method; and (iii) the uniform method titrating the serum sample against a red cell of specified phenotype (D+ C− c+ E+ e− for anti-D; A1 for anti-A) instead of the red cell of the same phenotype provided in the proficiency testing kit. Uniform method results were reported with 1+ and w+ end-points. Paired statistical analyses of variance were conducted using the F-test.

Results.—The variance between laboratories was not significantly reduced with the uniform method using a 1+ end-point. However, a statistically significant reduction in the variance of anti-D and anti-A titres by the tube-based uniform technique after 37°C incubation and conversion to the antiglobulin (AHG) phase was seen when 19 laboratories reanalysed their results using a w+ end-point. Too few laboratories reported results with a w+ end-point in gel card testing to allow analysis. Titration against red cells of the specified phenotype provided by the participating laboratory did not appear to introduce additional variance. Overall, results reported based on the gel card technique at the AHG phase (1+ end-point) showed reduced variance compared to tube-based techniques.

Conclusions.—A detailed, uniform method for antibody titration at 37°C and read at the AHG phase in a tube-based method with a w+ end-point reduced interlaboratory variability.
Polymeric Immunoglobulin Receptor–Negative Tumors Represent a More Aggressive Type of Adenocarcinomas of Distal Esophagus and Gastroesophageal Junction
Authors: Gologan Adrian , Acquafondata Marie , Dhir Rajiv , Sepulveda Antonia R.
Published: February 2021

Context.—Polymeric immunoglobulin receptor (PIgR) expression has been found in gastric mucosa and gastric cancers, but it is not known whether PIgR expression is related to background intestinal metaplasia nor the patterns of PIgR expression in tumors arising in the distal esophagus and gastroesophageal (GE) junction.

Objectives.—To identify clinicopathologic features of tumors associated with PIgR expression and to determine whether PIgR expression is associated with intestinal differentiation of tumors and intestinal metaplasia in background mucosa in 3 groups of upper gastrointestinal adenocarcinomas. These groups are (1) gastric adenocarcinomas, (2) adenocarcinomas of the distal esophagus and GE junction with background intestinal metaplasia, and (3) adenocarcinomas of the distal esophagus and GE junction without background intestinal metaplasia.

Design.—Expression of PIgR and CDX2 in nonneoplastic mucosa, intestinal metaplasia, and adenocarcinomas was examined by immunohistochemistry in 42 cases: 14 gastric and 28 from the distal esophagus and GE junction, including 13 with esophageal or GE junction intestinal metaplasia.

Results.—PIgR and CDX2 were expressed in all cases of intestinal metaplasia. PIgR expression was positive in 40% of group 3 versus 77% of group 2 and 71% of gastric adenocarcinomas (P = .06), and the expression of CDX2 was similar in all tumor groups (80%–83%). Metastatic-positive lymph nodes were more frequent in PIgR-negative tumors (94% vs 58%, P = .01).

Conclusions.—PIgR is uniformly expressed in intestinal metaplasia and in a subgroup of adenocarcinomas of the distal esophagus, GE junction, and stomach. Esophageal and GE junction adenocarcinomas that do not express PIgR show more frequent lymph node metastasis, suggesting that lack of expression of PIgR identifies a subgroup of more aggressive adenocarcinomas.
Metastasizing Pleomorphic Adenoma of the Salivary Gland
Authors: Manucha Varsha , Ioffe Olga B.
Published: February 2021

Metastasizing pleomorphic adenoma of salivary glands is a group of rare tumors that are histologically identical to benign mixed tumors and that inexplicably metastasize. A review of the literature revealed that it usually occurs after multiple local recurrences, and the interval between diagnosis of primary pleomorphic adenoma and metastases ranges between 3 and 52 years. The most common site for metastasis is bone, followed by the head and neck and lung. No histologic or molecular parameters exist at the present time that could predict the development of metastasis in these neoplasms. Metastasectomy confers significant survival advantage over nonoperative treatment for localized and accessible metastases, but there is no definite treatment protocol available in cases of widespread metastases.
Paraproteins Are a Common Cause of Interferences With Automated Chemistry Methods
Authors: Yang Yusong , Howanitz Peter J. , Howanitz Joan H. , Gorfajn Helen , Wong Keung
Published: February 2021

Context.—Previous studies have shown that paraproteins caused spurious results on individual analytes including total bilirubin (TBIL), direct bilirubin (DBIL), or HDL-cholesterol (HDL-C). Studies demonstrating paraprotein interferences with multiple analytes measured by different analyzers have not been reported.

Objective.—To systemically investigate interferences of paraproteins on TBIL, DBIL, and HDL-C measured by the Roche MODULAR and the Olympus AU2700.

Design.—Eighty-eight serum specimens with monoclonal gammopathies were analyzed using the Roche MODULAR and the Olympus AU2700. Paraprotein interferences with the MODULAR and AU2700 were identified by abnormal absorbance curves and confirmed by results from the Ortho Vitros 950 or inconsistent laboratory information.

Results.—Spurious results occurred in 89 of 528 measurements; 29 specimens did not demonstrate any interferences whereas 26 specimens gave spurious results in 2 to 4 of the 6 assays. Paraprotein interferences caused spuriously high levels of TBIL in 4 sera measured by the MODULAR. In contrast, paraprotein interferences on DBIL were observed by at least 1 method in 44% (39/88) of sera assayed, occurring almost exclusively with the AU2700. Paraprotein interferences with HDL-C results were present in 35% of specimens assayed with the MODULAR and 16% of specimens assayed with the AU2700. In specimens with interferences, spuriously low AU2700 DBIL, MODULAR HDL-C, and AU2700 HDL-C results occurred with 28%, 90%, and 91% of specimens, respectively.

Conclusions.—We demonstrated that paraprotein interferences with TBIL, DBIL, and HDL-C are relatively common and provided explanations why these interferences occurred. Although it is difficult to predict which specimens cause interferences, spurious results appeared method and concentration dependent.
The Differential Diagnosis of Central Nervous System Tumors: A Critical Examination of Some Recent Immunohistochemical Applications
Authors: Edgar Mark A. , Rosenblum Marc K.
Published: February 2021

Context.—As we write, novel antibodies that may well alter the routine practice of surgical neuropathology are in development, characterization, and the early stages of clinical use. These will be used for purposes of tumor subclassification, as prognostic markers, as identifiers of potential therapeutic targets, and as predictors of treatment response.

Objective.—To provide for nonspecialists a critical assessment of the peer-reviewed literature (necessarily colored by our own experience) as it pertains to several immunohistochemical reagents that have been recently forwarded as adjuncts to the histologic typing of central nervous system tumors.

Data Sources.—We address in these pages only antibodies that are commercially available, that have been the subjects of multiple published series, and that we have had occasion to use in the course of everyday problem solving.

Conclusions.—Discussion concentrates on the use of 4 antibodies: BAF47 in the diagnosis of atypical teratoid/ rhabdoid tumor, OCT4 in intracranial germinoma, β-catenin in craniopharyngioma, and NeuN as a marker of neuronal differentiation in neuroepithelial neoplasms.
HER2 Testing in a Population-Based Study of Patients With Metastatic Breast Cancer Treated With Trastuzumab
Authors: O'Malley Frances P. , Thomson Tom , Julian Jim , Have Cherry , Cosby Roxanne , Gelmon Karen , Andrulis Irene , Whelan Tim
Published: February 2021

Context.—The development of trastuzumab has led to new therapeutic strategies for patients with breast cancer. Trastuzumab has been shown to only be effective in those patients whose cancers are HER2 positive by either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH).

Objective.—To determine the accuracy of HER2 testing in 2 provinces in Canada.

Design.—Patients with metastatic breast cancer diagnosed between 1999 and 2002 who were HER2 positive in the local laboratories were included in this study. All cases were retested centrally, by IHC (using 4 methods) and FISH. In addition, 205 locally reported HER2-negative metastatic breast cancer cases were retested centrally.

Results.—Concordance between the 505 local IHC-positive cases with central IHC testing varied between 79.3% and 89.6% depending on the IHC method and scoring method used. HER2 gene amplification by FISH was present in 86.1% of local IHC-positive cases. Concordance between the 205 local IHC-negative tumors with central testing ranged between 94.8% and 100% for IHC and was 98.5% for FISH.

Conclusions.—This study demonstrated that locally reported HER2-negative results were highly accurate, but less accuracy was demonstrated with local HER2-positive results. These results emphasize the need for participation in a quality assurance program.
DNA Pyrosequencing–Based Identification of Pathogenic Candida Species by Using the Internal Transcribed Spacer 2 Region
Authors: Boyanton, Jr Bobby L. , Luna Ruth Ann , Fasciano Lea R. , Menne Kyle G. , Versalovic James
Published: February 2021

Context.—The incidence of infections due to diverse Candida species is increasing, with correspondingly different antifungal susceptibility patterns. Routine yeast identification methods cause significant delays in appropriate patient management.

Objective.—A DNA pyrosequencing strategy was evaluated for identification of pathogenic Candida species associated with human infections.

Design.—Clinical (n = 51) and commercial (n = 9) Candida isolates were identified in a blinded, parallel study consisting of routine fungal cultures and biochemical analyses in comparison with DNA pyrosequencing.

Results.—DNA pyrosequencing yielded species-level identification of all 60 Candida isolates, and sequencing interpretations agreed in all cases with results of biochemical and morphologic testing. Different Candida species were identified, such as C albicans, C dubliniensis, C glabrata, C guilliermondii, C krusei, C lusitaniae, C parapsilosis, and C tropicalis. Automated and manual approaches to DNA sequence interpretation, each coupled with the Identifire identification software, demonstrated 100% agreement with respect to Candida species identification. Twenty-one isolates yielded intraspecies DNA sequence differences (90%–98% nucleic acid sequence identity) by automated interpretation. Sequence differences resulted from single-nucleotide polymorphisms or single-base additions/deletions, in addition to interpretative challenges in homopolymeric tracts.

Conclusion.—DNA pyrosequencing coupled with automated DNA sequence alignment provides a practical approach for accurate and timely identification of Candida pathogens. Relatively rapid and facile genotypic studies by DNA pyrosequencing matched the effectiveness of extensive biochemical/morphologic studies for yeast identification.
The Utility of p16Ink4a in Discriminating Between Cervical Intraepithelial Neoplasia 1 and Nonneoplastic Equivocal Lesions of the Cervix
Authors: Redman Rachel , Rufforny Irina , Liu Chen , Wilkinson Edward J. , Massoll Nicole A.
Published: February 2021

Context.—The protein p16Ink4a is overexpressed in cervical lesions associated with high-risk human papillomavirus (HPV) subtypes 16 and 18, but not in low-risk HPV subtypes 6 and 11 or non–HPV-associated cervical lesions.

Objective.—To determine whether p16Ink4a expression in equivocal cervical lesions helps distinguish atypical non-HPV changes from HPV-related changes.

Design.—One hundred ninety-one cervical lesions, including 81 cervical intraepithelial neoplasia 1, 52 squamous metaplasia, 33 cellular features suggestive of HPV-related change, 9 reserve cell hyperplasia, 4 microglandular hyperplasia, and 12 inflammatory cervicitis, were randomly selected from archival cervical biopsy specimens. All 191 samples were studied with p16Ink4a (JC8 monoclonal antibody). Reactivity for p16Ink4a was scored on a 3-tier system as follows: negative, 0% to 5% cells reactive; focal/scattered positive, greater than 5% and less than or equal to 80% cells reactive; diffuse positive, greater than 80% cells reactive. Reactivity was based on normal/reactive cervical specimens where anti-p16 antibody was negative/weakly expressed in non–cervical epithelial cells. Cervical intraepithelial neoplasia 1 lesions not reactive for p16Ink4a were investigated for the presence of high-risk HPV by real-time polymerase chain reaction.

Results.—No p16Ink4a reactivity was detected in the cervical lesions associated with atypical non-HPV change. Eleven of the cervical intraepithelial neoplasia 1 lesions showed focal/scattered reactivity expression for p16Ink4a, and 19 of the CIN 1 lesions had diffuse reactivity. Fifty of 51 of the CIN 1 lesions negative for p16Ink4a were real-time polymerase chain reaction negative for the presence of high-risk HPV; 1 was real-time polymerase chain reaction positive for high-risk HPV.

Conclusions.—The data support the routine use of p16Ink4a immunohistochemical evaluation of cervical biopsy specimens for better discrimination of non–HPV-associated lesions from HPV-related lesions.
Pituicytoma: Characterization of a Unique Neoplasm by Histology, Immunohistochemistry, Ultrastructure, and Array-Based Comparative Genomic Hybridization
Authors: Phillips Joanna J. , Misra Anjan , Feuerstein Burt G. , Kunwar Sandeep , Tihan Tarik
Published: February 2021

The pituicytoma is a rare neoplasm whose histogenesis is debated partly because of the diversity of tissue types present in the sellar region. In this article we illustrate the characteristic histologic, immunohistologic, and ultrastructural features of this unique neoplasm. Furthermore, we use array-based comparative genomic hybridization to demonstrate a unique pattern of genomic copy number aberrations in pituicytomas. Tumors were composed of bipolar, spindle cells that were immunopositive for S100, vimentin, and Bcl-2 and immunonegative for synaptophysin, chromogranin, and glial fibrillary acidic protein. Ultrastructural analysis was remarkable for absence of secretory granules. Array comparative genomic hybridization demonstrated genomic copy number imbalances, including losses on chromosome arms 1p, 14q, and 22q and gains on 5p. This pattern of genetic changes only partially overlaps with the genomic alterations reported in pituitary adenomas. In summary, our data suggest that pituicytomas are a unique subset of tumors of the sellar region.
Adult Testicular Granulosa Cell Tumor: A Review of the Literature for Clinicopathologic Predictors of Malignancy
Authors: Hanson Joshua Anspach , Ambaye Abiy B.
Published: February 2021

Adult testicular granulosa cell tumors are rare sex cord–stromal tumors of which only 28 have been previously reported. As compared with their ovarian counterparts, these tumors may follow a more aggressive course because the proportion of malignant cases is higher. To date, there are no clinical or pathologic features that definitively predict malignancy. We reviewed all prior case reports for features that may predict their malignant potential. Tumor size greater than 5.0 cm is the only feature statistically associated with malignancy. Mitotic count, tumor necrosis, patient age, and the presence of gynecomastia do not, at present, predict benign versus malignant behavior.
Increased Levels of Nuclear Factor κB and Fos-Related Antigen 1 in Lung Tissues From Patients With Acute Respiratory Distress Syndrome
Authors: Fudala Rafal , Allen Timothy Craig , Krupa Agnieszka , Cagle Philip T. , Nash Sandra , Gryczynski Zygmunt , Gryczynski Ignacy , Kurdowska Anna K.
Published: February 2021

Context.—Both nuclear factor κB and Fos-related antigen 1 have been implicated in the pathogenesis of inflammatory lung diseases, including acute lung injury/acute respiratory distress syndrome.

Objective.—To evaluate lung tissues from patients with acute respiratory distress syndrome for presence of nuclear factor κB and Fos-related antigen 1.

Design.—Lung tissue sections from 5 patients with acute respiratory distress syndrome and sections of normal lung tissues of 4 patients were stained with antibodies against epithelial cell marker (surfactant protein B) and nuclear factor κB or Fos-related antigen 1. Samples were analyzed using confocal laser microscopy.

Results.—We have detected significantly increased levels of activated nuclear factor κB and Fos-related antigen 1 in lung tissues from patients with acute respiratory distress syndrome compared with control tissues, suggesting that these transcription factors undergo activation in lungs of patients suffering from acute respiratory distress syndrome.

Conclusions.—Our data demonstrate that activated nuclear factor κB and Fos-related antigen 1 are elevated in epithelial cells in lung tissues of patients with acute respiratory distress syndrome.
Four Years' Experience With an Interlaboratory Comparison Program Involving First-Trimester Markers of Down Syndrome
Authors: Palomaki Glenn E. , Knight George J. , Lambert-Messerlian Geralyn , Canick Jacob A. , Haddow James E.
Published: February 2021

Context.—We initiated a voluntary, self-funded interlaboratory comparison program in the fall of 2005 because no proficiency testing program was available to laboratories in North America offering first-trimester, combined serum and ultrasound, Down syndrome screening.

Objectives.—To evaluate the first 4 years of the interlaboratory comparison program against stated goals, to identify areas of concern, and to create new initiatives as indicated.

Design.—Five serum samples are distributed 3 times a year to be tested for pregnancy-associated plasma protein A, human chorionic gonadotropin or its β subunit, and dimeric inhibin-A; participants convert these results into multiples of the median. Patient histories include nuchal translucency information that enables the calculation of the risk of Down syndrome. Also included are educational components linked to interlaboratory comparison program results. Assessment of integrated (first- and second-trimester markers) risks is accomplished by having participants combine interlaboratory comparison program results with their results from a second-trimester proficiency testing program administered by the College of American Pathologists.

Results.—The precision profile for pregnancy-associated plasma protein A shows decreasing coefficients of variation with increasing pregnancy-associated plasma protein A concentrations and multiples of the median (25% to 11% and 30% to 15%, respectively). In contrast, coefficients of variation are a relatively constant 12% throughout the entire range of human chorionic gonadotropin results. On a logarithmic scale, the median coefficient of variation of the risk of Down syndrome is 9%.

Conclusions.—Participants in the interlaboratory comparison program reliably measure analytes, compute multiples of the median, and calculate consistent Down syndrome risks. Assays for the measurement of pregnancy-associated plasma protein A are not standardized and are less precise than those for human chorionic gonadotropin. Participants calculate reliable median equations given sonographer-specific sets of paired crown-rump length and nuchal translucency measurements.
Ultrasound Physics and Instrumentation for Pathologists
Authors: Lieu David
Published: February 2021

Context.—Interest in pathologist-performed ultrasound-guided fine-needle aspiration is increasing. Educational courses discuss clinical ultrasound and biopsy techniques but not ultrasound physics and instrumentation.

Objective.—To review modern ultrasound physics and instrumentation to help pathologists understand the basis of modern ultrasound.

Data Sources.—A review of recent literature and textbooks was performed.

Conclusions.—Ultrasound physics and instrumentation are the foundations of clinical ultrasound. The key physical principle is the piezoelectric effect. When stimulated by an electric current, certain crystals vibrate and produce ultrasound. A hand-held transducer converts electricity into ultrasound, transmits it into tissue, and listens for reflected ultrasound to return. The returning echoes are converted into electrical signals and used to create a 2-dimensional gray-scale image. Scanning at a high frequency improves axial resolution but has low tissue penetration. Electronic focusing moves the long-axis focus to depth of the object of interest and improves lateral resolution. The short-axis focus in 1-dimensional transducers is fixed, which results in poor elevational resolution away from the focal zone. Using multiple foci improves lateral resolution but degrades temporal resolution. The sonographer can adjust the dynamic range to change contrast and bring out subtle masses. Contrast resolution is limited by processing speed, monitor resolution, and gray-scale perception of the human eye. Ultrasound is an evolving field. New technologies include miniaturization, spatial compound imaging, tissue harmonics, and multidimensional transducers. Clinical cytopathologists who understand ultrasound physics, instrumentation, and clinical ultrasound are ready for the challenges of cytopathologist-performed ultrasound-guided fine-needle aspiration and core-needle biopsy in the 21st century.
An Update on Reporting Histopathologic Prognostic Factors in Melanoma
Authors: Ivan Doina , Prieto Victor G.
Published: February 2021

Context.—Accurate diagnosis of melanocytic lesions is essential for the adequate clinical management of patients. Thus, thorough reporting of histopathologic parameters, especially in the initial biopsies, is a critical component of both diagnosis and staging.

Objective.—o review current data on histopathologic prognostic factors for melanoma, with special emphasis on their use and applicability to clinical practice. Special attention is focused on the criteria highlighted by the new 2009 version of The American Joint Committee on Cancer (AJCC) system of melanoma staging and classification.

Data Sources.—Published peer-reviewed literature and personal experience of the authors.

Conclusions.—When reporting melanoma, we recommend that a template be provided, including all the histologic parameters that have been proved significant in determining the tumor staging and prognosis of a patient. The template may also include other details that may be helpful in further analysis of potential complete excisional biopsies or metastatic lesions, such as predominant type of tumor cells, presence or absence of desmoplastic component, or associated benign melanocytic lesions. Although there are several drawbacks in reporting some of these histopathologic parameters (interobserver variability, occasional lack of a perfectly reproducible method for quantifying these criteria), we suggest that at least the essential histopathologic parameters highlighted by the newest version of the AJCC system for melanoma staging and classification should be included in the report.