bluuebunny/crossref_metadata_2025 huggingface dataset:
IMAGERY, PERSONALITY AND INJURY PERCEPTION IN SPORT – MEDIATING THE EFFECT OF INJURY PERCEPTION AND IMAGERY
Authors: Budnik-Przybylska Dagmara , Karasiewicz Karol , Kukiełko Tatiana
Published: February 2021

Imagery is an often used technique in psychological mental training and here also during rehabilitation. Imagery ability enhances imagery use. The perception of injury but also individual differences themselves influence the rehabilitation outcome. The first purpose of the study was to examine the mediation effect of injury perception between general imagery and rehabilitation imagery. Our second aim was to examine the mediating effects of the general ten dency to employ imagery within the relationship between personality and the imagery of rehabilitation itself.

The studyinvolved 56 athletes (37 men and 19 women) suffered a physical injury. The respondents were asked to provide demographic information and then to complete following questionnaires: The Athletic Injury ImageryQuestionnaire-AIIQ-2, (Sordoni et al., 2002), The Imagination in Sport Questionnaire (Budnik-Przybylska, 2014) – short version, and Blecharz’s Scale of Perception of Injury in Sport (SPUwS) (Blecharz, 2008). Series of mediation analyses were performed to estimate the strength of the indirect relationship between the general tendency to use imagery and the use of imagery in rehabilitation.

It was fund that the general tendency to use imagery turned out to
have a strong direct effect on rehabilitation imagery. Reflection and
seeking positive sides turned out to be a mediator between general
tendency to use imagery and all rehabilitation imagery dimensions.
Reflection has the strongest effect between the general tendency
to use imagery and cognitive specific imagery. General tendency
to use imagery mediates the relationship between personality and
imagery of rehabilitation. Some personality traits also influence
directly imagery of rehabilitation.

Our findings have revealed that the general tendency to use ima - gery may strengthen the relationship between personality and rehabilitation imagery. It may help to adjust the methods which might positively influence the rehabilitation process.
HOW PURE IS PURE ALEXIA? A NEUROPSYCHOLOGICAL ANALYSIS OF A CASE SERIES OF PATIENTS WITH ALEXIA DUE TO LEFT HEMISPHERIC STROKES
Authors: Leśniak Marcin M. , Zielińska Aleksandra J. , Czepiel Wojciech , Seniów Joanna
Published: February 2021

The aim of this study was to analyze a case series with acquired alexia after stroke within the posterior areas of the left hemisphere, in the context of the current criteria for pure alexia and their relevance to the set of symptoms observable in clinical practice.

Seven patients with ischemic strokes and an initial diagnosis of pure alexia were enrolled for detailed analysis. The evaluation consisted of neuropsychological assessment in the form of standardized tests and non-standardized reading tasks, while oculomotor activity during reading was measured. Language functions, visual object and space perception, verbal and nonverbal memory, and visuospatial constructional ability were among the domains assessed.

In five of the participants, pure alexia was recognized based on sig- nificant and specific discrepancies between test scores, indicating primary abnormalities in the visual processing of letter strings as a basic mechanism of the disorder. In most of the patients, coexisting cognitive deficits were revealed; however, these were dispropor- tionately milder and less functionally significant than reading disturbances.

Pure alexia is a relatively rare disorder after a stroke, but it considerably affects the quality of everyday independent functioning. Its clinical characteristics in practice rarely meet all the criteria proposed in the subject literature. The differential diagnosis of this form of alexia and other reading disorders requires detailed clinical analysis.
Personnel security in Police Forces
Authors: Gwardyński Robert , Winiarska Agnieszka
Published: February 2021

Personnel security in Police Forces is of utmost importance for this institution since it contributes to the efficient implementation by the latter of its statutory tasks related to protecting people, and to maintaining public order and security. In order to find new methods of further development and training of the police, researchers should take into account the issue of police personnel safety understood as a certain state of affairs and a process. The authors of this publication define the term of personnel safety and point out to the reader its importance for the efficiency of activities undertaken by the Police.
Security in local communities from the perspective of the Police
Authors: Gwardyński Robert
Published: February 2021

The Police constitute a major element in the state security system. Their operation has both a national and local dimension. The Police have an impact on a local community’s security, ensuring the safety of people, their health, life, property, as well as maintaining public safety and order. This article aims to indicate the areas of the Police’s operation that result in an improvement of the residents’ safety and an increase in their sense of security.
Peculiarities of Portland Cement Clinker Synthesis in the Presence of a Significant Amount of SO3 in a Raw Mix
Authors: Sheshukov Oleg , Mikheenkov Michael
Published: February 2021

Due to the depletion of the raw material base and a technogenic materials addition into a raw mix for the Portland cement clinker synthesis, sulfur and its oxides amount in a raw mix increases. According to literature the Portland cement clinker synthesis in the presence of a sulfur oxides significant amount is difficult. As the content of SO3 in the raw mix increases the amount of C2S increases while C3S and C3A amount decrease. With an equal total content of C2S and C3S in the clinker their ratio C3S/C2S decreases with an increased content of SO3. These factors lead to a deterioration in the Portland cement clinker quality. The clinker formation reactions thermodynamic analysis and some experimental studies allow determining reasons for the Portland cement clinker quality deterioration. It was found that the presence significant amount of a SO3 in the raw mix the synthesis in solid phase of low-basic C4A3S¯ (ye’elimite) is the thermodynamically preferred rather than high-basic C3A and C4AF. As a result, excess and crystallized free lime inhibits the C3S synthesis through the liquid phase. The experimental studies result helped to develop a methodology for calculating the composition of a raw mix from materials with significant amount of SO3. It allows to reduce the SO3 negative effect on the Portland cement clinker synthesis and to obtain high-quality Portland cement.
Medical Humanism in Neurosurgery
Authors: Al-Ghanem Rajab
Published: February 2021

Patient-centered care means organizing health care that is respectful and responsive to the patient needs, preferences, and values, and ensuring that the patient values guide all clinical decisions. Teaching of medical humanism becomes a necessity to help neurosurgery residents in their future practice to do what they are already doing but in a more humanistic and empathic attitudes. A training programme to teach medical humanism core values through lectures, role modeling, and training in interpersonal skills, literature and humanities study can improve attitudes and behaviors. A set of 10 medical humanism values relevant to contemporary challenges, research, and practice of neurosurgery practice that can help residents and practicing physicians to maintain humanism behaviors in their practice are presented. A humanistic neurosurgeon provide a skilled, compassionate, and empathic care to her/his patients, and demonstrates respect for their values, autonomy, beliefs and cultural backgrounds. Neurosurgery is an apprenticeship profession, where humanism values can be taught and behaviors associated with humanism can be learned.
Non-Formal Education as a Foundation for Active Learning
Authors: Alonso Terrazas Marín Roy , Linda Alvarado Espinoza Brenda
Published: February 2021

This chapter will include several examples of how non-formal education serves as a foundation for active learning. It will relate how non-formal education organizations such as the scouting movement through the World Organization of the Scout Movement (WOSM), works to engage young people to be developed holistically. It will also mention non-formal active learning strategies and their relation to semiotic and esthetic stimuli. The role of semiotics in non-formal active learning will be exemplified, and the article will mention how self-commitment may be created when using non-formal education and active learning. Finally, it will be discussed how dialogism takes part in this process.
Ethics in Laboratory Medicine: An Overview of Considerations for Ethical Issues
Authors: Aggarwal Neerja , Kumar Kare Pawan , Kumar Datta Sudip
Published: February 2021

Several ethical issues exist within the diagnostic medical laboratory. The major ethical challenges such as; consent, confidentiality, codes of conduct, conflict of interest, lab utilisation, proficiency, and direct access testing are some times more prevalent in resource-limited settings. Presently, decisions regarding diagnosis and patient’s treatment are commonly taken on the basis of outcomes and interpretations of laboratory test results. Therefore, ethics plays a significant role in laboratory medicine. Apart from the lab results, laboratory staff is another important aspect of the laboratory. Hence, it is highly recommended that knowledge of ethics helps to protect confidence; operational integrity, capability, impartiality, and safety of the staff. Many countries and their professional societies have developed policies and guidance material with regard to ethical issues in the area of laboratory medicine. The organizations specially; International of federation of clinical chemistry (IFCC), American Association of Clinical Chemistry (AACC) and International Organization for Standardization (ISO) have defined ethical recommendations for clinical laboratories. They are, in general, outlined the responsibilities of laboratory professionals towards their profession, the patient, and the society. However, implication of ethical standards and guidelines are vary between different cultures, geographies, and according to available resources. In this chapter, we have mentioned the ethical consideration of IFCC, AACC and ISO 15189:2012 with regard to laboratory medicine and also addressed the various ethical issues that arises day to day in laboratory medicine in the current scenario.
Immunohistochemical Expression of Estrogen and Progesterone Receptors in Primary Pulmonary Neuroendocrine Tumors
Authors: Sica Gabriel , Wagner Patrick L. , Altorki Nassar , Port Jeffrey , Lee Paul C. , Vazquez Madeline F. , Saqi Anjali
Published: February 2021

Context.—Lung and breast carcinomas are among the most prevalent cancers. Advances in cancer therapies can provide survival benefit and be potentially curative, even in metastatic disease. Due to the high prevalence of these carcinomas, it is not unusual to encounter lung nodule(s) in a patient with breast carcinoma, and distinguishing between primary and metastatic disease is critical for management/treatment. Occasionally neuroendocrine differentiation is present in breast carcinoma, making its distinction from pulmonary/nonpulmonary neuroendocrine tumors in the lung difficult.

Objective.—To assess estrogen and progesterone receptor expression in the entire spectrum of pulmonary neuroendocrine tumors.

Design.—Seventy-one neuroendocrine neoplasms including typical carcinoids (42), atypical carcinoids (7), small cell carcinomas (14), large cell neuroendocrine carcinomas (2), and combined small cell carcinomas (6) were evaluated for estrogen and progesterone receptors. Mammary and non–small cell lung carcinomas were also stained for comparison.

Results.—The entire spectrum of neuroendocrine neoplasms demonstrated focal to diffuse estrogen (typical carcinoid, 23; atypical carcinoid, 6; small cell carcinoma, 8; large cell neuroendocrine carcinoma, 2; combined small cell carcinoma, 4) and progesterone (typical carcinoid, 11; atypical carcinoid, 2; small cell carcinoma, 7; large cell neuroendocrine carcinoma, 0; combined small cell carcinoma, 2) expression. There was no correlation between sex and estrogen/progesterone status. Estrogen and progesterone staining were also noted in endothelial cells. Relative to neuroendocrine carcinomas, mammary carcinomas expressed estrogen and progesterone more frequently. Non–small cell carcinomas had greater and similar immunoreactivity for estrogen and progesterone, respectively.

Conclusions.—Although estrogen and progesterone receptor staining is frequently associated with breast and gynecologic primaries, it can also be observed in “nontarget” organs. Therefore, presence of estrogen and/or progesterone expression in neuroendocrine tumors involving the lung should not exclude a primary pulmonary neoplasm.
The Role of KRAS Mutation Testing in the Management of Patients With Metastatic Colorectal Cancer
Authors: Monzon Federico A. , Ogino Shuji , Hammond M. Elizabeth H. , Halling Kevin C. , Bloom Kenneth J. , Nikiforova Marina N.
Published: February 2021

Context.—KRAS mutations can be detected in approximately 30% to 40% of all patients with colorectal cancer. Several recent studies have shown that patients with KRAS mutations in codons 12 or 13 in metastatic tumors do not benefit from anti–epidermal growth factor receptor therapy with cetuximab or panitumumab.

Objective.—To review the literature on the role of KRAS mutation testing for management of patients with metastatic colorectal cancer and to discuss testing strategies.

Data Sources.—This review is based on published, peer-reviewed literature; available information from medical organizations (eg, National Comprehensive Cancer Network, American Society of Clinical Oncology, College of American Pathologists); and information from clinical laboratories conducting KRAS mutation analysis.

Conclusions.—Multiple methods for detecting KRAS mutations in colorectal tumors are available, and all methods in current clinical use appear to have adequate clinical sensitivity for predicting a lack of response to cetuximab and panitumumab. Pathologist expertise is essential to quality KRAS testing and to determining effective treatment for patients with metastatic colorectal cancer.
Update on Selected Salivary Gland Neoplasms
Authors: McHugh Jonathan B. , Visscher Daniel W. , Barnes E. Leon
Published: February 2021

Context.—Malignancies of the salivary gland are uncommon and account for 0.3% of all malignancies. In addition to their rarity, diagnosing these tumors can be challenging given the histologic overlap among various subtypes, their morphologic heterogeneity, and the recent recognition of new entities.

Objective.—To provide an overview of 4 salivary gland malignancies that we often see in consultation, with a focus on essential diagnostic features and the importance of reporting pertinent diagnostic information to ensure appropriate clinical management.

Data Sources.—Review of the literature, supplemented by the personal experience of the authors, which is based on their respective institutional experiences and consultation services.

Conclusions.—When diagnosing carcinoma ex pleomorphic adenoma, pathologists must report several important pieces of information to allow for optimal clinical management. In addition to histologic subtype, the degree of differentiation as well as the degree of invasion, if any, must be reported because all have prognostic relevance. Polymorphous low-grade adenocarcinoma can be a challenging diagnosis on biopsy specimens. Evaluation of the tumor periphery and nuclear features should lead to the correct diagnosis in most cases. Salivary duct carcinoma is an aggressive malignancy characterized by histologic resemblance to breast carcinoma, high-grade cytologic features, and expression of androgen receptor. Benign and malignant myoepithelial neoplasms have a broad morphologic spectrum, and immunohistochemistry is important in reaching the correct diagnosis.
Changes in Participant Performance in the “Test-Taking” Environment: Observations From the 2006 College of American Pathologists Gynecologic Cytology Proficiency Testing Program
Authors: Hughes Jonathan H. , Bentz Joel S. , Fatheree Lisa , Souers Rhona J. , Wilbur David C.
Published: February 2021

Context.—Because the consequences of making an interpretive error on a proficiency test are more severe than those made on an educational challenge, the same slide may exhibit different performance characteristics in the 2 different settings.

Objective.—The results of the 2006 College of American Pathologists Gynecologic Cytology Proficiency Testing Program (PAP PT) provide the opportunity to compare the performance characteristics of the field-validated slides in the PAP PT environment with those of the same graded slides in the College of American Pathologists Educational Program (formerly known as the PAP Program).

Design.—All participant responses for negative (category B) and positive (categories C and D) validated slides in the 2006 PAP PT were used to determine the error rates of participants. These data were compared with the historical error rates observed on the same validated slides in the graded PAP Program.

Results.—The performance characteristics of the slides in the PAP PT environment were statistically different from those in the Educational PAP Program. In proficiency testing both cytotechnologists (P < .001) and pathologists (P = .002) were more likely to interpret validated category B slides as category C or D and less likely to interpret category C slides as category B (P < .001). These differences were more pronounced among cytotechnologists than among pathologists.

Conclusions.—In the test-taking environment, both cytotechnologists and pathologists appear to use a defensive strategy that results in “upgrading” of category B slides. This trend is more pronounced among cytotechnologists.
Pancreatic Intraepithelial Neoplasia and Pancreatic Tumorigenesis: Of Mice and Men
Authors: Ottenhof Niki A. , Milne Anya N. A. , Morsink Folkert H. M. , Drillenburg Paul , ten Kate Fiebo J. W. , Maitra Anirban , Offerhaus G. Johan
Published: February 2021

Context.—Pancreatic cancer has a poor prognosis with a 5-year survival of less than 5%. Early detection is at present the only way to improve this outlook. This review focuses on the recent advances in our understanding of pancreatic carcinogenesis, the scientific evidence for a multistaged tumor progression, and the role genetically engineered mouse models can play in recapitulating the natural course and biology of human disease.

Objectives.—To illustrate the stepwise tumor progression of pancreatic cancer and genetic alterations within the different stages of progression and to review the findings made with genetically engineered mouse models concerning pancreatic carcinogenesis.

Data Sources.—A review of recent literature on pancreatic tumorigenesis and genetically engineered mouse models.

Conclusions.—Pancreatic cancer develops through stepwise tumor progression in which preinvasive stages, called pancreatic intraepithelial neoplasia, precede invasive pancreatic cancer. Genetic alterations in oncogenes and tumor suppressor genes underlying pancreatic cancer are also found in pancreatic intraepithelial neoplasia. These mutations accumulate during progression through the consecutive stages of pancreatic intraepithelial neoplasia lesions. Also in genetically engineered mouse models of pancreatic ductal adenocarcinoma, tumorigenesis occurs through stepwise progression via consecutive mouse pancreatic intraepithelial neoplasia, and these models provide important tools for clinical applications. Nevertheless differences between mice and men still remain.
Current Concepts in Cervical Pathology
Authors: Park Kay J. , Soslow Robert A.
Published: February 2021

Context.—The correct diagnosis and reporting of cervical in situ and invasive carcinoma are essential for the appropriate clinical management of patients with human papillomavirus–associated disease.

Objectives.—To review common mistakes made in the diagnosis of cervical dysplasia and invasive carcinoma, describe variants and benign mimics of high-grade squamous intraepithelial lesion and adenocarcinoma in situ, and discuss available ancillary studies that can be useful in making the distinctions as well as to review important factors related to prognosis that should be included in the pathology report.

Data Sources.—Review of current literature.

Conclusions.—There are many mimics and variants of cervical squamous and glandular lesions that can be resolved with ancillary studies and careful histologic examination. Prognostically important features, such as tumor size, presence of vascular invasion, and margin status, should always be included in the pathology report.
Histopathologic Features and Clinical Outcomes in 71 Cases of Bladder Diverticula
Authors: Tamas Ecaterina F. , Stephenson Andrew J. , Campbell Steven C. , Montague Drogo K. , Trusty; Dante C. , Hansel Donna E.
Published: February 2021

Context.—Bladder diverticula often come to clinical attention when complications or malignancy occur, although limited information is available regarding histopathologic features and clinical outcomes.

Objective.—To identify the morphologic findings, neoplastic subtypes, and clinical outcomes by reviewing all bladder diverticula that underwent pathologic sampling for primary diverticular processes at the Cleveland Clinic.

Design.—Hematoxylin-eosin slides from 71 cases of bladder diverticula were reviewed. Clinicopathologic features and patient outcomes were obtained from a retrospective review of patient records.

Results.—Patient ages ranged from 1 to 81 years (mean, 55 years), and the ratio of males to females was 68:3. Diverticular size ranged from 1 to 18 cm (mean, 5.3 cm) and often involved the lateral walls (38/71; 54%). Neoplastic changes were present in half of cases (36/71; 51%), including both noninvasive (16/36; 44%) and invasive (20/ 36; 56%) carcinoma. Of the invasive carcinomas, less-common subtypes included small cell carcinoma (n = 3), squamous cell carcinoma (n = 2), and adenocarcinoma (n = 1); 9 cases were pT1 (45%) and 11 cases were pT3 (55%). Follow-up for patients with benign findings demonstrated no subsequent neoplastic bladder disease. Patient follow-up for neoplastic diverticula (median, 27 months) demonstrated 4 cases of local recurrence and 3 cases of subsequent metastases. Of 9 patients with pT1 disease, only 1 patient (11%) developed subsequent metastases, whereas patients with pT3 disease demonstrated a higher rate of both local recurrence (3/11; 27%) and subsequent metastases (2/11; 18%).

Conclusions.—Patients with invasive carcinoma in diverticula have an increased frequency of less-common bladder cancer subtypes, and those with pT3 disease are at increased risk for subsequent progression.
Papillary Neoplasms of the Breast: A Review
Authors: Ueng Shir-Hwa , Mezzetti Thomas , Tavassoli Fattaneh A.
Published: February 2021

Context.—Interpretation of papillary lesions of the breast remains a challenging task because of the wide morphologic spectrum encountered in the benign, atypical, and malignant subtypes. Data on clinical significance and outcome of papillary lesions, with superimposed atypia or areas similar to ductal carcinoma in situ partially replacing the benign elements, are sparse. Furthermore, complete excision of even a fully developed papillary carcinoma confined to a dilated or cystic duct is associated with an excellent prognosis, whereas a complex papilloma extending into multiple branches of a duct may ultimately recur as a carcinoma because of incomplete excision of microscopic foci. This makes an outcome-based classification difficult.

Objective.—An arbitrary yet practical approach to classification is outlined, with discussion of methods to circumvent the various diagnostic difficulties. The limitations in precise diagnosis of papillary lesions in aspirates are addressed, and the implications of finding papillary lesions in core biopsies are discussed. Although the focus is on intraductal lesions, associated invasive carcinomas and invasive micropapillary carcinoma are also presented.

Data Sources.—The literature on papillary lesions and invasive micropapillary carcinoma is reviewed.

Conclusions.—It would be prudent to completely excise any papillary lesion that has not been entirely removed by the initial core biopsy. The optimal management of localized papillary lesions is complete excision with a small rim of uninvolved breast tissue without any prior needle instrumentation if and when the papillary nature can be determined by imaging. Thus managed, most of these lesions behave indolently, and outcome is usually excellent.
Laboratory-Guided Detection of Disease Outbreaks: Three Generations of Surveillance Systems
Authors: Sintchenko Vitali , Gallego Blanca
Published: February 2021

Context.—Traditional biothreat surveillance systems are vulnerable to incomplete and delayed reporting of public health threats.

Objective.—To review current and emerging approaches to detection and monitoring of biothreats enabled by laboratory methods of diagnosis and to identify trends in the biosurveillance research.

Data Sources.—PubMed (1995 to December 2007) was searched with the combined search terms “surveillance” and “infectious diseases.” Additional articles were identified by hand searching the bibliographies of selected papers. Additional search terms were “public health,” “disease monitoring,” “cluster,” “outbreak,” “laboratory notification,” “molecular,” “detection,” “evaluation,” “genomics,” “communicable diseases,” “geographic information systems,” “bioterrorism,” “genotyping,” and “informatics.” Publication language was restricted to English. The bibliographies of key references were later hand searched to identify articles missing in the database search. Three approaches to infectious disease surveillance that involve clinical laboratories are contrasted: (1) laboratory-initiated infectious disease notifications, (2) syndromic surveillance based on health indicators, and (3) genotyping based surveillance of biothreats. Advances in molecular diagnostics enable rapid genotyping of biothreats and investigations of genes that were not previously identifiable by traditional methods. There is a need for coordination between syndromic and laboratory-based surveillance. Insufficient and delayed decision support and inadequate integration of surveillance signals into action plans remain the 2 main barriers to efficient public health monitoring and response. Decision support for public health users of biosurveillance alerts is often lacking.

Conclusions.—The merger of the 3 scientific fields of surveillance, genomics, and informatics offers an opportunity for the development of effective and rapid biosurveillance methods and tools.
Chromosomal 3 and 8 Status Within Hepatic Metastasis of Uveal Melanoma
Authors: Singh Arun D. , Tubbs Raymond , Biscotti Charles , Schoenfield Lynn , Trizzoi Pierre
Published: February 2021

Context.—Several studies have evaluated clinical, histopathologic, cytogenetic, and molecular prognostic variables in uveal melanoma. However, it is not known whether the primary tumor cells maintain these aggressive attributes at the metastatic sites.

Objective.—To determine the status of chromosomes 3 and 8q and c-myc amplification using fluorescence in situ hybridization on hepatic metastatic lesions of primary uveal melanoma.

Design.—Ten patients with uveal melanoma with needle core biopsy–confirmed hepatic metastasis. Representative paraffin blocks were selected based on review of hematoxylin-eosin–stained sections. Fluorescence in situ hybridization was performed for detection of monosomy 3 and amplification at the 8q24 MYC locus using standard methods. The tricolor chromosome enumeration probe 8 (CEP8)/ IGH/MYC and the Urovysion probe consisting of CEP3, CEP7, CEP17, and 9P21 probes were used. A total of 200 interphase cells were scored.

Results.—Hepatic metastasis was confirmed in each case by needle core biopsy. Fluorescence in situ hybridization analysis revealed chromosome 3 monosomy in 5 of the 8 cases that could be satisfactorily evaluated. Aneusomy of chromosome 8 was observed in 2 cases. MYC amplification was observed in 5 samples. In a single case where the primary tumor was treated by enucleation, the chromosomal monosomy 3 and aneusomy of chromosome 8 were present both in the primary tumor and its hepatic metastatic lesion.

Conclusions.—The presence of cytogenetic changes within the metastatic lesions confirms that chromosome 3 monosomy and aneusomy of chromosome 8 are not just markers of metastatic potential of the primary tumor but are also present within the hepatic metastatic lesions.
Idiopathic Fibroinflammatory Disease of the Face, Eyelids, and Periorbital Membrane With Immunoglobulin G4–Positive Plasma Cells
Authors: Mehta Manisha , Jakobiec Frederick , Fay Aaron
Published: February 2021

Progressive sclerosing orbital pseudotumors are a subset of usually primary and localized idiopathic fibroinflammatory disorders. We report on a 66-year-old man who developed this condition along the facial tissue planes with extension into the orbit and preferential involvement of the periorbital membrane. Fibrocollagenous tissue with scattered lymphoid aggregates without follicle formation dominated the process. There was a light dispersion of B and T lymphocytes and histiocytes in the stroma. Immunoglobulin G4 (IgG4)–positive plasma cells (>35 per high-power field) were identified mostly in the lymphoid clusters, as has been discovered in similar IgG4–related fibrosclerosing conditions of other nonorbital sites. No associated systemic disease emerged during a 20-year clinical course. Previously reported orbital cases of IgG4-positive disease have all involved the lacrimal gland, usually bilaterally, and more closely resembled hypercellular reactive lymphoid hyperplasias with moderate interlobular fibrosis, rather than representing an essentially sclerosing process from the beginning.
Diagnosis of Metastatic Neoplasms: A Clinicopathologic and Morphologic Approach
Authors: Marchevsky Alberto M. , Gupta Ruta , Balzer Bonnie
Published: February 2021

Context.—The diagnosis of the site of origin of metastatic neoplasms often poses a challenge to practicing pathologists. A variety of immunohistochemical and molecular tests have been proposed for the identification of tumor site of origin, but these methods are no substitute for careful attention to the pathologic features of tumors and their correlation with imaging findings and other clinical data. The current trend in anatomic pathology is to overly rely on immunohistochemical and molecular tests to identify the site of origin of metastatic neoplasms, but this “shotgun approach” is often costly and can result in contradictory and even erroneous conclusions about the site of origin of a metastatic neoplasm.

Objective.—To describe the use of a systematic approach to the evaluation of metastatic neoplasms.

Data Sources.—Literature review and personal experience.

Conclusions.—A systematic approach can frequently help to narrow down differential diagnoses for a patient to a few likely tumor sites of origin that can be confirmed or excluded with the use of selected immunohistochemistry and/or molecular tests. This approach involves the qualitative evaluation of the “pretest and posttest probabilities” of various diagnoses before the immunohistochemical and molecular tests are ordered. Pretest probabilities are qualitatively estimated for each individual by taking into consideration the patient's age, sex, clinical history, imaging findings, and location of the metastases. This estimate is further narrowed by qualitatively evaluating, through careful observation of a variety of gross pathology and histopathologic features, the posttest probabilities of the most likely tumor sites of origin. Multiple examples of the use of this systematic approach for the evaluation of metastatic lesions are discussed.
Kikuchi-Fujimoto Disease
Authors: Hutchinson Charles Blake , Wang Endi
Published: February 2021

Kikuchi-Fujimoto disease, or histiocytic necrotizing lymphadenitis, is a self-limited condition, characterized by benign lymphadenopathy with associated fevers and systemic symptoms. It most commonly affects adults younger than 40 years of age and of Asian descent. Involved lymph nodes demonstrate paracortical areas of apoptotic necrosis with abundant karyorrhectic debris and a proliferation of histiocytes, plasmacytoid dendritic cells, and CD8+ T cells in the absence of neutrophils. Kikuchi-Fujimoto disease is thought to have 3 evolving phases: proliferative, necrotizing, and xanthomatous. The etiology is unknown, although viruses and autoimmune mechanisms have been proposed. No specific laboratory tests contribute to the diagnosis. Diagnosis requires histopathologic examination and exclusion of other factors by ancillary studies. Non-Hodgkin lymphoma and systemic lupus erythematosus should be ruled out before diagnosis of Kikuchi-Fujimoto disease, given the overlapped clinical and histologic features as well as the different therapeutic approaches. Treatment involves supportive measures, and the symptoms usually resolve spontaneously within 4 months.
Selected Pseudoneoplastic Lesions of the Skin
Authors: Wick Mark R. , Patterson James W.
Published: February 2021

Context.—Pseudoneoplastic cutaneous lesions are diverse, not only morphologically but also with respect to their causes and cellular lineages. They include proliferations of epithelial, as well as mesenchymal, elements.

Objective.—This review aims to consider selected lesions in the aforementioned groups, contrasting them with histologically similar neoplasms of the skin in a differential diagnostic setting.

Data Sources.—Information used in assembling this discussion was drawn from the published literature on cutaneous pseudoneoplasms, using an Internet-based search engine. The authors' collective experience was also used in writing this review.

Conclusions.—Sufficient clinical and morphologic differences exist in virtually all instances to separate pseudoneoplastic cutaneous proliferations from the tumors that they imitate.
Quantitative Real-Time Polymerase Chain Reaction Detection of BK Virus Using Labeled Primers
Authors: Gu Zhengming , Pan Jianmin , Bankowski Matthew J. , Hayden Randall T.
Published: February 2021

Context.—BK virus infections among immunocompromised patients are associated with disease of the kidney or urinary bladder. High viral loads, determined by quantitative polymerase chain reaction (PCR), have been correlated with clinical disease.

Objective.—To develop and evaluate a novel method for real-time PCR detection and quantification of BK virus using labeled primers.

Design.—Patient specimens (n = 54) included 17 plasma, 12 whole blood, and 25 urine samples. DNA was extracted using the MagNA Pure LC Total Nucleic Acid Isolation Kit (Roche Applied Science, Indianapolis, Indiana); sample eluate was PCR-amplified using the labeled primer PCR method. Results were compared with those of a user-developed quantitative real-time PCR method (fluorescence resonance energy transfer probe hybridization).

Results.—Labeled primer PCR detected less than 10 copies per reaction and showed quantitative linearity from 101 to 107 copies per reaction. Analytical specificity of labeled primer PCR was 100%. With clinical samples, labeled primer PCR demonstrated a trend toward improved sensitivity compared with the reference method. Quantitative assay comparison showed an R2 value of 0.96 between the 2 assays.

Conclusions.—Real-time PCR using labeled primers is highly sensitive and specific for the quantitative detection of BK virus from a variety of clinical specimens. These data demonstrate the applicability of labeled primer PCR for quantitative viral detection and offer a simplified method that removes the need for separate oligonucleotide probes.
Asbestos Fiber Content of Lungs With Diffuse Interstitial Fibrosis: An Analytical Scanning Electron Microscopic Analysis of 249 Cases
Authors: Schneider Frank , Sporn Thomas A. , Roggli Victor L.
Published: February 2021

Context.—Asbestosis is one of many forms of diffuse interstitial pulmonary fibrosis. Its histologic diagnosis rests on the pattern of fibrosis and the presence of asbestos bodies by light microscopy in lung biopsies.

Objective.—To determine the asbestos fiber burden in patients with diffuse pulmonary fibrosis (DPF) who had a history of asbestos exposure, but whose biopsies did not meet established criteria for asbestosis, and compare it with the fiber burden in confirmed asbestosis cases.

Design.—Fiber burden analysis was performed using scanning electron microscopy and energy-dispersive x-ray analysis of lung parenchyma from 86 patients with DPF and 163 patients with asbestosis. The correlation of the number of asbestos fibers found for a quantitative degree of fibrosis was analyzed.

Results.—The fibrosis scores of the asbestosis cases correlated best with the number of uncoated commercial amphibole fibers. Seven DPF cases fell within the 95% interval of asbestos body count by light microscopy and 3 cases within that of the total commercial amphibole fiber count.

Conclusions.—Strict histologic criteria are useful for positive identification of asbestosis among cases of advanced pulmonary fibrosis. Few DPF patients with history of asbestos exposure whose biopsies did not meet the criteria for asbestosis may have asbestos fiber counts in the range seen in asbestosis, and fiber type identification by scanning electron microscopy with energy-dispersive x-ray analysis should be considered in these rare instances to avoid false-positive and false-negative diagnoses of asbestosis.
Variable Specimen Handling Affects Hormone Receptor Test Results in Women With Breast Cancer: A Large Multihospital Retrospective Study
Authors: Nkoy Flory L. , Hammond M. Elizabeth H. , Rees William , Belnap Tom , Rowley Braden , Catmull Steve , Sause William
Published: February 2021

Context.—Intermountain Healthcare hospitals use a single, standardized laboratory and automated testing process for estrogen receptor/progesterone receptor (ER/PR) tests to minimize testing errors.

Objectives.—To test the (1) variability in ER/PR negativity among hospitals and (2) association between specimen handling conditions and ER/PR negativity.

Design.—Retrospective study of women who had breast cancer surgery at 7 Intermountain hospitals and ER/PR tests ordered between 1997 and 2003. Data were extracted from cancer registry. Frequency of ER/PR negativity was calculated for each surgery day and compared among hospitals and between 2 groups: regular (specimens obtained Sunday through Thursday, more likely to be tested within 24 hours of surgery) and prolonged (specimens obtained on Friday and Saturday, more likely to be tested more than 24 hours after surgery) specimen handling conditions.

Results.—Five thousand seventy-seven women were tested for ER/PR. The frequency of ER and PR negativity was 20.9% and 27.9%, respectively. It increased with each day of the week for both ER (P  =  .03) and PR (P  =  .059) and tended to be higher for prolonged specimens for ER (23.6% versus 20.4%; P  =  .03) and for PR (30.1% versus 27.4%; P  =  .11) compared with regular specimens. After controlling for age and tumor size, both ER (P  =  .02) and PR (P  =  .02) negativity was significantly different among the hospitals and was associated with prolonged specimens for ER (P  =  .04) but not for PR (P  =  .09).

Conclusions.—Estrogen receptor and PR negativity remained highly variable among hospitals despite use of a single laboratory and tended to be significantly associated with prolonged specimen handling. More studies are needed to confirm these findings.
Pathology of Small Airways Disease
Authors: Allen Timothy Craig
Published: February 2021

Context.—The term small airways disease encompasses a generally poorly understood group of lung diseases that may arise primarily within the small airways or secondarily from diseases primarily affecting the bronchi or lung parenchyma. Their histology may be confusing; however, because treatments and prognoses vary, correct pathologic diagnosis is important.

Objective.—To present a nonexhaustive review of the pathology of primary and secondary small airways diseases, including small airways disease related to tobacco; to various other exposures, including mineral dusts; to diseases involving other areas of the lung with secondary bronchiolar involvement; and to recently described bronchiolitic disorders.

Data sources.—Current literature is reviewed.

Conclusions.—Small airways diseases include a wide variety of diseases of which the pathologist must consider. Uncommon conditions such as diffuse idiopathic neuroendocrine cell hyperplasia and diffuse panbronchiolitis may show relatively specific diagnostic features histologically; however, most small airways diseases exhibit nonspecific histologic features. Conditions not considered primary pulmonary diseases, such as collagen vascular diseases, bone marrow transplantation, and inflammatory bowel disease, must also be considered in patients with small airways changes histologically. Clinical and radiologic correlation is important for obtaining the best possible diagnosis.
TNM Staging System of Colorectal Carcinoma: A Critical Appraisal of Challenging Issues
Authors: Puppa Giacomo , Sonzogni Angelica , Colombari Romano , Pelosi Giuseppe
Published: February 2021

Context.—Colorectal cancer is the leading cause of morbidity and death among gastrointestinal tumors and ranks fourth after lung, breast, and ovarian cancers. Despite a continuous refinement of the T (tumor), N (node), and M (metastasis) staging system to express disease extent and define prognosis, and eventually to guide treatment, the outcome of patients with colorectal cancer may vary considerably even within the same tumor stage. Therefore, the need for new factors, either morphologic or molecular, that could more precisely stratify patients into different risk categories is clearly warranted.

Objectives.—To present the state of the art with regard to the colorectal cancer staging system and to discuss confusing and/or challenging issues, including the assessment of peritoneal membrane involvement, vascular invasion, tumor deposits, and pathologic tumor response to neoadjuvant chemoradiotherapy.

Data Sources.—Literature review of relevant articles indexed in PubMed (US National Library of Medicine) and primary material from the authors' institutions.

Conclusions.—Two emerging needs exist for the TNM system, namely, further stratification of patients with the same tumor stage and incorporation of nonanatomic factors, the latter including molecular and treatment factors. The identification and classification of morphologic features encountered in the pathologic examination of colorectal cancer specimens may be difficult and a source of subjective variability. Enhanced pathologic analysis, agreed-upon standard protocols, and standardization should improve the completeness and accuracy of pathology reports.
Observer Variability in the Interpretation of HER2/neuImmunohistochemical Expression With Unaided and Computer-Aided Digital Microscopy
Authors: Gavrielides Marios A , Gallas Brandon D , Lenz Petra , Badano Aldo , Hewitt Stephen M
Published: February 2021

Context.—Observer variability in digital microscopy and the effect of computer-aided digital microscopy are underexamined areas in need of further research, considering the increasing use and future role of digital imaging in pathology. A reduction in observer variability using computer aids could enhance the statistical power of studies designed to determine the utility of new biomarkers and accelerate their incorporation in clinical practice.

Objectives.—To quantify interobserver and intraobserver variability in immunohistochemical analysis of HER2/neu with digital microscopy and computer-aided digital microscopy, and to test the hypothesis that observer agreement in the quantitative assessment of HER2/neu immunohistochemical expression is increased with the use of computer-aided microscopy.

Design.—A set of 335 digital microscopy images extracted from 64 breast cancer tissue slides stained with a HER2 antibody, were read by 14 observers in 2 reading modes: the unaided mode and the computer-aided mode. In the unaided mode, HER2 images were displayed on a calibrated color monitor with no other information, whereas in the computer-aided mode, observers were shown a HER2 image along with a corresponding feature plot showing computer-extracted values of membrane staining intensity and membrane completeness for the particular image under examination and, at the same time, mean feature values of the different HER2 categories. In both modes, observers were asked to provide a continuous score of HER2 expression.

Results.—Agreement analysis performed on the output of the study showed significant improvement in both interobserver and intraobserver agreement when the computer-aided reading mode was used to evaluate preselected image fields.

Conclusion.—The role of computer-aided digital microscopy in reducing observer variability in immunohistochemistry is promising.
Cardiac Troponin T Measured With a Highly Sensitive Assay for Diagnosis and Monitoring of Heart Injury in Chronic Chagas Disease
Authors: Saravia Silvia Gilka Muñoz , Haberland Annekathrin , Bartel Sabine , Araujo Raul , Valda Gregorio , Reynaga Diana Duchen , Ramirez Ivan Diaz , Borges Adrian C , Wallukat Gerd , Schimke Ingolf
Published: February 2021

Context.—Chronic Chagas disease (15 million patients; annual incidence, 40 000 patients; annual mortality, 12 500 patients) is the most serious parasitic disease in Latin America. Between 10 and 30 years after infection, 30% of patients with Chagas disease develop heart injury, which is the main reason for its high mortality. Consequently, frequent cardiac diagnostics are required for patients with Chagas disease.

Objective.—To minimize time-intensive and cost-intensive diagnostics, such as electrocardiography, echocardiography, and radiologic imaging, we tested the effect of measuring serum cardiac troponin T (cTnT) with a highly sensitive assay. To indicate the pathophysiologic background for cTnT release in Chagas heart injury, inflammation markers, such as C-reactive protein and interleukin 6, were measured in parallel.

Design.—Serum cTnT was measured in 26 healthy subjects and in 179 patients with chronic Chagas disease who were asymptomatic (indeterminate stage, n  =  86), who were suffering from cardiomyopathy with or without megacolon (n  =  71), or who were suffering from megacolon exclusively (n  =  22).

Results.—Serum cTnT was significantly higher in patients with cardiomyopathy with or without megacolon than in healthy subjects, asymptomatic subjects, and patients with megacolon, and the cTnT value was correlated with the severity of the cardiomyopathy. The lower limit of detection for the highly sensitive assay (3 ng/L) was best at distinguishing patients with, and without, heart injury. C-reactive protein and interleukin 6 were found to parallel cTnT changes in both the different Chagas groups and the cardiomyopathy groups separated by disease severity.

Conclusions.—Highly sensitive cTnT measurement has the potential to contribute to diagnosis and monitoring of heart injury in patients with chronic Chagas disease. The highly sensitive assay of cTnT release seems to be related to Chagas heart disease–specific inflammation.