bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunohistochemistry of Pulmonary and Pleural Neoplasia
Authors: Beasley Mary Beth 
Published: February 2021

Abstract
Context.—The use of immunohistochemical stains has several applications in the evaluation of pulmonary and pleural neoplasms. The number of available immunohistochemical stains is continually expanding and, although these stains are an important diagnostic adjunct, their use is not without limitations and pitfalls.
Objective.—To review and summarize the primary immunohistochemical applications with regard to the most common pulmonary and pleural neoplasms and discuss newly developed markers and common pitfalls.
Data Sources.—Pertinent peer-reviewed literature emphasizing immunohistochemical applications in common lung and pleural tumors, unusual and problematic staining patterns in frequently encountered subtypes/histologic variants, and recently developed immunohistochemical stains of potential promise.
Conclusions.—Immunohistochemical stains provide the greatest aid in establishing the site of origin of adenocarcinomas encountered in the lung and in separating epithelioid mesothelioma from adenocarcinoma. Certain subtypes of pulmonary adenocarcinomas may exhibit unusual staining patterns that may be potentially problematic. Immunohistochemistry has a more limited role in separating small cell carcinoma from non–small cell carcinoma, and extreme caution must be used in the situation of crushed biopsy specimens.
Primary and Metastatic Lung Tumors in the Pediatric Population: A Review and 25-Year Experience at a Large Children's Hospital
Authors: Dishop Megan K. , Kuruvilla Supriya 
Published: February 2021

AbstractContext.—Primary lung neoplasms are rare in children, but they comprise a broad and interesting spectrum of lesions, some of which are familiar from other tissue sites, and some of which are unique to the pediatric lung.Objective.—To determine the relative incidence of primary and metastatic lung tumors in children and adolescents through a single-institution case series, to compare these data to reports in the medical literature, to discuss the clinical and pathologic features of primary tumors of the tracheobronchial tree and lung parenchyma in children, and to provide recommendations for handling pediatric lung cysts and tumors.Data Sources.—A 25-year single institutional experience with pediatric lung tumors, based on surgical biopsies and resections at Texas Children's Hospital from June 1982 to May 2007, an additional 40 lung tumors referred in consultation, and a review of the medical literature.Conclusions.—A total of 204 pediatric lung tumors were diagnosed at our institution, including 20 primary benign lesions (9.8%), 14 primary malignant lesions (6.9%), and 170 secondary lung lesions (83.3%). The ratio of primary benign to primary malignant to secondary malignant neoplasms is 1.4:1:11.6. The common types of lung cancer in adults are exceptional occurrences in the pediatric population. The most common primary lung malignancies in children are pleuropulmonary blastoma and carcinoid tumor. Other primary pediatric lung tumors include congenital peribronchial myofibroblastic tumor and other myofibroblastic lesions, sarcomas, carcinoma, and mesothelioma. Children with primary or acquired immunodeficiency are at risk for Epstein-Barr virus–related smooth muscle tumors, lymphoma, and lymphoproliferative disorders. Metastatic lung tumors are relatively common in children and also comprise a spectrum of neoplasia distinct from the adult population.
Avoiding Underdiagnosis, Overdiagnosis, and Misdiagnosis of Lung Carcinoma
Authors: Butnor Kelly J. 
Published: February 2021

AbstractContext.—Given the magnitude of the therapeutic and prognostic implications, it is critical that pathologists diagnose lung cancer accurately. This can sometimes be a formidable challenge, as a number of benign entities mimic lung carcinoma and vice versa.Objective.—To present strategies for recognizing benign entities likely to be confused with lung carcinoma, malignancies of the lung prone to misinterpretation as benign, and commonly misclassified pulmonary neoplasms.Data Sources.—The medical literature and experience from consultative and surgical practice.Conclusions.—In addition to understanding the clinical context in which a lung biopsy is procured and the radiographic findings, appreciating the histologic distribution of disease and what, if any, pathologic features are present in the background can go a long way toward averting a misdiagnosis of lung cancer. Recognizing the limitations posed by small samples and communicating clearly to clinicians the level of diagnostic uncertainty are equally as important for establishing an accurate diagnosis of lung cancer.
Diffuse Large B-Cell Lymphoma
Authors: Hunt Kristin E. , Reichard Kaaren K. 
Published: February 2021

AbstractDiffuse large B-cell lymphoma is the most common lymphoma worldwide. Both morphologically and prognostically it represents a diverse spectrum of disease. Traditional morphologic subclassification often results in poor interobserver reproducibility and has not been particularly helpful in predicting outcome. Recent gene expression profiling studies have classified diffuse large B-cell lymphoma into 2 main subtypes, germinal center B-cell and activated B-cell, with the germinal center type showing an overall better survival. Validation of these subtypes has become possible for the practicing pathologist with the use of surrogate immunohistochemical markers. Importantly however, these prognostic studies were performed on material from the pre-rituximab treatment era. With the now well-accepted addition of rituximab (anti-CD20 antibody) to the typical large B-cell lymphoma chemotherapeutic regimen, a revalidation of any survival differences between the large B-cell lymphoma subgroups is necessary. This short review covers the current clinical, morphologic, immunophenotypic, genetic, gene expression profiling, and prognostic (studies before and after the addition of rituximab) features of de novo diffuse large B-cell lymphoma.
The Thyroid Hürthle (Oncocytic) Cell and Its Associated Pathologic Conditions: A Surgical Pathology and Cytopathology Review
Authors: Montone Kathleen T. , Baloch Zubair W. , LiVolsi Virginia A. 
Published: February 2021

Abstract
Context.—Hürthle cells are eosinophilic, follicular-derived cells that are associated with a variety of nonneoplastic and neoplastic thyroid lesions. The differential diagnosis of Hürthle cell lesions is quite broad.
Objective.—To review the pathologic conditions associated with Hürthle cells in the thyroid and to discuss pathology of thyroid lesions associated with oncocytic cytology.
Data Sources.—A variety of thyroid nonneoplastic (autoimmune thyroiditis, multinodular goiter) and neoplastic conditions (Hürthle cell adenoma, Hürthle cell carcinoma) are associated with Hürthle cell cytology. In addition, there are several thyroid neoplasms that should be considered when one observes a Hürthle cell neoplasm in the thyroid (oncocytic variant of medullary carcinoma, several variants of papillary thyroid carcinoma).
Conclusions.—Oncocytic cytology is seen in a variety of thyroid conditions that are associated with a broad differential diagnosis and care must be used for accurate diagnosis. Newer molecular-based techniques may be useful for further classification of thyroid neoplasms with oncocytic pathology.
Nontuberculous Mycobacterial Infections
Authors: Jarzembowski Jason A. , Young Michael B. 
Published: February 2021

Abstract
Context.—Nontuberculous mycobacteria include numerous acid-fast bacilli species, many of which have only recently been recognized as pathogenic. The diagnosis of mycobacterial disease is based on a combination of clinical features, microbiologic data, radiographic findings, and histopathologic studies.
Objective.—To provide an overview of the clinical and pathologic aspects of nontuberculous mycobacteria infection, including diagnostic laboratory methods, classification, epidemiology, clinical presentation, and treatment.
Data Sources.—Review of the pertinent literature and published methodologies.
Conclusions.—Nontuberculous mycobacteria include numerous acid-fast bacilli species, many of which are potentially pathogenic, and are classified according to the Runyon system based on growth rates and pigment production. Their slow growth hinders cultures, which require special medium and prolonged incubation. Although such methods are still used, newer nucleic acid–based technologies (polymerase chain reaction and hybridization assays) can rapidly detect and speciate some mycobacteria—most notably, distinguishing Mycobacterium tuberculosis from other species. Infections caused by these organisms can present as a variety of clinical syndromes, not only in immunocompromised patients but also in immunocompetent hosts. Most common among these are chronic pulmonary infections, superficial lymphadenitis, soft tissue and osteoarticular infections, and disseminated disease. Treatment of nontuberculous mycobacterial infections is difficult, requiring extended courses of multidrug therapy with or without adjunctive surgical intervention.
Pulmonary and Cardiovascular Complications of Obesity: An Autopsy Study of 76 Obese Subjects
Authors: Haque Abida K. , Gadre Swarupa , Taylor Jerrod , Haque Sajid A. , Freeman Daniel , Duarte Alex 
Published: February 2021

AbstractContext.—Obesity is associated with sleep disordered breathing and cardiovascular morbidity, but the relationship between pulmonary hypertension, heart disease, and obesity is unknown.Objective.—To determine the prevalence of pulmonary and cardiovascular disease in obese subjects undergoing autopsy at a large medical center.Design.—A search through autopsy records from an 11-year period identified 76 subjects with a body mass index greater than 30 kg/m2 and 46 age-matched, nonobese controls. Clinical data were collected from medical charts and autopsy records. Formalin-fixed, paraffin-embedded sections of lungs and heart were reviewed for each subject. The presence of pulmonary edema, hemorrhage, diffuse alveolar damage, thrombi, and pulmonary hypertensive changes, including intimal fibrosis, medial hypertrophy, muscularization of arterioles, alveolar capillary hemangiomatosis, hemosiderosis, and iron encrustation were documented. Hearts were examined for the presence of cardiomegaly, ventricular hypertrophy, coronary artery atherosclerosis, acute infarction, fibrosis, and inflammation. Differences between the obese and control groups were compared using a statistical software program.Results.—The obese group demonstrated a greater occurrence of diabetes mellitus, systemic hypertension, pulmonary edema, hemorrhage, and pulmonary hypertensive changes compared with the control group. Alveolar capillary hemangiomatosis was exclusively observed in the obese subjects. Cardiomegaly and left ventricular hypertrophy were present in all obese subjects; approximately one third of the obese subjects had no coronary atherosclerosis.Conclusions.—Pulmonary hypertensive changes, including venous hypertension and capillary hemangiomatosis, were observed in 72% of obese subjects. Cardiomegaly with biventricular hypertrophy was present in all obese subjects and was suggestive of obesity cardiomyopathy.
No Correlation Between Lipoprotein(a) and Biochemical Markers of Renal Function in the General Population
Authors: Lippi Giuseppe , Salvagno Gian Luca , Montagnana Martina , Targher Giovanni , Franchini Massimo , Guidi Gian Cesare 
Published: February 2021

AbstractContext.—Lipoprotein(a) (Lp(a)) is receiving major emphasis as an independent risk factor for cardiovascular disease. Results of studies on Lp(a) in patients with impaired renal function are contradictory, and no information is available on the association between Lp(a) and estimated glomerular filtration rate and cystatin C.Objective.—To evaluate the potential relationships among the biochemical markers creatinine, estimated glomerular filtration rate, and cystatin C and their association with Lp(a) in patients with impaired renal function.Design.—We performed a retrospective analysis using the database of our laboratory to retrieve results of Lp(a), creatinine, and cystatin C tests performed on consecutive outpatients referred by general practitioners for routine blood testing during the last year.Results.—Cumulative results for all of the above-mentioned variables were retrieved for 150 adults older than 35 years. After stratifying Lp(a) values according to thresholds of creatinine, estimated glomerular filtration rate, and cystatin C, no significant differences in Lp(a) concentration were observed in subjects with abnormal values of these biochemical markers. The prevalence of Lp(a) values greater than or equal to 300 mg/L was not significantly different in subjects with biochemical markers suggestive of impaired renal function, as compared with those without such markers. In multivariable linear regression analysis, none of the parameters tested was significantly associated with Lp(a).Conclusions.—We suggest that unless renal function is completely compromised, measurement of biochemical markers of renal function might be relatively unimportant to improve clinical usefulness of Lp(a) testing.
Practical Approach to the Pathologic Diagnosis of Gastritis
Authors: Sepulveda Antonia R. , Patil Madhavi 
Published: February 2021

Abstract
Context.—Most types of gastritis can be diagnosed on hematoxylin-eosin stains. The most common type of chronic gastritis is Helicobacter pylori gastritis. Reactive or chemical gastropathy, which is often associated with nonsteroidal anti-inflammatory drug use or bile reflux, is common in most practices. The diagnosis of atrophic gastritis can be challenging if few biopsy samples are available and if the location of the biopsies in the stomach is not known, such as when random biopsies are sampled in one jar. If the biopsy site is not known, immunohistochemical stains, such as a combination of synaptophysin and gastrin, are useful in establishing the biopsy location.
Objective.—To demonstrate a practical approach to achieving a pathologic diagnosis of gastritis by evaluating a limited number of features in mucosal biopsies.
Data Source.—In this article, we present several representative gastric biopsy cases from a gastrointestinal pathology practice to demonstrate the practical application of basic histopathologic methods for the diagnosis of gastritis.
Conclusions.—Limited ancillary tests are usually required for a diagnosis of gastritis. In some cases, special stains, such as acid-fast stains, and immunohistochemical stains, such as for H pylori and viruses, can be useful. Helicobacter pylori immunohistochemical stains can particularly contribute (1) when moderate to severe, chronic gastritis or active gastritis is present but no Helicobacter organisms are identified upon hematoxylin-eosin stain; (2) when extensive intestinal metaplasia is present; and (3) in follow-up biopsies, after antibiotic treatment for H pylori.
“Give Us This Day Our Daily Bread”—Evolving Concepts in Celiac Sprue
Authors: Upton Melissa P. 
Published: February 2021

Abstract
Context.—Celiac sprue affects genetically susceptible individuals, who develop small intestinal injury and malabsorption following dietary exposure to gluten. The histologic features are nonspecific but characteristic.
Objectives.—To outline the histologic features of celiac sprue and the necessary clinical context to permit a diagnosis of celiac sprue, to assist the pathologist to identify artifactual biopsy changes that may mimic sprue, to define the differential diagnosis for conditions with a similar histology, and to review historic investigations of this disease.
Data Sources.—Sources include the historic experiments and clinical work of members of the Gastroenterology Division of the Department of Medicine and experiences with gastrointestinal pathology consultation material at the University of Washington, Seattle, with reference to selected peer-reviewed articles.
Conclusions.—Confirmation of a diagnosis of celiac sprue is 2-fold: first, biopsy evidence of a characteristic, but nonspecific, pattern of injury including villous blunting or flattening, surface enterocyte damage, and increased intraepithelial lymphocytes; and second, dramatic clinical response to a gluten-free diet. Complete gluten removal from the diet is effective treatment for patients with symptoms of malabsorption; however, lifelong adherence to the diet is expensive, socially limiting, and nearly impossible on a contemporary diet with manufactured foodstuffs. Therefore, pathologists should avoid overdiagnosis of celiac disease based on minimal, nonspecific histologic changes.
Colorectal Carcinoma: Selected Issues in Pathologic Examination and Staging and Determination of Prognostic Factors
Authors: Kay Washington Mary 
Published: February 2021

Abstract
Context.—Colorectal carcinoma is one of the most common types of cancer in Western countries and is consistently ranked among the top 3 causes of cancer-related deaths, with approximately 150 000 new cases in the United States and 55 000 deaths in 2006. The pathologist's assessment of tumor stage and stage-independent morphologic features, such as vascular/lymphatic invasion, influences treatment strategies for the individual patient, such as the decision to offer adjuvant therapy after surgery. However, although the pathologist influences clinical care in colorectal cancer, certain aspects of staging and evaluation of prognostic factors remain challenging and confusing.
Objectives.—To present the currently used colorectal cancer staging system; to address challenging areas in pathologic staging, including T category considerations and recommendations for the minimum number of lymph nodes sampled; and to discuss assessment of selected stage-independent prognostic factors, such as vascular/ lymphatic invasion.
Data Sources.—This review is based on the current staging manual from the American Joint Committee on Cancer, the College of American Pathologists Protocol for Examination of Specimens From Patients With Primary Carcinomas of the Colon and Rectum, and selected articles pertaining to colorectal carcinoma staging and prognostic factors accessible through Ovid Medline (National Library of Medicine, Bethesda, Md).
Conclusions.—Proper assessment of pathologic staging for colorectal cancer and of morphologic prognostic factors requires a thorough understanding of staging guidelines and careful specimen dissection and sampling.
Comparison of Quantitative Immunofluorescence With Conventional Methods for HER2/neuTesting With Respect to Response to Trastuzumab Therapy in Metastatic Breast Cancer
Authors: Giltnane Jennifer M. , Molinaro Annette , Cheng Huan , Robinson Andrew , Turbin Dmitry , Gelmon Karen , Huntsman David , Rimm David L. 
Published: February 2021

AbstractContext.—Selection for trastuzumab therapy depends on a companion diagnostic assessment of HER2 by either immunohistochemistry (IHC) for protein overexpression or fluorescence in situ hybridization (FISH) to detect gene amplification. Although many studies have compared IHC to FISH, few have compared the tests to the true gold standard, tumor response.Objective.—To compare HER2 testing by FISH and IHC along with a third immunofluorescence-based assay (automated quantitative analysis–tissue microarray [AQUA-TMA]) and to assess the value of each test for prediction of response to trastuzumab.Design.—Immunohistochemistry and FISH assays were done on both whole slides (IHC-WS and FISH-WS) and on TMAs (IHC-TMA and FISH-TMA). AQUA was only done on TMAs (AQUA-TMA). Response was assessed according to modified Response Evaluation Criteria in Solid Tumors.Results.—AQUA-TMA scores showed a significant linear relationship to both the FISH signal ratio and IHC scores on whole sections and TMAs. Assay assessment by outcome showed no association between response and FISH-WS ratio (P = .96), FISH-TMA (P = .55), IHC-WS (P = .75), or IHC-TMA (P = .06), but a significant relationship between AQUA score and categoric response was observed (P = .01). Assessed as a function of outcome using models of logistic regression, both AQUA-TMA and IHC-TMA were equally significant (P = .01). FISH-WS was the most sensitive assay, with a significantly higher true-positive fraction than all other tests except AQUA-TMA, although it was the least specific. IHC-TMA was the most specific assay. The lowest misclassification rate was achieved using AQUA-TMA (0.30).Conclusions.—Both AQUA-TMA and IHC-TMA were substantially more predictive than the FISH or IHC-WS tests. Although these results are derived from a small retrospective series, they suggest that accurate measurement of protein expression and unbiased selection of tissue for measurement may be key factors in prediction of response.
CpG Island Methylator Phenotype in Colorectal Cancers: Comparison of the New and Classic CpG Island Methylator Phenotype Marker Panels
Authors: Lee Sun , Cho Nam-Yun , Yoo Eun Joo , Kim Jung Ho , Kang Gyeong Hoon 
Published: February 2021

Abstract
Context.—CpG island methylator phenotype (CIMP) designates a subset of colorectal cancers featuring concordant hypermethylation of multiple promoter CpG islands. Little is known about the clinical outcome or histologic characteristics of CIMP-positive colorectal cancers defined by recently identified CpG island methylator phenotype panels.
Objective.—To investigate and compare the molecular and clinicopathologic features of CIMP-positive colorectal cancers defined by classic (p16, hMLH1, MINT1, MINT2, MINT31) and new (CACNA1G, IGF2, NEUROG1, RUNX3, SOCS1) CIMP panels.
Design.—We analyzed 130 colorectal cancers for hypermethylation of both panels using methylation-specific polymerase chain reaction.
Results.—With at least 2 markers methylated, both classic (39/130; 23.1%) and new (23.1%) CIMP-positive colorectal cancers were significantly associated with proximal tumor location, microsatellite instability, and BRAF mutation (all P values were less than .05). The new panel outperformed the classic panel in detecting these features. With at least 3 markers methylated, new CIMP-positive colorectal cancers (16.9%) were closely associated with proximal tumor location, low frequency of KRAS mutation, and high frequency of BRAF mutation (all P values were less than .05), whereas classic CIMP-positive colorectal cancers (18.5%) were closely associated with proximal tumor location, frequent microsatellite instability, and frequent BRAF mutation (all P values were less than .05). Analyzing a combination of CIMP and microsatellite instability status, CIMP-positive/microsatellite instability–negative colorectal cancers had the worst clinical outcomes.
Conclusions.—Whereas the classic panel outperformed in predicting clinical outcome, the new panel was superior in detecting known clinicopathologic features of CIMP but inferior in prognostication power.