bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunohistochemistry and Quantitative Analysis of Protein Expression
Authors: Cregger Melissa , Berger Aaron J. , Rimm David L. 
Published: February 2021

AbstractContext.—Immunohistochemistry has taken a central role in the field of pathology, and its role is destined to increase as companion diagnostics analogous to the HercepTest are required for new targeted therapeutics. However, the inherent subjectivity of the assessment of an objective value (the in situ protein concentration) suggests that new technologies to measure the protein concentration may be required to achieve the accuracy required for companion diagnostics.Objective.—This article discusses the state of immunohistochemistry and reviews the currently available devices for quantitative in situ assessment of protein expression.Data Sources.—Data for this work were collected from the published literature, the Internet, and from information provided by device vendors.Conclusions.—Although there is a long history of efforts to quantify immunohistochemistry, there has been a lack of broad acceptance because the resultant objective accuracy has not significantly improved outcome measures compared with the traditional, conventional analysis by eye. As the demand grows for companion diagnostics with complex assessment requirements, we are likely to see increased usage of quantitative platforms, especially those with the capacity to do multiplexed analysis. This most likely will be driven by a requirement for outcomes that cannot be achieved by traditional methods.
Middle Ear Adenoma
Authors: Berns Stephen , Pearl Gary 
Published: February 2021

Abstract
Middle ear adenoma is a benign tumor of the middle ear that can have exocrine (mucinous) and/or neuroendocrine differentiation. Early authors described a separate tumor with predominantly neuroendocrine differentiation as a middle ear carcinoid tumor, but these are now known to be the same tumor. We review the literature of this tumor, including the clinical presentation, gross pathology, histopathology, immunohistochemistry, differential diagnosis, and prognosis.
Cytogenetic Heteromorphisms: Survey Results and Reporting Practices of Giemsa-Band Regions That We Have Pondered for Years
Authors: Brothman Arthur R. , Schneider Nancy R. , Saikevych Irene , Cooley Linda D. , Butler Merlin G. , Patil Shivanand , Mascarello James T. , Rao Kathleen W. , Dewald Gordon W. , Park Jonathan P. , Persons Diane L. , Wolff Daynna J. , Vance Gail H. 
Published: February 2021

Abstract
Context.—Cytogenetic heteromorphisms (normal variants) pose diagnostic dilemmas. Common Giemsa-band heteromorphisms are not described in the literature, although Giemsa-banding is the method most frequently used in cytogenetic laboratories.
Objective.—To summarize the responses from more than 200 cytogeneticists concerning the definition and reporting of cytogenetic heteromorphisms, to offer these responses as a reference for use in clinical interpretations, and to provide guidance for interpretation of newly defined molecular cytogenetic heteromorphisms.
Design.—The Cytogenetics Resource Committee of the College of American Pathologists and the American College of Medical Genetics administered a proficiency testing survey in 1997 to 226 participant cytogenetic laboratories. Supplemental questions asked whether participants considered particular Giemsa-banded chromosomal features to be heteromorphisms and if these would be described in a cytogenetic clinical report.
Results.—Responses were obtained from 99% of participants; 61% stated they would include selected heteromorphism data in a clinical report. More than 90% considered prominent short arms, large or double satellites, or increased stalk length on acrocentric chromosomes to be heteromorphisms; 24% to 36% stated that they would include these in a clinical report. Heterochromatic regions on chromosomes 1, 9, 16, and Y were considered heteromorphisms by 97% of participants, and 24% indicated they would report these findings. Pericentric inversions of chromosomes 1, 2, 3, 5, 9, 10, 16, and Y were considered heteromorphisms with more than 75% of respondents indicating they would report these findings.
Conclusions.—Responses were not unanimous, but a clear consensus is presented describing which Giemsa-band regions were considered heteromorphisms and which would be reported.
Bilateral Presentation of Fibroadenoma With Digital Fibroma–like Inclusions in the Male Breast
Authors: Shin Sandra J. , Rosen Paul Peter 
Published: February 2021

Abstract
Fibroepithelial lesions are uncommon in the male breast. Most published reports describe phyllodes tumors. Fibroadenomas are very common in female breasts, but are exceedingly rare in the male breast. Gynecomastia and/or lobular differentiation have been known to coexist in both types of fibroepithelial lesions in men. We report an exceptional case of recurrent, bilateral fibroadenomas in a man under treatment for prostatic carcinoma. Intracytoplasmic inclusion bodies in stromal cells identical to those seen in infantile digital fibromatosis were identified in one fibroadenoma. To the best of our knowledge, this is the first reported case of bilaterally occurring fibroadenomas in the male breast, one of which also contained digital fibroma– like inclusions, a second unreported phenomenon.
Small Lymphoid Proliferations in Extranodal Locations
Authors: Rao Dinesh S. , Said Jonathan W. 
Published: February 2021

Abstract
Context.—Low-grade non-Hodgkin lymphomas frequently involve extranodal sites including the gastrointestinal tract, skin, and lung, either selectively or as part of widespread dissemination. Differentiation from inflammatory or infectious conditions requires knowledge of specific histologic characteristics of the various entities as well as ancillary techniques.
Objective.—To describe the key features and provide diagnostic clues to the identification of specific extranodal low-grade lymphomas of T-cell and B-cell types including small lymphocytic lymphoma, follicular lymphoma, mantle cell lymphoma, extranodal marginal zone B-cell lymphomas of mucosal-associated lymphoid tissue, and hairy cell leukemia. Histologic and cytologic features are highlighted, as well as appropriate integration of results of ancillary diagnostic studies including flow cytometry, immunohistochemistry, molecular features, and cytogenetics.
Data Sources.—The published literature as well as personal experience from a specialized hematopathology practice at a large university medical center.
Conclusions.—Correct identification of extranodal low-grade lymphomas and differentiation from hyperplastic and inflammatory or infectious processes require the ability to distinguish each of the specific entities discussed. Ancillary studies are often indispensable in reaching a correct diagnosis.
Serum Levels of Matrix Metalloproteinase 3 (Stromelysin 1) for Monitoring Synovitis in Rheumatoid Arthritis
Authors: Kobayashi Ari , Naito Satoko , Enomoto Hiroyuki , Shiomoi Takayuki , Kimura Tokuhiro , Obata Ken'ichi , Inoue Kazuhiko , Okada Yasunori 
Published: February 2021

AbstractContext.—Matrix metalloproteinase 3 (MMP-3) is expressed in synovial tissues and involved in cartilage destruction in rheumatoid arthritis and osteoarthritis.Objective.—To study whether measurement of MMP-3 serum concentrations is useful to monitor the activity of rheumatoid synovitis.Design.—Levels of MMP-3 in serum and synovial tissue samples obtained from 29 rheumatoid arthritis patients and 20 osteoarthritis patients were measured by the 1-step sandwich enzyme immunoassay system.Results.—Levels of MMP-3 in the serum and synovial samples were significantly higher in rheumatoid arthritis than in osteoarthritis (P &lt; .001), and the levels correlated directly with each other (r = 0.712, P &lt; .001; N = 49). Immunohistochemistry demonstrated almost exclusive localization of MMP-3 to the lining cells in rheumatoid synovium. The immunoreactivity correlated directly with the scores of synovial inflammatory cell infiltration (r = 0.606, P &lt; .001; n = 29) and the MMP-3 levels in the synovial tissues (r = 0.564, P = .001; n = 29) and those in the serum samples (r = 0.529, P = .003; n = 29) in rheumatoid arthritis. Levels of MMP-3 in rheumatoid serum samples dropped to low values at 1 and 2 weeks after total knee arthroplasty, while the levels of C-reactive protein increased at 1 week and the erythrocyte sedimentation rate and counts of white blood cells and platelets were unchanged at 1 and 2 weeks postoperative.Conclusions.—Our results demonstrate that MMP-3 levels in the serum of rheumatoid arthritis patients correlate with the levels produced by the synovial lining cells and suggest that the activity of rheumatoid synovitis can be monitored by measuring serum levels of MMP-3.
Distinguishing Prostatic From Colorectal Adenocarcinoma on Biopsy Samples: The Role of Morphology and Immunohistochemistry
Authors: Owens Christopher L. , Epstein Jonathan I. , Netto George J. 
Published: February 2021

Abstract
Context.—Poorly differentiated carcinoma on prostate or colorectal biopsy can occasionally present a diagnostic challenge in determining tumor source especially in locally advanced colorectal carcinoma (CRCa) or prostate carcinoma (PCa). Such determination can affect prognosis and therapy.
Objective.—To evaluate the role of morphology and immunohistochemistry in the previously mentioned setting.
Design.—Surgical pathology and consultation records. Hematoxylin-eosin sections were reviewed in 16 cases (11 PCa, 5 CRCa). Immunohistochemistry for 9 markers was performed in 15 cases.
Results.—Dirty necrosis, seen in 5 (100%) of 5 CRCa and 2 (18%) of 11 PCa cases, and the presence of columnar cells with basal nuclei, seen in 5 (100%) of 5 CRCa and 1 (9%) of 11 PCa cases, appear to be the most useful morphologic parameters. Immunohistochemistry confirmed the value of prostate-specific antigen (PSA), CDX2, cytokeratin (CK) 20, and β-catenin in the differential of CRCa (0% PSA+, 60% CDX2+, 80% CK20+, and 100% β-catenin+) versus PCa (80% PSA+, 0% CDX2+, 10% CK20+, and 0% β-catenin+). P501S had a similar sensitivity as PSA in detecting PCa (80%). Two (20%) of 10 PCa cases were positive for 1 of the 2 markers but not the other. P501S was negative in all 5 cases of CRCa.
Conclusions.—P501S is a useful marker in this setting when included together with PSA, CDX2, CK20, and β-catenin. P501S labels a subset of PCa cases that are negative for PSA. Dirty necrosis and/or columnar cells with basal nuclei could also be of help.
Leadership and Management Training for Residents and Fellows: A Curriculum for Future Medical Directors
Authors: Hemmer Patrick R. , Karon Brad S. , Hernandez James S. , Cuthbert Carla , Fidler Mary E. , Tazelaar Henry D. 
Published: February 2021

Abstract
Context.—Management of laboratories and pathology practices is increasingly complex. Residents and fellows in laboratory medicine and pathology need more structured curricula in leadership and management (L&M) training to function as medical and laboratory directors.
Objective.—To define a curriculum that provides basic competency in L&M for residents and fellows in pathology.
Design.—A year-long formal L&M course included didactic lectures, interactive sessions, case scenarios, team-building exercises, formal team presentations (capstone project), and precourse and postcourse assessment of L&M knowledge. The curriculum meets requirements of American College of Graduate Medical Education and supports goals for leadership training of the College of American Pathologists. Participants evaluated (5-point scale) the content and speakers of all sessions. Trainees were evaluated after considering postcourse examination results, quality of the capstone presentation, and a global assessment.
Results.—The 5 non-capstone sessions received evaluation scores ranging from 4.4 (informatics) to 5 (L&M basics). Postcourse test scores showed significant improvement when compared with the pretest scores for the 2003– 2004 and 2004–2005 trainee cohorts.
Conclusions.—Short-term results indicate that the course described improves trainee knowledge of L&M issues.
Interference of Asian, American, and Indian (Ashwagandha) Ginsengs in Serum Digoxin Measurements by a Fluorescence Polarization Immunoassay Can Be Minimized by Using a New Enzyme-Linked Chemiluminescent Immunosorbent or Turbidimetric Assay
Authors: Dasgupta Amitava , Kang Edward , Olsen Margaret , Actor Jeffrey K. , Datta Pradip 
Published: February 2021

Abstract
Context.—Ginsengs are widely used by the general population. These herbs interfere with serum digoxin measurement using the fluorescence polarization immunoassay.
Objective.—To assess potential interference of different ginsengs (Asian, American, and Indian, also known as Ashwagandha) in vitro and in vivo in a mouse model by using a new enzyme-linked chemiluminescent immunosorbent digoxin assay and an existing turbidimetric assay. Comparisons were made with the fluorescence polarization immunoassay.
Design.—Aliquots of drug-free serum pools were supplemented with ginseng and apparent digoxin concentrations were measured using enzyme-linked chemiluminescent immunosorbent digoxin assay, turbidimetric assay, and fluorescence polarization immunoassay digoxin assays. Mice were fed with different ginseng preparations and apparent digoxin concentrations were measured 1 and 3 hours later. In a separate experiment, aliquots of serum digoxin pools were further supplemented with ginsengs and the serum digoxin concentrations were measured again.
Results.—A significant apparent digoxin concentration was observed both in vitro and in vivo using the fluorescence polarization immunoassay, but no apparent digoxin concentration was observed using enzyme-linked chemiluminescent immunosorbent digoxin assay and turbidimetric assay. No interference was observed with enzyme-linked chemiluminescent immunosorbent digoxin assay and turbidimetric assay when digoxin serum pools were further supplemented with various ginsengs.
Conclusions.—It was concluded that both enzyme-linked chemiluminescent immunosorbent and turbidimetric digoxin assays are free from ginseng interferences.
Blood Management
Authors: Goodnough Lawrence T. , Shander Aryeh 
Published: February 2021

AbstractContext.—We provide an overview of the principles of blood management: the appropriate use of blood and blood components, with a goal of minimizing their use.Objective.—To review the strategies that exploit combinations of surgical and medical techniques, technologic devices, and pharmaceuticals, along with an interdisciplinary team approach that combines specialists who are expert at minimizing allogeneic blood transfusion.Data Sources.—A search on Medline and PubMed for the terms English and humans used in articles published within the last 20 years.Conclusions.—Blood management is most successful when multidisciplinary, proactive programs are in place so that these strategies can be individualized to specific patients.
Emerging Eosinophilic (Allergic) Esophagitis: Increased Incidence or Increased Recognition?
Authors: Vanderheyden Andrew D. , Petras Robert E. , DeYoung Barry R. , Mitros Frank A. 
Published: February 2021

Abstract
Context.—Eosinophilic esophagitis is a disease of the esophagus with distinct histologic features (prominent intraepithelial eosinophils, particularly superficial with clustering) and characteristic endoscopic features (trachealization, white plaques). The presence of intraepithelial eosinophils had been recognized since 1982 as indicative of reflux esophagitis but little attention was initially paid to their numbers or location. Eosinophilic esophagitis has been recently described and there have been a number of reports that its incidence is on the rise. It had been our impression that eosinophilic esophagitis was being seen more frequently, perhaps resulting from some environmental change.
Objective.—To investigate the increased prevalence of eosinophilic esophagitis.
Design.—We analyzed a similar group of cases from 2005 (n = 150) as compared with 1990 (n = 115). Consecutive patients with mucosal esophageal biopsies from May through June of the respective years were included in the analysis. Patients with Barrett metaplasia or with carcinoma were excluded. The highest density of intraepithelial eosinophils for each patient was recorded as the number of intraepithelial eosinophils per single high-power field. The patients were categorized by the number of intraepithelial eosinophils per high-power field with those cases with greater than 20 intraepithelial eosinophils per high-power field representing eosinophilic esophagitis.
Results.—There was no difference in the incidence of eosinophilic esophagitis between 1990 and 2005.
Conclusions.—The apparent increased incidence of eosinophilic esophagitis is largely a result of an increase in recognition rather than an increase in disease resulting from an environmental factor.
Primary Osteosarcoma of the Breast: Report of 2 Cases
Authors: Bahrami Armita , Resetkova Erika , Ro Jae Y. , Ibañez Joe D. , Ayala Alberto G. 
Published: February 2021

Abstract
Two distinct histologic variants of primary breast osteosarcoma in 2 elderly women are described. The first patient was an 88-year-old woman with a long-standing, slow-growing, 18-cm mass in her right breast. The second patient was a 96-year-old woman with a recently self-detected, painless, 7.5-cm lump in her left breast. Clinically, there was no evidence of metastasis, and both women underwent simple mastectomy. Histologic features of both specimens were those of high-grade primary breast osteosarcoma. The first patient's tumor was classified as a chondroblastic variant, and the second as an osteoblastic variant of osteosarcoma. The patients were alive without evidence of local recurrence or hematogenous spread at a 16- and 4-month follow-up, respectively. Primary mammary osteosarcoma should be distinguished from metaplastic/ sarcomatoid carcinoma with heterologous osseous/cartilaginous differentiation or malignant phyllodes tumor because it has a different biological behavior and requires a different treatment approach.
Breast Carcinoma in Uganda: Microscopic Study and Receptor Profile of 45 Cases
Authors: Roy Indrojit , Othieno Emmanuel 
Published: February 2021

Abstract
Context.—Histologic and receptor data on breast carcinoma in Uganda are scarce. Estrogen receptor status is not routinely available. Breast cancer blocks from Uganda were studied in Montreal, Canada, and clinical correlations subsequently discussed in Kampala, Uganda.
Objective.—To correlate histologic features (tumor type, histologic grade), receptor profile (estrogen receptor, progesterone receptor, and HER2/neu), and age in Ugandan women.
Design.—Pathology reports for 2000–2004 from Nsambya Hospital, reporting invasive breast carcinoma, provided 45 microscopically confirmed cases.
Results.—Seventy-three percent of patients were 50 years or younger. Histologic types were invasive ductal carcinoma (78%) and “good” prognosis types (11%). Overall 40% were grade 3, but 48% of invasive ductal carcinomas were grade 3. Estrogen receptor was positive in 60% overall and in 51% of invasive ductal carcinomas. HER2/neu was overexpressed in 11%; 36% were “triple” negative (estrogen receptor, progesterone receptor, HER2/neu negative).
Conclusions.—Breast carcinoma in Ugandan women presents at a younger age and is histologically and by receptor profile more aggressive than carcinoma in Caucasian women.
Postmortem Whole-Body Computed Tomography Angiography Visualizing Vascular Rupture in a Case of Fatal Car Crash
Authors: Flach Patricia M. , Ross Steffen G. , Bolliger Stephan A. , Preiss Ulrich S. , Thali Michael J. , Spendlove Danny 
Published: February 2021

Abstract
In addition to the increasingly significant role of multislice computed tomography in forensic pathology, the performance of whole-body computed tomography angiography provides outstanding results. In this case, we were able to detect multiple injuries of the parenchymal organs in the upper abdomen as well as lesions of the brain parenchyma and vasculature of the neck. The radiologic findings showed complete concordance with the autopsy and even supplemented the autopsy findings in areas that are difficult to access via a manual dissection (such as the vasculature of the neck). This case shows how minimally invasive computed tomography angiography can serve as an invaluable adjunct to the classic autopsy procedure.
Intradural Extramedullary Leptomeningeal Hemangioblastomatosis and Paraneoplastic Limbic Encephalitis Diagnosed at Autopsy: An Unlikely Pair
Authors: Ramachandran Rageshree , Lee Han Sung , Matthews Brandy , Shatzel Alan , Tihan Tarik 
Published: February 2021

Abstract
Typical cerebellar or spinal cord hemangioblastoma is often solitary and has a benign clinical course, whereas disseminated hemangioblastomatosis is extremely rare. We report a 75-year-old man with disseminated “leptomeningeal” hemangioblastomatosis and concurrent paraneoplastic limbic encephalitis who died of this disease. The patient presented with gait problems and cognitive deficits, and was diagnosed with a cervical spinal tumor. Surgical resection achieved an apparent gross total resection, but later the patient began experiencing severe cognitive decline. His condition progressively deteriorated during the next few months, and he died 15 months after his initial surgery. Autopsy revealed disseminated extramedullary intradural hemangioblastomatosis with extensive leptomeningeal nodules involving the entire spinal cord, medulla, pons, and midbrain, as well as histologic features of limbic encephalitis. There was no evidence of von Hippel–Lindau disease, and no specific etiology was identified for the dementia. To the best of our knowledge, this is the first case of limbic encephalitis occurring in the setting of disseminated hemangioblastomatosis.
A Unique Case of Mantle Cell Lymphoma With an Aberrant CD5−/CD10+ Immunophenotype and Typical Morphology
Authors: Sriganeshan Vathany , Blom Thomas R. , Weissmann David J. 
Published: February 2021

Abstract
Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma with a poor prognosis that may be confused with less aggressive diseases, such as small lymphocytic lymphoma and follicular lymphoma. In many cases immunophenotyping, particularly analysis of reactivity for CD5 and CD10, is an important adjunct to morphology that usually distinguishes MCL from follicular lymphoma; the former is CD5+/CD10−, whereas follicular lymphoma is the reverse. We report a case of MCL, initially diagnosed as follicular lymphoma, that at presentation expressed neither CD5 nor CD10. At relapse, it was still CD5−, but CD10 was now detected. Studies for a t(11;14) translocation and CYCLIN D1 protein expression, however, permitted a revised diagnosis of MCL. An MCL with this immunophenotype and classical morphology has not been previously reported.