bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can Features Evaluated in the Routine Pathologic Assessment of Lymph Node–Negative Estrogen Receptor–Positive Stage I or II Invasive Breast Cancer Be Used to Predict the Oncotype DX Recurrence Score?
Authors: Auerbach Jena , Kim Mimi , Fineberg Susan 
Published: February 2021

Abstract
Context.—Oncotype DX is a multigene reverse transcription–polymerase chain reaction assay used to quantify recurrence risk in patients with stage I or II estrogen receptor–positive, lymph node–negative invasive breast cancer. The results are reported as a Recurrence Score (RS). The 16 cancer genes evaluated include a proliferation set, hormone receptor set, and HER2 set. The activity of these genes is addressed by pathologic assessment of breast cancers.
Objective.—To determine if factors evaluated in pathologic evaluation of breast cancer could be used to predict Oncotype DX results.
Design.—We studied 138 cases of invasive breast cancer for which Oncotype DX results and pathology data were available. Grading was performed by using Nottingham grading system. For hormone receptor immunostaining, 10% nuclear staining was considered a positive result.
Results.—Oncotype DX RS was low in 81 cases, intermediate in 44 cases, and high in 13 cases. All 6 cases with both a negative progesterone receptor (PR) and a mitotic count score of 3 had a high RS. All 12 cases with both a negative PR and a mitotic count score greater than 1 had either an intermediate or high RS. Although Nottingham grade, PR status, mitotic count score, tumor size, and nuclear grade were each significantly associated with RS, in bivariate analyses the only variables that remained independently predictive of an intermediate or high RS score in a multivariate logistic regression model were negative PR and mitotic count score greater than 1.
Conclusions.—Our study suggests that a mitotic count score greater than 1 combined with a negative PR result, as determined by pathologic assessment, could serve as a marker for an intermediate or high Oncotype DX RS.
Ocular Melanoma
Authors: Laver Nora V. , McLaughlin Margaret E. , Duker Jay S. 
Published: February 2021

Abstract
Context—Intraocular melanoma of the ciliary body and choroid is the most common primary ocular malignant tumor in adults and the most common noncutaneous melanoma.
Objective—To describe the most salient clinical features, histopathologic findings, and treatment modalities of intraocular melanoma, as well as the novel therapies currently being tested.
Data Sources—Clinically, it is important to determine which lesions carry a worse prognosis so as to offer patients the best treatment modalities available. Tumor location, size, histopathology, cytogenetic abnormalities, and tumor profiling are all used in determining the risk of death from metastatic disease of uveal melanocytic lesions. Despite successful local tumor control, up to 50% of patients have metastatic disease within 15 years of diagnosis; there is no effective treatment for metastatic disease.
Conclusions—Pathologists should be aware of the importance of tumor gross description, cellular histopathology classification, the use of fine-needle aspiration biopsy coupled with cytogenetics, and the new classification of uveal malignant melanomas that is based on chromosome 3 status.
Primary Mediastinal (Thymic) Large B-Cell Lymphoma: A Short Review With Brief Discussion of Mediastinal Gray Zone Lymphoma
Authors: Hutchinson Charles Blake , Wang Endi 
Published: February 2021

AbstractPrimary mediastinal (thymic) large B-cell lymphoma (PMBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL). It commonly presents as a bulky lesion in the anterior-superior mediastinum with symptoms related to local invasion or compression. Microscopic examination typically shows infiltration of medium-large cells surrounded by collagen fibrosis. The neoplastic cells express B-cell markers, and CD30 often shows heterogeneous staining. Comparative genomic hybridization has identified gains in loci of 9p24 and 2p15 as well as Xp11.4-21 and Xq24-26. Amplification of REL and BCL11A at 2p as well as elevated expression of JAK2, PDL1, and PDL2 at 9p has been demonstrated. Nodular sclerosis classic Hodgkin lymphoma needs to be differentiated from PMBCL and cases with overlapped features have been described as mediastinal gray zone lymphoma. Primary mediastinal (thymic) large B-cell lymphoma carries a favorable prognosis in comparison to conventional DLBCL.
Proficiency Survey-Based Evaluation of Clinical Total and Allergen-Specific IgE Assay Performance
Authors: Hamilton Robert G. 
Published: February 2021

Abstract
Context.—The diagnostic algorithm for human allergic disease involves confirmation of sensitization by detection of allergen-specific immunoglobulin E (IgE) antibody in individuals suspected of having allergic disease because of a history of allergic symptoms after known allergen exposure. Previous studies showed wide disparity among clinically reported allergen-specific IgE levels from different serologic assays.
Objective.—To validate the relative analytic performance (sensitivity, interassay reproducibility, linearity/parallelism, intermethod agreement) of clinically used total and allergen-specific IgE assays by using College of American Pathologists' Diagnostic Allergy “SE” Proficiency Survey data.
Design.—Data from 2 SE survey cycles were used to assess relative analytic performance of the ImmunoCAP (Phadia), Immulite (Siemens Healthcare-Diagnostics), and HYTEC 288 (HYCOR-Agilent Technologies) total and allergen-specific IgE assays. In each cycle, 2 recalcified plasma pools from atopic donors were diluted twice with IgE-negative serum and evaluated in approximately 200 federally certified clinical laboratories for total IgE and IgE antibody to 5 allergen specificities. Statistical analysis evaluated analytic sensitivity, linearity, reproducibility, and intermethod agreement.
Results.—Interlaboratory intramethod, intermethod, and interdilution agreement of all 6 clinically used total serum IgE assays were excellent, with coefficients of variation (CVs) below 15%. Interlaboratory intramethod, and interdilution agreement of 3 clinically used allergen-specific IgE assays were also excellent with CVs below 15%. However, intermethod CVs identified between-assay disagreement greater than 20% in 80% of allergen-specific IgE measurements. Allergen reagents and patients' immune response heterogeneity are suggested probable causes.
Conclusions.—Clinical total and allergen-specific IgE assays display excellent analytic sensitivity, precision, reproducibility, and linearity. Marked variability in quantitative estimates of allergen-specific IgE from clinically used automated immunoassays is a concern that may be ameliorated with component allergen use.
Utilization of Fluorescence In Situ Hybridization in the Diagnosis of 230 Mesenchymal Neoplasms: An Institutional Experience
Authors: Tanas Munir R. , Rubin Brian P. , Tubbs Raymond R. , Billings Steven D. , Downs-Kelly Erinn , Goldblum John R. 
Published: February 2021

Abstract
Context—Mesenchymal neoplasms harbor characteristic translocations and amplification of gene regions amenable to evaluation by fluorescence in situ hybridization (FISH).
Objective—To determine the utility of FISH in the diagnosis of mesenchymal neoplasms.
Design—Two hundred thirty soft tissue cases analyzed by FISH were reviewed retrospectively.
Results—Morphologic patterns where FISH was used included high-grade round cell sarcomas (n  =  67), nonmyogenic spindle cell sarcomas (n  =  40), low-grade myxoid neoplasms (n  =  34), adipocytic neoplasms (n  =  20), and melanocytic neoplasms (n  =  19). Fifty cases did not fit into the previously mentioned categories. SYT FISH (96% of monophasic synovial sarcomas were positive; 0% of malignant peripheral nerve sheath tumor were positive) and DDIT3 FISH (100% of myxoid/round cell liposarcomas; no other neoplasm positive) were very sensitive and specific. EWSR1 FISH was very sensitive and specific in the differential diagnosis of melanocytic neoplasms (88% of clear cell sarcomas were positive; all melanomas were negative). EWSR1 FISH was sensitive among high-grade round cell sarcomas (positive in 100% of desmoplastic small round cell tumors and 96% of Ewing sarcoma/primitive neuroectodermal tumors) but not specific because clear cell sarcoma, extraskeletal myxoid chondrosarcoma, and a subset of round cell liposarcomas also harbor rearrangements of EWSR1. FUS FISH was very sensitive in detecting low-grade fibromyxoid sarcomas (91% positive) but not specific because most myxoid/round cell liposarcomas also contain rearrangements of FUS. All atypical lipomatous tumors were positive for amplification of MDM2, whereas all lipomas were negative. FOXO1A FISH was positive in ∼70% of cases of alveolar rhabdomyosarcoma.
Conclusion—FISH is a useful adjunct in the diagnosis of mesenchymal neoplasms.
Parathyroid Pathology: Hyperparathyroidism and Parathyroid Tumors
Authors: Carlson Diane 
Published: February 2021

Abstract
Context.—Primary hyperparathyroidism is the most common cause of hypercalcemia in the outpatient setting. Parathyroid adenomas are common, unlike other parathyroid tumors. This review presents a brief summary of current updates in parathyroid pathology.
Objective.—To review parathyroid development and discuss issues in hyperparathyroidism and diagnosis of parathyroid lesions, including the application of immunohistochemistry and molecular biology.
Data Sources.—Current texts, PubMed (National Library of Medicine) articles, and Memorial Sloan-Kettering Cancer Center archives.
Conclusions.—Primary hyperparathyroidism is most commonly seen with sporadic adenomas, followed by hyperplasia, multiple adenomas, and carcinoma. Autosomal dominant familial hyperparathyroidism syndromes should be considered in the evaluation of patients with parathyroid lesions, particularly in association with parathyroid carcinoma. While the incidence of parathyroid carcinoma is quite low, it is seen with a greater frequency in those patients with hyperparathyroidism-jaw tumor syndrome. Inactivation of the tumor suppressor gene HRPT2 can be identified in a large number of parathyroid carcinomas. Hence, germline HRPT2 gene mutations may reflect unrecognized syndromic patients.
Use of a Linear Array for the Detection of Human Papillomavirus Genotypes in Head and Neck Cancer
Authors: Black Candice C. , Bentley Heather A. , Davis Thomas H. , Tsongalis Gregory J. 
Published: February 2021

Abstract
Context—Tumors of the head and neck commonly arise from the squamous and respiratory mucosa that lines the nasal and oral cavity, sinuses, pharynx, and larynx. The rate of oropharyngeal cancers diagnosed among Americans younger than 50 years is increasing. Infection of the oropharynx and tonsils by the human papillomavirus (HPV) has been linked to preneoplasia and cancer.
Objectives—To evaluate the Roche Linear Array HPV Genotyping test kit to identify, and then specifically genotype, HPV in formalin-fixed, paraffin-embedded tissues.
Design—We evaluated the performance of this assay for accuracy, for intra-assay and interassay precision, and for its limit of detection, using materials with known HPV status. Sixteen tumor tissues with the following origins were evaluated: 1 ocular, 1 hypopharynx, 8 tonsil, 1 retromolar trigone, 3 tongue, 1 anal, and 1 lymph node. DNA from formalin-fixed, paraffin-embedded tumor sections was isolated and amplified in duplicate, with positive and negative controls, using primers specific to the polymorphic L1 region of the HPV genome. Thirty-seven genotypes were tested using the linear array. The amplified product (450 base pairs) was visualized by gel electrophoresis and, if positive, reflexed to HPV genotyping.
Results—Nine of the 16 tumors analyzed were HPV positive. The detected genotypes included HPV 6, 16, and 69.
Conclusions—The Roche Linear Array HPV Genotyping test is an easy-to-use method for determining HPV genotype in the routine analysis of formalin-fixed, paraffin-embedded tumors. This assay is robust and can be performed routinely in a clinical laboratory setting.
Molecular Diagnostics in Melanoma: Current Status and Perspectives
Authors: Dadras Soheil S. 
Published: February 2021

Abstract
Context.—In the current “molecular” era, the advent of technology, such as array-based platforms, systems biology, and genome-wide approaches, has made it possible to examine human cancers, including melanoma, for genetic mutations, deletions, amplification, differentially regulated genes, and epigenetic changes. Advancement in current technologies is such that one can now examine ribonucleic acid (RNA), deoxyribonucleic acid (DNA), and protein directly from the patient's own tumor.
Objective.—To apply these new technologies in advancing molecular diagnostics in melanoma has historically suffered from a major obstacle, namely, the scarcity of fresh frozen, morphologically defined tumor banks, annotated with clinical information. Recently, some of the new platforms have advanced to permit utilization of formalin-fixed, paraffin-embedded (FFPE) tumor specimens as starting material.
Data Sources.—This article reviews the latest technologies applied to FFPE melanoma sections, narrowing its focus on the utility of transcriptional profiling, especially for melastatin; comparative genomic hybridization; BRAF and NRAS mutational analysis; and micro ribonucleic acid profiling.
Conclusion.—New molecular approaches are emerging and are likely to improve the classification of melanocytic neoplasms.
Epithelioid Angiomyolipoma: A Morphologically Distinct Variant That Mimics a Variety of Intra-abdominal Neoplasms
Authors: Mete Ozgur , van der Kwast Theodorus H. 
Published: February 2021

Abstract
This review examines the histopathologic, immunohistochemical, ultrastructural, and molecular biologic features of epithelioid angiomyolipoma (EAML), with an emphasis on the differential diagnosis of intra-abdominal EAML. Epithelioid angiomyolipoma is an uncommon mesenchymal tumor with malignant potential, frequently associated with tuberous sclerosis complex. Histologically, EAML is characterized by sheets or nests of large polygonal epithelioid cells with abundant eosinophilic or occasionally clear cytoplasm, often with prominent nucleoli, and EAML may include multinucleated and markedly pleomorphic forms. As these tumors share a distinctive perivascular epithelioid cell phenotype, they belong to the PEComa tumor family. Nearly all EAMLs show immunoreactivity for both melanocytic and myoid markers. Ultrastructurally, EAMLs show evidence of melanogenesis by the presence of premelanosomes. Epithelioid angiomyolipoma can pose significant diagnostic challenges as it mimics morphologically a variety of neoplasms including renal cell carcinoma, renal oncocytoma, adrenal cortical neoplasm, epithelioid smooth muscle tumor, epithelioid peripheral nerve sheath tumor, epithelioid gastrointestinal stromal tumor, epithelioid melanoma, hepatoblastoma, and hepatocellular carcinoma. The variation in immunophenotype in these tumors requires a prudent use of immunohistochemistry, which may occasionally need complementation by electron microscopy to establish the correct diagnosis.
Blood Bank Safety Practices: Mislabeled Samples and Wrong Blood in Tube—A Q-Probes Analysis of 122 Clinical Laboratories
Authors: Grimm Erin , Friedberg Richard C. , Wilkinson David S. , AuBuchon James P. , Souers Rhona J. , Lehman Christopher M. 
Published: February 2021

Abstract
Context.—Although a rare occurrence, ABO incompatible transfusions can cause patient morbidity and mortality. Up to 20% of all mistransfusions are traced to patient misidentification and/or sample mislabeling errors that occur before a sample arrives in the laboratory. Laboratories play a significant role in preventing mistransfusion by identifying wrong blood in tube and rejecting mislabeled samples.
Objectives.—To determine the rates of mislabeled samples and wrong blood in tube for samples submitted for ABO typing and to survey patient identification and sample labeling practices and sample acceptance policies for ABO typing samples across a variety of US institutions.
Design.—One hundred twenty-two institutions prospectively reviewed inpatient and outpatient samples submitted for ABO typing for 30 days. Labeling error rates were calculated for each participant and tested for associations with institutional demographic and practice variable information. Wrong-blood-in-tube rates were calculated for the 30-day period and for a retrospective 12-month period. A concurrent survey collected institution-specific sample labeling requirements and institutional policies regarding the fate of mislabeled samples.
Results.—For all institutions combined, the aggregate mislabeled sample rate was 1.12%. The annual and 30-day wrong-blood-in-tube aggregate rates were both 0.04%. Patient first name, last name, and unique identification number were required on the sample by more than 90% of participating institutions; however, other requirements varied more widely.
Conclusions.—The rates of mislabeled samples and wrong blood in tube for US participants in this study were comparable to those reported for most European countries. The survey of patient identification and sample labeling practices and sample acceptance policies for ABO typing samples revealed both practice uniformity and variability as well as significant opportunity for improvement.
Pathologic Evaluation of Axillary Dissection Specimens Following Unexpected Identification of Tumor Within Sentinel Lymph Nodes
Authors: Gutierrez Jessica , Dunn Daniel , Bretzke Margit , Johnson Eric , O'Leary John , Stoller Diane , Fraki Sally , Diaz Leslie , Lillemoe Tamera 
Published: February 2021

AbstractContext—Axillary lymph node dissection has been the standard of care after identification of a positive sentinel lymph node for breast cancer patients.Objective—To determine the likelihood of non–sentinel lymph node involvement for patients with negative sentinel node by frozen section, who are subsequently found to have tumor cells in the sentinel node by permanent section levels and/or cytokeratin immunohistochemistry.Design—One hundred three patients with invasive breast cancer exhibiting negative frozen section evaluation of their sentinel node, but later found to have isolated tumor cells (n  =  46), micrometastasis (n  =  46), or metastases (n  =  11) in their sentinel node by permanent sections or immunohistochemistry, were enrolled in this prospective cohort study and underwent completion axillary dissection.Results—Six of 46 patients (13%) with isolated tumor cells in their sentinel node, 15 of 46 patients (33%) with micrometastasis in their sentinel node, and 2 of 11 patients (18%) with metastasis in their sentinel node had additional findings in the nonsentinel nodes. These findings resulted in a pathologic stage change in 2 patients. Predictors of positive nonsentinel nodes were 2 or more positive sentinel nodes (P  =  .002), sentinel nodes with micrometastasis versus isolated tumor cells (P  =  .03), and those with angiolymphatic invasion (P  =  .04).Conclusions—Our findings lend support to axillary node dissection for patients with micrometastasis or metastasis in their sentinel nodes. However, studies with clinical follow-up are needed to determine whether axillary node dissection is necessary for patients with isolated tumor cells in sentinel nodes.
The Impact of Specially Designed Digital Games-Based Learning in Undergraduate Pathology and Medical Education
Authors: Kanthan Rani , Senger Jenna-Lynn 
Published: February 2021

AbstractContext—The rapid advances of computer technologies have created a new e-learner generation of “Homo-zappien” students that think and learn differently. Digital gaming is an effective, fun, active, and encouraging way of learning, providing immediate feedback and measurable process. Within the context of ongoing reforms in medical education, specially designed digital games, a form of active learning, are effective, complementary e-teaching/learning resources.Objective—To examine the effectiveness of the use of specially designed digital games for student satisfaction and for measurable academic improvement.Design—One hundred fourteen students registered in first-year pathology Medicine 102 had 8 of 16 lecture sessions reviewed in specially designed content-relevant digital games. Performance scores to relevant content sessions were analyzed at midterm and final examinations. Seventy-one students who registered in second-year pathology Medicine 202 were exposed to the games only during the final examination, with the midterm examination serving as an internal matched-control group. Outcome measures included performance at midterm and final examinations. Paired 2-tailed t test statistics compared means. A satisfaction survey questionnaire of yes or no responses analyzed student engagement and their perceptions to digital game-based learning.Results—Questions relevant to the game-play sessions had the highest success rate in both examinations among 114 first-year students. In the 71 second-year students, the examination scores at the end of the final examination were significantly higher than the scores on the midterm examination. Positive satisfaction survey noted increased student engagement, enhanced personal learning, and reduced student stress.Conclusions—Specially constructed digital games-based learning in undergraduate pathology courses showed improved academic performance as measured by examination test scores with increased student satisfaction and engagement.
Expression and Phosphorylation of Eukaryotic Translation Initiation Factor 4E Binding Protein 1 in B-Cell Lymphomas and Reactive Lymphoid Tissues
Authors: Kodali Dhatri , Rawal Ajay , Ninan Mary J , Patel Manish R , Mesa Hector , Knapp Dennis , Schnitzer Bertram , Kratzke Robert A , Gupta Pankaj 
Published: February 2021

AbstractContext.—Cap-mediated messenger RNA translation controlled by the eukaryotic initiation factor 4F (eIF-4F) complex plays a key role in human cancer. eIF-4F activity is controlled by a repressor binding protein (4E-BP1), which promotes translation when phosphorylated.Objective.—To examine the level of expression and phosphorylation of 4E-BP1 in various subtypes of B-cell lymphoma and reactive lymphoid tissues.Design.—Archival formalin-fixed, paraffin-embedded B-cell lymphoma samples and reactive lymphoid tissues were immunostained and examined for expression of 4E-BP1 and phosphorylated 4E-BP1. Expression of components of the eIF-4F complex and unphosphorylated and phosphorylated 4E-BP1 was confirmed using Western immunoblotting on lysates of frozen lymphoma samples and reactive tissues.Results.—Immunohistochemical analysis demonstrated weak to undetectable 4E-BP1 staining within benign, reactive germinal centers (N  =  10). In contrast, 4E-BP1 was consistently expressed (moderate to strong staining) in 98% of various subtypes of mature B-cell lymphoma (N  =  50). 4E-BP1 expression was also demonstrable in all 4 lymph nodes with in situ or partial involvement by follicular lymphoma and in all 12 cases of BCL2-negative lymphoma. The level of phosphorylation of 4E-BP1 in lymphomas, evaluated by immunohistochemistry, was heterogeneous.Conclusions.—The immunohistochemical expression pattern of 4E-BP1 exhibits regional and cellular specificity in reactive lymphoid tissues and may offer a diagnostic tool for distinguishing reactive follicles from neoplastic B-cell proliferations.