bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mönckeberg Sclerosis Revisited: A Clarification of the Histologic Definition of Mönckeberg Sclerosis
Authors: Micheletti Robert G. , Fishbein Gregory A. , Currier Judith S. , Fishbein Michael C. 
Published: February 2021

Abstract
Context.—Medial calcification of muscular arteries is known as Mönckeberg sclerosis (MS). Although this was first described in 1903, disagreement persists over its precise histologic appearance. Some, including Mönckeberg, have written that the media alone are calcified, whereas others maintain that both the media and internal elastic lamina (IEL) are involved. Since vascular calcification is of great interest to investigators and clinicians, defined criteria for classifying calcified arterial lesions are important.
Objective.—To clarify the histologic definition of MS with regard to calcification of the IEL.
Design.—We reviewed slides from 14 incisional and excisional surgical biopsies and autopsy specimens containing arteries with previously diagnosed MS. We looked specifically for medial and IEL calcification and used von Kossa, alizarin red, and trichrome/elastic stains to confirm our findings. We also performed a literature search on the histologic appearance of MS.
Results.—Both medial and IEL calcification were present in all specimens. Medial calcification extended alongside calcified IEL. In focal regions, calcification appeared limited to the IEL, with minimal medial calcification. Occasionally, calcified nodules in the media appeared separated from the IEL yet were connected to it in other planes of section. Despite these variations in appearance, IEL involvement was universal. Of 25 journal articles and texts, 10 state that MS involves the IEL with calcification, whereas 15 state or suggest that it does not.
Conclusions.—Our findings indicate MS involves both the IEL and media with calcification in spite of inconsistencies on this point in the medical literature.
Flat Epithelial Atypia of the Breast
Authors: Lerwill Melinda F. 
Published: February 2021

Abstract
Flat epithelial atypia is a presumably neoplastic alteration of terminal duct-lobular units that is characterized by the replacement of the native luminal epithelium by ductal cells demonstrating low-grade cytologic atypia. The atypical cells maintain a “flat” pattern of growth without evidence of architectural atypicality. Morphologic, immunohistochemical, and molecular investigations support that flat epithelial atypia represents an early step in the evolution of low-grade ductal carcinomas. It is frequently seen in association with atypical ductal hyperplasia, low-grade ductal carcinoma in situ, invasive tubular carcinoma, and lobular neoplasia. The risk for subsequent breast carcinoma remains to be defined, but flat epithelial atypia likely represents a nonobligate precursor with an extended time course to progression. Certain benign alterations may superficially mimic its appearance; careful attention to cytologic and architectural characteristics can help one distinguish these unrelated entities from flat epithelial atypia.
The Thyroid Gland: Recurring Problems in Histologic and Cytologic Evaluation
Authors: Faquin William C. 
Published: February 2021

Abstract
Nodules of the thyroid gland are frequently encountered, occurring in up to 7% of the population, and although most of these nodules are benign, carcinomas of the thyroid gland are the most common malignancy of the endocrine system. Although the different types of thyroid carcinoma are few, a wide variety of recurring problems exists in both their histologic and cytologic evaluation. Here, I will review a selected group of problematic areas, including unusual histologic variants of follicular adenoma, criteria for diagnosing minimally invasive follicular carcinoma, the use of fine-needle aspiration as a screening test for follicular neoplasia, challenging variants of papillary carcinoma, and features of poorly differentiated carcinoma.
The Diagnostic Value of Ki-67 and repp86 in Distinguishing Between Benign and Malignant Mesothelial Proliferations
Authors: Taheri Zohreh Mohammad , Mehrafza Mehdi , Mohammadi Forozan , Khoddami Maliheh , Bahadori Moslem , Masjedi Mohammad Reza 
Published: February 2021

AbstractContext.—The differentiation of benign mesothelial proliferations from malignant mesotheliomas may be difficult, especially when evaluating small specimens from pleural biopsies.Objective.—To explore the potential value of 2 proliferative cell markers, Ki-67 and restrictedly expressed proliferation–associated protein 86 kDa (repp86), in distinguishing between malignant mesothelioma (MM) and benign reactive mesothelial hyperplasia (MH).Design.—Thirty-six cases of MM from 26 men and 10 women with a mean age of 62.9 years (range, 36–80 years) and 22 cases of benign reactive MH from 14 male and 8 female patients with a mean age of 51.5 years (range, 15– 88 years) were included in this study. The proliferative status of the lesions was assessed by immunohistochemistry using monoclonal antibodies to Ki-S2 (repp86) and Ki-S5 (Ki-67). The labeling indices were quantified.Results.—The mean labeling indexes for Ki-67 in MM and benign reactive MH were 24.6% (range, 1%–66%) and 6.23% (range, 0%–25%), respectively. The mean labeling indexes for repp86 in MM and benign reactive MH were 26.3% (range, 0%–50%) and 3.26% (range, 0%– 21%), respectively. The average proliferative cell count was significantly higher in MM compared with benign reactive MH (P &lt; .001). Furthermore, both markers showed a significant correlation in their expression in MM and benign reactive MH (r = 77.5, P &lt; .001). Sensitivities of 88% and 92% and specificities of 92% and 94% were obtained at a cutoff point of 9% for Ki-67 and repp86, respectively.Conclusions.—Used in combination, Ki-67 and repp86 appear to be useful markers in differentiating MM from benign reactive MH.
Posttransplant Adenoviral Enteropathy in Patients With Small Bowel Transplantation
Authors: Adeyi Oyedele A. , Randhawa Parmjeet A. , Nalesnik Michael A. , Ochoa Erin R. , Abu-Elmagd Kareem M. , Demetris Anthony J. , Wu Tong 
Published: February 2021

Abstract
Transplant patients on immunosuppression represent a risk group for opportunistic infections, including adenoviral infections. The clinical and histopathologic findings of posttransplant adenoviral enteropathy in 3 adult intestinal transplant patients are described. The histopathologic pitfalls for the differential diagnosis between intestinal adenoviral enteropathy and acute rejection are discussed. Adenoviral enteropathy is an opportunistic infection that may follow aggressive treatment for small bowel allograft rejection, but which may require no specific treatment. It is associated with mild mixed inflammation in the lamina propria and slight increase of crypt apoptosis, resembling low-grade acute rejection. The identification of characteristic viral inclusions in the surface or crypt epithelium points to the diagnosis of adenoviral enteropathy, in spite of the increased crypt apoptosis.
Epstein-Barr Virus–Associated Lymphoepithelioma-like Gastric Carcinoma
Authors: Pavithra Herath Chaturika Harshini , Chetty Runjan 
Published: February 2021

Abstract
This article provides an overview of the pathology of Epstein-Barr virus (EBV)–associated lymphoepithelioma-like gastric carcinoma, highlighting its unique morphology and clinical features. Lymphoepithelioma-like gastric carcinoma is a rare neoplasm of the stomach with a better prognosis than conventional adenocarcinoma. Most lymphoepithelioma-like gastric carcinomas are associated with EBV infection, while a subset is associated with microsatellite instability. Even though there is a very strong association with EBV, its exact role in carcinogenesis still remains to be elucidated in those cancers that harbor EBV. Distinctive histology and demonstration of EBV using in situ hybridization, polymerase chain reaction, or Southern blotting and immunohistochemistry for the DNA mismatch repair genes or polymerase chain reaction analysis of microsatellite loci to assess microsatellite instability helps to make the diagnosis.
A Teaching Database for Diagnosis of Hematologic Neoplasms Using Immunophenotyping by Flow Cytometry
Authors: Nguyen Andy N. D. , De Jitakshi , Nguyen Jacqueline , Padula Anthony , Qu Zhenhong 
Published: February 2021

Abstract
Context.—In the diagnosis of lymphomas and leukemias, flow cytometry has been considered an essential addition to morphology and immunohistochemistry. The interpretation of immunophenotyping results by flow cytometry involves pattern recognition of different hematologic neoplasms that may have similar immunologic marker profiles. An important factor that creates difficulty in the interpretation process is the lack of consistency in marker expression for a particular neoplasm. For this reason, a definitive diagnostic pattern is usually not available for each specific neoplasm. Consequently, there is a need for decision support tools to assist pathology trainees in learning flow cytometric diagnosis of leukemia and lymphoma.
Objective.—Development of a Web-enabled relational database integrated with decision-making tools for teaching flow cytometric diagnosis of hematologic neoplasms.
Design.—This database has a knowledge base containing patterns of 44 markers for 37 hematologic neoplasms. We have obtained immunophenotyping data published in the scientific literature and incorporated them into a mathematical algorithm that is integrated to the database for differential diagnostic purposes. The algorithm takes into account the incidence of positive and negative expression of each marker for each disorder.
Results.—Validation of this algorithm was performed using 92 clinical cases accumulated from 2 different medical centers. The database also incorporates the latest World Health Organization classification for hematologic neoplasms.
Conclusions.—The algorithm developed in this database shows significant improvement in diagnostic accuracy over our previous database prototype. This Web-based database is proposed to be a useful public resource for teaching pathology trainees flow cytometric diagnosis.
Poorly Differentiated Gastroenteropancreatic Neuroendocrine Carcinoma Associated With X-Linked Hyperimmunoglobulin M Syndrome
Authors: Malhotra Reenu K. , Li Wei 
Published: February 2021

AbstractGastroenteropancreatic neuroendocrine tumors are uncommon tumors representing 2% of all gastrointestinal tumors. We report a case of a 21-year-old man with X-linked hyperimmunoglobulin M (hyper-IgM) syndrome who presented with diarrhea and jaundice. An ultrasound and magnetic resonance imaging showed multiple variable-sized lesions in the liver and peripancreatic lymphadenopathy. The morphologic and immunohistochemical features of the biopsies from the liver and lymph node were consistent with poorly differentiated neuroendocrine carcinoma. Hyper-IgM syndrome is a rare primary immunodeficiency disease characterized by low serum IgG, IgA, and IgE levels with normal or elevated IgM levels. These patients are at a higher risk for developing malignancies, particularly adenocarcinoma of the gastrointestinal tract and lymphoma. A review of the literature of gastroenteropancreatic neuroendocrine tumors is presented with the discussion of a possible relationship of these tumors with immunodeficiency.
Translocations and Amplifications of Chromosome 12 in Liposarcoma Demonstrated by the LSI CHOP Breakapart Rearrangement Probe
Authors: Willmore-Payne Carlynn , Holden Joseph , Turner Kristi C. , Proia Alan , Layfield Lester J. 
Published: February 2021

Abstract
Context.—Liposarcomas display a number of molecular abnormalities involving chromosome 12. Myxoid and round cell liposarcomas are characterized by t(12;16)(q13; p11) or t(12;22)(q13;q12) translocations. Amplifications occur within the 12q13-15 region of atypical lipomatous tumors and well-differentiated liposarcomas but not lipomas.
Objective.—To investigate the performance characteristics of the LSI CHOP Breakapart Rearrangement Probe for the diagnosis of myxoid/round cell liposarcomas and atypical lipomas/well-differentiated liposarcomas.
Design.—We investigated a series of lipomatous neoplasms (5 lipomas, 5 well-differentiated liposarcomas, 22 myxoid/round cell liposarcomas, 2 liposarcomas not otherwise specified, and 2 dedifferentiated liposarcomas) and normal myometrium for abnormalities in the q13-15 region of chromosome 12. Cases were studied for the presence or absence of t(12;16)(q13;p11) or t(12;22)(q13;q12) translocations by the LSI CHOP Breakapart Rearrangement Probe. These probes contain a sequence encompassing the SAS and CDK4 genes. Four or more copies of this sequence were considered to represent amplification of these genes.
Results.—Rearrangement of the CHOP gene was seen in all evaluable myxoid liposarcomas. Rearrangements were seen in 1 dedifferentiated liposarcoma but not in normal myometrium or lipomas. Probe signal amplification was seen in all 5 well-differentiated liposarcomas and 1 myxoid liposarcoma. No signal amplification was seen in lipomas or myometrium.
Conclusions.—Demonstration of translocations t(12; 16)(q13;p11) and t(12;22)(q13;q12) by the LSI CHOP Breakapart Rearrangement Probe appears to correlate with round cell/myxoid liposarcoma. The probe also demonstrated amplification of the 12q13-15 region in well-differentiated liposarcomas, making it useful for the diagnosis of these neoplasms. In a significant percentage of cases, high background fluorescence or poor probe staining made interpretation difficult.
Clinicopathologic Characteristics, CpG Island Methylator Phenotype, and BRAF Mutations in Microsatellite-Stable Colorectal Cancers Without Chromosomal Instability
Authors: Kakar Sanjay , Deng Guoren , Sahai Vaibhav , Matsuzaki Koji , Tanaka Hirofumi , Miura Soichuro , Kim Young S. 
Published: February 2021

Abstract
Context.—The 2 chief pathways implicated in colorectal carcinogenesis, microsatellite instability and chromosomal instability, are not present in 20% to 37% of cases.
Objective.—To determine whether the CpG island methylator phenotype (CIMP) pathway, characterized by simultaneous methylation of several known tumor suppressor genes, is the principal underlying mechanism in cases without chromosomal or microsatellite instability, and to determine the significance of CIMP pathway and BRAF mutations in microsatellite-stable (MSS) cases.
Design.—Clinicopathologic features and chromosomal instability status by loss of heterozygosity analysis were determined in 83 cases of colorectal cancer in which microsatellite instability, CIMP status, BRAF mutations, and KRAS mutations were previously known.
Results.—Microsatellite instability was present in 14 cases (17%). Of the 69 MSS cases (83%), chromosomal instability manifested by LOH involving at least one locus was observed in 53 cases (64%). Hence, 16 (19%) of 83 colorectal cancer cases showed neither microsatellite instability nor chromosomal instability. These cases had a low incidence of CIMP (3/16; 19%) and BRAF mutation (1/16; 6%). The 5-year survival in these cases was significantly better compared with MSS cases with chromosomal instability (80% vs 54%, P = .02). BRAF mutations were identified in 10 MSS cases (15%). BRAF mutation in MSS cases correlated significantly with high-level chromosomal instability (P = .009) and poor 5-year survival (0% vs 70%, P &lt; .001).
Conclusions.—CIMP does not appear to play a key role in colorectal cancer without microsatellite instability and chromosomal instability. These cases have a better survival, probably related to absence of significant chromosomal instability. BRAF mutations in MSS cases are associated with high levels of chromosomal instability that are likely responsible for the adverse outcomes in these cases.
Cytogenetic Studies of 24 Renal Epithelial Tumors With von Hippel-Lindau and Fragile Histidine Triad Protein Expression Correlation
Authors: Gayrard Nathalie , Cacheux Valère , Iborra François , Mourad Georges , Argilés Àngel 
Published: February 2021

Abstract
Context.—Deletion of the short arm of chromosome 3 (3p deletion) is a cytogenetic abnormality generally associated with clear cell renal cell carcinoma, the most aggressive form of renal epithelial tumor.
Objective.—To cytogenetically characterize 24 renal tumors in order to check the incidence and the type of 3p deletions, as well as to identify new genes putatively participating in renal tumorigenesis and test the protein products of the von Hippel-Lindau (VHL) and fragile histidine triad (FHIT) genes.
Design.—We analyzed 24 renal tumors by conventional cytogenetics, comparative genomic hybridization, and fluorescence in situ hybridization. We then performed a comparative expression study of the proteins pVHL and Fhit.
Results.—In our series of 24 renal tumors, the 3p deletion was the most frequent genetic alteration (15/24); the other features were partial trisomy 5q, 8p deletion, and monosomy 9 and 14. The 3p deletion was long and terminal, and no interstitial deletion was identified. By immunohistochemistry, we found that for the 2 genes of interest, VHL and FHIT, loss or decrease in protein expression were very frequently observed in clear cell renal cell carcinoma and not always associated with a 3p deletion (14/20 in clear cell renal cell carcinoma).
Conclusions.—Our studies characterize the 3p deletion as long and terminal and identify no interstitial deletion in that chromosome. Fhit and pVHL protein expression loss appear to be independent, as they can be dissociated. Our data are supportive of a role for FHIT (in addition to VHL) in renal tumorigenesis. No other gene with particular potential interest in renal tumorigenesis could be identified among the selected genes.
Dramatically Elevated Circulating Tumor Cell Numbers in a Patient With Small Cell Neuroendocrine Carcinoma of the Prostate
Authors: Chan Fanny , Goodman Oscar , Fink Louis , Vogelzang Nicholas J. , Pomerantz David , Khoury Joseph D. 
Published: February 2021

Abstract
Detection of circulating tumor cells in whole blood is a useful prognostic tool for patients with castration-resistant prostate cancer, as well as for patients with metastatic breast cancer and colorectal carcinoma. In this report, we present the case of a patient with neuroendocrine small cell prostate cancer with normal prostate-specific antigen levels throughout the course of disease but who had markedly elevated circulating tumor cells, as detected with the CellSearch (Veridex) system.
BRAF Mutation Testing in Colorectal Cancer
Authors: Sharma Shree G. , Gulley Margaret L. 
Published: February 2021

Abstract
Colorectal cancer is the second most common cause of cancer death in the United States. Understanding the biochemical pathways underlying carcinogenesis has paved the way for more effective treatments and better outcomes. BRAF mutation testing has a role in (1) differentiating sporadic colorectal cancer from Lynch syndrome, (2) identifying cancers lacking BRAF mutation that are more likely to respond to epidermal growth factor receptor inhibitor therapy, and (3) conferring worse prognosis in colorectal cancer that is microsatellite stable. Several analytic methods are available to reliably detect BRAF mutations. Real-time polymerase chain reaction identifies the most common BRAF mutation, V600E, in frozen or paraffin-embedded colorectal cancer tissue. Traditional DNA sequencing and the somewhat more-sensitive pyrosequencing method can detect multiple alternative BRAF mutations that are predicted to constitutively activate signaling through the MAPK pathway, promoting tumor growth and survival. Pathologists play an important role in assay validation as well as in consulting with clinicians about indications for testing, ensuring quality of testing, and interpreting results in conjunction with other clinicopathologic factors important in the management of affected patients.
Cardiac Sarcoidosis: A Pathology-Focused Review
Authors: Lagana Stephen M. , Parwani Anil V. , Nichols Larry C. 
Published: February 2021

AbstractContext.—Sarcoidosis is a granulomatous disease of unclear etiology. It is not commonly fatal, but when sarcoidosis is fatal, it is most often from cardiac involvement and when sarcoidosis involves the heart, it frequently causes death. The disease presents diagnostic challenges both clinically and histologically.Objectives.—To review the histology of cardiac sarcoidosis and the histologic differential diagnosis of cardiac granulomatous disease and to review the epidemiology and gross pathology of cardiac sarcoid as well as discuss current controversies, clinical diagnostic criteria, and proposed mechanisms of pathogenesis.Data Sources.—We reviewed the literature searchable on PubMed as well as selected older studies revealed by our review of the recent literature. Photographs were taken from cases on file at the University of Pittsburgh Medical Center (Pittsburgh, Pennsylvania) and Columbia University Medical Center (New York, New York).Conclusions.—Sarcoidosis is a focal or disseminated granulomatous disease that likely represents the final common pathway of various pathogenic insults in a genetically susceptible host. The type of insult may influence the specific sarcoid phenotype. Controversy still abounds, but many areas of investigation around sarcoidosis are yielding exciting discoveries and bringing us closer to a richer understanding of this puzzling disease.
Implementation and Assessment of a Resident Curriculum in Evidence-Based Transfusion Medicine
Authors: Haspel Richard L. 
Published: February 2021

Abstract
Context.—Given the number of controversial issues in transfusion medicine, an understanding of biostatistics and evidence-based medicine is invaluable. No detailed curricula that address teaching critical appraisal of the transfusion medicine literature have been published or evaluated.
Objective.—To design, implement, and evaluate an evidence-based transfusion medicine curriculum.
Design.—Four hour-long training sessions in journal club format were designed for a 2-month transfusion medicine rotation for clinical pathology residents. A previously validated survey was administered precurriculum and postcurriculum to gauge changes in resident self-reported attitudes and confidence regarding biostatistics methods and critical appraisal of the medical literature. Residents were also asked to evaluate the course regarding content, execution, and utility.
Results.—Seven second-year residents participated in the sessions. Following the curriculum there were statistically significant increases in the residents’ self-reported ability to appraise critically and search the medical literature (P  =  .05). Resident confidence interpreting an article's statistical results also significantly improved (P  =  .01). There was also a significant change in the residents' desire to learn more about statistics (P  =  .02). Resident reviews of the curriculum were overall extremely positive.
Conclusion.—A 4-session curriculum can have a significant effect on resident self-reported ability to appraise critically and understand the medical literature and help foster interest in biostatistics. Although based on small numbers, this study represents one of the first efforts to evaluate the efficacy of a transfusion medicine curriculum and can potentially serve as a starting point to better integrate and evaluate knowledge of evidence-based transfusion medicine during residency training.