bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal Clinical Evaluation of a Novel Antibody Cocktail for Detection of High-Grade Squamous Intraepithelial Lesions on Cervical Cytology Specimens
Authors: Tambouret Rosemary H. , Misdraji Joseph , Wilbur David C. 
Published: February 2021

Abstract
Context.—Although cervical cancer screening by cytology is successful, the test continues to show relatively poor operating characteristics. Cell cycle markers may enhance detection of high-grade squamous intraepithelial lesions.
Objective.—To determine the clinical usefulness of ProExC, an immunocytochemical assay for cell cycle components, performed on routine cervical cytology samples.
Design.—Cervical cytology samples were collected using the SurePath method. Residual cells remaining after preparation of the Papanicolaou-stained slide were used to make a second slide for ProExC staining using an indirect polymer-based immunoperoxidase method. Only adequately cellular slides were evaluated for the presence of nuclear staining within cytologically abnormal epithelial cells. Results were correlated with clinical follow-up.
Results.—Six hundred twenty-four samples were satisfactorily cellular and stained. Correlation with clinical follow-up for subsequent cervical intraepithelial neoplasia 2+ on biopsy/high-grade squamous intraepithelial lesion on cytology (CIN 2+/HSIL) showed that 434 results were true negative, 78 true positive, 18 false-negative, and 94 false-positive, resulting in a sensitivity/specificity of 81%/82%. When ProExC results were combined with any level of cytologic atypia, sensitivity for CIN 2+/HSIL was 92% and specificity was 84%.
Conclusions.—ProExC shows promise as an aid in enhancing the sensitivity and specificity of cervical cytology for subsequent CIN 2+/HSIL and may be useful in identifying those cervical lesions most apt to progress.
Touch Imprint Cytology in Tumor Tissue Banks for the Confirmation of Neoplastic Cellularity and for DNA Extraction
Authors: Mangia Anita , Chiriatti Annalisa , Chiarappa Patrizia , Incalza Maria Angela , Antonaci Giovanni , Pilato Brunella , Simone Giovanni , Tommasi Stefania , Paradiso Angelo 
Published: February 2021

Abstract
Context.—Learning the characteristics of frozen tissue samples stored in tumor banks for biological studies remains a problem.
Objective.—To assess the use of touch imprint cytology on fresh tissue samples as a rapid and reliable method of determining the presence and quantity of neoplastic cells before freezing.
Design.—Touch imprint cytology was performed on 259 specimens of operable breast cancer. Touch imprints were prepared from fresh tissue specimens before freezing samples for storage. Each tumor sample was imprinted on a glass slide and stained with hematoxylin-eosin. Tumor cellularity was quantified as negative, poor, moderate, or rich.
Results.—A significant correlation was found between samples with a tumor size greater than 2 cm and high tumor cellularity (P = .03; χ2 test). Furthermore, 35% of ductal tumors showed higher tumor cellularity compared with lobular tumors (P &lt; .001; χ2 test). No association was found between lymph node status and tumor grade. When samples for which more than 2 imprints were available were examined, tumor cellularity among imprints of the same sample showed an overall agreement of 0.67 (P &lt; .001; κ statistic). It was also determined that the higher the cellularity, the higher the agreement. Our data also showed concordance of 0.87 (P &lt; .001; κ statistic) between touch imprint cytology imprints and histologic sections from contiguous tumor. Moreover, 11 randomly selected samples underwent DNA extraction, polymerase chain reaction, and sequencing to verify the feasibility of DNA analyses. We found that DNA from touch imprint cytology was amplifiable and suitable for direct sequencing.
Conclusions.—Touch imprint cytology may represent an important step in the quality control of tumor cellularity of breast cancer specimens designed to be stored in tumor biobanks and a valid method for assessing the suitability of such tissue for further biomorphologic and biomolecular applications.
Myelodysplastic Syndromes Arising in Patients With Germline TP53 Mutation and Li-Fraumeni Syndrome
Authors: Talwalkar Sameer S. , Cameron Yin C. , Naeem Rizwan C. , John Hicks M. , Strong Louise C. , Abruzzo Lynne V. 
Published: February 2021

Abstract
Context.—Li-Fraumeni syndrome (LFS), characterized by predisposition to early onset of a variety of malignancies, is usually associated with germline mutation of the tumor-suppressor gene, TP53. Mutation carriers are at increased risk of multiple primary tumors, many of which arise in previous radiation-therapy sites. In patients with LFS, acute myeloid leukemia is uncommon and myelodysplastic syndrome (MDS) is rare.
Objective.—To evaluate the morphologic, cytogenetic, and molecular diagnostic findings of 3 unique cases of MDS arising in patients with germline TP53 mutation, 2 with classic LFS.
Design.—We searched the Li-Fraumeni Syndrome Registry in the Department of Genetics at the University of Texas M. D. Anderson Cancer Center (Houston, Texas) and identified 3 patients with documented germline TP53 mutations or LFS who had developed MDS during a period of 6 years (2000–2005). The clinical, cytogenetic, and molecular diagnostic data and bone marrow aspirate smears and biopsies on all patients were reviewed. Immunohistochemical staining with antibody to p53 was also performed.
Results.—Two patients met the criteria for classic LFS; one had no history of malignancy in first-degree relatives. The MDS followed chemotherapy and radiation therapy and progressed to acute myeloid leukemia in 2 patients. Cytogenetic analysis demonstrated chromosome 5 abnormalities in a complex karyotype in all cases. Two patients died, one of acute myeloid leukemia and one with glioblastoma multiforme, MDS, and persistent pancytopenia.
Conclusions.—Patients with LFS may develop MDS, which is most likely therapy-related and is associated with cytogenetic markers of poor prognosis.
Clinicopathologic Analysis of Cutaneous Lymphoma in Taiwan: A High Frequency of Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type, With an Extremely Poor Prognosis
Authors: Liao Jia-Bin , Chuang Shih-Sung , Chen Hsiu-Chiung , Tseng Hui-Hwa , Wang Jyh-Seng , Hsieh Pin-Pen 
Published: February 2021

Abstract
Context.—Primary cutaneous lymphoma is an uncommon, extranodal lymphoma, and it is usually more indolent with a better prognosis than its histologically similar systemic counterpart is.
Objectives.—To illustrate the clinicopathologic features of cutaneous lymphomas in Taiwan and to compare the relative frequencies of subtypes of cutaneous lymphoma among different geographic areas.
Design.—A total of 56 patients with cutaneous lymphomas were retrospectively collected and were reclassified according to the 2005 World Health Organization and the European Organization for Research and Treatment of Cancer and the 2008 World Health Organization classifications. The data were compared with those from other studies for different geographic areas.
Results.—Thirty-one (55%) tumors were primary cutaneous lymphomas, and twenty-five (45%) tumors were secondary or concurrent cutaneous lymphomas. Among primary cutaneous lymphomas, 23 cases (74%) were T-cell or natural killer–cell lymphomas, and 8 cases (26%) were B-cell lymphomas. The most common types were extranodal natural killer/T-cell lymphoma, nasal type, and primary cutaneous peripheral T-cell lymphoma, unspecified (5 cases each; 16%). In contrast with other primary cutaneous B-cell and T-cell lymphomas, either primary or secondary extranodal cutaneous natural killer/T-cell lymphomas, nasal type, had extremely poor prognoses (1-year overall survival, 0%).
Conclusions.—This study showed that the frequency of subtypes of primary cutaneous lymphoma varied in different geographic areas. Compared with the Western countries, there was a higher frequency of extranodal natural killer/T-cell lymphoma, nasal type, and a lower frequency of mycosis fungoides in Taiwan. Extranodal natural killer/T-cell lymphoma, nasal type, also had an extremely poor prognosis compared with other lymphomas.
Intrapulmonary Ectopic Liver After Orthotopic Heart Transplantation
Authors: Mehta Rupal I. , Lai Chi K. , Kee Stephen , Fishbein Michael C. 
Published: February 2021

Abstract
We report a case of a 54-year-old woman who was found to have multiple intrapulmonary nodules detected on imaging 33 months after orthotopic heart transplantation. Needle biopsy of 2 discrete nodules showed benign hepatic tissue, consistent with intrapulmonary foci of ectopic liver. In this report, the clinical, radiologic, microscopic, and fluorescent in situ hybridization results of 2 biopsied nodules are described. A brief review of the published information on ectopic liver is also presented. To our knowledge, multiple ectopic foci of the liver have never been reported at any site. Furthermore, this is the first reported case that involves a transplant recipient, thereby introducing additional, unique ramifications to this rare but intriguing entity.
Merkel Cell Carcinoma
Authors: Wong Hannah H. , Wang Jun 
Published: February 2021

Abstract
Merkel cell carcinoma is a rare, highly aggressive neuroendocrine cutaneous neoplasm with a variable clinical presentation. Histologically, it is a predominantly dermal-based lesion composed of monotonous small round cells with scanty cytoplasm, often difficult to differentiate from small round cell tumors, metastatic small cell carcinoma, blastic hematologic malignancies, and melanoma. The malignant cells express both epithelial and neuroendocrine immunohistochemical markers, a unique feature that helps differentiate this neoplasm from other entities. The pathogenesis of Merkel cell carcinoma has remained a mystery despite its association with various chromosomal abnormalities and with growth signaling and apoptotic pathways. The discovery of the Merkel cell polyomavirus suggests another clue to its pathogenesis. This virus integrates into band 3p14 and promotes carcinogenesis by altering the activity of tumor suppressor and cell cycle regulatory proteins. This discovery of the Merkel cell polyomavirus may greatly enhance our understanding of this rare aggressive neoplasm and allow further advancements in treatment.
Comparison of ThinPrep Preparations to Other Preparation Types in Gastrointestinal Cytology: Observations From the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology
Authors: Clayton Amy C. , Bentz Joel S. , Wasserman Patricia G. , Schwartz Mary R. , Souers Rhona J. , Chmara Beth Anne , Laucirica Rodolfo , Clary Karen M. , Moriarty Ann T. ,   for the College of American Pathologists Cytopathology Resource Committee
Published: February 2021

Abstract
Context.—Differences in participant responses for ThinPrep (TP) and non-ThinPrep (NTP) preparations for gastrointestinal cytology challenges, which circulated in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology (CAP NGC), may help to identify performance variations between preparation types.
Objective.—To compare the performance of TP-prepared slides of gastrointestinal exfoliative cytology specimens to that of NTP preparations in the CAP NGC program.
Design.—Participant responses between 2000 and 2007 were evaluated for esophageal wash/brush, gastric wash/brush, and biliary tract brush specimens with a reference diagnosis of adenocarcinoma, squamous cell carcinoma, carcinoid, or spindle cell neoplasm. ThinPrep challenges were compared with NTP preparations (conventional smears, cytospins) for discordant responses.
Results.—In all, 6023 pathologist responses and 3825 cytotechnologist responses were reviewed. Non-ThinPrep preparations comprised 93% (n  =  11 588) of the challenges, while 7% (n  =  912) were TP material. A match for a “positive/suspicious” diagnosis was seen in 88.5% of NTP and 95.9% of TP preparations (P &lt; .001). These results were statistically significant when the specific reference diagnosis was adenocarcinoma (P &lt; .001). Overall performance of cytotechnologists was not different from that of pathologists (89.2% versus 89.0%; P  =  .75). Cytotechnologists had better performance for detecting squamous cell carcinoma (96.3% versus 92.6%; P &lt; .001), while pathologists had better performance for detecting spindle cell neoplasm (79.7% versus 42.9%; P &lt; .001).
Conclusions.—ThinPrep preparations performed significantly better than NTP preparations in gastrointestinal cytology specimens circulated in an interlaboratory comparison program. Performance varied by reference interpretation, with the best performance for the interpretation of adenocarcinoma. Cytotechnologists and pathologists performed at the same level overall, but with differences for the diagnosis of spindle cell neoplasm and squamous carcinoma.
Acute Erythroid Leukemia
Authors: Zuo Zhuang , Polski Jacek M. , Kasyan Armen , Medeiros L. Jeffrey 
Published: February 2021

Abstract
Context.—Acute erythroid leukemia (AEL) is an uncommon type of acute myeloid leukemia (AML), representing less than 5% of all cases. Acute erythroid leukemia is characterized by a predominant erythroid proliferation, and in the current World Health Organization (WHO) classification scheme there are 2 subtypes: erythroleukemia (erythroid/myeloid leukemia) and pure erythroid leukemia. Morphologic findings are most important for establishing the diagnosis. The erythroleukemia subtype, which is most common, is defined as the presence of 50% or more erythroid precursors and 20% or more blasts in the nonerythroid component. The pure erythroid leukemia subtype is composed of 80% or more immature erythroblasts. Although these morphologic criteria appear straightforward, AEL overlaps with other types of AML and myelodysplastic syndrome that are erythroid rich.
Objective.—To provide an update of AEL, including clinical presentation, morphologic features, immunophenotype, and cytogenetic and molecular data. As the erythroleukemia subtype is most common, the literature and this review are biased towards this subtype of AEL.
Data Sources.—Clinicopathologic, cytogenetic, and molecular information were extracted from our review of pertinent literature and a subset of AEL cases in the files of The University of Texas M. D. Anderson Cancer Center (Houston) and University of South Alabama (Mobile).
Conclusions.—The current WHO criteria for establishing the diagnosis of AEL reduce the frequency of this entity, as cases once classified as the erythroleukemia subtype are now reclassified as other types of AML, particularly AML with myelodysplasia-related changes and therapy-related AML. This reclassification also may have prognostic significance for patients with the erythroleukemia subtype of AEL. In contrast, the current WHO criteria appear to have little impact on the frequency and poor prognosis of patients with the pure erythroid leukemia subtype of AEL. Molecular studies, preferably using high-throughput methods, are needed for a better understanding of the pathogenesis of AEL, and for developing diagnostic and prognostic markers.
Challenges and Opportunities in the Adoption of College of American Pathologists Checklists in Electronic Format: Perspectives and Experience of Reporting Pathology Protocols Project (RPP2) Participant Laboratories
Authors: Hassell Lewis A. , Parwani Anil V. , Weiss Lawrence , Jones Michael A. , Ye Jay 
Published: February 2021

Abstract
Context.—The site-specific cancer checklists developed by the College of American Pathologists have the potential to improve the quality of data derived from pathology reports and incorporated into cancer registry databases and are now mandated report elements by various accrediting bodies. A pilot project, funded by the Centers for Disease Control National Project for Cancer Registries in 2004, brought 4 pathology services in 3 states, with differing baseline implementations of the checklists, the opportunity to partner with their state National Project for Cancer Registry and their laboratory information system vendors to evaluate the feasibility of using electronically encoded College of American Pathologists cancer checklists for melanoma and tumors of the breast and prostate.
Objectives.—To identify existing and potential barriers to adoption of electronically encoded checklists and to also identify unique benefits not associated with text-only uses of the checklists.
Design.—Participants mapped an implementation process from their current state to an electronic checklist–capable state. For a sample of cases of melanoma, prostate, and breast cancers, the checklist elements were captured and transmitted to the registry using Health Level 7 (version 2.3.1). Process assessments with adoption of electronic checklists were conducted to assess pathologist effect and other potential barriers. An evaluation of the utility and usefulness of electronic checklists was performed after the project.
Results.—All 4 laboratories successfully performed the capture of individual data elements from the College of American Pathologists checklist into a discrete format suitable for electronic transmission. The effect on pathologist performance and laboratory workflow was neutral. Points of resistance were identified in the checklists and in individual users. Specific challenges in individual laboratories varied according to the personnel and the baseline system in use. Clinical responses to implemented changes were generally positive. Analysis of the postproject experiences of the laboratories showed expansion of use and additional utility in some, but not all, laboratories.
Conclusions.—Pathology laboratory adoption of the College of American Pathologists cancer checklists in an electronic format suited to direct transmission to cancer registries poses business case, information technology, and human resource challenges. Laboratory information system vendor readiness to upgrade systems to facilitate this process helps to reduce some of these challenges. Personalities and preferences in practices may yet pose barriers to widespread adoption.
Interference of Hawthorn on Serum Digoxin Measurements by Immunoassays and Pharmacodynamic Interaction With Digoxin
Authors: Dasgupta Amitava , Kidd Laura , Poindexter Brian J. , Bick Roger J. 
Published: February 2021

Abstract
Context.—Hawthorn is an herb indicated for treating cardiac illness. Because a patient taking digoxin may also take hawthorn, we investigated potential interference of hawthorn in serum digoxin measurements using immunoassays as well as pharmacodynamic interaction between hawthorn and digoxin. Hawthorn contains alkaloids that are structurally similar to digoxin and may interfere with serum digoxin measurement using immunoassays. In addition, hawthorn has cardioactive properties similar to digoxin.
Objective.—To study potential pharmacodynamic interaction between hawthorn and digoxin.
Design.—The effects of hawthorn extract on serum digoxin measurements using Digoxin III (Abbott Laboratories, Abbott Park, Illinois) and the Tina-Quant digoxin assay (Roche Diagnostics, Indianapolis, Indiana) were investigated using 2 different brands of extract. To study the pharmacodynamic interaction between hawthorn and digoxin, we used an isolated adult rat cardiomyocyte system, measuring calcium transients by real-time fluorescence spectrophotometry.
Results.—Hawthorn interfered only with the Digoxin III immunoassay but had no effect on the Tina-Quant assay. Both hawthorn extracts increased intracellular calcium levels, but the lack of additive response with digoxin suggests both may bind to the same site of Na, K adenosine triphosphatase.
Conclusion.—Because of interference of hawthorn with a digoxin immunoassay and pharmacodynamic interaction with digoxin, a patient receiving digoxin should avoid hawthorn.
Molecular Pathogenesis of Sporadic Melanoma and Melanoma-Initiating Cells
Authors: Kong Yunyi , Kumar Suresh M. , Xu Xiaowei 
Published: February 2021

Abstract
Recent advances in molecular genetics and cancer stem cell biology have shed some light on the molecular basis of melanomagenesis. In this review, we will focus on major genetic alterations in the melanoma, particularly pathways involved in cell proliferation, apoptosis, and tumor suppression. The potential role of melanoma-initiating cells during melanomagenesis and progression will also be discussed. Understanding pathogenesis of melanoma may uncover new diagnostic clues and therapeutic targets for this increasingly prevalent disease.
Thin Melanoma
Authors: Elder David E 
Published: February 2021

Abstract
Context.—The incidence of malignant melanoma is increasing and a preponderance of the melanomas diagnosed today are “thin” in terms of Breslow criteria. Although thin melanomas, as a group, are associated with a very good prognosis, a subset of these tumors may metastasize and cause death. These cases can be identified by using prognostic models, including the “standard” American Joint Committee on Cancer criteria, and other attributes identified in follow-up studies.
Objective.—To review the history of concepts of prognostic modeling in melanoma, focusing on thin melanomas.
Data Sources.—Selected literature.
Conclusions.—About 40 years ago, it was realized that malignant melanoma, once almost uniformly fatal, could be divided into categories with better or worse prognosis through the use of prognostic models. The first simple models, Clark levels of invasion and Breslow thickness, are still in use. Thickness remains the single most useful variable. Breslow recognized that melanomas less than 0.76 mm in thickness were associated with a very good prognosis, with no metastases in his limited initial study. The American Joint Committee on Cancer selected a cutoff of 1.0 mm, which achieves a similar result, with stage modifiers, although some metastases and deaths do occur with stage I lesions. Clark demonstrated an almost equally good prognosis for his level II invasive melanomas and recognized that most of these lesions, although invasive, lacked the ability to form tumors or to undergo mitosis in the dermis and were therefore “nontumorigenic” and “nonmitogenic” and lacked competence for metastasis. Studies of these low-risk melanomas have led to the development of criteria for earlier diagnosis and a steady, but still inadequate, improvement in prognosis for melanoma overall. Multivariable models currently can identify groups of patients within the “thin melanoma” category whose prognosis varies, from a disease-free survival of close to 100% to about 70%. Prognosis declines more or less linearly with increasing thickness, modified by ulceration, mitotic rate, and other attributes.