bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Gene Expression Microarrays in the Evaluation of Lung Carcinoma Subtypes and DNA Copy Number
Authors: Sanchez-Cespedes Montserrat 
Published: February 2021

Abstract
Context.—The development of targeted therapies creates a need to accurately classify tumors. Among the more pressing needs are the identification of the complete catalog of genes that are altered in cancer and the accurate discrimination of tumors based on their genetic background.
Objectives.—To discuss the use of gene expression profiles to recapitulate the pathology and to distinguish the genetic background of non–small cell lung cancer. Also, to comment on using global analysis of gene expression to identify chromosomal regions carrying clusters of highly expressed genes, likely due to gene amplification. Gene amplification at these regions may target the activation of an oncogene critical to tumor development and potentially important in therapy.
Data Sources.—Review of relevant, recent literature on molecular alterations and expression analysis in lung cancer.
Conclusions.—The complexity of genetic and epigenetic alterations and the cell type of origin confer marked patterns of gene expression to lung tumors, which differentiate different tumor entities.
Reporting Guidelines for Clinical Laboratory Reports in Surgical Pathology
Authors: Goldsmith Jeffrey D. , Siegal Gene P. , Suster Saul , Wheeler Thomas M. , Brown Richard W. 
Published: February 2021

Abstract
Context.—The surgical pathology report (SPR) is an essential part of patient care because it documents the pathologic findings in tissues removed from patients for diagnostic or therapeutic reasons. Despite the importance of the SPR, exhaustive guidelines outlining the various elements of the SPR have not, to our knowledge, been published.
Objectives.—To outline recommendations delineating the required, preferred, and optional elements that should be included in the SPR. These guidelines, if implemented, will bring uniformity to the reporting of surgical pathology specimens.
Data Sources.—The Surgical Pathology Resource Committee of the College of American Pathologists compiled and prioritized the elements that have been included in various institutional SPRs. Additional data sources include the College of American Pathologists Laboratory Accreditation Program checklists and the recommendations of the Association of Directors of Anatomic and Surgical Pathology. Each element was assigned a priority of required, preferred, or optional. These priorities were discussed and consensus was reached. This report does not address issues of formatting or style substantively.
Conclusions.—These recommendations afford a framework for the creation of an SPR containing all of the components that are required or optimal for patient care.
Hepatic Angiomyolipoma
Authors: Petrolla Amber A. , Xin Wei 
Published: February 2021

Abstract
Hepatic angiomyolipoma is a rare, benign, hepatic mesenchymal neoplasm found in both males and females, and most commonly in adult females. Angiomyolipoma occurs most commonly in the kidneys. The liver represents the second most frequent site of involvement. Hepatic angiomyolipomas are composed of varying amounts of smooth muscle cells, adipose tissue, and vessels. The smooth muscle cell component is the most specific to the diagnosis. The smooth muscle cells can have varying morphologies and are positive for homatropine methylbromide–45 but are negative for hepatocyte paraffin 1 and S100 protein. The definitive diagnostic study remains the histologic examination of the surgically resected lesion coupled with immunohistochemical stains. The differential diagnosis includes hepatocellular carcinoma, hepatic adenoma, leiomyoma, hepatoblastoma, melanoma, and gastrointestinal stromal tumor. The immunohistochemical staining pattern differentiates this lesion from other malignant and benign liver lesions. If the diagnosis of hepatic angiomyolipoma has been made, it can be followed conservatively or surgically resected.
National HER2 Proficiency Test Results Using Standardized Quantitative Controls: Characterization of Laboratory Failures
Authors: Vani Kodela , Sompuram Seshi R. , Fitzgibbons Patrick , Bogen Steven A. 
Published: February 2021

Abstract
Context.—An important component in fostering test standardization for HER2 testing by immunohistochemistry is an appropriate positive control. We developed a new standardized, quantitative immunohistochemical HER2 control using a HER2 peptide covalently attached to glass microscope slides. The peptide controls can be formalin fixed or unfixed, providing the new capability of distinguishing errors associated with antigen retrieval from errors associated with the staining process itself.
Objective.—To investigate the causes of variability in HER2 immunohistochemistry staining performance. By comparing laboratory performance with both formalin-fixed and unfixed analyte controls, we aimed to distinguish problems associated with antigen retrieval from reagent or staining protocol deficiencies.
Design.—HER2 peptide analyte controls were printed on 2 slides that also contained unstained sections of invasive breast carcinomas and were mailed with the College of American Pathologists' 2006 HER2-B proficiency testing survey. Laboratory participants were asked to stain the 2 slides and return them for central review and quantification. This study is unique in combining central review with new quantitative HER2 controls.
Results.—Of 109 participants who returned evaluable stained slides, staining was suboptimal in 20 (18.3%) as judged by quantification of the peptide analyte controls and review of tissue sections. Of those, 35% failed due to antigen retrieval errors, 20% failed due solely to antibody or staining protocol problems, and the remainder failed due to a combination of the two.
Conclusions.—In practice, errors in HER2 testing are caused by variables associated with antigen retrieval and the reagents and staining protocol, as well as interpretive error. Analyte controls help distinguish these different causes.
Intraoperative Consultation/Final Diagnosis Correlation: Relationship to Tissue Type and Pathologic Process
Authors: White Valerie A. , Trotter Martin J. 
Published: February 2021

Abstract
Context.—The correlation of the diagnosis made at intraoperative consultation (IC) with the final diagnosis is one of the cornerstones of quality assurance in the anatomic pathology laboratory.
Objective.—To review correlation of IC diagnoses with final diagnoses during a 1-year period in a regionalized, multisite hospital setting in a major Canadian city.
Design.—One pathologist reviewed all surgical pathology cases at Calgary Laboratory Services from June 2004 through May 2005 that had an IC to extract the following data points: intraoperative diagnoses, final diagnoses, correlation between the two, anatomic site of the tissue on which the IC was requested, pathologic procedure requested of the IC, types of disagreements encountered, reasons for disagreement, and deferrals.
Results.—Intraoperative consultations occurred for 2812 specimens, of which 87 were discordant and 135 were deferred. Percent agreement was 96.75% (95% confidence interval, 96.08–97.42) with a κ statistic of 0.94 (95% confidence interval, 0.92–0.95). Lymph nodes for evaluation for metastases (427), thyroid/parathyroid (401), and central/peripheral nervous system (378) specimens were sent most frequently for IC, and the latter 2 tissue types accounted for the greatest number of disagreements. The most common assessments requested were the presence/ typing of a neoplasm (1161) and assessment of margins (730), which also accounted for the largest number of disagreements. Disagreements were most frequently due to interpretive (53) and gross sampling (23) errors; false-negative disagreements were nearly 3 times as common as false positives.
Conclusions.—The IC was an excellent diagnostic test. Agreement and deferral rates varied by specimen site and by type of assessment requested.
The Pathology of Pulmonary Disorders Due to Aspergillus spp
Authors: Kradin Richard L. , Mark Eugene J. 
Published: February 2021

Abstract
Diagnosing the range of pulmonary disorders caused by Aspergillus spp can be challenging. In instances of hypersensitivity responses to Aspergillus spp (ie, allergic bronchopulmonary aspergillosis, bronchocentric granulomatosis, and hypersensitivity pneumonitis), the surgical pathologist must be cognizant of their relationship to infection, as fungal organisms may be rare or absent from the biopsy specimens. Within the spectrum of opportunistic infection, it is critical to distinguish Aspergillus spp from other fungal mimics, as well as to discern whether infection is limited, progressive, or immanently life threatening. However, the surgical pathologist who establishes expertise in this area will be rewarded by the satisfaction of having contributed primarily to an important area of patient care. This article reviews the spectrum of pulmonary disorders due to infection by Aspergillus spp, with emphasis on the clinical implications of diagnosis.
Interface Dermatitis
Authors: Crowson A. Neil , Magro Cynthia M. , Mihm, Jr Martin C. 
Published: February 2021

AbstractInterface dermatitis can be classified based upon the cell type that dominates the infiltrate (ie, neutrophilic, lymphocytic, or lymphohistiocytic) or by the intensity of the interface inflammation. Regarding lymphocytic interface dermatitis, there are 2 broad categories: cell-poor interface dermatitis, when only a sparse infiltrate of inflammatory cells is present along the dermoepidermal junction, or cell rich, which typically occurs as a heavy bandlike infiltrate that obscures the basal layers of the epidermis. In the case of lymphocytic interface dermatitis, the latter is often termed a lichenoid interface dermatitis. This review focuses upon the mononuclear cell-predominant forms of interface dermatitis.
Lesions of the Bones of the Hands and Feet: A Study of 50 Cases
Authors: Uppin Shantveer G. , Sundaram C. , Umamahesh Matapathi , Chandrashekar P. , Rani Y. Jyotsna , Prasad V. B. N. 
Published: February 2021

AbstractContext.—The bones of the hands and feet constitute more than half of the bones in the human skeleton (106/ 206), but lesions occurring in them are infrequently reported. Although many of the lesions that occur in the rest of the skeletal bones can occur in bones of the hands or feet, their distribution and frequency differ.Objective.—To study lesions involving bones of the hands or feet.Design.—Retrospective study of all lesions involving bones of the hands or feet during the period from January 2000 to September 2006 from a university hospital in southern India. Clinical, radiologic, and pathologic features were reviewed.Results.—The 50 lesions encountered included 23 (46.0%) infections/inflammatory lesions, 16 (32.0%) benign tumors, 6 (12.0%) malignant tumors, and 5 (10.0%) tumorlike lesions. Giant cell tumor was the most common benign tumor. Malignant tumors involved the nonphalangeal bones, with chondrosarcoma the most common.Conclusions.—Lesions of the bones of the hands or feet are uncommon. Awareness and correlation of clinical, radiologic, and pathologic features help in making correct diagnoses.
Clinicopathologic Significance of Nuclear Grooves and Inclusions in Renal Cell Carcinoma: Image Database Construction and Quantitative Scoring
Authors: Lee Ju-Han , Han Eun Mee , Lin Zhen-Hua , Wu Zheng-Sheng , Lee Eung-Seok , Kim Young-Sik 
Published: February 2021

Abstract
Context.—Nuclear grooves and inclusions are major features of cancer. However, the nuclear irregularities in renal cell carcinoma (RCC) have not yet been well characterized.
Objective.—To determine the clinicopathologic significance of nuclear grooves and inclusions in RCC.
Design.—The frequencies or scores of nuclear grooves and inclusions were compared with the histologic subtype, nuclear grade, and TNM stage, as well as overall survival of RCC patients. For objective counting of nuclear irregularities, a relational image database was constructed and used for quantitative assessment.
Results.—Nuclear grooves and inclusions were seen in 96% and 65% of 110 RCC cases, respectively. The intranuclear inclusions were found more frequently in chromophobe and papillary types than in clear cell carcinoma (P &lt; .001). The nuclear scores, the sum of grooves or inclusions per 5000 tumor cells, were highly related to the histologic subtype (P &lt; .001). Clear cell RCCs with high inclusion scores (2 or more) were correlated with poorer overall survival in comparison to clear cell carcinomas with low inclusion scores (P = .04). The groove scores were highly associated with Fuhrman grade (P = .003) but not with overall survival of clear cell RCC patients (P = .65). In multivariate analysis, higher inclusion scores and advanced tumor stages (III/IV) were correlated with worse outcomes of clear cell RCC.
Conclusions.—Nuclear grooves and inclusions are histologic components of RCCs, especially chromophobe and papillary carcinomas. Furthermore, nuclear inclusions might be an independent prognostic factor for clear cell RCC.
Pancreatic Manifestations of von Hippel-Lindau Disease
Authors: Safo Anthony-Osei F. , Pambuccian Stefan E. 
Published: February 2021

Abstract
Von Hippel-Lindau disease is an uncommon, multisystem, multitumor disorder that can present in sporadic form but is more commonly inherited as an autosomal-dominant disease with high penetrance. Affected patients are at increased risk for developing multiple synchronous or metachronous benign or malignant, cystic, and vascular neoplasms of various organs. The characteristic neoplasms associated with von Hippel-Lindau are hemangioblastoma of the central nervous system and retina, clear cell renal cell carcinoma, and pheochromocytoma, but other lesions are well recognized. Pancreatic lesions, both primary and metastatic, are common, and several differential diagnostic possibilities must be considered.
MicroRNAs in Benign and Malignant Hematopoiesis
Authors: Bhagavathi Sharathkumar , Czader Magdalena 
Published: February 2021

AbstractMicroRNAs (miRNAs) are a family of 19- to 24-nucleotide noncoding RNAs that regulate messenger RNA function at the posttranscriptional and translational level. Recent literature demonstrates a significant role of miRNAs in normal and malignant hematopoiesis. Specific miRNAs have been shown to regulate each step of hematopoiesis starting at the level of multipotent progenitors through terminal stages of myeloid and lymphoid differentiation. Similarly, individual miRNAs and miRNA signatures have been associated with specific hematologic malignancies. There is accumulating evidence that miRNAs can be used for diagnostic, prognostic, and therapeutic purposes. This review highlights the current status of knowledge on miRNA in normal and malignant hematopoiesis.
Legal Aspects of Laboratory Medicine and Pathology for Residents and Fellows: A Curriculum for Pathology Training Programs
Authors: Otte Kimberly K. , Zehe Sharon C. , Wood Angela J. , Hernandez James S. , Karon Brad S. 
Published: February 2021

Abstract
Context.—Preparing residents and fellows to manage laboratories and pathology practices increasingly requires awareness of the law and a framework within which to manage legal risk in dealing with compliance, malpractice, and human resources issues.
Objectives.—To describe a curriculum for pathology and laboratory medicine residents and fellows that highlights activities most likely to result in adverse legal outcomes and to help trainees understand when the services of an attorney may be required.
Design.—The 3-hour course evolved as part of a comprehensive leadership and management curriculum designed to help meet systems-based practice and professionalism requirements. Didactic lectures and interactive case scenarios were presented, and participants then evaluated the course content and speakers on a 5-point scale (5  =  high). Short-term knowledge accumulation was assessed by comparison of performance on the laboratory administration section of the Resident In-Service Examination between junior residents who had not taken the course and senior residents who did take the course.
Results.—The course was evaluated by 72 trainees during a 5-year period (2004–2008); the mean overall rating was 4.6 (range, 3.5–5.0). Senior residents (n  =  37) had a mean (SD) score on the Resident In-Service Examination laboratory administration section of 521 (67) for 2004 through 2008. Junior residents (n  =  51), who had not yet completed the course, scored 470 (70) (P &lt; .001) for the same period.
Conclusions.—This curriculum met the needs of professionals entering careers in laboratory medicine and pathology and can be modified for other pathology and laboratory medicine training programs.
FLT3 Mutations at Diagnosis and Relapse in Acute Myeloid Leukemia: Cytogenetic and Pathologic Correlations, Including Cuplike Blast Morphology
Authors: McCormick Stanley R. , McCormick Matthew J. , Grutkoski Patricia S. , Ducker Gregory S. , Banerji Nilanjana , Higgins Rodney R. , Mendiola John R. , Reinartz John J. 
Published: February 2021

Abstract
Context.—Acquired mutations in the fms-like tyrosine kinase 3 gene (FLT3) adversely impact relapse risk after chemotherapy in patients with acute myeloid leukemia (AML). The FLT3 mutation status may differ at diagnosis and relapse, suggesting a potential role in chemoresistance, yet few reports have addressed the cytogenetic and pathologic correlates of FLT3 mutations in relapsed AML.
Objectives.—To determine FLT3 mutations at diagnosis and relapse in a cohort of adult patients with chemoresistant AML and to correlate mutation status with multiple variables.
Design.—We retrospectively determined FLT3 internal tandem duplication (FLT3/ITD) and FLT3 tyrosine kinase domain mutations in 50 diagnosis/relapse pairs. We correlated FLT3 status with karyotype, World Health Organization 2008 subtype, white blood cell count, biopsy cellularity, blast percentage, and the presence of invaginated (“cuplike”) blast nuclei.
Results.—In 11 of 50 patients (22%) the FLT3 mutation status differed at relapse and diagnosis, with a trend toward gain of FLT3/ITD (n  =  7) and loss of FLT3 tyrosine kinase domain (n  =  5) mutations. FLT3-mutated AMLs correlated with the World Health Organization 2008 subtype, AML, not otherwise specified, hyperproliferative features at diagnosis and relapse, and cytogenetic evolution. FLT3-wild type AMLs correlated with the subtype AML with myelodysplasia-related changes and frequently had adverse presentation karyotypes. Cuplike blast morphology was associated with FLT3/ITD+ status and with high mutation levels. Four of 7 patients with relapse-only FLT3/ITD mutations exhibited cuplike blasts at relapse after being noncuplike at diagnosis.
Conclusions.—In addition to well-known correlates in pretreatment specimens, FLT3 mutation status has pathologic and cytogenetic significance at relapse. A shift to cuplike blast morphology at relapse may herald emergence of a previously undetected FLT3/ITD mutation.
The Use of Autopsy in Preclinical Medical Education: A Survey of Pathology Educators
Authors: Talmon Geoffrey 
Published: February 2021

Abstract
Context.—Declining rates and increased competition for student contact hours pose challenges to integrating autopsies into preclinical curricula. Some have stated that the practice is minimally used with few students having the opportunity to observe necropsies.
Objective.—To determine the degree to and manner in which autopsies are used in the preclinical medical education.
Design.—A survey was distributed to the membership of the Group for Research in Pathology Education, an organization of preclinical pathology educators, assessing the nature of preclinical student exposure to postmortem examinations, how the experience was integrated in curricula, and attitudes toward the practice.
Results.—Fifty-one of 131 instructors (38.9%) responded. Most (86.2%) integrated autopsy material into coursework, usually in pathology education (63.1%) with 10.7% using it in discussions on end-of-life issues. The majority (74.5%) furnish students the opportunity to observe autopsies, typically in small groups. Volume was the only variable significantly related to whether the opportunity was provided (P &lt; .001). The experience was required in 56.3% of schools and usually less than 10% of students attended voluntarily. Although most educators felt it was important in general and pathology curricula, responses were mixed regarding autopsy's utility in discussions on death and dying. Common challenges were low autopsy numbers and busy class schedules.
Conclusions.—Most surveyed schools formally offer the opportunity to observe autopsies and incorporate autopsy themes in curricula. However, as only 41% of these institutions require the practice and most medical students did not view an autopsy voluntarily, less than half of preclinical students actually observe postmortem examinations.
Cellular Heterogeneity in Vertical Growth Phase Melanoma
Authors: Laga Alvaro C. , Murphy George F. 
Published: February 2021

Abstract
Context—Melanoma growing as a tumorigenic nodule is one of the most virulent neoplasms to which the flesh is heir. At a considerably small tumor size, it incurs significant risk for widespread metastatic dissemination. There are no effective means of surgical intervention, chemical therapy, or immunologic therapy for advanced and metastatic melanoma.
Objective—To review the literature and highlight recent cardinal advances in the understanding of melanoma vertical growth, with specific emphasis on how its recognition and characterization may be applied to diagnostic practice and development of novel investigative approaches.
Data Sources—Literature review, archival material, personal experience, and research collaborators.
Conclusions—The study of tumorigenic melanoma, both in primary lesions and in metastases, is the key to the eventual eradication of this highly virulent neoplasm that may disseminate widely when only occupying the volume of a grain of rice. Morphology often provides the first insight into structure and function. A growing database using meticulous and inclusive criteria to define tumor stem cells in the context of clinically relevant models now indicates that the key to melanoma heterogeneity may reside in a small subpopulation with the ability to self-renew and form tumors despite most cells present being significantly less virulent. Hopefully, from these insights into melanoma tumor progression from radial growth phase to heterogeneous and tumorigenic vertical growth phase will come additional answers to how smart therapies may be developed that specifically target those vertical growth phase cells that most pertain to patient survival.