bluuebunny/crossref_metadata_2025_split huggingface dataset:
Angiosarcoma, Radiation-Associated Angiosarcoma, and Atypical Vascular Lesion
Authors: Lucas David R. 
Published: February 2021

AbstractAngiosarcoma, one of the least common sarcomas, has become increasingly important because of its association with radiation therapy, especially for breast cancer. Most are sporadic, presenting as cutaneous tumors in the scalp/face of elderly patients. However, angiosarcoma has a wide anatomic distribution including soft tissue, visceral organ, and osseous locations. Predisposing conditions include environmental exposures to chemical or radioactive sources. Radiation-associated angiosarcoma typically presents as a cutaneous tumor several years posttherapy. The latency for radiation-associated mammary angiosarcoma is relatively short, sometimes less than 3 years. Atypical vascular lesion refers to a small, usually lymphatic-type vascular proliferation in radiated skin. Although most atypical vascular lesions pursue a benign course, they recur and very rarely progress to angiosarcoma. Distinguishing this lesion from well-differentiated angiosarcoma in a biopsy can be challenging, especially because areas indistinguishable from atypical vascular lesion are found adjacent to angiosarcoma. Recently, vascular-type atypical vascular lesion, which resembles hemangioma, has been described, thus expanding the definition of this entity.
CD10 Is Expressed in Most Epithelioid Hemangioendotheliomas: A Potential Diagnostic Pitfall
Authors: Weinreb Ilan , Cunningham Kristopher S. , Perez-Ordoñez Bayardo , Hwang David M. 
Published: February 2021

Abstract
Context.—Epithelioid hemangioendothelioma (EHE) is a vascular neoplasm that occasionally is difficult to distinguish from primary/metastatic carcinomas, particularly when EHEs express keratins. We recently encountered an EHE with strong CD10 positivity mimicking renal cell carcinoma.
Objective.—To examine sensitivity and specificity of CD10 in EHE.
Design.—Nine EHEs were stained with keratins, factor VIII, CD31, CD34, and CD10. Mimics of EHE were also retrieved and stained with CD10.
Results.—The EHE patients included 5 men and 4 women. Patients ranged in age from 24 to 74 years. Tumors were located in liver (3), skin (2), lung/pleura (2), and sternomastoid and mediastinum (1 each). Two had skin metastases. All EHEs were positive for vascular markers. A total of 7 of 9 primary tumors expressed cytoplasmic and intracytoplasmic luminal CD10. The 2 skin metastases were positive, whereas 2 primary skin EHEs were negative. Of the mimics, CD10 showed staining in 7 of 23 cases: 3 of 3 renal cell carcinomas, 1 of 7 other carcinomas, 2 of 3 epithelioid angiosarcomas, 1 of 3 melanomas, 0 of 3 mesotheliomas, and 0 of 4 epithelioid hemangiomas.
Conclusions.—CD10 has a sensitivity of 78% (confidence interval, 63.6%–92.4%) and specificity of 70% (confidence interval, 54%–85.9%) for EHE. There is a growing list of tumors that show expression of CD10. Pathologists should be aware of this diagnostic pitfall.
Document Control Practices in 120 Clinical Laboratories
Authors: Valenstein Paul N. , Stankovic Ana K. , Souers Rhona J. , Schneider Frank , Wagar Elizabeth A. 
Published: February 2021

Abstract
Context.—A variety of document control practices are required of clinical laboratories by US regulation, laboratory accreditors, and standard-setting organizations.
Objective.—To determine how faithfully document control is being implemented in practice and whether particular approaches to document control result in better levels of compliance.
Design.—Contemporaneous, structured audit of 8814 documents used in 120 laboratories for conformance with 6 generally accepted document control requirements: available, authorized, current, reviewed by management, reviewed by staff, and archived.
Results.—Of the 8814 documents, 3113 (35%) fulfilled all 6 document control requirements. The requirement fulfilled most frequently was availability of the document at all shifts and locations (8564 documents; 97%). Only 4407 (50%) of documents fulfilled Clinical Laboratory Improvement Amendment requirements for being properly archived after updating or discontinuation. Policies and procedures were more likely to fulfill document control requirements than forms and work aids. Documents tended to be better controlled in some laboratory sections (eg, transfusion service) than in others (eg, microbiology and client services). We could not identify document control practices significantly associated with higher compliance rates.
Conclusions.—Most laboratories are not meeting regulatory and accreditation requirements related to control of documents. It is not clear whether control failures have any impact on the quality of laboratory results or patient outcomes.
New Variants of Epithelial-Myoepithelial Carcinoma: Oncocytic-Sebaceous and Apocrine
Authors: Seethala Raja R. , Richmond Jeffrey A. , Hoschar Aaron P. , Barnes E. Leon 
Published: February 2021

AbstractContext.—Recently described variants of epithelial-myoepithelial carcinoma have not been well characterized but raise a distinct set of differential diagnostic considerations than the classic type.Objective.—To report a detailed analysis of oncocytic-sebaceous epithelial-myoepithelial carcinoma (OEMCa) and a similar, but novel, variant, apocrine epithelial-myoepithelial carcinoma (ApEMCa).Design.—Clinical, histologic, and immunophenotypic features of 5 OEMCas and 5 ApEMCas were analyzed. Ultrastructural examination was also performed on 3 OEMCa and 1 ApEMCa tumors.Results.—The mean age for OEMCa (74.4 years; range, 58–82 years) was slightly higher than for ApEMCa (61.6; range, 46–79 years). All tumors arose in the parotid glands and demonstrated a multinodular pattern of growth with an average size of 3.3 cm (range, 2.3–6.5 cm). Available follow-up (n = 6; 3 OEMCas, 3 ApEMCas) shows a favorable course (no evidence of disease; mean, 17.4 months). Both were morphologically similar, but only OEMCa had sebaceous elements. Phosphotungstic acid hematoxylin staining, antimitochondrial antibody immunohistochemistry, and ultrastructural examination confirm the abundance of mitochondria in OEMCa but not in ApEMCa. The ductal component in ApEMCa was distinguished from that of OEMCa by apical snouts, intracytoplasmic vacuoles, nuclear pleomorphism, prominent nucleoli, and androgen receptor immunoreactivity.Conclusions.—Oncocytic-sebaceous epithelial-myoepithelial carcinoma and ApEMCa should be considered in the differential diagnosis of oncocytic/oncocytoid salivary gland tumors. Oncocytic-sebaceous epithelial-myoepithelial carcinoma morphology may reflect a senescent phenotype, similar to other oncocytic lesions. The ductal component of ApEMCa shares some similarities with salivary duct carcinoma and supports the notion that epithelial-myoepithelial carcinoma can serve as the progenitor tumor for hybrid tumors.
Update in Nonneoplastic Lung Diseases
Authors: Gordon Ilyssa O. , Cipriani Nicole , Arif Qudsia , Mackinnon A. Craig , Husain Aliya N. 
Published: February 2021

AbstractContext.—Nonneoplastic lung diseases include a wide range of pathologic disorders from asthma to interstitial lung disease to pulmonary hypertension. Recent advances in our understanding of the pathophysiology of many of these disorders may ultimately impact diagnosis, therapy, and prognosis. It is important for the practicing pathologist to be aware of this new information and to understand how it impacts the diagnosis, treatment, and outcome of these diseases.Objective.—To update current progress toward elucidating the pathophysiology of pulmonary alveolar proteinosis, idiopathic pulmonary hemosiderosis, and pulmonary arterial hypertension, as well as to present classification systems for pulmonary hypertension, asthma, and interstitial lung disease and describe how these advances relate to the current practice of pulmonary pathology.Data Sources.—Published literature from PubMed (National Library of Medicine) and primary material from the authors' institution.Conclusions.—Improved understanding of the pathophysiology of pulmonary alveolar proteinosis, pulmonary hypertension, and idiopathic hemosiderosis may impact the role of the surgical pathologist. New markers of disease may need to be assessed by immunohistochemistry or molecular techniques. The classification systems for interstitial lung disease, asthma, and pulmonary hypertension are evolving, and surgical pathologists should consider the clinicopathologic context of their diagnoses of these entities.
Epstein-Barr Virus–Associated Smooth Muscle Tumor of the Iris in a Patient With Transplant: A Case Report and Review of the Literature
Authors: Yu Le , Aldave Anthony J. , Glasgow Ben J. 
Published: February 2021

Abstract
Epstein-Barr virus infection has been linked to the development of smooth muscle tumors in immunocompromised patients with organ transplants and acquired immunodeficiency syndrome. A 52-year-old female recipient of a renal transplant presented with enlarging masses of the left iris. Incisional biopsy of the mass revealed a smooth muscle tumor of the iris. Epstein-Barr virus infection was confirmed by in situ hybridization for Epstein-Barr virus–encoded, small RNA in tumor cells. Eight months after total iridectomy the patient was free of disease. Although the prognosis and classification of Epstein-Barr virus–associated smooth muscle tumors are controversial, mortalities caused by these tumors are rare.
KRas and BRaf Mutational Status Analysis From Formalin-Fixed, Paraffin-Embedded Tissues Using Multiplex Polymerase Chain Reaction–Based Assay
Authors: Jakubauskas Arturas , Griskevicius Laimonas 
Published: February 2021

Abstract
Context.—Monoclonal anti–epidermal growth factor receptor antibodies bind to the epidermal growth factor receptor and inhibit receptor kinase activity. Clinical trials have indicated that evaluation of the mutational status of KRas and BRaf is necessary to exclude patients who are resistant to the clinical benefit of anti–epidermal growth factor receptor therapy.
Objective.—To develop a multiplex polymerase chain reaction–based assay for the evaluation of KRas and BRaf mutational status.
Design.—A sample-saving and cost-effective, multiplex polymerase chain reaction–based assay to detect somatic mutations in KRAS exon 2 and exon 3 as well as in BRAF exon 15 was developed. The same primer pairs could be successfully used in amplification of a single DNA fragment under the same conditions.
Results.—DNA isolated from 20 retrospective formalin-fixed, paraffin-embedded samples of colorectal cancer was screened for mutations using the multiplex polymerase chain reaction assay followed by dideoxy-termination sequencing. Five samples bearing mutations—p.G12D (identified twice), p.G12V, p.G12S, and p.G13D, all encoded in KRAS exon 2—were identified. Three samples were found bearing amino acid substitution p.V600E of BRaf. The detected KRas and BRaf mutations were found to be mutually exclusive.
Conclusions.—A multiplex polymerase chain reaction–based amplification followed by dideoxy-termination sequencing may be used advantageously for the evaluation of KRas and BRaf mutational status from formalin-fixed, paraffin-embedded samples.
Multiple Patient Samples of an Analyte Improve Detection of Changes in Clinical Status
Authors: Kroll Martin H. 
Published: February 2021

Abstract

Context.
When comparing results over time, biologic variation must be statistically incorporated into the evaluation of laboratory results to identify a physiologic change. Traditional methods compare the difference in 2 values with the standard deviation (SD) of the biologic variation to indicate whether a “true” physiologic change has occurred.

Objective.
To develop methodology to reduce the effect of biologic variation on the difference necessary to detect changes in clinical status in the presence of biologic variation.

Design.
The standard test for change compares the difference between 2 points with the 95% confidence limit, given as . We examined the effect of multiple data pairs on the confidence limit.

Results.
Increasing the number of data pairs using the formula , where n  =  number of data pairs, significantly reduces the difference between values necessary to achieve a 95% confidence limit.

Conclusions.
Evaluating multiple paired sets of patient data rather than a single pair results in a substantial decrease in the difference between values necessary to achieve a given confidence interval, thereby improving the sensitivity of the evaluation. A practice of using multiple patient samples results in enhanced power to detect true changes in patient physiology. Such a testing protocol is warranted when small changes in the analyte precede serious clinical events or when the SD of the biologic variation is large.
Reducing the Variation in Performance of Antibody Titrations
Authors: AuBuchon J. P. , de Wildt-Eggen J. , Dumont L. J. 
Published: February 2021

AbstractBackground.—Antibody titration is difficult to standardize. We investigated whether a detailed, uniform procedure for antibody titration would reduce variation in both tube-based and gel card titres in an international study.Methods.—Laboratories (n = 35) tested proficiency testing material provided by the College of American Pathologists each according to (i) their routine method; (ii) a detailed, uniform method; and (iii) the uniform method titrating the serum sample against a red cell of specified phenotype (D+ C− c+ E+ e− for anti-D; A1 for anti-A) instead of the red cell of the same phenotype provided in the proficiency testing kit. Uniform method results were reported with 1+ and w+ end-points. Paired statistical analyses of variance were conducted using the F-test.Results.—The variance between laboratories was not significantly reduced with the uniform method using a 1+ end-point. However, a statistically significant reduction in the variance of anti-D and anti-A titres by the tube-based uniform technique after 37°C incubation and conversion to the antiglobulin (AHG) phase was seen when 19 laboratories reanalysed their results using a w+ end-point. Too few laboratories reported results with a w+ end-point in gel card testing to allow analysis. Titration against red cells of the specified phenotype provided by the participating laboratory did not appear to introduce additional variance. Overall, results reported based on the gel card technique at the AHG phase (1+ end-point) showed reduced variance compared to tube-based techniques.Conclusions.—A detailed, uniform method for antibody titration at 37°C and read at the AHG phase in a tube-based method with a w+ end-point reduced interlaboratory variability.
Polymeric Immunoglobulin Receptor–Negative Tumors Represent a More Aggressive Type of Adenocarcinomas of Distal Esophagus and Gastroesophageal Junction
Authors: Gologan Adrian , Acquafondata Marie , Dhir Rajiv , Sepulveda Antonia R. 
Published: February 2021

Abstract
Context.—Polymeric immunoglobulin receptor (PIgR) expression has been found in gastric mucosa and gastric cancers, but it is not known whether PIgR expression is related to background intestinal metaplasia nor the patterns of PIgR expression in tumors arising in the distal esophagus and gastroesophageal (GE) junction.
Objectives.—To identify clinicopathologic features of tumors associated with PIgR expression and to determine whether PIgR expression is associated with intestinal differentiation of tumors and intestinal metaplasia in background mucosa in 3 groups of upper gastrointestinal adenocarcinomas. These groups are (1) gastric adenocarcinomas, (2) adenocarcinomas of the distal esophagus and GE junction with background intestinal metaplasia, and (3) adenocarcinomas of the distal esophagus and GE junction without background intestinal metaplasia.
Design.—Expression of PIgR and CDX2 in nonneoplastic mucosa, intestinal metaplasia, and adenocarcinomas was examined by immunohistochemistry in 42 cases: 14 gastric and 28 from the distal esophagus and GE junction, including 13 with esophageal or GE junction intestinal metaplasia.
Results.—PIgR and CDX2 were expressed in all cases of intestinal metaplasia. PIgR expression was positive in 40% of group 3 versus 77% of group 2 and 71% of gastric adenocarcinomas (P = .06), and the expression of CDX2 was similar in all tumor groups (80%–83%). Metastatic-positive lymph nodes were more frequent in PIgR-negative tumors (94% vs 58%, P = .01).
Conclusions.—PIgR is uniformly expressed in intestinal metaplasia and in a subgroup of adenocarcinomas of the distal esophagus, GE junction, and stomach. Esophageal and GE junction adenocarcinomas that do not express PIgR show more frequent lymph node metastasis, suggesting that lack of expression of PIgR identifies a subgroup of more aggressive adenocarcinomas.
Metastasizing Pleomorphic Adenoma of the Salivary Gland
Authors: Manucha Varsha , Ioffe Olga B. 
Published: February 2021

Abstract
Metastasizing pleomorphic adenoma of salivary glands is a group of rare tumors that are histologically identical to benign mixed tumors and that inexplicably metastasize. A review of the literature revealed that it usually occurs after multiple local recurrences, and the interval between diagnosis of primary pleomorphic adenoma and metastases ranges between 3 and 52 years. The most common site for metastasis is bone, followed by the head and neck and lung. No histologic or molecular parameters exist at the present time that could predict the development of metastasis in these neoplasms. Metastasectomy confers significant survival advantage over nonoperative treatment for localized and accessible metastases, but there is no definite treatment protocol available in cases of widespread metastases.
Paraproteins Are a Common Cause of Interferences With Automated Chemistry Methods
Authors: Yang Yusong , Howanitz Peter J. , Howanitz Joan H. , Gorfajn Helen , Wong Keung 
Published: February 2021

Abstract
Context.—Previous studies have shown that paraproteins caused spurious results on individual analytes including total bilirubin (TBIL), direct bilirubin (DBIL), or HDL-cholesterol (HDL-C). Studies demonstrating paraprotein interferences with multiple analytes measured by different analyzers have not been reported.
Objective.—To systemically investigate interferences of paraproteins on TBIL, DBIL, and HDL-C measured by the Roche MODULAR and the Olympus AU2700.
Design.—Eighty-eight serum specimens with monoclonal gammopathies were analyzed using the Roche MODULAR and the Olympus AU2700. Paraprotein interferences with the MODULAR and AU2700 were identified by abnormal absorbance curves and confirmed by results from the Ortho Vitros 950 or inconsistent laboratory information.
Results.—Spurious results occurred in 89 of 528 measurements; 29 specimens did not demonstrate any interferences whereas 26 specimens gave spurious results in 2 to 4 of the 6 assays. Paraprotein interferences caused spuriously high levels of TBIL in 4 sera measured by the MODULAR. In contrast, paraprotein interferences on DBIL were observed by at least 1 method in 44% (39/88) of sera assayed, occurring almost exclusively with the AU2700. Paraprotein interferences with HDL-C results were present in 35% of specimens assayed with the MODULAR and 16% of specimens assayed with the AU2700. In specimens with interferences, spuriously low AU2700 DBIL, MODULAR HDL-C, and AU2700 HDL-C results occurred with 28%, 90%, and 91% of specimens, respectively.
Conclusions.—We demonstrated that paraprotein interferences with TBIL, DBIL, and HDL-C are relatively common and provided explanations why these interferences occurred. Although it is difficult to predict which specimens cause interferences, spurious results appeared method and concentration dependent.
The Differential Diagnosis of Central Nervous System Tumors: A Critical Examination of Some Recent Immunohistochemical Applications
Authors: Edgar Mark A. , Rosenblum Marc K. 
Published: February 2021

AbstractContext.—As we write, novel antibodies that may well alter the routine practice of surgical neuropathology are in development, characterization, and the early stages of clinical use. These will be used for purposes of tumor subclassification, as prognostic markers, as identifiers of potential therapeutic targets, and as predictors of treatment response.Objective.—To provide for nonspecialists a critical assessment of the peer-reviewed literature (necessarily colored by our own experience) as it pertains to several immunohistochemical reagents that have been recently forwarded as adjuncts to the histologic typing of central nervous system tumors.Data Sources.—We address in these pages only antibodies that are commercially available, that have been the subjects of multiple published series, and that we have had occasion to use in the course of everyday problem solving.Conclusions.—Discussion concentrates on the use of 4 antibodies: BAF47 in the diagnosis of atypical teratoid/ rhabdoid tumor, OCT4 in intracranial germinoma, β-catenin in craniopharyngioma, and NeuN as a marker of neuronal differentiation in neuroepithelial neoplasms.
HER2 Testing in a Population-Based Study of Patients With Metastatic Breast Cancer Treated With Trastuzumab
Authors: O'Malley Frances P. , Thomson Tom , Julian Jim , Have Cherry , Cosby Roxanne , Gelmon Karen , Andrulis Irene , Whelan Tim 
Published: February 2021

Abstract
Context.—The development of trastuzumab has led to new therapeutic strategies for patients with breast cancer. Trastuzumab has been shown to only be effective in those patients whose cancers are HER2 positive by either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH).
Objective.—To determine the accuracy of HER2 testing in 2 provinces in Canada.
Design.—Patients with metastatic breast cancer diagnosed between 1999 and 2002 who were HER2 positive in the local laboratories were included in this study. All cases were retested centrally, by IHC (using 4 methods) and FISH. In addition, 205 locally reported HER2-negative metastatic breast cancer cases were retested centrally.
Results.—Concordance between the 505 local IHC-positive cases with central IHC testing varied between 79.3% and 89.6% depending on the IHC method and scoring method used. HER2 gene amplification by FISH was present in 86.1% of local IHC-positive cases. Concordance between the 205 local IHC-negative tumors with central testing ranged between 94.8% and 100% for IHC and was 98.5% for FISH.
Conclusions.—This study demonstrated that locally reported HER2-negative results were highly accurate, but less accuracy was demonstrated with local HER2-positive results. These results emphasize the need for participation in a quality assurance program.