bluuebunny/crossref_metadata_2025_split huggingface dataset:
Update on Nonneoplastic Pulmonary Lymphoproliferative Disorders and Related Entities
Authors: Guinee Donald G. 
Published: February 2021

AbstractContext.—Recent discoveries have expanded the spectrum of nonneoplastic pulmonary lymphoproliferative disorders and have provided new insights into their pathogenesis and treatment.Objective.—To review the thoracic manifestations of immunoglobulin (Ig) G4–related sclerosing disease and summarize current concepts and differential diagnosis of follicular bronchiolitis, lymphocytic interstitial pneumonitis, and nodular lymphoid hyperplasia.Data sources.—Data sources include recent and old articles, cases from the personal files of the author, and cases borrowed with permission from other authors.Conclusions.—Additional studies will be needed to further refine and add to observations in this evolving area of pulmonary pathology.
Intraorbital Meningiomas: A Pathologic Review Using Current World Health Organization Criteria
Authors: Jain Deepali , Ebrahimi Katayoon B. , Miller Neil R. , Eberhart Charles G. 
Published: February 2021

Abstract
Context.—Meningiomas represent approximately 4% of all intraorbital tumors and can arise from the optic nerve or extend into the orbit from adjacent structures.
Objective.—To examine a cohort of intraorbital meningiomas and use the current World Health Organization (WHO) scheme to assess the effect of changes to the classification of tumors at this site.
Design.—The histopathology and clinical findings of intraorbital meningiomas resected between 1968 and 2008 at our institution were reviewed according to the WHO 2007 classification scheme.
Results.—A total of 51 intraorbital meningiomas were reviewed. The mean age at presentation was 45 years, but 5 tumors arose in children. Two patients were known to have neurofibromatosis type 2, and 1 had inherited retinoblastoma. Orbital meningiomas were more frequently encountered in women (30 cases) than in men (21 cases). In 21 patients, the tumor was associated with the optic nerve. The most common (25 of 51 tumors; 49%) histopathologic subtype was meningothelial. Most (47 of 51; 92%) of the tumors were WHO grade I. Four tumors (8%) were WHO grade II, with 4 or more mitotic figures per 10 high-power fields, brain invasion, chordoid histology, or a combination of these features.
Conclusions.—Intraorbital meningiomas were most frequently of the meningothelial or transitional subtypes and were WHO grade I. One relatively common intracranial subtype, fibrous meningioma, was not encountered. The percentage of WHO grade II tumors in the orbit (8%) is similar to that reported for intracranial tumors using the current grading scheme.
Colorectal Dysplasia in Chronic Inflammatory Bowel Disease: Pathology, Clinical Implications, and Pathogenesis
Authors: Harpaz Noam , Polydorides Alexandros D. 
Published: February 2021

Abstract
Context.—Colorectal cancer, the most lethal long-term complication of chronic inflammatory bowel disease (IBD), is the culmination of a complex sequence of molecular and histologic derangements of the intestinal epithelium that are initiated and at least partially sustained by chronic inflammation. Dysplasia, the earliest histologic manifestation of this process, plays an important role in cancer prevention by providing the first clinical alert that this sequence is underway and serving as an endpoint in colonoscopic surveillance of patients at high risk for colorectal cancer.
Objective.—To review the histology, nomenclature, clinical implications, and molecular pathogenesis of dysplasia in IBD.
Data Source.—Literature review and illustrations from case material.
Conclusions.—The diagnosis and grading of dysplasia in endoscopic surveillance biopsies play a decisive role in the management of patients with IBD. Although interpathologist variation, endoscopic sampling problems, and incomplete information regarding the natural history of dysplastic lesions are important limiting factors, indirect evidence that surveillance may be an effective means of reducing cancer-related mortality in the population with IBD has helped validate the histologic criteria, nomenclature, and clinical recommendations that are the basis of current practice among pathologists and clinicians. Emerging technologic advances in endoscopy may permit more effective surveillance, but ultimately the greatest promise for cancer prevention in IBD lies in expanding our thus far limited understanding of the molecular pathogenetic relationships between neoplasia and chronic inflammation.
Advances in Microscopy Techniques
Authors: Schmolze Daniel B , Standley Clive , Fogarty Kevin E , Fischer Andrew H 
Published: February 2021

Abstract
Context.—Advances in microscopy enable visualization of a broad range of new morphologic features.
Objective.—To review and illustrate advances in microscopy with relevance to pathologists.
Data Sources.—Literature review and new observations.
Results.—Fluorescence microscopy enables multiantigen detection; allows novel optical-sectioning techniques, with some advantages compared to paraffin sectioning; and permits live-cell imaging. Live-cell imaging allows pathologists to move from a period when all diagnostic expertise was reliant on interpreting static images to a period when cellular dynamics can play a role in diagnosis. New techniques have bypassed by about 100-fold what had long been believed to be a limit to the resolution of light microscopy. Fluorescence resonance energy transfer (FRET) appears capable of visualizing diagnostically relevant molecular events in living or fixed cells that are immeasurable by other molecular techniques. We describe applications of 2-photon microscopy, FRET, structured illumination, and the subdiffraction techniques of near-field microscopy, photoactivated localization microscopy, stochastic optical reconstruction microscopy, and stimulated emission depletion microscopy.
Conclusion.—New microscopy techniques present opportunities for pathologists to develop improved diagnostic tests.
Pathology Economic Model Tool: A Novel Approach to Workflow and Budget Cost Analysis in an Anatomic Pathology Laboratory
Authors: Muirhead David , Aoun Patricia , Powell Michael , Juncker Flemming , Mollerup Jens 
Published: February 2021

Abstract
Context.—The need for higher efficiency, maximum quality, and faster turnaround time is a continuous focus for anatomic pathology laboratories and drives changes in work scheduling, instrumentation, and management control systems.
Objective.—To determine the costs of generating routine, special, and immunohistochemical microscopic slides in a large, academic anatomic pathology laboratory using a top-down approach.
Design.—The Pathology Economic Model Tool was used to analyze workflow processes at The Nebraska Medical Center's anatomic pathology laboratory. Data from the analysis were used to generate complete cost estimates, which included not only materials, consumables, and instrumentation but also specific labor and overhead components for each of the laboratory's subareas. The cost data generated by the Pathology Economic Model Tool were compared with the cost estimates generated using relative value units.
Results.—Despite the use of automated systems for different processes, the workflow in the laboratory was found to be relatively labor intensive. The effect of labor and overhead on per-slide costs was significantly underestimated by traditional relative-value unit calculations when compared with the Pathology Economic Model Tool. Specific workflow defects with significant contributions to the cost per slide were identified.
Conclusions.—The cost of providing routine, special, and immunohistochemical slides may be significantly underestimated by traditional methods that rely on relative value units. Furthermore, a comprehensive analysis may identify specific workflow processes requiring improvement.
Pick Disease: A Brief Overview
Authors: Frederick Justin 
Published: February 2021

Abstract
This article is a brief review of the clinical, radiographic, and pathologic features of Pick disease. It is directed toward residents and fellows in training as well as practicing physicians who might wish to find a concise treatise on this clinicopathologic entity. The pathogenesis and genetics of this disorder are discussed. Included are medical journal articles accessed from computerized medical literature searches of articles published in the last 10 years. Pertinent images have been included where necessary. Although ubiquitously discussed in medical school and residency, Pick disease is nevertheless a relatively uncommon clinicopathologic entity. Recognition of its clinical and pathologic manifestations is critical in correctly diagnosing this illness and subsequently educating family members of the deceased.
Malpractice in Pathology: What to Do When You Are Sued
Authors: Davis Gregory G. 
Published: February 2021

Abstract
A malpractice suit arises when a patient brings legal charges against a physician for suffering that the patient claims to have endured because the physician failed to provide appropriate care. Suffering usually encompasses a measure of misdiagnosis and of rude treatment of the patient by medical staff. Polite treatment of all patients by all laboratory staff will prevent some disputes from ever forming, thus preventing some charges of malpractice. Even if a patient is treated rudely, that rudeness alone is insufficient to justify a charge of malpractice. Attorneys must follow legal guidelines to determine whether the physician's actions caused actual damage. As soon as a physician is served notice of a lawsuit, the physician must notify the office that insures him or her against claims of malpractice (eg, the office of risk management or the physician's malpractice insurance carrier). Being sued creates an overwhelming urge to talk about the case, but a physician who has been sued must not talk to anyone about the lawsuit or the case involved. Conversations about the lawsuit may only safely be had with the attorney who will defend the physician against the charge of malpractice. Despite any frustrations with the legal system, the physician must work with and even trust the attorney handling the defense. It is possible to overcome a charge of malpractice, but not if the physician creates an indefensible situation by committing fraud. Examples of fraud are changing the medical record or destroying the pertinent microscope slide.
Thyroid Tumors With a Follicular Growth Pattern: Problems in Differential Diagnosis
Authors: Suster Saul 
Published: February 2021

Abstract
Tumors of the thyroid characterized by a follicular growth pattern constitute the most common type of lesion of this organ encountered by pathologists. The vast majority of such lesions do not pose difficulties for histopathologic interpretation. A subset of these tumors, however, can represent a serious challenge for diagnosis. Thyroid tumors with a follicular growth pattern include a broad range of lesions that range from benign, hyperplastic nodules to follicular adenomas to follicular carcinomas. In addition, other types of tumors belonging in separate diagnostic categories can also present histologically with a follicular growth pattern, including the follicular variant of papillary thyroid carcinoma and medullary carcinoma. The histologic features and diagnostic criteria used for distinguishing among these conditions can often be subtle and subjective.
Detection of the JAK2V617F Mutation in Myeloproliferative Disorders by Melting Curve Analysis Using the LightCycler System
Authors: Olsen Randall J. , Tang Zhouwen , Farkas Daniel H. , Bernard David W. , Zu Youli , Chang Chung-Che 
Published: February 2021

Abstract
Context.—A specific mutation, JAK2V617F, was recently recognized as having diagnostic value for myeloproliferative disorders. No practical assay is currently available for routine use in a clinical laboratory.
Objective.—We report the development of a real-time polymerase chain reaction melting curve analysis assay that is appropriate for molecular diagnostics testing.
Design.—Specific primers and fluorescence resonance energy transfer probes were designed, and patients with a previously diagnosed myeloproliferative disorder, de novo acute myeloid leukemia, or reactive condition were selected. The DNA was extracted from fresh and archived peripheral blood and bone marrow specimens, and real-time polymerase chain reaction melting curve analysis was performed on the LightCycler platform (Roche Applied Science, Indianapolis, Ind).
Results.—The JAK2 region was successfully amplified, and wild-type amplicons were reproducibly discriminated from JAK2V617F amplicons. Titration studies using homozygous wild-type and mutant cell lines showed the relative areas under a melting curve were proportional to allele proportion, and the assay reliably detected one mutant in 20 total cells. JAK2V617F was identified in patients previously diagnosed with a myeloproliferative disorder or acute myeloid leukemia transformed from myeloproliferative disorder, whereas a wild-type genotype was identified in patients with reactive conditions or de novo acute myeloid leukemia.
Conclusions.—These findings demonstrate the suitability of this assay for identifying JAK2V617F in a clinical laboratory setting. Furthermore, the semiquantitative detection of JAK2V617F in archived specimens provides a new tool for studying the prognostic significance of this mutation.
BRAF Mutations in Melanocytic Lesions and Papillary Thyroid Carcinoma Samples Identified Using Melting Curve Analysis of Polymerase Chain Reaction Products
Authors: Hay Robert , MacRae Erin , Barber Duane , Khalil Moosa , Demetrick Douglas J. 
Published: February 2021

Abstract
Context.—Mutations of the proto-oncogene B-raf (BRAF) have been detected in melanocytic lesions and papillary carcinomas of the thyroid, and identification of these mutations could be useful in resolving some diagnostic problems.
Objective.—To develop a method to evaluate mutations of BRAF that could provide results much more rapidly than conventional polymerase chain reaction and DNA sequencing assays.
Design.—An assay using a LightCycler was developed to evaluate DNA sequences encoding amino acids within the activation loop of BRAF.
Results.—Using this real-time polymerase chain reaction method, we analyzed 55 paraffin-embedded melanoma or nevus samples. The V600E mutation was found in 0 (0%) of 13 samples diagnosed histologically as Spitz nevi, 9 (24.3%) of 37 invasive melanomas, and 5 (100%) of 5 other melanocytic nevi. Two additional mutations, V600K and VK600-1E, also were identified in cases of invasive melanoma. We analyzed 14 paraffin-embedded papillary thyroid cancer (PTC) samples, 6 of which showed the V600E mutation. We found that our test worked efficiently with fine-needle aspirate specimens, and it identified 6 V600E mutations in 10 fine-needle aspirate specimens diagnosed as PTC. We also identified 4 V600E mutations in 6 specimens of PTC metastatic to lymph node. Unlike the melanocytic lesions, the PTC specimens yielded only V600E mutations. Comparison of our real-time polymerase chain reaction results with conventional polymerase chain reaction and DNA sequencing demonstrated 100% concordance. Surprisingly, we did not identify the previously reported VK600-1E or K601E mutations in our PTC specimens.
Conclusions.—Our results show that the real-time polymerase chain reaction method is a rapid and accurate method for identifying BRAF mutations, such as V600E, in both paraffin-embedded tissue and fine-needle aspirate specimens.
Epithelioid and Epithelial Neoplasms of Bone
Authors: Deyrup Andrea T. , Montag Anthony G. 
Published: February 2021

AbstractContext.—Epithelioid and epithelial neoplasms seen in bone are rare and include epithelioid variants of vascular lesions, osteoblastoma, osteosarcoma, chordoma, and chondroblastoma as well as adamantinoma and metastatic carcinoma.Objective.—To provide an overview of tumors with epithelioid histology and address the clinical context and diagnostic issues.Data Sources.—Pertinent literature is reviewed with emphasis on recent and controversial issues.Conclusions.—The differential diagnosis in epithelioid/ epithelial lesions of bone is limited. The primary consideration in many cases is distinguishing primary from metastatic lesions.
Overexpression of CD24: Association With Invasiveness in Urothelial Carcinoma of the Bladder
Authors: Choi Yoon-La , Lee Seung-Hyun , Kwon Ghee-Young , Park Cheol-Keun , Han Jae-Joon , Choi Jong Sun , Choi Han Yong , Kim Seok-Hyung , Shin Young Kee 
Published: February 2021

AbstractContext.—CD24, originally described as a B-cell marker, has gained considerable attention in tumor research. High rates of CD24 expression have been found in several types of carcinomas that are significantly associated with a more aggressive course of the disease. To our knowledge, the expression of CD24 in urothelial carcinoma (UC) of the bladder has not been previously reported.Objective.—To determine the expression of CD24 in UCs and the association between CD24 levels and tumor grade and stage.Design.—Urothelial carcinomas (48 cystectomy, 87 transurethral biopsy), including 56 pTa, 29 pT1, 19 pT2, and 31 pT3, were analyzed immunohistochemically using an anti-CD24 monoclonal antibody. The intensity of CD24 staining was semiquantitatively scored as high-level or low-level expression.Results.—In normal urothelium, CD24 was localized to the cytoplasm of the luminal cell layer with very low intensity. CD24 expression was upregulated in noninvasive UCs, and a high level of expression was correlated with the tumor grade (P = .003). Invasive UCs demonstrated strong diffuse cytoplasmic overexpression of CD24 and the difference in CD24 expression between invasive and noninvasive UC was statistically significant (P &lt; .001).Conclusions.—CD24 protein is overexpressed in a significant number of bladder UCs. The high level of CD24 expression with loss of apical localization is a marker for stromal invasion and high tumor grade in UC. This study provides the basis for future investigations of CD24 as a potential serum marker or target of antibody-based therapeutics in bladder UC.
Selected Diagnostic Problems in Neoplastic Dermatopathology
Authors: DiCaudo David J. , McCalmont Timothy H. , Wick Mark R. 
Published: February 2021

Abstract
Context.—Selected cutaneous neoplasms share features with benign counterparts or have subtle morphologic features that could be overlooked by the pathologist.
Objective.—To present clues to the diagnosis of potentially deceptive malignancies, including desmoplastic malignant melanoma, nevoid malignant melanoma, subcutaneous lymphoma, metastatic breast carcinoma, and epithelioid sarcoma.
Data Sources.—Published literature and personal experience.
Conclusions.—Knowledge of commonly misdiagnosed cutaneous neoplasms will help the general surgical pathologist avoid these potential pitfalls in neoplastic dermatopathology.
Histopathology of Serrated Adenoma, Its Variants, and Differentiation From Conventional Adenomatous and Hyperplastic Polyps
Authors: Li Shuan C. , Burgart Lawrence 
Published: February 2021

Abstract
Context.—Serrated adenomas can be morphologically subdivided into traditional and sessile types. They are thought to have a comparable rate of cancer progression like conventional adenomas, but they potentially have a faster rate of growth through methylation pathway(s). They share similar morphologic features with both the conventional adenoma and the hyperplastic polyp in a fashion that is different from a mixed adenoma and a hyperplastic polyp.
Objective.—To describe the histopathologic features of traditional serrated adenoma and sessile serrated adenoma and their comparison with traditional adenomas and hyperplastic polyp.
Data Sources.—Relevant articles in peer-review journals and the authors' working experience as practicing surgical pathologists with a specific interest in gastrointestinal pathology.
Conclusions.—Both types of serrated adenomas, traditional serrated adenoma and sessile serrated adenoma, are morphologically distinct, clinically important entities, and they can be diagnosed accurately in routine practice.
Basal/Myoepithelial Cells in Chronic Sinusitis, Respiratory Epithelial Adenomatoid Hamartoma, Inverted Papilloma, and Intestinal-Type and Nonintestinal-Type Sinonasal Adenocarcinoma: An Immunohistochemical Study
Authors: Ozolek John A. , Barnes E. Leon , Hunt Jennifer L. 
Published: February 2021

AbstractContext.—The pathogenesis of respiratory epithelial adenomatoid hamartoma (REAH) and inverted papilloma (IP) is poorly understood, especially compared with sinonasal adenocarcinoma (SNAC). One feature of malignant glandular lesions is loss of the basal/myoepithelial layer. The immunophenotype of the basal/myoepithelial layer has not been fully examined in benign glandular lesions of the sinonasal tract.Objective.—To examine benign and malignant glandular lesions in the sinonasal tract for the immunophenotype of basal/myoepithelial cells, proliferation index, and cytokeratin and intestinal differentiation profiles.Design.—Sinonasal adenocarcinoma (intestinal-type adenocarcinoma [ITAC] and nonintestinal type adenocarcinoma [non-ITAC]), REAH, IP, and chronic sinusitis (CS) were stained for cytokeratin (CK) 7, CK20, 34βE12, CDX-2, p63, Ki-67, smooth muscle actin (SMA), S100 protein, and calponin.Results.—Basal/myoepithelial cells in CS and REAH were positive for p63 and 34βE12 but negative for SMA, S100 protein, and calponin. Proliferative activity was localized to the compartment containing p63-positive cells. Inverted papilloma demonstrated broad areas staining for p63 and 34βE12, with intermediate proliferative activity in these areas. Sinonasal adenocarcinoma had the highest Ki-67 labeling index, and p63-positive SNACs had higher proliferation indices than p63-negative SNACs. REAH, IP, CS, and most SNACs expressed CK7. Only SNAC expressed CK20. Sixty percent of morphologic ITACs expressed CDX-2.Conclusions.—Basal/myoepithelial cells in CS and REAH should be considered basal and not myoepithelial cells. In benign lesions, proliferative activity is limited to the compartments with p63 staining. In SNAC and IP, p63 expression correlates with proliferation index. REAH, IP, and CS share similar immunoprofiles (CK7+, CK20−, and CDX-2−), contrasting with SNAC (CK7+, CK20+/−, CDX-2−/+).