bluuebunny/crossref_metadata_2025_split huggingface dataset:
Production and Activation of Matrix Metalloproteinase 7 (Matrilysin 1) in the Lungs of Patients With Idiopathic Pulmonary Fibrosis
Authors: Fujishima Seitaro , Shiomi Takayuki , Yamashita Shuji , Yogo Yurika , Nakano Yasushi , Inoue Takashi , Nakamura Morio , Tasaka Sadatomo , Hasegawa Naoki , Aikawa Naoki , Ishizaka Akitoshi , Okada Yasunori 
Published: February 2021

Abstract
Context.—Idiopathic pulmonary fibrosis (IPF) is characterized by diffuse interstitial inflammation and fibroblast proliferation with accelerated remodeling of extracellular matrix, which result in irreversible destruction of the lung's architecture.
Objective.—To elucidate the production levels, tissue localization, and activation of matrix metalloproteinase 7 (MMP-7) in the lungs of patients with IPF.
Design.—Bronchoalveolar lavage analysis was performed in 17 IPF patients and 6 healthy volunteers. Levels of MMP-7 in blood were assayed in 23 IPF patients and 20 controls. Histologic and immunohistochemical analyses were performed on paraffin sections of the lung tissues from patients with IPF, interstitial pneumonia associated with rheumatoid arthritis, or nonspecific interstitial pneumonia.
Results.—The proMMP-7 levels in bronchoalveolar lavage fluids from IPF patients were significantly higher than those from healthy controls, although there was no difference in the serum levels between the 2 groups. By immunohistochemistry, proMMP-7 was localized mainly to the hyperplastic alveolar and metaplastic bronchiolar epithelial cells in the lung tissues from IPF patients. Active MMP-7 was immunolocalized on alveolar macrophages and hyperplastic epithelial cells, which were also immunostained with antibody against CD151, a molecule associated with activation of proMMP-7. Immunoblot analysis indicated the overproduction of proMMP-7 together with a small amount of active MMP-7 in bronchoalveolar lavage fluids from IPF patients. The MMP-7 activity was detected in a cross-linked carboxymethylated transferrin film assay.
Conclusions.—proMMP-7 is excessively produced by hyperplastic alveolar and metaplastic bronchiolar epithelial cells and activated locally in the lungs of IPF patients, suggesting that MMP-7 may contribute to the pathology of IPF.
The Prognostic Value of Ki-67, p53, Epidermal Growth Factor Receptor, 1p36, 9p21, 10q23, and 17p13 in Skull Base Chordomas
Authors: Horbinski Craig , Oakley Gerard J. , Cieply Kathleen , Mantha Geeta S. , Nikiforova Marina N. , Dacic Sanja , Seethala Raja R. 
Published: February 2021

AbstractContext.—Skull base chordomas are rare, locally aggressive, notochord-derived neoplasms for which prognostically relevant biomarkers are not well established.Objective.—To evaluate whether newly discovered molecular alterations in chordomas have prognostic significance similar to what has been described regarding Ki-67 proliferation index.Design.—We conducted a retrospective study of 28 cases of primary clival chordomas.Results.—Ki-67 proliferation index 5% or more, p53 accumulation, and epidermal growth factor receptor expression were seen in 32%, 44%, and 8% of chordomas, respectively. 1p loss of heterozygosity (LOH) and/or 1p36 hemizygous deletion was seen in 30% of tumors, while 9p LOH and/or 9p21 homozygous deletion was seen in 21% of cases. Loss of heterozygosity at 10q23 and 17p13 were identified in 57% and 52% of cases, respectively. Ki-67 proliferation index 5% or more and 9p LOH were significantly associated with a shorter overall survival, while homozygous deletion at 9p21 via fluorescence in situ hybridization approached significance. No correlation with survival was found for p53 or epidermal growth factor receptor expression, 1p36 hemizygous deletion, or LOH at 1p, 10q23, or 17p13.Conclusions.—Chordomas with elevated Ki-67 proliferation index or deletion at 9p21 may be at risk for a more aggressive clinical course and shorter survival. These biomarkers may thus be used to improve therapeutic stratification.
Deep Penetrating Nevus: A Review
Authors: Luzar Boštjan , Calonje Eduardo 
Published: February 2021

Abstract
Context.—Deep penetrating nevus is a distinctive melanocytic lesion that may simulate melanoma both clinically and histologically.
Objective.—To review clinical and histologic features of deep penetrating nevi and discuss their differential diagnosis, especially regarding melanoma.
Data Sources.—The literature on deep penetrating nevi is reviewed and supplemented by our experiences with deep penetrating nevi.
Conclusions.—One or more disturbing histologic features may frequently be found in deep penetrating nevi, including asymmetry, plump but fairly regular nests of melanocytes in the dermis, cytologic atypia with some nuclear pleomorphism, a small to medium-sized eosinophilic nucleolus, absence of maturation, occasional presence of normal dermal mitoses, and a patchy mononuclear inflammatory cell infiltrate. Although unusual, such histologic features should not be regarded as a sign of malignancy in deep penetrating nevi.
Detection of C4d Deposition in Cardiac Allografts: A Comparative Study of Immunofluorescence and Immunoperoxidase Methods
Authors: Miller Dylan V. , Roden Anja C. , Gamez Jeffrey D. , Tazelaar Henry D. 
Published: February 2021

Abstract
Context.—Complement activation, evidenced by deposition of C4d, is important in the diagnosis of antibody-mediated rejection of cardiac allografts. C4d deposition can be assessed by either immunofluorescence (IF)– or immunoperoxidase (IP)–based methods. The use of methods varies considerably among institutions, but there are few data addressing their diagnostic equivalence.
Objective.—To compare IF and IP C4d staining on paired endomyocardial biopsy samples from a large number of heart transplant patients.
Design.—Retrospectively selected paired frozen and paraffin-embedded samples from the same biopsy were stained for C4d by IF and IP methods. Capillary staining was scored by using a 0, 1+, 2+, 3+ scale.
Results.—A total of 296 biopsy pairs from 70 patients were studied. There were two hundred forty-three cases that were scored 0, twenty-four scored 1+, sixteen scored 2+, and thirteen scored 3+ by IF. Two hundred thirty-one cases scored 0, forty scored 1+, ten scored 2+, and fifteen scored 3+ by IP. Complete agreement was seen in 81% of cases. Among discrepant cases, 89% (n  =  51) were minor (±1) and 11% (n  =  6) were major (±2). Five of the 6 major discrepancy biopsies came from 2 patients, both of whom had concordant (IF and IP) 3+ results on prior biopsies. The weighted κ value for the entire sample set was 0.78 and for the first biopsy only set (to correct for bias introduced by multiple biopsies from the same patient) the weighted κ value was 0.88.
Conclusions.—Immunofluorescence and IP C4d staining methods are highly comparable and are both viable options for antibody-mediated rejection surveillance in transplant heart biopsies.
Lentiginous Melanoma
Authors: King Roy 
Published: February 2021

Abstract
Context.—Atypical lentiginous melanocytic lesions, particularly in older individuals, continue to pose a diagnostic challenge. Such lesions often show features intermediate between lentiginous nevus and melanoma in situ. We have recently defined within this group of lesions a histologic pattern of lentiginous melanoma, a slowly progressing variant of melanoma typically found on the trunk and proximal extremities of middle-aged and older individuals.
Objective.—To review the clinical and histologic features of lentiginous melanoma and its histologic differential diagnosis.
Data Sources.—Review of pertinent published literature and work in our laboratory.
Conclusions.—Lentiginous melanoma defines a subset of slowly progressing melanoma occurring in middle-aged and older patients. It is histologically characterized by a broad atypical lentiginous growth pattern of moderately atypical melanocytes showing focal nesting and pagetoid spread without significant dermal fibroplasia or alteration of the rete ridges. Lentiginous melanoma shows significant overlap in clinical and histologic features with atypical lentiginous nevus (of the elderly). Relationship between these entities requires further investigations. Given the risk of progression to invasive melanoma, all lesions showing features of lentiginous melanoma should be treated with adequately wide excision.
Neoplasia of Gallbladder and Biliary Epithelium
Authors: Katabi Nora 
Published: February 2021

Abstract
Context.—Diagnosis of biliary neoplasia can be challenging but is essential for the appropriate clinical management of patients. Therefore, it is important to recognize the morphologic features of the biliary neoplasms to report a correct diagnosis.
Objectives.—(1) To discuss the differential diagnosis of dysplasia in the gallbladder and differentiate dysplasia from reactive atypia and invasive carcinoma, (2) review the histologic features of adenoma and polypoid biliary lesions, (3) highlight the differential diagnosis of adenocarcinoma in liver biopsy, and (4) discuss the differential diagnosis of atypical biliary glandular lesions.
Data Sources.—Current English literature related to gallbladder and biliary neoplasia.
Conclusions.—Biliary glandular neoplasms show a wide spectrum of morphology and have many mimics. Careful examination of the histologic features of these lesions and familiarity with their morphology can help to achieve the correct diagnosis.
Collagenous Sprue: A Rare, Severe Small-Bowel Malabsorptive Disorder
Authors: Zhao Xiangrong , Johnson Rebecca L. 
Published: February 2021

Abstract
Collagenous sprue is a severe malabsorptive disorder, histologically characterized by small intestinal villous and crypt atrophy, and a subepithelial collagen deposit, thicker than 12 µm, that entraps lamina propria cellular elements. Collagenous sprue is a rare disease entity, with only about 60 sporadic cases reported worldwide since it was first described in 1947. Its exact etiology is still under investigation, and its relationship with classic celiac disease and other refractory, spruelike intestinal disorders remains controversial. Two larger-scale studies, in 2009, brought new insights into this elusive, yet emerging, topic. Here, we present a review of the literature on the possible etiology of collagenous sprue, its proposed links to classic celiac disease and to refractory sprue, and its clinical, biochemical, histologic, and molecular features. To our knowledge, all case reports on collagenous sprue in the medical literature to date are summarized.
The Significance of “Indefinite for Dysplasia” Grading in Barrett Metaplasia
Authors: Younes Mamoun , Lauwers Gregory Y , Ertan Atilla , Ergun Gulchin , Verm Ray , Bridges Margaret , Woods Karen , Meriano Frank , Schmulen Carl , Johnson Craig , Barroso Alberto , Schwartz Jim , McKechnie John , Lechago Juan 
Published: February 2021

Abstract
Context.—For a confident diagnosis of dysplasia in Barrett metaplasia, the epithelial atypia should also involve the surface epithelium. However, pathologists are often faced with biopsies where the crypts show dysplasia, but the surface epithelium is either uninvolved or unevaluable. We previously grouped these cases with indefinite for dysplasia (IND).
Objective.—To determine the clinical significance of IND grading in Barrett metaplasia.
Design.—All biopsies from 276 prospectively followed patients with Barrett metaplasia, who did not have high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) on initial biopsy, were graded as negative for dysplasia, IND, low-grade dysplasia (LGD), HGD, and EAC. Biopsies with multifocal IND or LGD were graded as INDM or LGDM, respectively.
Results.—Only 3 of 193 patients (2%) with an initial diagnosis of negative for dysplasia and only 1 of 48 patients (2%) diagnosed with IND progressed to HGD or EAC. By contrast, 1 of 7 patients (14%) with INDM, 2 of 21 (10%) with LGD, and 1 of 7 (14%) with LGDM progressed to HGD or EAC. There was no significant difference in progression rate between patients with an initial diagnosis of negative for dysplasia and those diagnosed IND nor were there significant differences among patients with initial diagnoses of INDM, LGD, or LGDM. Kaplan-Meier analysis showed that patients with INDM, LGD, or LGDM on initial biopsy (group 1) were more likely to progress to HGD or EAC than were those patients who were diagnosed negative for dysplasia or IND (group 2; log-rank test, P &lt; .001).
Conclusions.—Multifocal IND in an esophageal biopsy from a patient with Barrett metaplasia has the same clinical implication as LGD.
A Case of Black Esophagus With Histopathologic Description and Characterization
Authors: Altenburger Dana L. , Wagner Aaron S. , Li Shuan , Garavaglia Jan 
Published: February 2021

Abstract
Black esophagus, or acute necrotizing esophagitis, is a blackening of the esophagus that is usually distal with a sharp demarcation at the gastroesophageal border. Black esophagus is known to the gastroenterology community; however, to our knowledge it is virtually unknown in the pathology literature with only a single instance described in 1967. It is thought to occur as a poorly elucidated ischemic phenomenon. We report a case of black esophagus in a 45-year-old woman with a history of cocaine and alcohol abuse who was found unresponsive after a vague 2-day illness. On autopsy examination, the esophagus was black with ischemic necrosis of the mucosa, submucosa, and muscularis propria including a diffuse acute inflammatory infiltrate and brown pigmentation limited to the mucosa. Positive periodic acid–Schiff and negative iron stains suggest that the pigment is lipofuscin, likely secondary to ischemia.
Osteoblastoma
Authors: Lucas David R. 
Published: February 2021

Abstract
Osteoblastoma is a rare benign bone tumor. Although the histologic features in most cases are distinctive, there are various permutations that make the diagnosis challenging. It can mimic a variety of other benign bone tumors, but more importantly, distinguishing it from osteoblastoma-like osteosarcoma can be difficult. In this case report, I describe the clinicopathologic findings for a 13-year-old adolescent boy with T7 spinal osteoblastoma and review salient clinical, radiographic, and pathologic features of osteoblastoma, as well as the differential diagnoses.
Diagnosing Emerging and Reemerging Infectious Diseases: The Pivotal Role of the Pathologist
Authors: Olano Juan P. , Walker David H. 
Published: February 2021

Abstract
Context—Molecular diagnostics continues to evolve very rapidly, and its impact in the diagnosis of infectious diseases is undeniable. Molecular tools have played a pivotal role in discovering and characterizing several emerging infectious agents and have now become the gold standard for the diagnosis of infectious diseases caused by fastidious or uncultivable agents. Multiple challenges still remain for the widespread use of cost-effective, validated, and commercially available molecular tools. Automated instruments capable of sample processing and multiplex nucleic acid amplification and postamplification analysis have already been approved by the US Food and Drug Administration (FDA) for use in the clinical setting. Nanobiotechnology is beginning to impact laboratory diagnostics in the clinical setting.
Objective—To address current nucleic acid techniques used in the clinical laboratory for diagnosis of infectious diseases. FDA-approved tests are listed, as well as molecular techniques (amplification and postamplification analysis). A comprehensive list of emerging pathogens during the last 4 decades is also presented. Biosurveillance systems are discussed in the context of molecular tools. The rapidly evolving field of nanobiotechnology is briefly addressed.
Data Sources—Original publications, major reviews, and book chapters were used to present a comprehensive, yet short, review of molecular diagnostics in infectious diseases.
Conclusions—We will continue to witness an exponential growth of molecular techniques used for the initial diagnosis of infectious diseases. Molecular tools will also continue to have an impact on disease prognosis and response to therapeutic interventions. Automation, multiplexing, and miniaturization will continue to be driving forces in the development of new instruments.
Development of an Evidence-Based Approach to External Quality Assurance for Breast Cancer Hormone Receptor Immunohistochemistry: Comparison of Reference Values
Authors: Makretsov Nikita , Gilks C. Blake , Alaghehbandan Reza , Garratt John , Quenneville Louise , Mercer Joel , Palavdzic Dragana , Torlakovic Emina E. ,   on behalf of the Canadian Immunohistochemistry Quality Control Program, Canadian Association of Pathologists
Published: February 2021

Abstract
Context.—External quality assurance and proficiency testing programs for breast cancer predictive biomarkers are based largely on traditional ad hoc design; at present there is no universal consensus on definition of a standard reference value for samples used in external quality assurance programs.
Objective.—To explore reference values for estrogen receptor and progesterone receptor immunohistochemistry in order to develop an evidence-based analytic platform for external quality assurance.
Design.—There were 31 participating laboratories, 4 of which were previously designated as “expert” laboratories. Each participant tested a tissue microarray slide with 44 breast carcinomas for estrogen receptor and progesterone receptor and submitted it to the Canadian Immunohistochemistry Quality Control Program for analysis. Nuclear staining in 1% or more of the tumor cells was a positive score. Five methods for determining reference values were compared.
Results.—All reference values showed 100% agreement for estrogen receptor and progesterone receptor scores, when indeterminate results were excluded. Individual laboratory performance (agreement rates, test sensitivity, test specificity, positive predictive value, negative predictive value, and κ value) was very similar for all reference values. Identification of suboptimal performance by all methods was identical for 30 of 31 laboratories. Estrogen receptor assessment of 1 laboratory was discordant: agreement was less than 90% for 3 of 5 reference values and greater than 90% with the use of 2 other reference values.
Conclusions.—Various reference values provide equivalent laboratory rating. In addition to descriptive feedback, our approach allows calculation of technical test sensitivity and specificity, positive and negative predictive values, agreement rates, and κ values to guide corrective actions.
An Update on Molecular Diagnostics of Squamous and Salivary Gland Tumors of the Head and Neck
Authors: Hunt Jennifer L. 
Published: February 2021

AbstractContext.—Molecular testing in anatomic pathology is becoming standardized and can contribute valuable diagnostic, therapeutic, and prognostic information for the clinical management of patients. In head and neck pathology, recent advances in molecular testing have provided important targets in several different diagnostic areas, with particular emerging clinical applications in squamous and salivary gland pathology. In squamous mucosal-derived lesions, human papilloma virus has emerged as an important pathogenic etiology in a subset of oropharyngeal squamous cell carcinomas. Within the category of salivary gland tumors, 3 tumors have recently been recognized that contain oncogenic translocations.Objective.—To describe the current state of information about the molecular alterations in squamous lesions and in salivary gland tumors of the head and neck.Data Sources.—Published literature on squamous and salivary gland tumors of the head and neck.Conclusions.—The different approaches to identification of viral-associated tumors include assays using polymerase chain reaction, in situ hybridization, and immunohistochemistry. Most mucoepidermoid carcinomas harbor MECT1-MAML2 gene rearrangement. The MYB-NFIB translocations have recently been identified in adenoid cystic carcinomas. Finally, a newly described tumor of salivary gland, mammary analogue secretory carcinoma, harbors the ETV6-NTRK3 translocation. Although these translocations are just emerging as diagnostic targets, future roles may evolve as potential therapeutic targets.
New Kids on the Block
Authors: Karamchandani Dipti M. , Hammad Hazed , Chetty Runjan , Arnold Christina A. 
Published: February 2021

Context.—
With the increasing development and use of iatrogenic agents, pathologists are encountering more novel foreign materials in retrieved gastrointestinal specimens. These colorful and unusual-appearing foreign materials can pose a diagnostic dilemma to those unaware of their morphology, especially if the relevant clinical history is lacking.

Objective.—
To discuss the histopathologic features, clinical scenarios and significance, and differential diagnosis of relatively recently described, yet quickly expanding, family of iatrogenic agents that can present as foreign materials in gastrointestinal specimens—pharmaceutical fillers (crospovidone and microcrystalline cellulose), submucosal lifting agents (Eleview and ORISE), lanthanum carbonate, hydrophilic polymers, OsmoPrep, yttrium 90 microspheres (SIR-Sphere and TheraSphere), and resins (sodium polystyrene sulfonate, sevelamer, and bile acid sequestrants).

Data Sources.—
We collate the findings of published literature, including recently published research papers, and authors' personal experiences from clinical sign-out and consult cases.

Conclusions.—
Correct identification of these iatrogenic agents is important because the presence of some novel agents can explain the histopathologic findings seen in the background specimen, and specific novel agents can serve as diagnostic clues to prompt the pathologist to consider other important and related diagnoses. Awareness of even biologically inert agents is important for accurate diagnosis and to avoid unnecessary and expensive diagnostic studies.
Performance Characteristics of Mutational Signature Analysis in Targeted Panel Sequencing
Authors: Lawrence Lauren , Kunder Christian A. , Fung Eula , Stehr Henning , Zehnder James 
Published: February 2021

Context.—
Mutational signatures have been described in the literature and a few centers have implemented pipelines for clinical reporting.

Objective.—
To describe the performance of a mutational signature caller with clinical samples sequenced on a targeted next-generation sequencing panel with a small genomic footprint.

Design.—
One thousand six hundred eighty-two clinical samples were analyzed for the presence of mutational signatures using deconstructSigs on variant calls with at least 20 variant reads.

Results.—
Signature 10 (associated with POLe mutation) achieved separation of cases and controls in hypermutated samples. Signatures 4 (associated with tobacco smoking) and 7 (associated with ultraviolet radiation) as an indicator of pulmonary or cutaneous primary sites showed moderate sensitivity and high specificity at optimal cutpoints. Mutational signatures in malignancies with unknown primaries were somewhat consistent with the clinically suspected primary site, with an apparent dose-response relationship between the number of variants analyzed and the ability of mutational signature analysis to correctly suggest a primary site.

Conclusions.—
Mutational signatures represent an opportunity for orthogonal testing of primary site, which may be particularly useful in supporting cutaneous or pulmonary sites in poorly differentiated neoplasms. Tobacco smoking, ultraviolet radiation, and POLe mutational signatures are the most appropriate signatures for implementation. Even relatively small numbers of variants appear capable of supporting a clinically suspected primary.