bluuebunny/crossref_metadata_2025_split huggingface dataset:
Panels of Immunohistochemical Markers Help Determine Primary Sites of Metastatic Adenocarcinoma
Authors: Park Seog-Yun , Kim Baek-Hee , Kim Jung-Ho , Lee Sun , Kang Gyeong Hoon 
Published: February 2021

Abstract
Context.—Although identification of the primary tumor in patients with metastatic adenocarcinoma has a profound clinical impact, diagnosing the organ of origin is frequently difficult. Because none of the individual immunohistochemical markers used for tissue identification are both site specific and site sensitive, multiple markers are needed to improve the prediction of primary sites.
Objective.—To develop an effective approach to immunohistochemically evaluate metastatic adenocarcinoma for the assignment of a likely primary site of origin.
Design.—Expression profiles of CDX2, cytokeratin (CK) 7, CK20, thyroid transcription factor 1 (TTF-1), carcinoembryonic antigen (CEA), MUC2, MUC5AC, SMAD4, estrogen receptor (ER), and gross cystic disease fluid protein 15 (GCDFP-15) were generated in adenocarcinomas from 7 primary sites, followed by construction of a decision tree and design of multiple-marker panels. Expression of these markers was evaluated immunohistochemically in 314 primary adenocarcinomas (50 cases each of colorectal, gastric, lung, pancreatic, bile duct, and breast, and 14 cases of ovarian origin) using the tissue array method. Results were validated using 60 cases of metastatic adenocarcinoma with known primaries.
Results.—Organ-specific immunostaining profiles using multiple markers provided high sensitivity, specificity, and positive predictive value in detecting primary adenocarcinomas, as follows: colorectal, TTF-1−/CDX2+/CK7−/CK20+ or TTF-1−/CDX2+/CK7−/CK20−/(CEA+ or MUC2+); ovarian, CK7+/MUC5AC+/TTF-1−/CDX2−/CEA−/GCDFP-15−; breast, GCDFP-15+/TTF-1−/CDX2−/CK7+/CK20− or ER+/ TTF-1−/CDX2−/CK20−/CEA−/MUC5AC−; lung, TTF-1+ or TTF-1−/CDX2−/CK7+/CK20−/GCDFP-15−/ER−/CEA−/ MUC5AC−; pancreaticobiliary, TTF-1−/CDX2−/CK7+/ CEA+/MUC5AC+; and stomach, TTF-1−/CDX2+/CK7+/ CK20−. Overall, these combined phenotypes correctly predicted the tester samples (metastatic adenocarcinomas with known primaries) in 75% of cases.
Conclusions.—Determination of tissue-specific immunostaining profiles is valuable in the diagnostic differentiation of metastatic adenocarcinomas from seven common primary sites and should help to correctly predict the organ of primary tumor origin.
Cytology of Nonneoplastic Occupational and Environmental Diseases of the Lung and Pleura
Authors: Laucirica Rodolfo , Ostrowski Mary L. 
Published: February 2021

AbstractContext.—Cytologic examination of the respiratory tract has been a useful diagnostic tool when evaluating neoplastic lesions of the respiratory tract. However, we have limited experience in the application of this technique in the management of nonneoplastic occupational and environmental diseases of the lung and pleura. This review focuses on the cytologic characteristics of a variety of occupational lung diseases, grouping them into 2 broad diagnostic categories: reactive cellular changes and noncellular elements. The former includes entities such as reactive mesothelial proliferation, goblet cell metaplasia, Creola bodies, and reserve cell hyperplasia, and the latter encompasses Curschmann spirals, Charcot-Leyden crystals, and asbestos bodies.Objective.—To illustrate the cytologic features of several nonneoplastic occupational and environmental diseases and correlate the cytology with various etiologic agents.Data Sources.—Case-derived material and literature review.Conclusions.—The role of cytology in the diagnosis of nonneoplastic occupational and environmental lung diseases is limited. This may be because more than one agent can elicit a similar host reaction and/or the offending agent can be associated with more than one pathologic process. However, in the appropriate clinical and radiographic setting, the cytology can render valuable diagnostic information. Examples include pulmonary alveolar proteinosis in patients with acute silicoproteinosis and asbestos bodies in bronchoalveolar lavage samples of patients with asbestos exposure.
Transformation of Polycythemia Vera to Chronic Myelogenous Leukemia
Authors: Mirza Imran , Frantz Christine , Clarke Gwendolyn , Voth Arnold J. , Turner Robert 
Published: February 2021

Abstract
Transformation of polycythemia vera to chronic myelogenous leukemia is a rare event. We report 2 women with long-standing polycythemia vera who developed chronic myelogenous leukemia. Both patients had no BCR/ABL1 fusion at the time of polycythemia vera diagnosis but were positive for the fusion at chronic myelogenous leukemia onset. Most patients with polycythemia vera have JAK2V617F mutation. Analysis of an archival bone marrow aspirate sample from 1 patient showed a heterozygous mutation status. The blood and bone marrow samples from the other patient showed the presence of homozygous JAK2V617F mutation and BCR/ABL1 fusion. The possible pathogenesis of such an event is discussed in the light of current literature.
A Pilot Study of Vasculogenic Mimicry Immunohistochemical Expression in Hepatocellular Carcinoma
Authors: Guzman Grace , Cotler Scott J. , Lin Amy Y. , Maniotis Andrew J. , Folberg Robert 
Published: February 2021

Abstract
Context.—The “de novo” formation of fluid-conducting patterns by tumor cells, termed vasculogenic mimicry (VM), is associated with increased mortality in many different solid tumors.
Objective.—To identify VM patterns in hepatocellular carcinoma (HCC) and to determine whether these patterns were associated with more rapid tumor recurrence after orthotopic liver transplantation.
Design.—Subjects included 20 patients who underwent orthotopic liver transplantation and were found to have HCC in the liver explant. Samples from 5 normal postmortem livers and 5 explanted livers with hepatitis C virus cirrhosis without HCC served as control tissues. Patterned matrix VM expression in HCC was identified by the presence of laminin-positive loops surrounding packets of tumor cells. Time to HCC recurrence after orthotopic liver transplantation was compared between patients with and without patterned VM expression. The relationships among VM in HCC, cause of chronic liver disease, serum α-fetoprotein level at the time of diagnosis, tissue expression by epidermal growth factor receptor, and endothelial markers including vascular endothelial growth factor and CD31 were assessed.
Results.—Patterned matrix VM was identified in 11 of 20 primary HCC tissue samples. Vasculogenic mimicry was absent in all 10 control cases and was not identified in any area of dysplasia. The expression of VM in HCC lesions in liver explants was associated with more rapid posttransplant recurrence (P = .01). Vasculogenic mimicry was not associated with the cause of liver disease, serum α-fetoprotein level at time of diagnosis, or expression of epidermal growth factor receptor, vascular endothelial growth factor, or CD31.
Conclusions.—Vasculogenic mimicry of the patterned matrix type is present in hepatocellular carcinoma and is associated with tumor recurrence after orthotopic liver transplantation. Vasculogenic mimicry lesions are not associated with endothelial markers in HCC.
Polymorphisms inTGFβandTNFαAre Associated With the Myelodysplastic Syndrome Phenotype
Authors: Powers Martin P. , Nishino Ha , Luo Yamin , Raza Alina , Vanguri Amulya , Rice Lawrence , Zu Youli , Chang Chung-Che(Jeff) 
Published: February 2021

AbstractContext.—Myelodysplastic syndromes (MDSs) are characterized by ineffective hematopoiesis, excessive apoptosis, and the aberrant expression of a number of cytokines. The genes encoding these cytokines are significantly polymorphic. It is unknown whether these cytokine polymorphisms are associated with, and may therefore be playing a role in the pathogenesis of, MDS.Objective.—To determine if certain polymorphisms in the tumor necrosis factor α (TNF-α) and transforming growth factor β (TGF-β) cytokines are overrepresented in a cohort of patients with MDSs.Design.—DNA was isolated from the peripheral blood or bone marrow aspirate of 21 patients with MDS. The genotypes for 4 different polymorphisms, 2 in TNFα and 2 in TGFβ1, were determined using single-specific-primer polymerase chain reaction. The allele and genotype frequencies were compared with similar populations in the National Cancer Institute SNP500 database.Results.—In our MDS population, the −308A/A genotype of the TNFα gene and the TGFβ1 allele +29T and genotype +29T/T, each associated with higher levels of expression, were overrepresented in our MDS population.Conclusions.—Polymorphisms associated with increased expression in the cytokines TNFα and TGFβ1 are overrepresented in the MDS population suggesting that increased TNF-α and TGF-β1 activity may contribute to the susceptibility and/or pathogenesis of MDS. Further studies with larger sample sizes are warranted to confirm our observation.
Tissue Handling for Genome-Wide Expression Analysis: A Review of the Issues, Evidence, and Opportunities
Authors: Medeiros Fabiola , Rigl C. Ted , Anderson Glenda G. , Becker Shawn H. , Halling Kevin C. 
Published: February 2021

AbstractContext.—Molecular diagnostic applications that use microarrays to analyze large numbers of genes simultaneously require high-quality mRNA. As these genome-wide expression assays become more commonly used in medical practice, pathologists and oncologists will benefit from understanding the importance of obtaining high-quality RNA in order to generate reliable diagnostic and prognostic information, especially as these relate to cancer.Objective.—To review the effects that different tissue preservation techniques have on RNA quality and to provide practical advice on changes in tissue acquisition and handling that may soon be needed for certain clinical situations.Data Sources.—A review of recent literature on RNA quality, tissue fixation, cancer diagnosis, and gene expression analysis.Conclusions.—Studies have consistently shown that frozen tissue yields more intact RNA than formalin-fixed, paraffin-embedded tissue. The chemical modification, cross-linking, and fragmentation caused by formalin fixation often render RNA unsuitable for microarray analysis. Thus, when expression analysis involving hundreds or more than 1000 gene markers is contemplated, pathologists should consider freezing a specimen within half an hour (preferably within minutes) of surgical resection and storing it at −80°C or below. In coming years, pathologists will need to work closely with oncologists and other clinicians to determine when saving frozen tissue for microarray expression analysis is both practical and necessary. In select cases, the benefit of implementing a few extra tissue-handling steps may improve diagnostic and prognostic capability.
Thrombotic Microangiopathy in Cocaine Abuse–Associated Malignant Hypertension: Report of 2 Cases With Review of the Literature
Authors: Gu Xin , Herrera Guillermo A. 
Published: February 2021

Abstract
Cocaine is one of the most commonly used illicit drugs. Acute renal failure is an emergent complication in patients with acute cocaine intoxication. It is well known that rhabdomyolysis and vasoconstriction can be important pathogenetic mechanisms resulting in acute renal failure in these patients. Clinically, although cocaine abuse is associated with elevated blood pressure, persistent accelerated hypertension reaching levels diagnostic of malignant hypertension is uncommon. Cocaine-induced malignant hypertension associated with morphologic features of thrombotic macroangiopathy has been rarely mentioned in the literature. We report 2 cases of cocaine abuse–associated malignant hypertension with renal failure. Kidney biopsies revealed thrombotic microangiopathy with fibrinoid necrosis of arterioles and glomerular tufts. Cocaine-mediated endothelial injury and platelet activation may play important pathogenetic roles in cocaine abusers who develop acute renal failure and malignant hypertension.
Diffuse Filiform Polyposis With Unique Histology Mimicking Familial Adenomatous Polyposis in a Patient Without Inflammatory Bowel Disease
Authors: Oakley III Gerard J. , Schraut Wolfgang H. , Peel Robert , Krasinskas Alyssa 
Published: February 2021

Abstract
Filiform polyposis is an uncommon entity that is most often encountered in the colon of patients with a history of inflammatory bowel disease (IBD). Filiform polyposis is characterized by a large number of “wormlike” polyps lined by histologically normal colonic mucosa. These polyps can mimic adenomatous polyps. Only rare cases without a history or evidence of IBD have been reported. Neuromuscular and vascular hamartoma of the small bowel is a rare, focal disorder characterized by disorganized smooth muscle fascicles throughout the submucosa accompanied by fibrosis, nerve fibers, ganglion cells, and vessels. To our knowledge, there is only one report of this lesion in the large bowel (cecum), where it presented as a mass. Here we report the case of a 50-year-old man with no known history or symptoms of IBD presenting with filiform polyposis involving the entire colon, clinically mimicking familial adenomatous polyposis, and showing histologic features similar to neuromuscular and vascular hamartoma of the small bowel.
Bernard-Soulier Syndrome: An Inherited Platelet Disorder
Authors: Pham Angie , Wang Jun 
Published: February 2021

AbstractBernard-Soulier syndrome is an inherited platelet disorder, which is transmitted in an autosomal recessive manner. This syndrome is characterized by variable thrombocytopenia and large defective platelets. Bernard-Soulier syndrome often presents early with bleeding symptoms, such as epistaxis, ecchymosis, menometrorrhagia, and gingival or gastrointestinal bleeding. Diagnosis can be confirmed by platelet aggregation studies and flow cytometry. The differential diagnosis includes the other inherited giant platelet disorders, as well as von Willebrand disease and immune thrombocytopenia purpura. Treatment is generally supportive with platelet transfusions when absolutely necessary and avoidance of antiplatelet medications. Recombinant activated factor VII and desmopressin have been used in attempts to shorten bleeding times; however, no definitive studies regarding their effectiveness have been reported.
Assessment Monitoring of Laboratory Critical Values: A College of American Pathologists Q-Tracks Study of 180 Institutions
Authors: Wagar Elizabeth A. , Stankovic Ana K. , Wilkinson David S. , Walsh Molly , Souers Rhona J. 
Published: February 2021

Abstract
Context.—Critical laboratory value reporting is a highly visible and essential key activity for clinical laboratories.
Objective.—To measure critical laboratory value reporting in multiple institutions over time and to examine the practice patterns and demographic factors associated with sustained improvement in critical value reporting.
Design.—A longitudinal cohort study of 180 clinical laboratories that provided quarterly critical values reporting data for 2 to 16 quarters was conducted using a uniform definition of successful caregiver notification. Mixed linear model analysis of the 2001 through 2004 dataset was performed.
Results.—A decrease in total and inpatient rates of undocumented critical values per 1000 results was associated with (1) the American Association of Blood Banks inspection within the past 2 years (P = .01, for both total and inpatient rates); (2) unit secretary/clerical staff not authorized to accept inpatient critical value notification (P = .004 [total] and .001 [inpatient]); and (3) the mandatory practice of requiring notification of health care providers when handling inpatients known to have results repeatedly in the critical range (P = .01, for both total and inpatient rates). Continued participation in the Q-Tracks monitoring program was associated with significant and progressive improvement in total, inpatient, and outpatient critical value reporting (P = .02, .01, and .003, respectively).
Conclusions.—Critical value reporting improved as the duration of participation in the Q-Tracks monitoring program increased. Improved total and inpatient critical value reporting was associated with factors that may be markers for institutions with priorities of quality management and enhanced communication with responsible caregivers.
Flow Cytometric Detection of ZAP-70 in Chronic Lymphocytic Leukemia: Correlation With Immunocytochemistry and Western Blot Analysis
Authors: Slack Graham W. , Wizniak Juanita , Dabbagh Laith , Shi Xinzhe , Gelebart Pascal , Lai Raymond 
Published: February 2021

Abstract
Context.—Expression of ZAP-70 in chronic lymphocytic leukemia (CLL) predicts worse clinical outcome in patients with early-stage disease. It has become important to include ZAP-70 in the immunophenotyping panel used to diagnose CLL, commonly performed by flow cytometry (FC). Nevertheless, the methodology used to detect ZAP-70 by FC has not been extensively evaluated.
Objective.—To describe our FC method for detecting ZAP-70 in CLL and assess whether this assay is useful in estimating the ZAP-70 protein level in CLL cells.
Design.—ZAP-70 expression was assessed by FC in 45 consecutive newly diagnosed CLL patients, and the results were correlated with those of immunocytochemistry and Western blot analysis.
Results.—With &gt;25% ZAP-70–positive B cells as the cutoff, the FC results had a perfect concordance with those of immunocytochemistry (39/39, 100%) and Western blot analysis (7/7, 100%). The use of autofluorescence controls was found to be superior to other alternatives. Overall, 19 (42%) of 45 cases were ZAP-70 positive in our series. Since only 7 cases (16%) had &gt;20% to 30% ZAP-70–positive B cells, the cutoff of &gt;25% readily separated CLL into positive and negative groups in most cases. ZAP-70 positivity was significantly associated with atypical morphology but not other laboratory parameters evaluated.
Conclusions.—With proper specimen processing and the use of directly fluorescence-conjugated anti–ZAP-70 antibody, one can readily incorporate ZAP-70 into the routine FC study panel for CLL. Our data suggest that FC is a rapid and useful method to estimate the ZAP-70 protein expression level in CLL.
Analysis of Loss of Heterozygosity in Atypical and Negative Bile Duct Brushing Cytology Specimens With Malignant Outcome: Are “False-Negative” Cytologic Findings a Representation of Morphologically Subtle Molecular Alterations?
Authors: Krishnamurti Uma , Sasatomi Eizaburo , Swalsky Patricia A. , Finkelstein Sydney D. , Ohori N. Paul 
Published: February 2021

Abstract
Context.—Conventional cytologic evaluation of bile duct brushings for neoplasia has high specificity but relatively low sensitivity.
Objective.—The aim of this pilot study was to examine whether K-ras mutations and loss of heterozygosity for multiple microsatellite markers in bile duct brushings would contribute to the detection of malignancy in cases initially reported as “negative” or “atypical.”
Design.—Bile duct brushing specimens with a negative or an atypical cytologic result (9 cases) had a benign result on the surgical pathology specimen, and 9 additional negative or atypical cases demonstrated adenocarcinoma on the resected surgical specimen. Cells from representative cytopathology and histology slides were microdissected and analyzed for K-ras mutations and for loss of heterozygosity with a panel of 15 polymorphic markers on chromosomes 1p, 3p, 5q, 9p, 9q, 10q, 17p, and 22q.
Results.—Among cytology cases with malignant outcome, loss of heterozygosity or K-ras mutation was detected in 8 (88.8%) of 9 cases. In the corresponding 9 surgical pathology specimens with adenocarcinoma, K-ras mutations and/or allelic losses were detected in all (100%). Loss of heterozygosity or K-ras mutation was not detected in cytology cases that had a benign surgical outcome. The fractional allelic loss of these 9 cytology specimens ranged from 0 to 0.25 (mean, 0.14). This compared with the fractional allelic loss ranging from 0.15 to 0.42 (mean, 0.27) for the corresponding surgical specimens.
Conclusions.—This pilot study suggests that low-level fractional allelic loss or K-ras mutation in the negative/ atypical cytology samples with malignant outcome is a representation of morphologically subtle molecular alterations.
Mucin Expression in Reactive Gastropathy: An Immunohistochemical Analysis
Authors: Mino-Kenudson Mari , Tomita Shigeki , Lauwers Gregory Y. 
Published: February 2021

Abstract
Context.—Reactive gastropathy is the second most common diagnosis made on gastric biopsies. Increased epithelial proliferation and modifications of epithelial cytokeratin profile, distinct from those of Helicobacter pylori gastritis, have been previously reported. However, the evaluation of mucins, important components of the protective mucosal mucous layer, has not been reported.
Objective.—To investigate alterations of membrane and secreted mucins in reactive gastropathy of various etiologies using antibodies against mucin glycoproteins.
Design.—Thirty-eight gastric biopsies diagnosed as reactive gastropathy, related to nonsteroidal anti-inflammatory drugs (n = 18) or bile reflux (n = 6) or of indeterminate etiology (n = 14), were evaluated using antibodies to MUC1, MUC5AC, MUC6, and MUC2. All cases were confirmed to be negative for H pylori. The biopsies were classified in 3 groups based on the severity of cytoarchitectural changes (mild, moderate, and severe). Mucin expression and its distribution were recorded and the results correlated with the cytoarchitectural alterations and etiologies.
Results.—Loss of MUC1, either patchy or complete, was noted in 67% of the cases. Aberrant expression of MUC5AC in pyloric glands was observed in 81% of the cases, and aberrant expression of MUC6 in the upper foveolar epithelium was diffusely seen in 14% of the cases. Aberrant expression of MUC2 in non-goblet cells was observed in a single case. Aberrant expression of MUC6 was less extensive in the nonsteroidal anti-inflammatory drugs group than in other 2 groups (P = .03). Concurrently, the diffuse distribution of aberrant MUC6 expression was seen only in the cases of severe gastropathy (P = .09). There was no correlation between modifications in expression of other mucins and either the etiologies or the severity of cytoarchitectural changes.
Conclusions.—Expressions of membrane (MUC1) and secreted (MUC5AC, MUC6) mucins are frequently modified in reactive gastropathy. The alteration of MUC1, which is involved in cell adhesion and polarity, may play a role in the development of the serrated profile of reactive gastropathy. Milder modifications of the secreted mucins may be explained by the reactive/regenerative nature of the process. Importantly, theses changes are different from the increase in MUC6 and reduction of MUC5AC expression reported in H pylori gastritis, underlying their mechanistic differences. It is worth noting that similar alterations of mucin expression are shared by various etiologies, that is, nonsteroidal anti-inflammatory drugs and bile reflux, consistent with the nonspecific nature of reactive gastropathy.