bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anaplastic Glioneuronal Tumor With KIAA1549/BRAF Fusion
Authors: Xiong Zhenggang , Narayan Prithvi 
Published: September 2019

Abstract

Introduction
Glioneuronal tumors are usually low grade and have a favorable prognosis. The anaplastic glioneuronal tumor with KIAA1549/BRAF fusion has not yet been documented. This article reports a pediatric case of glioneuronal tumor with anaplasia and KIAA1549/BRAF fusion to illuminate the importance of KIAA1549/BRAF fusion in the tumorigenesis and clinical management of high-grade glioneuronal tumors.

Case Presentation
A 10-year-old boy presented with 1 year of headache and 3 months of blurry vision and proptosis. Ophthalmologic evaluation revealed bilateral papilledema. Magnetic resonance imaging showed a large mixed cystic and solid mass in the left frontal lobe of cerebrum. Histologic analysis demonstrated a glioneuronal tumor with papillary/pseudopapillary growth pattern, focal necrosis, microcalcification, and brisk mitotic activity with a high Ki-67 labeling index of focally up to 20%. Immunohistochemical assessment identified a mixed glial and neuronal neoplastic cell population. Molecular studies revealed a KIAA1549/BRAF fusion.

Conclusion
KIAA1549/BRAF fusion may play an important role in the oncogenesis of high-grade glioneuronal tumors. In view of the fact that effective, targeted therapies for the tumors with KIAA1549/BRAF fusion are clinically available, detection of KIAA1549/BRAF fusion for glioneuronal tumors, particularly high-grade glioneuronal tumors, is helpful.
Immunohistochemical Study of M1 and M2 Macrophages Population in Chronic Villitis of the Placenta
Authors: Egal Erika , Rodrigues Natalia de Magalhães , Mariano Fernanda , Souza Reydson , Scarini Joao , Sabino Welligton , Aguiar Leisa , Montalli Victor , Gondak Rogerio , Soares Ciro , Morais Thayná , Altemani Albina 
Published: September 2019

Abstract

Introduction
Villitis is characterized by the presence of inflammatory infiltrate (CD8 lymphocyte) in the placental villous and is classified as to the etiology in known and unknown. In most cases, villitis is idiopathic (villitis of unknown etiology [VUE]) because no microorganisms are evident and there are no maternal symptoms or signs. It has recently been proposed that pregnancy is, in fact, an active and highly regulated immune process in which macrophages play an important role. Macrophages may present with M1 phenotype, important effector cells, or M2 phenotype, capable of suppressing the function of M1 macrophages and influencing immunoregulation and tissue repair. CD68 antibody recognizes macrophages M1 and M2, whereas CD11c and CD163 antibodies are specific for the identification only of M1 and M2 macrophages, respectively. The objective of our study is to characterize in human placentas in the subpopulation of M1 and M2 macrophages in VUE.

Methods
Sixteen cases of chronic villitis (all without an identifiable etiologic agent) and three control placentas were examined using immunohistochemistry with antibodies for CD68, CD11c, CD163, and CD3.

Results
CD68 and CD163 were present in all cases in the normal areas. CD68, CD163, and CD11c were present in the villous stroma and in the intervillous space in the inflamed areas. The percentage of CD68-positive macrophages was higher than CD163- and CD11c-positive macrophages in all specimens studied. A total increase of CD68, CD163, and CD11c with the predominance of CD11c over CD163 in the inflamed areas was observed.

Conclusion
The predominance of M1 macrophages (CD11c) in the inflamed areas suggests the influence of these cells in the pathogenesis VUE. The higher amount of M2 (CD163) in the inflamed villous compared to normal areas suggests a possible immunoregulatory mechanism of the inflammatory process in VUE.
Fibrin-Associated Diffuse Large B-Cell Lymphoma Occurring as a Pararenal Pseudocyst
Authors: Mohlman Jeffrey , Rets Anton 
Published: September 2019

Abstract
A 60-year-old male underwent nephrectomy for a tumor on the posterior aspect of the right kidney. Grossly, a completely encapsulated 8 × 8 × 6.8-cm nodule was found in the perinephric fat adjacent to the renal capsule and indenting the renal surface. The renal parenchyma was microscopically unremarkable. The capsule of the lesion was composed of dense fibrous tissue with chronic inflammation, remote hemorrhage, and prominent calcifications. The nodule/pseudocyst contained predominantly amorphous, eosinophilic material with cholesterol clefts and calcifications. Within the pseudocyst, clusters of large cells were identified. These cells showed abundant amphophilic cytoplasm and large pleomorphic nuclei with dispersed chromatin, prominent nucleoli, and occasional mitotic figures. Immunohistochemical (IHC) staining showed that these cells were positive for CD20, CD79a, IRF4, BCL2 (>90%), C-MYC (70-80%), and EBV-ISH; variably positive for CD30 and PAX5; and negative for CD3, CD10, CD68, CD138, ALK1, and BCL6. MYC FISH break-apart probe demonstrated no rearrangements or copy number changes. Based on the overall features, the diagnosis of fibrin-associated diffuse large B-cell lymphoma (FA-DLBCL) was rendered. This entity has been recently recognized under a larger category of diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI). Unlike DLBCL-CI, which is considered clinically aggressive, FA-DLBCL typically demonstrates a favorable outcome with surgical resection alone. FA-DLBCL is usually incidentally found at unusual sites (cardiac myxomas, prosthetic cardiac valves, thrombi, hematomas, and pseudocysts including intracranial, splenic, retroperitoneal, paratesticular, adrenal, and renal). To our knowledge, this is the first report of a FA-DLBCL arising in a pararenal location. In addition, our case demonstrates unusually high MYC IHC positivity. Although rare, this entity should be kept in mind, especially in an appropriate clinical setting, and should not be misclassified into a more aggressive category, such as “double expressor” DLBCL or DLBCL-CI.
Flow Cytometry Signature for Kikuchi-Fujimoto/Lupus Lymphadenitis Derived From 975 Benign and Malignant Lymphadenopathies
Authors: Kumar Jyoti , Scott Gregory , Oak Jean , Raess Philipp , Gratzinger Dita 
Published: September 2019

Abstract

Introduction
Kikuchi lymphadenitis is a benign disease with histologic features that can be challenging to discern from malignant or infectious diagnoses. Furthermore, Kikuchi lymphadenitis and systemic lupus erythematosus–associated lymphadenitis (KD/SLE) show overlapping histologic features. We used flow cytometry to evaluate if KD/SLE has a distinct immunophenotype from other lymphadenopathies.

Methods and Materials
Sixteen cases of KD/SLE were compared to 959 control cases at Stanford by flow cytometry for three scenarios: KD/SLE versus T-cell lymphomas, all benign cases, and all benign and malignant cases. Select cases of KD/SLE and benign lymph nodes were analyzed by immunohistochemistry to evaluate the B-cell characteristics. A test set of five KD cases were compared to five normal controls from an independent institution to evaluate cross-platform reproducibility of the KD/SLE flow cytometry signature.

Results
The most discriminatory signature for KD/SLE versus all other benign cases comprised two surface antigen pairs (high CD38+ CD19+, low large-cell CD57+ CD3+), patient age, lymph node location, and four additional flow antigens (100% sensitivity, 99.6% specificity). The signature for KD/SLE versus T-cell lymphomas consisted of two flow antigens (high CD38+ CD19+ and high CD3) and patient age (100% sensitivity, 100% specificity). Based on the flow data, immunohistochemistry was performed to evaluate the B-cell characteristics. We observed clusters of IgD-positive B cells surrounding activated T-cell foci without IgM expression, suggesting that these cells represent either naive cells or memory IgD-positive B cells. Flow cytometry showed increased CD23 with minimal CD5 expression, supporting the hypothesis of naive functional anergic/autoreactive IgD+ IgM– B cells.

Conclusion
We have identified a signature that can distinguish Kikuchi disease and systemic lupus erythematosus from a large cohort of benign and malignant entities, likely reflecting a shared stable underlying etiology of KD/SLE. Our study provides a valuable tool to enhance the ability to accurately diagnose KD/SLE.
Cytogenetic and Molecular Profile Analysis in Hispanic Chronic Myelomonocytic Leukemia Patients From Puerto Rico
Authors: Matti Nawar , Zheng Ruifang , Algarrahi Khalid , Alhatem Albert , Sun Xinlai , Jiang Jie-Gen , NJMS Rutgers 
Published: September 2019

Abstract

Objectives
Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy with both myelodysplastic and myeloproliferative features. The clinical and pathological features of CMML are highly heterogeneous. It was reported that Hispanic whites had an age-adjusted lower incidence rate of CMML compared to non-Hispanic whites. The aim of this study is to define the cytogenetic and genomic landscape of Hispanic CMML patients and explore their potential clinical significance.

Methods
Clinically relevant cytogenetic results and 40-gene molecular profiles of Hispanic CMML patients in Puerto Rico (PR) from 2009 to 2018 were obtained retrospectively.

Results
Total 111 Hispanic CMML patients from PR were diagnosed in our institute from 2009 to 2018. The age range was from 46 to 96 years with a median age of 74. Sixty-five were male and 46 were female. The epidemiological features are similar to that in a general CMML patient population. In total, 107 patients had karyotypes available; 17 patients had abnormal karyotype (17/107, ~16%). Compared with general CMML patients, Hispanic CMML patients had a significantly lower rate of cytogenetic abnormalities (30% vs 16%). Among total 111 Hispanic CMML patients, 40-gene myeloid molecular profiles were performed in 56 CMML patients. Fifty-five out of 56 patients had mutations identified (~98.2%). The most frequent mutated genes were TET2, SRSF2, ASXL1, NRAS, and ZRSR2. Twenty-six of 56 patients (~46.4%) had mutated TET2/wild-type ASXL1.
Previous studies indicated that mutated ASXL1, NRAS, RUNX1, and SETBP1 likely associate with an unfavorable prognosis in a general CMML patient population. Mutated TET2 with wild-type ASXL1 (muTET2/wtASXL1) may associate with a favorable prognosis. Compared with general CMML patients, Hispanic CMML patients in this study had relatively lower mutational rates in ASXL1 (30.4% vs 37.0%), NRAS (10.7% vs 11.7%), RUNX1 (5.3% vs 7.9%), and SETBP1 (5.3% vs 8.9%) and a higher rate of muTET2/wtASXL1 (46.4% vs 37.8%).

Conclusion
Hispanic CMML patients from PR had a significantly lower rate in cytogenetic abnormalities; relatively lower mutational rates in ASXL1, NRAS, RUNX1, and SETBP1; and a higher mutational rate in muTET2/wtASXL1. The findings raise a possibility of a better prognosis in Hispanic CMML patients and could be one of the explanations of a lower incidence rate of CMML in Hispanic population.
Hepatitis C Virus (HCV) Transmitted Transfusion Risk Among β-Thalassemia Patients in Egypt
Authors: Boraik Ayman , Fyala Amira , Abdelmonem Mohamed , Shedid Mohamed , Naguib Saeed , Mohamed Amira 
Published: September 2019

Abstract
Introduction: β-Thalassemia is an inherited abnormal condition that results in hemolytic anemia. It is the most common monogenic disorder in the world. The Mediterranean countries have the highest prevalence of β-thalassemia (2%-18%), and in Egypt, it is 9% to 10%. Regular multiblood transfusion and iron chelation are the major line of therapy for thalassemic patients. There are relatively low blood transfusion safety standards in the Third World countries. Hepatitis C virus (HCV) has the highest risk of transfusion transmitted diseases and Egypt has the highest HCV prevalence worldwide.
Method: Our study is aimed to assess the risk of HCV transmitted to thalassemic patients that receive regular blood transfusions by focusing on the statistics of this population. The study covered most Egyptian governorates from Nile Delta and Upper Egypt by collecting patients’ data between 2015 and 2018.
Results: Consecutive studies were done on 946 β-thalassemic patients as demonstrated from the following: Cairo (205), Mansoura (36), Tanta (120), Damanhur (125), Alexandria (119), Zagazig (73), AlFayoum (121), and Sohag and Minia (147). Studies showed that the HCV-transmitted infection in thalassemia patients in Upper Egypt were detected at 37%, while some Nile Delta studies illustrated that 20% were infected with HCV from transfused thalassemia patients due to multiple blood transfusions.
Conclusion: Blood transfusion–transmitted hepatitis C virus has a very high rate among Egyptian thalassemic patients compared to the worldwide rate. Common anti-HCV antibody screening assay has a low sensitivity and specificity compared to nucleic acid amplification testing (NAT). Therefore, our study recommends following the American Association of Blood Bank (AABB) guidelines for blood donation screenings and implementation of viral NAT testing to reduce the risk of viral transmission during the “window period.” This will reduce the time for effective detection from 70 to 10 days for HCV.
Ultrasensitive RNA In Situ Hybridization for Kappa and Lambda Light Chain mRNA in Marginal Zone Lymphoma Demonstrates Comparable Performance to Flow Cytometry
Authors: Franklin Michael , Deel Chelsey , Vasef Mohammad 
Published: September 2019

Abstract

Objectives
Evaluation of light chain restriction is critical to establish clonality in B-cell lymphoproliferative disorders (LPDs). Immunohistochemistry (IHC) and in situ hybridization (ISH) are commonly used to assess light chain restriction in formalin-fixed, paraffin-embedded (FFPE) tissues. However, except for cases with plasma cell differentiation, these techniques often fail to identify immunoglobulin light chains. An ultrasensitive technique, RNAscope, has been recently introduced that can identify light chains in cases of B-cell LPDs. We analyzed the utility of this ultrasensitive method in detection of clonality and correlated with flow cytometry results when available.

Methods
A tissue microarray was constructed using 1.6-mm diameter tissue punches of 31 FFPE tissue blocks from 27 cases that were previously characterized as marginal zone lymphoma (MZL) by a combination of morphology, IHC, and/or flow cytometry. Cases included 8 nodal and 19 extranodal MZLs. In two cases, additional blocks were included to assess reproducibility. For ultrasensitive ISH RNAscope assay, 4-µm thickness tissue sections were hybridized using kappa and lambda probes, incubated overnight, counterstained with hematoxylin, cover-slipped, and reviewed blindly without knowledge of prior flow cytometry results.

Results
Of 18 cases with evaluable staining, 15 were clonal and 3 were polytypic. Flow cytometry was available in 14 of these 18 cases with concordance in 13 of 14 (93%). The discordant case was polytypic by flow cytometry but kappa restricted by RNAscope. The false-negative flow results could be due to sampling issues. In six cases, staining failed and could not be evaluated.

Conclusion
Ultrasensitive RNAscope is a reliable assay in the detection of clonality in FFPE tissue, particularly where fresh tissue is not available for flow cytometry. In addition, our results confirm and further expand prior observations that RNAscope is a highly sensitive and specific assay with high concordance with flow cytometry.
Classic Hodgkin Lymphoma With Intrasinusoidal Pattern of Infiltration and Concurrent Plasma Cell Variant of Castleman Disease
Authors: Barrett Sean , Laziuk Katsiaryna , Hammer Richard 
Published: September 2019

Abstract
The relationship between Hodgkin lymphoma and plasma cell variant of Castleman disease is uncommon but has been previously described. Most reported cases were diagnosed concurrently. However, sinusoidal involvement by Hodgkin lymphoma is very rare and morphologically can mimic anaplastic large cell lymphoma. Here we present a case of classic Hodgkin lymphoma with a sinusoidal pattern of infiltration coexisting with the plasma cell variant of Castleman disease. A 16-year-old male presented to clinic with shortness of breath and a worsening cough with yearlong duration. Medical history revealed no autoimmune disease, but there was a prolonged allergy history with chronic sinusitis. Imaging showed a right sided mediastinal mass, supraclavicular lymphadenopathy, and pleural effusion. CBC demonstrated anemia, neutrophilia, lymphopenia, and thrombocytosis. Excision of a supraclavicular lymph node revealed effaced architecture with marked plasmacytosis in the interfollicular areas and permeation of sinusoidal spaces by neoplastic cells with morphological features of classic Reed-Sternberg/Hodgkin cells; histiocytes, neutrophils, and residual follicles with regressed germinal centers were seen in the background. Immunohistochemistry revealed strong positivity for CD30 and CD15 by the neoplastic cells as well as positivity for PAX5, MUM1, and CD200 and faint membrane positivity for CD20. The neoplastic cells were negative for CD79a, CD45, EMA, ALK1, and associated T-cell markers. CD138 highlighted increased plasma cells that were negative for CD56, CD200 and polytypic for kappa and lambda. Concurrent bone marrow biopsy revealed a normocellular bone marrow with mild plasmacytosis and no evidence of involvement by lymphoma. Both lymph node and bone marrow were negative for HHV-8. Flow cytometry of the lymph node revealed no monotypic B-cell population and T cells showed predominance of CD4-positive cells with no aberrant antigen expression. The unusual morphologic pattern of classic Hodgkin lymphoma made the diagnosis challenging, and demonstration of proper immunophenotype is required for diagnosis.
Primary Dural Lymphoma Masquerading as a Meningioma: A Rare Clinical Entity
Authors: Sakshi Sakshi , Bains Ashish 
Published: September 2019

Abstract
Primary dura mater–based lymphomas are extremely uncommon and when detected are often clinically and radiologically misidentified. As per literature search, they account for <0.1% of all non-Hodgkin lymphomas; however, a precise incidence is unknown since only a few cases have been described in the literature.
Here we report a case of a 64-year-old female who presented for evaluation of a newly diagnosed left tentorial tumor, diagnosed as “consistent with meningioma” on imaging studies with significant mass effect on the left occipital lobe and left cerebellum with effacement of the fourth ventricle. She had been experiencing disabling headaches, balance dysfunction, and reduced vision. On examination, the patient had right visual field defect with wide-based gait. No evidence of systemic lymphoma or clinically suspicious lymphadenopathy was documented. An intraoperative consultation revealed sheets of lymphocytes, rather highly concerning for lymphoma. H&E sections showed dense fibroconnective tissue heavily infiltrated by mature small- to intermediate-sized lymphocytes with irregular nuclei and condensed chromatin without a discernible architecture. Only sparse and scattered larger lymphocytes were seen. Flow cytometry identified a subset of B cells with lambda-restricted immunophenotype expressing CD19+, CD20+, CD10+, CD5–, and CD23–. On tissue sections, Ki-67 showed an overall proliferation index of 10% to 20%. However, no residual follicular dendritic cell meshwork was detected by CD21 or CD23. PCR analysis detected clonal B-cell IgH and IgKappa gene rearrangements. A diagnosis of low-grade CD10-positive B-cell lymphoma (likely follicle center-cell origin) was made and the patient was discharged after 3 days of surgery for outpatient follow-up and treatment.
In conclusion, low-grade dural-based lymphomas are extremely rare and often misdiagnosed as meningiomas clinically and radiologically. Additionally, it is important distinguish lymphomas of the dura mater, which are excluded from the definition of primary CNS lymphomas and may have a different clinical management and outcome.
Asymptomatic Malaria Infection and Their Antibodies Against Malaria: A Study in Abra de Ilog, Occidental Mindoro, Philippines
Authors: Ledesma Carlo , Sadang Ma Gina 
Published: September 2019

Abstract
Human malaria, caused by four species of Plasmodium, namely P falciparum, P vivax, P malariae, and P ovale, remains a health problem of global concern, with one to two million deaths annually and risking about two billion people worldwide. Alternative ways of controlling the incidence of malaria through understanding the host’s immune response to monoinfection and the detection of the presence of asymptomatic malaria infection are the factors being addressed in this study. The determination of the possible existence of cross-antigenic stimulation is a matter of great significance for future research and development. The isolation of these antigenic structures may give the first step to the development of better vaccines that may protect the general population who are at risk of developing malaria. Prior to blood collection, a memorandum of agreement was signed between the researcher and the Iraya-Mangyan leaders of Abra de Ilog, Occidental Mindoro. A Certificate Precondition was issued by the National Commission of Indigenous Peoples, which was required by the Graduate School Ethics Review Committee. Determination of the presence of malaria parasite on blood samples of residents of two barangays in Abra de Ilog, Occidental Mindoro, was performed using two methods: microscopic examination of stained blood smears for the presence of malaria parasite and polymerase chain reaction. Blood smears were prepared and eventually stained using Giemsa and Dip Quick stains. The detection of 5 positive cases of malaria infection with ring/schizont stage among the 53 cases was a clear indication of positive asymptomatic cases. Nested PCR using Plasmodium spp.–specific primer as well as P falciparum–specific and P vivax–specific primers showed the absence of bands so that one of the recommendations in this study is the performance of real-time PRC using more sensitive primers. Levels of P falciparum and P vivax–specific immunoglobulin were measured using an enzyme-linked immunosorbent assay revealing a higher level of PF-specific IgG than PV-specific IgG. Whole blood samples were saved for future determinations such as real-time PCR, immunophenotypic analysis, and possible parasitic culture. Further similar studies may also be done by increasing the number of respondents as well as the areas of concern for a more extensive scope.