bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequence Analysis of MPL Exon 10 of ET and MF JAK2 V617F Negative Patients Reveals a New Mutation
Authors: Bento Celeste , Duarte Marta , Almeida Helena , Menezes Cristina , Estevinho Alexandra , Coucelo Margarida , Kaeda Jaspal , Ribeiro Maria Leticia 
Published: April 2020

Abstract
Background. Diagnosis and classification of myeloproliferative disorders was greatly enhanced by reports describing JAK2V617F mutation in Polycythemia Rubra Vera (PRV) patients and approximately 50% of Essential Thrombocythemia (ET) and Myelofibrosis (MF) patients. More recently mutations mapping to the juxtamembrane region of the thrombopoietin receptor MPL were described in 5–10% of the patients with MF and 1% of the patients with ET. The reported data imply the Exon 10 MPL mutations lead to receptor activation in the absence of thrombopoietin binding and constitutive phosphorylation of JAK2, STAT3, STAT5, AKT and ERK. However, thus far only mutations mapping to codons 515 and 505 have been published. The aim of this study was to determine the frequency of JAK2V617F and MPL exon 10 mutations in MF and ET patients seen at the Hematology Department, Centro Hospitalar de Coimbra.
Methods. Sixty three patients with ET and 12 with MF, diagnosed according to the Polycythemia Vera Study Group (PVSG) criteria, were studied. Genomic DNA was extracted from peripheral blood samples collected into EDTA. Samples were tested for JAK2 V617F mutation by allele specific polymerase chain reaction (ASO-PCR). Subsequently these samples were screened for MPL exon 10 mutations by direct sequencing.
Results. 45 (71.4%) of the 63 patients with ET and 6 (50%) of the 12 MF patients had JAK2V617F mutation. Of the remaining 6 MF patients 3 had MPL mutations; two with W515L and one with W515K amino acid substitutions. Direct sequencing failed to detect exon 10 MPL mutations in 17 of the 18 ET JAK2 V617F negative patients. The remaining patient had a previously unreported MPL mutation mapping to codon 524 where C was substituted by T, predicting a replacement of arginine residue by cysteine (R524C).
Conclusions. JAK2 V617F mutation was detected in 71% of the ET patients and in 50% of the MF. MPL mutations were found in 2 out of 12 MF patients (17%) and in one of the 63 ET patients (1.6%). The MPL codon 515 mutations are reported to activate mpl protein independent of ligand binding. The prevalence of MPL mutations among MF patients is higher than the described in previous reports, however this maybe due to the small number of patients studied. Whilst there is genotype and phenotype correlation between MPD and MPL mutations described the precise functional role in the development of MPD remain unclear. Similarly, whether the previously unreported MPL R524C mutant allele presented here leads to activation of mpl protein like codon 515 mutations is unclear. But nonetheless such mutations assist in accurate diagnosis and classification of Philadelphia negative MPD patients with the view to optimization of clinical management of these patients.
JAK2V617F Mutation Status and Thrombosis in Essential Thrombocythemia
Authors: Cacciola Emma , Di Francesco Ernesto , Pezzella Francesca , Tibullo Daniele , Cacciola Rossella R 
Published: April 2020

Abstract
Thrombosis frequently complicates the essential thrombocythemia (ET) and hypercytosis may play a role in the its occurrence as well as the platelet and coagulant activation. Therefore, we evaluated myeloproliferative and platelet and coagulant activation markers such as platelets (plts), white blood cell (WBC), haemoglobin (Hb) and hematocrit (Hct) and β-thromboglobulin (βTG) and platelet factor 4(PF4) and prothrombin fragment 1+2 (F1+2), thrombin-antothrombin (TAT), tissue factor (TF), von Willebrand factor (vWF) and d-dimer (DD), respectively in ET patients and thrombosis. As has been reported that the Janus Kinase 2 (IAK2) V617F mutation gives ET a proliferative advantage, we also evaluated the JAK2 mutation. The study group consisted of fifty ET patients (24 males and 26 females, mean age 58 years) who fulfilled PVSG and WHO. Their mean duration of disease was 7 years. Of 50 patients, 18 were on hydroxyurea whereas 32 were not receiving any cytoreduction. All patients were on antiplatelets. Plts, WBC, HB and HCT were measured by automated analyser. βTG, PF4, F1+2, TAT, TF and DD and vWF were assayed by ELISA and immunoturbimetric assay, respectively. Jak2 mutation was analysed by melt curve analysis. Of 50 patients, 24 were JAK2 V617F-positive and 26 were wild-type (WT). Among JAK2-positive ET, 11 experienced thrombosis including 5 episodes of myocardial infarction (MI), 3 of deep vein thrombosis (DVT), 2 of transient ischemic attack (TIA) and 1 of erytromelalgia (E), whereas of WT ET, 5 developed thrombosis such as 1 DVT, 2 TIA and 2 E. All patients had thrombocytosis (684±299×109/l) and normal WBC (7.8±2.2×109/l) and HB(13±1.8 g/dl) whereas HCT and βTG were higher in JAK2-positive ET than WT (41±5.2 % vs 37±5.2 %) ( p=0.034) (266±83 IU/ml vs 193±18 IU/ml) (p&lt;.0001). PF4 (113±39 IU/ml vs 6.9±2.2 IU/ml), F1+2 (3.4±3.6 nmol/l vs 0.7±0,2 nmol/l), TAT (16.9±28 μg/l vs 2.6±0.9 μg/l) and TF (93±132 pg/ml vs 6.4±2.8 pg/ml) (p&lt;.0001 and p&lt;.0001 and p=0.001 and p&lt;.0001, respectively) were increased in all patients whereas vWF and DD were normal (56±42 % and 185±208 ng/l). There was no correlation between JAK2 mutation and plts and WBC and HB and any activation marker. A positive correlation there was between JAK2 mutation and HCT (p=0.034) and thrombosis (p=0.059). These data suggest that JAK2 V617F mutation is responsible for a hematopoietic expansion which might play a role in the pathogenesis of thrombosis in ET.
Concurrent Chromosomal Alterations at 3q27, 8q24 and 18q21 in An Atypical Form of Burkitt’s Lymphoma
Authors: Hamarshi Majdi SM , Kishk Maha abu , Mahafzah Mahmoud , Walloch Jami 
Published: April 2020

Abstract
Introduction: Chromosomal translocations are common in non-Hodgkin’s lymphomas (NHL), most frequently involving the genes bcl-2 in the t(14;18) of follicular lymphoma (FL), c-myc in the t(8;14) of Burkitt’s lymphoma (BL) and bcl-6 in the t(3;14) of follicular or diffuse large B-cell (DLBC) lymphoma. We report the clinical features, pathology and genetic findings in an exceedingly rare case of Burkitt’s lymphoma that showed concurrent involvement of these three chromosomal loci.
Case Report: This is a 65 year old Caucasian female who presented with a rapidly growing right supraclavicular lymph node over a few weeks. FNA biopsy showed typical morphology of Burkitt’s lymphoma. Similar morphologic features were found on the bone marrow biopsy. There was widespread disease with no CNS involvement. Flow cytometry from peripheral blood and immunohistochemistry on the cellblock showed B-cell phenotype positive for CD 10, CD19, CD20 (negative CD20 by immunohistochemistry), HLA-DR, cytoplasmic CD79a, and negative for CD34 and TdT. The interesting finding was the lack expression of surface or cytoplasmic immunoglobulin and expression of weak Bcl-6. Almost 90–95% expressed Ki67. The cytogenetic analysis reportedly demonstrated a complex karyotype t(3;8;14), and t(14;18) involving c-myc (8q24), bcl-2 (18q21), and bcl-6 (3q27). After 7 cycles of hyper CVAD-R she had bone marrow biopsy which showed residual disease. She also had a biopsy confirmed relapse as left arm nodule and left leg nodular infiltrate at 8 and 12 months form the diagnosis, respectively.
Discussion: This is a complex case of high grade B-cell lymphoma with morphology suggestive of Burkitt’s lymphoma. However the classification was challenging by the lack of surface immunoglobulin expression that might be expected in mature B-cell neoplasm “DLBCL, FL”, and the lack of TdT and CD34 that might be expected in precursor B-cell neoplasm “BL”. The diagnosis was highly dependent on the cytogenetic findings, which was significant for the presence of t(8;14) albeit in a three way translocation t(3;8;14), and t(14;18) involving c-myc (8q24), bcl-2 (18q21), and bcl-6 (3q27). The lymphoma was therefore described as “Burkitt’s transformation”. This is a rare translocation pattern, but has been described in follicular lymphoma, grade 3; diffuse large cell lymphoma; and Burkitt’s lymphoma.
Conclusion: BL might lack surface immunoglobulin expression making the diagnosis of high grade B-cell lymphoma challenging if based on the morphology and immunophenotyping alone. The cytogentetic findings better delineate sub-types of lymphoma. Molecular evidence of multiple oncogene deregulations, especially when involving the c-myc gene, appears to be associated with a dire clinical outcome.
Immunohistochemical Prognostic Marker for Diffuse Large B Cell Lymphoma in Patients Treated with CHOP Like Chemotherapy: Validation of the Algorithm by Hans Et Al. and Analysis of Individual Markers
Authors: Suh Cheolwon , Huh Jooryung , Oh Sukjoong , Jo Jeong-Hyeon , Kim Shin , Khang Joon 
Published: April 2020

Abstract
Background) Recently, many predictive models of the clinical outcome of diffuse large B cell lymphoma (DLBCL) have been proposed for better stratification of subgroups. However, studies of the protein expression have reported conflicting results, predominantly due to the lack of universally accepted cut-off value for positivity. Here we retrospectively analyzed the expression of CD10, BCL6, MUM1, BCL2, and CD5 in Korean DLBCL patients treated with CHOP like regimen using the widely used algorithm by Hans et al. (Blood 2004) and compared the results with different cut-off values. We also investigated the clinical significance of individual biomarkers.
Methods) Of the DLBCL cases retrieved from the file of Pathology, Asan medical center (1999–2004). Ninety four (94) cases with adequate tissue were included. Clinical characteristics, treatment and outcome of these patients were collected from the AMC data base. Immunohistochemical stains were performed on tissue microarray (TMA) sections of the archival material. According to Hans’ algorithm, cases were divided into germinal center B-cell like (GCB) (either CD10+ or BCL6+MUM1−)(19.1%) and activated B cell-like (ABC) (CD10−BCL6− or BCL6+MUM1+), with a universal cut-off value of 30% or more of the positively-stained tumor cells. The percentage of the positivity was also recorded in each case. The four cutpoints (0%, 1–30%, 31–50%, 51–75%, and 76–100%) were investigated for each marker for best correlation with the clinical outcome.
Results) During the 5-year median follow up, median overall survival was not reached. Hans’ algorithm divided the cases into 18 GCB (19.1%) and 76 ABC tumors (80.9%), with no clinical significance (3-year PFS: GCB group 63%, ABC group 62%). Among individual biomarkers, CD5− group (cut point: any positivity), bcl-6+ group (cut point: any positivity) and CD10+ group (cut point: 30%) had longer PFS, and bcl-6+ group (cut point: any positivity) had longer OS in univariate analysis. Multivariate Cox regression analysis showed CD10 (p=0.003) as independent prognostic marker in PFS; and bcl-6 (p=0.03) as independent prognostic marker in OS.
Conclusion) The present study shows the lack of predictability of Hans’ algorithm in DLBCL patients treated with CHOP like regimen among Koreans, while CD10, Bcl-6, and CD5 had the prognostic significance using different cut-off values. The result suggests that the proposed cut-off value may not be applied universally for best correlation, and that the optimal cut-off value may need to be optimized for individual laboratory.
Immunohistochemical Expression of Germinal Center and Non-Germinal Center Markers in Primary Gastric Diffuse Large B-Cell Lymphoma
Authors: Hurtado Fernando , Beltran Brady , Riva Luis , Salas Renzo , Morales Domingo , Carrasco Antonio , Quinones Pilar , Castillo Jorge 
Published: April 2020

Abstract
BACKGROUND: Recent studies have shown a correlation between diffuse large B-cell lymphoma (DLCBL) prognosis and molecular features using genome profiles by cDNA microarrays. Later reports have shown that immunohistochemical tests using markers as CD10, bcl-6 and MUM-1 to identify germinal center B-cell (GCB) and non-GCB patterns can have a similar value and are gaining major importance in assessing prognosis in patients with DLBCL. Gastric DLCBL is the most frequent extranodal non-Hodgkin lymphoma.
AIM: To evaluate the frequency of GCB and non-GCB subgroups in primary gastric DLCBL and the impact of these tests in prognosis.
PATIENTS AND METHODS: Patients older than 18 years with a diagnosis of primary gastric DLBCL were identified in a single institution from January 2002 to December 2005 and included in this analysis. Immunohistochemical stains were performed using antibodies against CD20, CD10, bcl-6 and MUM1 in all cases. Survival curves were obtained using the Kaplan-Meier method.
RESULTS: Twenty-nine patients were included in this study. The median age at diagnosis was 68 years (range 40 to 86 years). Thirteen male and 16 female patients were included. All cases received chemotherapy with CHOP regimen. Cases were subclassified in GCB and non-GCB using CD10, bcl-6, and MUM1 expression. Four cases (14%) were considered GCB and 25 cases (86%) non-GCB. There were no statistical differences between both groups in the following variables: age, ECOG performance status, serum LDH levels, clinical stage and International Prognostic Index (IPI) score. No statistical difference in survival was observed between the GCB and non-GCB groups. The 3-year overall survival for the entire group was 30%.
CONCLUSION: Immunohistochemical expression of non-GCB pattern is very frequent in primary gastric DLBCL in Peru. However, it does not show an effect in survival, probably related to the small number of cases included in the present study.
Age-Related EBV-Associated B-Cell Lymphoproliferative Disorders: Comparison with EBV-Positive Classical Hodgkin Lymphoma in Elderly Patients
Authors: Asano Naoko , Yamamoto Kazuhito , Tamaru Jun-Ichi , Oyama Takashi , Ishida Fumihiro , Ohshima Koichi , Yoshino Tadashi , Nakamura Naoya , Mori Shigeo , Yoshie Osamu , Shimoyama Yoshie , Morishima Yasuo , Kinoshita Tomohiro , Nakamura Shigeo 
Published: April 2020

Abstract
Age-related Epstein-Barr virus-associated (EBV+) B-cell lymphoproliferative disorder (LPD) is a disease group of EBV+ large B-cell lymphoma characteristically seen in elderly patients without predisposing immunodeficiency. This disease is now going to be listed in the up-coming WHO classification the 4th version. Age-related EBV+ LPD, especially of a polymorphous subtype, which occupied about one-third of cases, is often featured by a rich infiltration of reactive cells in the background, posing the differential diagnostic issue with classical Hodgkin lymphoma (cHL) associated with EBV. However, the clinicopathological differentiation between these two EBV-positive diseases remains to be elucidated. The aim of this study is to clarify the clinicopathological differences between the polymorphic subtype of age-related EBV+ LPD (n=34) and EBV+ cHL (n=108) of patients of 50 years and more of age. Age-related LPD was more closely associated with the following clinical parameters than cHL: a higher age at onset (71 vs. 63 years), lower male predominance (male:female ratio, 1.4 vs. 3.3), and a higher ratio of involvement of the skin (18% vs. 2%), the gastrointestinal tract (15% vs. 4%) and the lung (12% vs. 2%). Furthermore, age-related LPD was histopathologically characterized by a higher ratio of geographical necrosis, a greater increase (&gt;30%) of cytotoxic T cells in the background lymphocytes, a higher positive rate for CD20 and EBNA2 together with an absence of CD15 expression than EBV+ cHL. As predicted by the clinical profile, age-related LPD had a significantly poorer prognosis than EBV+ cHL (P = 0.0001). This analysis has clearly demonstrated that the polymorphous subtype of age-related LPD constitutes an aggressive group with an immune response distinct from those of EBV+ cHL.
Bilateral Optic Nerve Invasion of Extranodal Marginal Zone B Cell Lymphoma with Leukemic Subtype
Authors: Sung Hwa Jung , Kim Eui Bae , Lee Se Ryeon , Park Kyong Hwa , Choi In Keun , Oh Sang Chul , Kim Byung Soo , Kim Yeul Hong , Kim Jun Suk , Seo Hee Yun , Kim Sun Hyung , Yoon Soo-Young 
Published: April 2020

Abstract
Extranodal marginal zone B cell lymphoma(MZBL), leukemic subtype is a rare B cell neoplasm characterized by peripheral lymphocytosis and bone marrow infiltration without nodal involvement. We report the case of a man who presented a simultaneous bilateral optic neuropathy as the initial clinical manifestation of extranodal MZBL. A 62-year-old man was referred to the Neuro-Ophthalmology Department because of a decrease in visual acuity, dyschromatopsia, visual field defects. Optic disc swelling was present in both eyes with peripapillary hemorrhages. Bilateral anterior ischemic optic neuropathy was diagnosed. Marked visual improvement occurred after 24 hours of intravenous methylprednisolone therapy, and vision completely recovered within a week. Eight weeks later, vision deteriorated again with bilateral optic disc swelling. A magnetic resonance image of the brain and orbit showed only enhancement of the optic nerve. Complete blood count(CBC) studies revealed hyperleukocytosis (13699/uL) with 72 % lymphocytes. There was no anemia and thrombocytopenia. Bone marrow(BM) study showed hypercellular with diffuse infiltration of small lymphocytic cells comprising 65.5% of all nucleasted cells. On immunophenotyping of BM aspirate, lymphocytic cells were CD2-CD3-CD5-CD10-CD23-CD33-CD34-CD117-CD138-cMPO-CD7+CD13+CD19+CD20+CD22+CD45+CD79+FMC7+kappa+lamda-. Cervicothoracic & abdominal CT scan showed no hepatosplenomegaly and no systemic lymphadenopathy. Depending on findings of BM and CT scan, extranodal marginal zone B cell lymphoma, leukemic subtype was diagnosed. Lumbar puncture revealed a white blood cell count of 790/uL with 90% lymphocyte. Flow cytometry was significant for a predominant population of CD3-CD4-CD8-CD20+CD13+ B-cell lymphocytes, diagnostic of cerebrospinal fluid involvement by lymphoma. So we could diagnosed the patient as optic nerve invasion of MZBL without optic nerve biopsy. The patient took several intrathecal chemotherapy with MHA(methotrexate, hydrocortisone, cytosine arabinoside)and 4th systemic treatment with R-CVP(rituximab, cyclophosphamide, prednosone). After all the visual acuity were improved and the infiltrative lesion of lymphoma on both optic nerve was found improved on the following MRI of orbit. The laboratory finding of CBC and CSF were completely normalized.
Nasal-Type NK/T Cell Lymphoma: Clinical Features, Immunophenotype and Treatment Outcome
Authors: Qian Shenxian , Shi Pengfen , Gao DaQian , Chen Kuang , Tan Junfeng , Liu LiRong , Xie Yaping 
Published: April 2020

Abstract
The clinical characteristics and prognosis remain unclear for nasal-type NK/T-cell lymphoma. The aim of this study is to determine the clinical features and outcome. 26 patients diagnosed as nasal-type NK/T cell lymphoma were included in the analysis. Immunophenotype was analyzed by immunohistochemical staining for LCA, CD79α, CD20, CD56, CD3, CD45RO, All the cases of nasal NK/T cell lymphoma were LCA, The positivity rates of CD45RO and CD56 were 89.8%, and 66%, respectively. Tumor cells didn’t express antigens of B and histiocyte, According to Ann Arbor system, 2, 7, 12, and 5 patients had stage I, II, III, and IV. 24 patients received combined chemotherapy(CHOP plus Ara-c) and radiotherapy, and 2 patients received chemotherapy alone. The disease is characterized by predominant young males, a propensity for nodal involvement, frequent stage II–III diseases, low frequency of elevated LDH, low-risk international prognostic index (IPI), high sensitivity to radiotherapy, and intermediate sensitivity to chemotherapy. The 3-year overall survival and progression-free survival for all patients were 88% and 71%, respectively The age, B symptoms, stage, and IPI were important prognostic factors. Combined chemotherapy(CHOP plus Ara-c) and radiotherapy tended to improve the survival for patients with stage and II or III diseases. The distant extranodal dissemination were the primary failure patterns. nasal-type NK/T-cell lymphoma appears to have distinct clinical characteristics and favorable outcomes.
Assessment of FDG-PET Imaging in T-Cell and NK-Cell Lymphomas
Authors: Chalapud-Revelo Juan , Sobrevilla-Calvo Pedro , Carlos Cadena-Eumaña , Silvia Rivas-Vera , Omar Lopez-Navarro , Juan Labardini 
Published: April 2020

Abstract
BACKGROUND: Malignant T-cell lymphomas are a heterogeneous group of disorders that frequently involve extranodal regions. Treatment and prognosis depend on accurate staging and histological evaluation. PET is widely used in staging and response evaluation of B-cell lymphomas, however, the use of FDG-PET have not been well studied for T-cell and natural killer cell lymphomas, and there is controversy if PET can detect accurately extranodal tumor activity.
PATIENTS AND METHODS: We retrospectively evaluated FDG-PET in 38 patients with active T-cells, and T/NK-cells lymphoma diagnosed according to the World Health Organization (WHO) classification, from May 2007 to May 2008. We also evaluated the Standard Uptake values (SUV) according the different subtypes and the accuracy of PET in detecting tumor activity in the skin and nasal region.
RESULTS: Histological subtypes included were extranodal NK/T-cell lymphoma nasal type (ENKL, n=12); Anaplastic T-cell lymphoma (ATCL, n=11); peripheral T-cell lymphoma (PTL, n=7); mycosis fungoides and Sezary syndrome (MF/SS, n=5), angioimmunoblastic (An=3). FDG-PET detected a lymphoma lesion in at least one site in 35 out of 38 patients (91%). The positivity rate was high in all histological subtypes ENKL 92%, ATCL 100%, PTL 86%, MF/SS 80%, A 100%. Among 13 patients who had cutaneous lesions only 7 had FDG-avid skin lesions (sensitivity =53.8% and specificity=100%) and among 11 patients with nasal region lesions, 91% had FDG-avid cutaneous lesions (sensibility = 91%, specificity=100%). The SUV Value in the different subtypes is shown in the table and there was not statistical differences between the groups (p= 0.067)
Lymphoma N Mean SD(+/−) Range An 3 4.1 1.7 2.7–6 MF/SS 5 4.2 3.0 1.9–8.6 ATCL 11 8.3 5.3 1.6–20.8 PTL 7 3.5 1.6 2.2–6.0 ENKL 12 7.2 4.1 2.2–13.8 Total 38 6.35 4.3 1.6–20.8
CONCLUSIONS: Most of the T and T/NK cell lymphomas were detected by FDGPET. All cases, except one, of ENKL nasal type were FDG-avid, but only half of cutaneous lesions were detected by PET. In the whole T-Cell lymphomas group the mean SUV was 6.35, ATCL had the highest SUV, and we did not find any statistically differences between the groups. We conclude that PET has a high sensitivity for detection of active ENNK nasal type lymphomas and this information should be the basis for designing further studies to assess its value in staging, tumor response and as a prognostic factor.