scholarly journals NFATc1 and Tumor Associated Macrophages Affect Progression of Certain Subsets of Diffuse Large B Cell Lymphoma Non-GCB Subtypes

2021 ◽  
Vol 5 (3) ◽  
pp. 320-328
Author(s):  
Krisna Murti ◽  
Muslina Muslina ◽  
Ika Kartika ◽  
Rachmat Hidayat ◽  
Ella Amalia

Introduction: Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma among B cell lymphomas. The interaction of tumor cells with their microenvironment (tumor microenvironment, TME) leads to progressivity of malignancy. CD163 + macrophages known as components of TME. Nuclear factor of activated T cell (NFATc1) and MYC are important transcription factors in malignant transformation and progression. Therapeutic strategies were fast developed, nevertheless, efforts to decrease DLBCL morbidity and mortality are unsatisfied, therefore,new markers for prognosis and or therapeutic options of the patients are necessary. This study was aimed to investigate NFATc1 expression in DLBCL and its TME. Methods: Thirty-two paraffin blocks were selected then immunostained for expression of NFATc1, MYC, and CD163. Clinopathologic data i.e. ages, gender, and proliferation index Ki-67 were obtained. Data was analyzed by statistics Result: Positive expression of CD163 and NFATc1 was among 55% and 45% of cases respectively. All DLBCL cases in this study were non-GCB subtype and more patients were under 60 years (66%). Positive expression of CD163 was higher in males (69%) and in patients under 60 years (63%). Tissues positive for both NFATc1 and CD163 was observed higher among males and patients under 60 years. Conclusion: NFATc1 may affect development and or progression of certain subsets of DLBCL non-GCB subtype.

2021 ◽  
Vol 5 (2) ◽  
pp. 345-353
Author(s):  
Krisna Murti ◽  
Muslina Muslina ◽  
Ika Kartika ◽  
Rachmat Hidayat ◽  
Ella Amalia

A B S T R A C TIntroduction Diffuse large B cell lymphoma (DLBCL) is the most common type ofnon-Hodgkin lymphoma among B cell lymphomas. The interaction of tumor cellswith their microenvironment (tumor microenvironment, TME) leads to progressivityof malignancy. CD163 + macrophages known as components of TME. Nuclear factorof activated T cell (NFATc1) and MYC are important transcription factors inmalignant transformation and progression. Therapeutic strategies were fastdeveloped, nevertheless, efforts to decrease DLBCL morbidity and mortality areunsatisfied, therefore,new markers for prognosis and or therapeutic options of thepatients are necessary. This study was aimed to investigate NFATc1 expression inDLBCL and its TME. Methods: Thirty-two paraffin blocks were selected thenimmunostained for expression of NFATc1, MYC, and CD163. Clinopathologic datai.e. ages, gender, and proliferation index Ki-67 were obtained. Data was analyzedby statistics Result: Positive expression of CD163 and NFATc1 was among 55%and 45% of cases respectively. All DLBCL cases in this study were non-GCBsubtype and more patients were under 60 years (66%). Positive expression ofCD163 was higher in males (69%) and in patients under 60 years (63%). Tissuespositive for both NFATc1 and CD163 was observed higher among males andpatients under 60 years. Conclusion: NFATc1 may affect development and orprogression of certain subsets of DLBCL non-GCB subtype.


2009 ◽  
Vol 27 (30) ◽  
pp. 5039-5048 ◽  
Author(s):  
Amy Chadburn ◽  
April Chiu ◽  
Jeannette Y. Lee ◽  
Xia Chen ◽  
Elizabeth Hyjek ◽  
...  

Purpose Diffuse large B-cell lymphoma (DLBCL) represents a clinically heterogeneous disease. Models based on immunohistochemistry predict clinical outcome. These include subdivision into germinal center (GC) versus non-GC subtypes; proliferation index (measured by expression of Ki-67), and expression of BCL-2, FOXP1, or B-lymphocyte-induced maturation protein (Blimp-1)/PRDM1. We sought to determine whether immunohistochemical analyses of biopsies from patients with DLBCL having HIV infection are similarly relevant for prognosis. Patients and Methods We examined 81 DLBCLs from patients with AIDS in AMC010 (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] v CHOP-rituximab) and AMC034 (etoposide, doxorubicin, vincristine, prednisone, and dose-adjusted cyclophosphamide plus rituximab concurrent v sequential) clinical trials and compared the immunophenotype with survival data, Epstein-Barr virus (EBV) positivity, and CD4 counts. Results The GC and non-GC subtypes of DLBCL did not differ significantly with respect to overall survival or CD4 count at cancer presentation. EBV could be found in both subtypes of DLBCL, although less frequently in the GC subtype, and did not affect survival. Expression of FOXP1, Blimp-1/PRDM1, or BCL-2 was not correlated with the outcome in patients with AIDS-related DLBCL. Conclusion These data indicate that with current treatment strategies for lymphoma and control of HIV infection, commonly used immunohistochemical markers may not be clinically relevant in HIV-infected patients with DLBCL. The only predictive immunohistochemical marker was found to be Ki-67, where a higher proliferation index was associated with better survival, suggesting a better response to therapy in patients whose tumors had higher proliferation rates.


2019 ◽  
Vol 50 (3) ◽  
pp. 109-115
Author(s):  
Beata Grygalewicz

StreszczenieB-komórkowe agresywne chłoniaki nieziarnicze (B-cell non-Hodgkin lymphoma – B-NHL) to heterogenna grupa nowotworów układu chłonnego, wywodząca się z obwodowych limfocytów B. Aberracje cytogenetyczne towarzyszące B-NHL to najczęściej translokacje onkogenów takich jak MYC, BCL2, BCL6 w okolice genowych loci dla łańcuchów ciężkich lub lekkich immunoglobulin. W niektórych przypadkach dochodzi do wystąpienia kilku wymienionych aberracji jednocześnie, tak jak w przypadkach przebiegających z równoczesną translokacją genów MYC i BCL2 (double hit), niekiedy także z obecnością rearanżacji BCL6 (triple hit). Takie chłoniaki cechuje szczególnie agresywny przebieg kliniczny. Obecnie molekularna diagnostyka cytogenetyczna przy użyciu techniki fluorescencyjnej hybrydyzacji in situ (FISH) oraz, w niektórych przypadkach, aCGH jest niezbędnym narzędziem rozpoznawania, klasyfikowania i oceny stopnia zaawansowania agresywnych, nieziarniczych chłoniaków B-komórkowych. Technika mikromacierzy CGH (aCGH) była kluczowym elementem wyróżnienia prowizorycznej grupy chłoniaków Burkitt-like z aberracją chromosomu 11q (Burkitt-like lymphoma with 11q aberration – BLL, 11q) w najnowszej klasyfikacji nowotworów układu chłonnego Światowej Organizacji Zdrowia (World Health Organization – WHO) z 2016 r. Omówione zostaną sposoby różnicowania na poziomie cytogenetycznym takich chłoniaków jak: chłoniak Burkitta (Burkitt lymphoma – BL), chłoniak rozlany z dużych komórek B (diffuse large B-cell lymphoma – DLBCL) oraz 2 nowych jednostek klasyfikacji WHO 2016, czyli chłoniaka z komórek B wysokiego stopnia złośliwości z obecnością translokacji MYC i BCL2 i/lub BCL6 (high-grade B-cell lymphoma HGBL, with MYC and BCL2 and/or BCL6 translocations) oraz chłoniaka BLL, 11q.


2014 ◽  
Vol 38 ◽  
pp. S36
Author(s):  
P. Haciboncuk ◽  
M. Yilmaz ◽  
G. Soylu ◽  
E. Gundogan ◽  
D. Yanardag Acık ◽  
...  

2016 ◽  
Vol 9 ◽  
pp. CCRep.S39052 ◽  
Author(s):  
Sarah A. Elkourashy ◽  
Abdulqadir J. Nashwan ◽  
Syed I. Alam ◽  
Adham A. Ammar ◽  
Ahmed M. El Sayed ◽  
...  

Extranodal lymphoma (ENL) occurs in approximately 30%–40% of all patients with non-Hodgkin lymphoma and has been described in almost all organs and tissues. However, diffuse large B-cell lymphoma is the most common histological subtype of non-Hodgkin lymphoma, primarily arising in the retroperitoneal region. In this article, we report a rare case of an adult male diagnosed with primary diffuse large B-cell lymphoma of the gluteal and adductor muscles with aggressive bone involvement. All appropriate radiological and histopathological studies were done for diagnosis and staging. After discussion with the lymphoma multidisciplinary team, it was agreed to start on R-CHOP protocol (rituximab, cyclophosphamide, doxorubicin (Adriamycin), vincristine (Oncovin®), and prednisone) as the standard of care, which was later changed to R-CODOX-M/R-IVAC protocol (rituximab, cyclophosphamide, vincristine (Oncovin®), doxorubicin, and high-dose methotrexate alternating with rituximab, ifosfamide, etoposide, and high-dose cytarabine) due to inadequate response. Due to the refractory aggressive nature of the disease, subsequent decision of the multidisciplinary team was salvage chemotherapy and autologous stem cell transplant. The aim of this case report was to describe and evaluate the clinical presentation and important radiological features of extranodal lymphoma affecting the musculoskeletal system.


2021 ◽  
Author(s):  
Thomas Drago

Diffuse large B-cell lymphoma (DLBCL) is the most common form of Non-Hodgkin Lymphoma (NHL) in adults. Affecting nearly 7 out of every 100,000 people in the United States annually, this hematogenous neoplasm is known for its aggressiveness and rapid development. Being the most common NHL, it has been divided into several subgroups based on pathogenesis and treatment methods. In particular, subtypes such as germinal center, activated B-cell-like, and primary mediastinal diffuse large B-cell lymphomas  have been divided by their uniqueness of pathology at the cellular level. Knowing the numerous cytokines, inflammatory markers, and other microcellular processes that these lymphomas disrupt can help target an effective therapeutic at the disease.


2021 ◽  
Vol 6 (1) ◽  
pp. 15-20
Author(s):  
Mahmoud Tag El-Hussien ◽  
Nadia Mokhtar ◽  
Eman Naguib Khorshed

Objective: To evaluate the status of C-MYC protein expression and Ki-67 proliferative index and to clarify their role in predicting relapse of diffuse large B cell lymphoma (DLBL). Materials and Methods: A retrospective study conducted on 50 cases diagnosed as DLBL in a 3 years’ time period from January 2014 till December 2016, collected from the archive of Pathology Departments of the National Cancer Institute Cairo - Egypt, Misr University for Science and Technology and private labs of authors. The diagnosis of DLBL for all cases, both nodal and extranodal, was confirmed by histopathologic examination and immunophenotyping. Automated immunohistochemical staining using antibodies against C-MYC protein and MIB-1 was used to evaluate the C-MYC expression in tumor cells and to assess their proliferative ability by calculating Ki-67 labelling index. The relation between the percentage of C-MYC protein expression, Ki-67 proliferative index, clinical data and the relapse status during the follow up period were analyzed. Results: A total of 50 cases of DLBL in both nodal and extra-nodal sites were included. Twenty-three cases (46%) were expressing the C-MYC protein, and 29 cases (58%) showed high Ki-67 proliferative index. Twenty-two cases (44%) relapsed during the follow-up period. Positive C-MYC protein expression was significantly associated with high Ki-67 proliferative index. C-MYC protein expression and high Ki-67 proliferative index were independently associated with disease relapses in 81.8% and 86.4% of cases respectively. Cases with combined C-MYC protein expression and high Ki-67 proliferative index showed statistical prediction of relapse in 81.8% of cases. Conclusion: C-MYC protein expression and high Ki-67 proliferative index were independently associated with relapse of diffuse large B cell lymphoma. Furthermore, the combined positive C-MYC protein expression and high Ki-67 proliferative index is better than a single positive test in predicting relapses among DLBL patients.


2019 ◽  
Vol 6 (1) ◽  
pp. e07-e07
Author(s):  
Hossein Rahimi ◽  
Zahra Rezaei Borojerdi ◽  
Sajad Ataei Azimi ◽  
Elnaz Rashidian ◽  
Amirhossein Jafarian

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphatic neoplasm, accounting for about 30–40% of non-Hodgkin’s lymphoma cases. Objectives: DLBCL is a progressive disease with clinical, genetic and molecular heterogeneity. The prognostic value of B-cell lymphoma 2 (BCL2) and Ki-67 in DLBCL patients has been controversial. Patients and Methods: In this study, we investigated the correlation of BCL2 and Ki-67 expression with clinical features such as age, gender, B symptoms and lactate dehydrogenase (LDH) levels, subtypes of DLBCL, its staging and prognosis in 36 cases of DLBCL. The expression of BCL2 and Ki-67 was measured by immunohistochemistry. Results: There was no significant correlation between BCL2 expression and staging (P=0.082), however Ki-67 expression had a significant correlation with staging (P=0.002). There was no statistically significant correlation between BCL2 and Ki-67 with prognosis of the disease. We found a significant correlation between the germinal center B-cell (GCB) and non- GCB subtypes with BCL2 expression (P=0.024), since patients with non- GCB subtype had a higher BCL2 expression. Our study also demonstrated a significant relationship between BCL2 and Ki-67 expression, therefore, with the increase of the expression of a marker, another increases (P=0.045). Conclusion: BCL2 and Ki-67 expressions were not associated with prognosis. Overexpression of Ki-67 was associated with higher clinical stages. BCL2 expression is higher in non-GCB subtype of DLBCL. Therefore, our study shows that the subsequent studies of BCL2 and other biomarkers in the DLBCL should be based on the DLBCL subtypes.


2017 ◽  
Vol 126 (5) ◽  
pp. 1725-1730 ◽  
Author(s):  
Vijay M. Ravindra ◽  
Amol Raheja ◽  
Heather Corn ◽  
Meghan Driscoll ◽  
Corrine Welt ◽  
...  

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma and comprises approximately 30% of all lymphomas. Patients typically present with a nonpainful mass in the neck, groin, or abdomen associated with constitutional symptoms. In this report, however, the authors describe a rare case of a 61-year-old woman with hyperprolactinemia, hypothyroidism, and acromegaly (elevation of insulin-like growth factor-1 [IGF-1]) with elevated growth hormone–releasing hormone (GHRH) in whom an MRI demonstrated diffuse enlargement of the pituitary gland. Despite medical treatment, the patient had persistent elevation of IGF-1. She underwent a transsphenoidal biopsy, which yielded a diagnosis of DLBCL with an activated B-cell immunophenotype with somatotroph hyperplasia. After stereo-tactic radiation therapy in combination with chemotherapy, she is currently in remission from her lymphoma and has normalized IGF-1 levels without medical therapy, 8 months after her histopathological diagnosis. This is the only reported case of its kind and displays the importance of a broad differential diagnosis, multidisciplinary evaluation, and critical intraoperative decision-making when treating atypical sellar lesions.


2021 ◽  
Vol 148 (12) ◽  
pp. 102-107
Author(s):  
Trinh Le Huy ◽  
Tran Dinh Anh

Primary breast diffuse large B-cell lymphoma (DLBCL) is a rare non-Hodgkin’s lymphoma with limited data. We here report a case of primary breast diffuse large B-cell lymphoma mimicking breast cancer. A 52-year-old woman had a painless mass in her right breast. Fine needle aspiration cytology and core biopsy were performed which suggested malignant features but could not confirm the specific subtype. Excisional biopsy then was conducted revealing non-Hodgkin lymphoma, which was subsequently confirmed with histopathology and diagnosed as diffuse large B-cell lymphoma (DLBCL). A chest computed tomography scan revealed a 3.5 cm sized breast mass with skin thickening and modest lymphadenopathy in the ipsilateral axilla. The patient received six courses of R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone plus rituximab) chemotherapy, then whole breast radiation (30Gy in 15 fractions). At 12 months of follow-up, the patient survives with no evidence of disease. No morbidities occurred in this patient during the follow-up period. We briefly review the current practice pattern in patients with primary breast diffuse large B-cell lymphoma.


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