Castleman’s disease in the HIV-endemic setting

Castleman’s disease (CD), first described by Benjamin Castleman in 1954, is a giant or angiofollicular lymph node hyperplasia, described as a rare monotypic polyclonal B-cell lymphoproliferative disorder with an incompletely understood pathogenesis and variable clinical behavior. This study aimed to determine the incidence of CD diagnosis over an 11-year period. Additionally, the study aimed to describe the demographic, laboratory, and pathological features of CD. Methods: This is a retrospective study where the demographic and laboratory data were retrieved from the Tygerberg Academic Hospital (TAH) patient electronic records and Tygerberg Lymphoma Study Group (TLSG) and statistical analysis performed on the patients diagnosed with CD. Results: Fifty-four patients were diagnosed with CD during this period. The median age at presentation was 39 years (range: 9–58). HIV serology was available in 53 patients, of which 51 were HIV-positive and two were HIV-negative. The history of initiation of antiretroviral therapy at diagnosis was available in 43 patients (38 on treatment, four were not on treatment, and one defaulted treatment). The median CD4 count was 232.50 cells/μL (range: 2–883). The HIV viral load was performed in 43 patients at diagnosis, which was <49 HIV-1 RNA copies/ μL in more than half of the patients (58%). Diagnosis was made on lymph node biopsies in 53 patients, with one case diagnosed on a spleen biopsy. Kaposi sarcoma was found on the same tissue biopsy in 13 cases. A bone marrow biopsy was performed in 31 patients. The predominant features noted were a disorganized hypercellular marrow with plasmocytosis. Conclusion: CD is a rare polyclonal B-cell lymphoproliferative disorder. However, we demonstrated a significant increase in the incidence of HIV-associated multicentric CD over the last decade in our area in South Africa

B Cells versus T Cells in the Tumor Microenvironment of Malignant Lymphomas. Are the Lymphocytes Playing the Roles of Muhammad Ali versus George Foreman in Zaire 1974?

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadMalignant lymphomas are a heterogeneous group of malignancies that develop both in nodal and extranodal sites. The different tissues involved and the highly variable clinicopathological characteristics are linked to the association between the lymphoid neoplastic cells and the tissues they infiltrate. The immune system has developed mechanisms to protect the normal tissue from malignant growth. In this review, we aim to explain how T lymphocyte-driven control is linked to tumor development and describe the tumor-suppressive components of the resistant framework. This manuscript brings forward a new insight with regard to intercellular and intracellular signaling, the immune microenvironment, the impact of therapy, and its predictive implications. A better understanding of the key components of the lymphoma environment is important to properly assess the role of both B and T lymphocytes, as well as their interplay, just as two legendary boxers face each other in a heavyweight title final, as was the case of Ali versus Foreman. Keywords: B lymphocytes; T lymphocytes; lymphocyte inter-talk; malignant lymphomas; tumor microenvironment.Iuliu Hatieganu University, School of Doctoral Studies RomanianMinistry of Research and Innovation, CCCDI-UEFISCDI within PNCDI III European Economic Spac

B Cells versus T Cells in the Tumor Microenvironment of Malignant Lymphomas. Are the Lymphocytes Playing the Roles of Muhammad Ali versus George Foreman in Zaire 1974?

Publisher's version (útgefin grein)Malignant lymphomas are a heterogeneous group of malignancies that develop both in nodal and extranodal sites. The different tissues involved and the highly variable clinicopathological characteristics are linked to the association between the lymphoid neoplastic cells and the tissues they infiltrate. The immune system has developed mechanisms to protect the normal tissue from malignant growth. In this review, we aim to explain how T lymphocyte-driven control is linked to tumor development and describe the tumor-suppressive components of the resistant framework. This manuscript brings forward a new insight with regard to intercellular and intracellular signaling, the immune microenvironment, the impact of therapy, and its predictive implications. A better understanding of the key components of the lymphoma environment is important to properly assess the role of both B and T lymphocytes, as well as their interplay, just as two legendary boxers face each other in a heavyweight title final, as was the case of Ali versus Foreman.The research on the lymphoma microenvironment was funded by an internal grant of the Iuliu Hatieganu University, School of Doctoral Studies (PCD 2018-2021) (Minodora Desmirean), under the frame of European Social Found, Human Capital Operational Program 2014-2020, project no. POCU/380/6/13/125171 (Minodora Desmirean) and the Romanian Ministry of Research and Innovation, CCCDI-UEFISCDI, Project No. PN-III-P4-ID-PCCF-2016-0112 within PNCDI III, by an award for Young Research Teams 2020-2022 (Grant No. PN-III-P1-1.1-TE-2019-0271) (both Ciprian Tomuleasa) as well as by an international collaborative grant of the European Economic Space between Romania and Iceland 2020-2022 (Grant No. 19-COP-0031) (Ciprian Tomuleasa)."Peer Reviewed

Transforming growth factor β-mediated micromechanics modulates disease progression in primary myelofibrosis.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadPrimary myelofibrosis (PMF) is a Ph-negative myeloproliferative neoplasm (MPN), characterized by advanced bone marrow fibrosis and extramedullary haematopoiesis. The bone marrow fibrosis results from excessive proliferation of fibroblasts that are influenced by several cytokines in the microenvironment, of which transforming growth factor-β (TGF-β) is the most important. Micromechanics related to the niche has not yet been elucidated. In this study, we hypothesized that mechanical stress modulates TGF-β signalling leading to further activation and subsequent proliferation and invasion of bone marrow fibroblasts, thus showing the important role of micromechanics in the development and progression of PMF, both in the bone marrow and in extramedullary sites. Using three PMF-derived fibroblast cell lines and transforming growth factor-β receptor (TGFBR) 1 and 2 knock-down PMF-derived fibroblasts, we showed that mechanical stress does stimulate the collagen synthesis by the fibroblasts in patients with myelofibrosis, through the TGFBR1, which however seems to be activated through alternative pathways, other than TGFBR2. Keywords: TGF-β; fibroblast activation; invasion; micromechanics; myelofibrosis; proliferation.School of Doctoral Studies-Iuliu Hatieganu University Romanian Government Ion Chiricuta Oncology Institute Cluj Napoca international collaborative grant of the European Economic Space between Romania and Iceland 2020-2022 1

Differential Diagnosis of Malignant Lymphadenopathy Using Flow Cytometry on Fine Needle Aspirate: Report on 269 Cases

Introduction: Fine needle aspiration (FNA) is frequently the first noninvasive test used for the diagnostic workup of lymphadenopathy. There have been many studies showing its usefulness, especially in conjunction with other techniques for the diagnosis of lymphoma, but it remains inferior to histological examination. The data regarding this subject have mostly been reported mostly from first-world countries, but are scarce for emerging economies. Thus, the current study assesses the agreement between fine needle aspiration flow cytometry (FNA FC) and histology in the aforementioned region. Material and Methods: We conducted a retrospective study including the FNA FC adenopathy diagnoses made between January 2011 and December 2016 at the Tygerberg Hospital, Cape Town, South Africa. Additional variables included were the histological diagnosis, sex and age of the included patients. Results: In the descriptive part of the current study, 269 FNA FC samples were included. The most frequent diagnoses made on these were represented by B-cell lymphoma, reactive adenopathy, no abnormality detected (NAD), and non-hematological malignancy. In the analytical part of the current study, there were 115 cases included that had both valid FNA FC and histological diagnoses. It could be observed that FNA FC can correctly diagnose B-cell lymphoma in most cases, but it is a poor diagnostic tool especially for Hodgkin lymphoma in this setting as only a four-color flow cytometer was available for diagnosis. Moreover, FNA FC diagnosis of reactive adenopathy and of no abnormalities detected was shown to frequently hide a malignant disease. Conclusion: In countries with scarce resources, FNA FC represents a useful diagnostic tool in the case of B-cell lymphoma, but may misdiagnose reactive adenopathy. Thus, FNA FC should be used in a case-specific manner, in addition to as a screening tool, with the knowledge that in cases with a high clinical suspicion of lymphoma, histological diagnosis is a necessity

Next-generation sequencing-based characterization of the invasion by anatomical contiguity in a primary osseous diffuse large B-cell lymphoma. Correlation between the genetic profile of the malignancy and the clinical outcome of the patient

Primary bone lymphoma is now a welldescribed entity in the World Health Organization (WHO) Classification of Tumors of Soft Tissue and Bone as a malignancy of the lymphoid tissue, with at least one mass within bone, without involvement of supraregional lymph nodes or other extranodal sites. In the current paper, we describe the complete characterization of the mutational landscape of a diffuse large B cell non-Hodgkin's lymphoma (DLBLCL) of the tibial plateau. Currently, there is very little data about the genetic landscape of primary osseous lymphomas and about the genetic background of this type of malignancy, resistant to chemotherapy and invading the surrounding tissues. In the current paper, we describe the complete characterization of the mutational landscape of a DLBCL of the tibial plateau. Our data is consistent with already published data, that have shown that MKI67 activation is correlated with lymphoma progression. Along with a high Ki67 index, resistance to chemotherapy occurs with neurogenic locus notch homolog protein 1 (Notch) and KRAS activation. This is the first molecular characterization for the invasion by anatomical contiguity for a primary bone lymphoma and while we only characterized one case and further deep sequencing analyses are required, we can explain the clinical dismal evolution of the patient by correlating them with the genetic landscape of this type of lymphoma