Use of flow cytometry in the phenotypic diagnosis of hodgkin's lymphoma.

Hodgkin's lymphoma (HL) has a unique immunophenotype derived from immunohistochemistry (positive for CD15, CD30, and Pax-5; negative for CD3, CD20 in most cases, and CD45). The knowledge gained over recent years enables better diagnosis, prognosis, and treatment of HL. Flow cytometry as a tool for the diagnosis of classic HL has not been useful in the past due to the difficulty in isolating Reed-Sternberg cells as they are admixed in a rich inflammatory background which consists mainly of T cells, B cells, eosinophils, histiocytes, and plasma cells. However, in the recent past, several studies have tried to identify Reed-Sternberg cells using flow cytometry on fine needle aspiration or tissue biopsy of lymph nodes to confirm or supplement immunohistochemistry staining in diagnosis. Newer and more sensitive tools such as flow cytometry can be used for diagnosis, technology that may have been difficult in the past for diagnosis of this lymphoma subtype. Using flow cytometry, diagnosis is faster and could lead to point-of-care technology especially where we have typical immunophenotype signatures. © 2018 International Clinical Cytometry Society.

Castleman's disease in the HIV-endemic setting.

INTRODUCTION: 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.

Hodgkin's lymphoma and its association with EBV and HIV infection.

Hodgkin's lymphoma (HL) constitutes a clonal expansion of what appears to be malignant B cells. Viruses are involved in its pathogenesis, such as the Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV). Since these viral infections have been shown to play key roles in the pathogenesis of HL, countries with a prevalence of HIV and EBV represent interesting population targets to study the pathogenesis of HL, linking the evolution of the disease with viral infections. Usually, patients present with late stage disease often involving the bone marrow at the time of diagnosis. The present paper discusses the role of viral infection in African countries, as HL is considered to be a malignant disease characterized by an inflammatory reaction to an aberrant B cell clone that is well known as the Reed-Sternberg cell (HRS).

The human immunodeficiency virus, (HIV-1), pandemic: cellular therapies, stem cells and biobanking.

The Human Immunodeficiency Virus, (HIV-1), has become a major global health threat with recent estimates suggesting that 68% of people living with HIV (PLWH) reside in Sub-Saharan Africa. The current strategies for containment of this disease in the absence of an effective vaccine are of concern in terms of long-term fiscal sustainability and cost effectiveness. HIV prevalence rates are set to rise, not because of increasing incidence but rather because of the effort involved in implementing the anti-retroviral (ARV) programmes, especially on the African continent. Even when sub-optimally delivered, these therapies will lead to a decrease in mortality rates and prevent early death from opportunistic infections. However, evidence is emerging for long-term systemic effects of chronic HIV infection in persons on ARV therapy, including increased incidence of Haematological abnormalities and malignancies.

AIDS defining lymphomas in the era of highly active antiretroviral therapy (HAART): an African perspective.

The intermediate to high grade B-cell non-Hodgkin lymphomas are now one of three malignant AIDS defining conditions. The others being Kaposi's sarcoma and cervical carcinoma. While co-infection with oncogenic agents including the human herpes 8 or Epstein-Barr virus offer targets in preventive treatment strategies for these AIDS defining lymphomas (ADL), administration of highly active antiretroviral therapy leading to immune reconstitution permits use of standard or even high-dose cytotoxic drug regimens with curative intent. It is not certain whether this should be done concomitantly or sequentially. Additional benefit may derive from infusional or high-dose chemotherapy regimens depending on the histological subtype while use of monoclonal antibodies such as rituximab or immunohaematopoietic stem cell transplantation needs to be further evaluated within controlled studies. Socio-economic considerations have an impact especially in resource limited settings while availability of tools for appropriate geno-phenotypic diagnosis and immunological monitoring such as the CD4 cell count will play an important role in the risk stratification as well as disease management. While it is generally accepted that the impact of HAART has an overall benefit both in incidence and treatment outcome in ADL, the expanded access to HAART programs are falling short of all targets in Africa. Accordingly focus is given to some of these controversies, including epidemiology, pathogenesis, clinical features, therapeutic options and ethical considerations.

Use of novel proteosome inhibitors as a therapeutic strategy in lymphomas current experience and emerging concepts.

Precedent from preclinical experiments coupled with two pivotal phase 2 studies in myeloma has focused attention on a potential role for ubiquitin-proteasome pathway in modulating a number of events that occur commonly in the neoplastic process involving proteins in the regulation of cells cycling, growth and differentiation. This influence is vested in the proteasomes which are large complexes of proteolytic enzymes responsible for degradation of many of these intracellular messengers. Logically interest has centred on molecules having the capacity to influence, by degradation, such molecules and although a number of agents are in development bortezomib is the only one currently in clinical use. Velcade, formerly PS-341, is a novel dipeptide boronic acid capable of reversibly inhibiting the 26S proteasome through a range of activities. The latter are anti-proliferative and proapoptotic with the latter blocking nuclear transcription via NF-kappa B in addition to down regulating adhesion and inhibiting angiogenesis. Additional changes are mediated in protein folding within the endoplasmic reticulum and contribute to cell death. These concepts are given focus by considering their introduction into treatment of lymphoreticular malignancy.