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Background and aims. Alcohol is a psychoactive substance that causes dependence, with many thousands of years in the history of mankind, being widely used in different cultures. According to the International Agency for Research on Cancer, alcohol is involved in the development of cancer, being directly associated with it. Considering that alcohol is involved in the initiation and dissemination of gastrointestinal malignancies, the objective of the study was to assess its role in the pathogenesis of T-cell lymphomas, as well as its possible correlation with chronic consumption. Methods. The patient cohort was compiled from the Sixth Medical Center of the People’s Liberation Army Navy General Hospital in Beijing, China. A total of 30 patients matched the criteria and were enrolled in the study. Statistical analysis of the raw data was performed using R Statistics version R 3.5.1. released on the 29.08.2018. Results. Our data demonstrate that the most common extranodal involvment of T-cell lymphoma patients is represented in decreasing order by bone marrow, peritoneum, rhino-oropharynx and the liver-biliary system. Nodal involvement is mainly represented in decreasing order by the laterocervical, axillary, mediastinal and inguinal regions. Conclusions. These findings may be of value in further research and practical/clinical settings. Fever is the most common clinical feature and was present in most studied patients.

Primary myelofibrosis (PMF) is the most aggressive Philadelphia-negative (Ph-) myeloproliferative neoplasm (MPN), characterized by bone marrow (BM) insufficiency, myelofibrosis (MF), osteosclerosis, neoangiogenesis, and extramedullary hematopoiesis (EMH) in spleen and liver. Presently, there is no curative treatment for this disease and therapy consists primarily of symptom relief and, in selected cases, allogeneic hematopoietic stem cell transplant (alloHSCT). PMF's major defining characteristics, as well as several recently described aspects of its cellular and molecular pathophysiology all support a critical role for dysregulated cell-cell/cell-extracellular matrix interactions and cytokine/chemokine signaling within the BM niche in the natural history of this disease. This review will highlight current data concerning the involvement of the BM niche, particularly of mesenchymal stem cells (MSC), in PMF, and will then discuss the rationale for a stroma-directed treatment, and the advantages such an approach would offer over the current treatments focused on targeting the malignant clone.

Chronic lymphocytic leukemia (CLL) is a malignancy defined by the accumulation of mature lymphocytes in the lymphoid tissues, bone marrow, and blood. Therapy for CLL is guided according to the Rai and Binet staging systems. Nevertheless, state-of-the-art protocols in disease monitoring, diagnostics, and prognostics for CLL are based on the assessment of minimal residual disease (MRD). MRD is internationally considered to be the level of disease that can be detected by sensitive techniques and represents incomplete treatment and a probability of disease relapse. MRD detection has been continuously improved by the quick development of both flow cytometry and molecular biology technology, as well as by next-generation sequencing. Considering that MRD detection is moving more and more from research to clinical practice, where it can be an independent prognostic marker, in this paper, we present the methodologies by which MRD is evaluated, from translational research to clinical practice.

Sergiu Susman,1,2 Ioana Berindan-Neagoe,3 Bobe Petrushev,3 Radu Pirlog,2 Ioan-Stefan Florian,4 Carmen-Mihaela Mihu,2 Cristian Berce,3 Lucian Craciun,2 Ravnit Grewal,5 Ciprian Tomuleasa3,6,7 1Department of Pathology, Imogen Research Center, 2Department of Morphological Sciences, 3Research Center for Functional Genomics and Translational Medicine, 4Department of Neurosurgery, Iuliu Hatieganu University of Medicine and Pharmacy, 5Department of Hematology, Ion Chiricuta Oncology Institute, 6Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 7Department of Haematopathology, Tygerberg Academic Hospital, Tygerberg, South Africa Abstract: After introducing the new molecules for the treatment of patients with tumoral pathology, the therapeutical decision will be taken depending on the molecular profile performed upon the harvested tissues. This major modification makes the molecular and morphological analysis an essential part in the clinical management of patients and the pathologist plays an important role in this process. The quality and reproducibility of the results are imperative today and they depend on both the reliability of the molecular techniques and the quality of the tissue we use in the process. Also, the genomics and proteomics techniques, used increasingly often, require high-quality tissues, and pathology laboratories play a very significant role in the management of all phases of this process. In this paper the parameters which must be followed in order to obtain optimal results within the techniques which analyze nucleic acids and proteins were reviewed. Keywords: nucleic acids, proteins, fixation, freezing, molecular techniques

Additional file 3: Table S2. Shortlist of three candidate variants identified as plausible disease-causing variants.

Additional file 4: Table S3. Details of the candidate variant narrowed down using consecutive filters based on an autosomal recessive model of inheritance and low frequency.

Additional file 2: Table S1. Summary of exome sequencing data for the patient and his parents.

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.

Additional file 1: Figure S1. Timeline of symptoms presented by the index case.

BackgroundThe X-linked recessive primary immunodeficiency disease (PIDD) Wiskott-Aldrich syndrome (WAS) is identified by an extreme susceptibility to infections, eczema and thrombocytopenia with microplatelets. The syndrome, the result of mutations in theWASgene which encodes the Wiskott-Aldrich protein (WASp), has wide clinical phenotype variation, ranging from classical WAS to X-linked thrombocytopaenia and X-linked neutropaenia. In many cases, the diagnosis of WAS in first affected males is delayed, because patients may not present with the classic signs and symptoms, which may intersect with other thrombocytopenia causes.Case presentationHere, we describe a three-year-old HIV negative boy presenting with recurrent infections, skin rashes, features of autoimmunity and atopy. However, platelets were initially reported as normal in numbers and morphology as were baseline immune investigations. An older male sibling had died in infancy from suspected immunodeficiency. Uncertainty of diagnosis and suspected severe PIDD prompted urgent further molecular investigation. Whole exome sequencing identifiedc. 397 G > Aas a novel hemizygous missense mutation located in exon 4 ofWAS.ConclusionWith definitive molecular diagnosis, we could target treatment and offer genetic counselling and prenatal diagnostic testing to the family. The identification of novel variants is important to confirm phenotype variations of a syndrome.

In the March 2016 issue of the Lancet Haematology, the editorial office published a paper stating the roadmap for European research in hematology, based on the European Hematology Association (EHA) consensus document that outlines the directions in hematology for the following years across the continent. The meeting entitled “Insights in hematology” is organized a support for the initiative of a roadmap for European hematologists regarding research, may it be basic research or clinical research, but this consensus should not be focused mainly on European institutions, but rather form the backbone of global research between Europe and the United States, Japan or any other country. This will allow Europeans to learn as well as to share their experience with the rest of the scientific and medical community. And the Cluj-Napoca meeting should be followed by other such meetings all across the EU.

Esam-Rajab Mahroug,1 Candice Sher-Locketz,1 Minodora-Silvia Desmirean,2,3 Emmanuel-Akinola Abayomi,1,4 Ciprian Tomuleasa,3,5,6 Ravnit Grewal1,7 1Division of Haematology, Department of Pathology, University of Stellenbosch, Tygerberg Academic Hospital, Cape Town, South Africa; 2Department of Pathology, Military Hospital of Cluj Napoca, Cluj Napoca, Romania; 3Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania; 4Department of Hematology, Nigeria Institute for Medical Research, Lagos, Nigeria; 5Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania; 6Department of Hematology, Ion Chiricuta Clinical Research Center, Cluj Napoca, Romania; 7Department of Pathology, South African Bioinformatics Institute, University of The Western Cape, Bellville, South Africa 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

The incidence of HIV-related lymphomas (HRLs) is increased by 60-100 times in patients with HIV. When compared to the general population, patients with HRLs often present with extranodal lymphoid proliferation, most frequently of the gastrointestinal tract, central nervous system, liver and bone marrow. MicroRNAs (miRs) are non-coding double-stranded RNA molecules of 18-25 nucleotides that regulate post-translational gene expression by inhibiting translation or promoting degradation of messenger RNA complementary sequences. Before their discovery, tumorigenesis was thought to have been caused by the alteration of protein-coding oncogenes and tumor-suppressor genes, but once identified in B-cell chronic lymphocytic leukemia, miRs function as either oncogenes or tumor-suppressor genes was confirmed in different types of malignancies. Since miRs are clearly involved in tumorigenesis in many cancers, their role in HRLs is now receiving attention. A few studies have been conducted thus far in some HRLs on the involvement of miR in the pathogenesis of lymphoid malignancies. Since B-cell lymphomas arise from various stages of B-cell development in both HIV-infected and HIV-naïve patients, investigators have tried to determine the different miR signatures in B-cell development. As classic immunohistochemistry staining is sometimes not enough for the differential diagnosis of HRLs, in the present review, we have described the potential use of miRs in the prognosis and diagnosis of these diseases.

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 high burden of infectious diseases and the growing problem of noncommunicable and metabolic disease syndromes in South Africa (SA) forces a more focused research approach to facilitate cutting-edge scientific growth and public health development. Increased SA research on these diseases and syndromes and the collection of associated biospecimens has ensured a plethora of biobanks created by individuals, albeit without the foresight of prospective and collective use by other local and international researchers. As the need for access to high-quality specimens in statistically relevant numbers has increased, so has the necessity for the development of national human biobanks in SA and across the Continent. The prospects of achieving sustainable centralized biobanks are still an emerging and evolving concept, primarily and recently driven by the launch of the H3Africa consortium, which includes the development of harmonized and standardized biobanking operating procedures. This process is hindered by a myriad of complex societal considerations and ethico-legal challenges. Efforts to consolidate and standardize biological sample collections are further compromised by the lack of full appreciation by national stakeholders of the biological value inherent in these collections, and the availability of high quality human samples with well-annotated data for future scientific research and development. Inadequate or nonexistent legislative structures that specifically regulate the storage, use, dispersal, and disposal of human biological samples are common phenomena and pose further challenges. Furthermore, concerns relating to consent for unspecified future uses, as well as access to information and data protection, are all new paradigms that require further consideration and public engagement. This article reviews important fundamental issues such as governance, ethics, infrastructure, and bioinformatics that are important foundational prerequisites for the establishment and evolution of successful human biobanking in South Africa.

The Tygerberg Lymphoma Study Group was constituted in 2007 to quantify the impact of HIV on the pattern and burden of lymphoma cases in the Western Cape of South Africa which currently has an HIV prevalence of 15%. South Africa has had an Anti-Retroviral Treatment (ART) policy and roll out plan since 2004 attaining 31% effective coverage in 2009. This study is designed to qualify and establish what impact the HIV epidemic and the ARV roll-out treatment program is having on the incidence of HIV related Lymphoma (HRL). Early data documents that despite the ART roll out, cases of HRL are increasing in this geographical location, now comprising 37% of all lymphomas seen in 2009 which is an increase from 5 % in 2002. This is in contrast to trends seen in developed environments following the introduction of ART. Also noted, are the emergence of subtypes not previously seen in this location such as Burkitt and plasmablastic lymphomas. Burkitt lymphoma is now the commonest HRL seen in this population followed by diffuse large B Cell lymphoma subtypes. The reasons for this observed increase in HRL is not ascribable to improved diagnostic capacity as the tertiary institute in which these diagnosis are made, has had significant expertise in this regard for over a decade. We ascribe this paradoxical finding to an ART treatment environment that is ineffective for a diversity of reason, paramount of which are poor coverage, late commencement of ART and incomplete viral suppression.

Background. Hodgkin lymphoma (HL) is the most common non-AIDS-defining cancer in HIV-positive patients. Studies on South African (SA) populations have described the prevalence as 7 - 17% of all lymphomas, 8 - 27% of head and neck lymphomas, 9% of lymph node biopsies and 4% of HIV-related malignancies. Objectives. To describe the incidence of HL at our centre between 2005 and 2016 by year, gender, HIV status, histological subclassification and bone marrow involvement, and compare these findings with similar SA and African studies. Methods. This was a retrospective study of all incident HL cases diagnosed in the Department of Pathology, National Health Laboratory Service, Tygerberg Academic Hospital, Cape Town. Follow-up, relapsed and referral cases were excluded. A positive diagnosis of HL was confirmed by either lymph node or bone marrow biopsy and was based on morphological and immunohistochemical findings in accordance with the World Health Organization classification. Results. There were 303 incident cases of HL diagnosed. The incidence increased from 2005 to 2011, with a spike in cases in 2008 and a subsequent decline overall after 2011. The highest proportion of cases was in the 25 - 49-year-old age category (51.1%). There were 77 HIV-positive patients (25.4%), of whom 53 (68.8%) had CD4+ counts

H3Africa is developing capacity for health-related genomics research in Africa

Background The incidence of malignant lymphomas (ML) in the Western Cape, a province of South Africa (SA), with a population of 5 million and an estimated HIV prevalence of 15% (census report 2002) has not been previously documented. Highly active antiretroviral therapy (HAART) was introduced into the public patient sector in 2004, with 28% estimated coverage by 2007 (UNAIDS/WHO 2008). People living with HIV (PLWH) have 60-200 times increased risk of developing HIVrelated lymphoma (HRL). Therefore, based on HIV prevalence, HRL would be expected to increase but is undocumented.