Occurrence Of Lymphoma Research Articles

Classificação do linfoma em gatos e sua relação com a detecção do DNA pró-viral do vírus da leucemia felina

ABSTRACT: In this retrospective and prospective study, histopathological and immunohistochemical analyses of 62 cases of lymphomas in cats were performed to classify the anatomic forms and subtypes, according to the WHO guidelines, and correlate it to FeLV proviral DNA detected using PCR. The most common anatomical form was gastrointestinal (40.3%, 25/62), followed by multicentric (29%, 18/62), mediastinal (17.7%, 11/62) and extranodal (12,9%, 8/62). Among the lymphoma subtypes, diffuse large B-cell lymphoma (DLBCL) (30.6%, 19/62) was the most commonly diagnosed followed by peripheral T-cell lymphoma (PTCL) (29%, 18/62) and enteropathy associated T-cell lymphoma type 2 (14.5%, 9/62). DNA extraction from paraffin-embedded neoplastic tissue was obtained in 28 cases and FeLV proviral DNA was detected by PCR, in 23 of these. Of the cases presenting with FeLV proviral DNA, nine (32%) were of the multicentric form, five (22%) of the mediastinal and extranodal forms and four (17%) of the gastrointestinal form. The most frequent subtypes with FeLV proviral DNA, independent of the anatomical form, were DLBCL (39.1%, 9/23) and PTCL (34.7%, 8/23). The presence of the FeLV proviral DNA in 23 cats of this study, probably had association with the multicentric form of lymphoma and higher occurrence in the DLBCL and PTCL subtypes.

ML-13 Primary central nervous system malignant lymphoma in a patient with rheumatoid arthritis receiving tocilizumab

Background: Although the risk of developing malignant lymphoma is higher in patients with rheumatoid arthritis (RA) than in the general population, the occurrence of primary central nervous system lymphoma (PCNSL) in patients with RA is extremely rare. In recent years, there has been concern that biological disease-modifying antirheumatic drugs (DMRADs), which are widely administered to patients with RA, may increase the risk of developing cancer. We report the first case of PCNSL in a patient with RA who was treated with the biological DMRADs, tocilizumab. Case description: A 70-year-old man, who was diagnosed with RA in 2010 was treated with low-dose methotrexate from 2010 to 2015. He was started on tocilizumab in 2012. In 2018, he suffered from gait disturbance and was diagnosed with lumbar spinal stenosis. He underwent L2/3 posterior fusion surgery, but his paraplegia gradually deteriorated. Two months after the surgery, a head Gd-MRI showed multiple contrast-enhanced lesions in the basal ganglia and brain stem. A stereotactic brain biopsy was performed and DLBCL was diagnosed, and finally PCNSL was diagnosed because of no neoplastic lesions in other organs. He was treated with 5 courses of MTX 3.5g/m2 with rituximab and has been in remission for 23 months. He has maintained an independent life with residual paraplegia, but his ADLs gradually worsened. He was restarted on tocilizumab with a diagnosis of worsening RA. Conclusion: Low-dose methotrexate and biological DMRADs including tocilizumab, have been concerned to increase the risk of cancer in patients with RA, but there is no solid evidence. Since it has been a short time since the use of biological DMRADs, further accumulation of cases and careful follow-up are necessary.

Tre-P-26 - Cutaneous and systemic lymphomas of concordant or discordant B- and T-cell phenotype in the same patient: two case reports

<h3>Background:</h3> The development of two different non-Hodgkin lymphomas in the same patient is an unlikely coincidence due to the low prevalence of each malignancy. However, a significantly increased risk of developing a second lymphoma was observed in patients with cutaneous T-cell lymphoma (CTCL) in both population-based and clinic-based data [1]. Most cases reported describe the occurrence of concomitant lymphomas of discordant B- and T-cell phenotypes, mainly MF and chronic lymphocytic leukemia [2]. On the opposite, few cases of concomitant systemic and cutaneous B-cell lymphomas have been reported [3,4]. <h3>Case 1:</h3> A young woman with the diagnosis of three B-cell lymphomas. At 37 years-old, primary cutaneous marginal zone lymphoma (pcMZL) was diagnosed on a right cervical cutaneous nodule and relapsed 3 years later on the temporal region; both lesions were excised. One year later, diffuse large B-cell lymphoma (DLBCL) diagnosis was made on an isolated cervical right lymphadenopathy. She was staged as Ann Arbor stage I and treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) regimen for 6 cycles with complete response (CR). Two years later, the diagnosis of follicular lymphoma was made on a lymph node biopsy. The patient remained with asymptomatic cervical and inguinal lymph node enlargement for 10 years until extra-nodal involvement ensued. At that time, treatment with R-FC (rituximab-fludarabine and cyclophosphamide) followed by radiotherapy achieved partial response (PR). In the following 3 years, follicular lymphoma progressed twice and was retreated with radiotherapy with PR. After 5 years of follow-up, the patient remains asymptomatic without further treatment. <h3>Case 2:</h3> A patient with two lymphomas of discordant phenotype. The 51 years-old Caucasian man presented at our dermatology clinic with a 10-years history of cutaneous erythematous patches and plaques on the abdomen and upper limbs. The 3 cutaneous biopsies made were consistent with the diagnosis of mycosis fungoides and workup excluded systemic involvement. As such, a diagnosis of mycosis fungoides (MF) stage IB was made. The patient had been observed on another hospital facility 3 months before, when he presented bilateral inguinal lymph node enlargement. The excisional biopsy revealed follicular lymphoma but the pathology examination review of the sample at our hospital diagnosed DLBCL, non-germinal center type, that was staged as Ann Arbor II. He started chemoimmunotherapy with R-CHOP regimen for 6 cycles, leading to CR and a mild improvement on MF (downstaging to IB). The patient is currently on topical steroids for MF and DLBC lymphoma is still on remission after 1 year of follow-up. <h3>Conclusions:</h3> The occurrence of concomitant systemic and cutaneous lymphomas of discordant or concordant lineages may represent a diagnostic challenge. As the treatment of each lymphoma is often different, their correct identification is critical for optimal management of both diseases.

66. LINKING GWAS TO DRUG-BASED TREATMENTS FOR PSYCHIATRIC DISORDERS

Lymphomas associated with Warthin's tumor (WT) are extremely rare. Here, we report the simultaneous occurrence of lymphocyte-rich classical Hodgkin's lymphoma (LRCHL) and WT in a 78-year-old patient whose symptoms included an enlargement of the left parotid gland. Upon parotidectomy, the tissue specimen showed a WT with extensive replacement of the lymphoid stroma by small lymphocytes and some scattered Reed–Sternberg cells; however, the oncocytic epithelium was preserved. Further investigation revealed mediastinal and abdominal lymphadenopathy, consistent with stage IVB disease. To our knowledge, this is the first case report of LRCHL associated with WT. The lymphoid stroma in WT is part of the systemic lymphoid tissue and thus may be involved in the dissemination of the lymphoma. This case serves as a reminder that a careful evaluation of the histomorphological and immunohistological features of the lymphoid tissue is required for a WT biopsy.

Co-occurrence of immature T-lymphoblastic lymphoma and acute myeloid leukemia\u2014microenvironment-dependent lineage differentiation derived from a common progenitor?

Mixed phenotype acute leukemia (MPAL) is an uncommon disease characterized by currently only limited knowledge concerning biology, clinical presentation, and treatment outcome. We here describe a most unusual case of simultaneous occurrence of T-lymphoblastic lymphoma in cervical and mediastinal lymph nodes and acute myeloid leukemia in the bone marrow (BM) successfully treated with allogeneic stem cell transplantation (SCT). Although the blasts in both locations showed additional aberrant expression of other lineage markers (even B-cell markers), diagnostic criteria of MPAL were not fulfilled either in the LN or in the BM. We performed next generation sequencing (NGS) with the objective to look for common genetic aberrations in both tissues. Histology, immunohistochemistry, flow cytometry, AML-associated genetic alterations (FLT3, NPM1, KIT D816V, CEPBA), and clonal T-cell receptor β and γ gene rearrangements were performed according to routine diagnostic workflows. Next generation sequencing and Sanger sequencing were additionally performed in BM and LN. Somatic mutation in the EZH2 gene (p.(Arg684Cys)) was detected in the BM by NGS, and the same mutation was found in the LN. Since an identical genetic aberration (EZH2 mutation) was detected in both locations, a common progenitor with regional dependent differentiation may be involved.

Lymphoma complicating rheumatoid arthritis: results from a French case–control study

ObjectivesTo study the characteristics of B-cell non-Hodgkin’s lymphoma (NHL) or Hodgkin lymphoma complicating rheumatoid arthritis (RA) and to identify RA-related factors associated with their occurrence.MethodsA multicentre case–control study was performed...

Research Advances in the Mechanisms of BRD4 and Its Inhibitors in Hematologic Malignancies--Review

Bromodomain-containing protein 4 (BRD4) is one of the most important members in the bromodomain and extra terminal domain(BET) family, it plays an important role in cellular physiology in human body, such as cell cycles, cell proliferation, and immune response. Recent studies have shown that BRD4 is associated with occurrence and development of acute myeloblastic leukemia, multiple myeloma and lymphoma. The mechanisms of BRD4 in hematologic malignancies including the regulation of c-Myc expression, and participation of the composition of super-enhancer, etc. At present, many kinds of inhibitors have been developed to target inhibit BRD4 for therapy in hematologic malignancies, and some of BRD4 inhibitors have entered phase Ⅱ clinical trials, which suggested that BRD4 inhibitors are expected to become new therapeutic agents for hematologic malignancies. In this review, the research advance of BRD4 and BRD4 inhibitors in hematologic malignancies was summarized briefly.

The Role of Epstein–Barr virus-encoded Latent Membrane Proteins in Host Immune Escape

Epstein–Barr virus (EBV) is a type IV herpesvirus that widely infects the vast majority of adults, and establishes a latent infection pattern in host cells to escape the clearance of immune system. The virus is intimately associated with the occurrence and progression of lymphomas and epithelial cell cancers. EBV latent membrane proteins (LMPs) can assist its immune escape by downregulating host immune response. Besides EBV, LMPs have important effects on the functions of exosomes and autophagy, which also help EBV to escape immune surveillance. These escape mechanisms may provide conditions for further development of EBV-associated tumors. In this article, we discussed the potential functions of EBV-encoded LMPs in promoting immune escape.

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Following Chimeric Antigen Receptor T-cell Therapy in Large B-cell Lymphoma.

18F-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is a well-established imaging modality to assess responses in patients with B-cell neoplasms. However, there is limited information about the utility of FDG PET/CT after chimeric antigen receptor T-cell (CART) therapies for large B-cell lymphomas. In this retrospective analysis, we aimed to evaluate how FDG PET/CT performs in patients receiving commercially available anti-CD19 CART therapies for relapsed/refractory (r/r) large B-cell lymphomas. In addition, we examined the time to repeat scan and the rate of pseudoprogression within this population. Lastly, the rates of radiographic response to CART therapy using FDG PET/CT are reported. The pre-treatment and post-treatment scans were analyzed from a selected cohort of 43 patients from a single institution. Patients were stratified by diagnosis of either a first occurrence of diffuse large B-cell lymphoma: de novo diffuse large B-cell lymphoma (DLBCL); or a transformed diffuse large B-cell lymphoma arising from indolent non-Hodgkin lymphoma (t-iNHL). More patients received CART therapy for DLBCL than t-iNHL (65 % vs 35 %). FDG PET/CT had a 99 % sensitivity and 100 % specificity for detecting recurrent disease in this group. The median time to initial response assessment was 86 days (IQR 79-91; full range 24-146) after infusion. There were no biopsy-proven cases of pseudoprogression identified. In this selected group of patients, the overall response rate by Lugano 2014 criteria was 56 %. All patients with a partial response (N = 6) eventually progressed despite additional therapy. Due to its excellent test characteristics and ability to detect asymptomatic disease, routine surveillance with PET/CT at 3 months after CART infusion is supported by our data. Earlier PET/CT may be of value in select situations as we did not find any cases of pseudoprogression.

Sequential Lymphoma between Classical Hodgkin Lymphoma and Diffuse Large B Cell Lymphoma: Clinicopathological Characteristics and Outcome of 18 Patients from Lysa Center

Sequential Lymphoma between Classical Hodgkin Lymphoma and Diffuse Large B Cell Lymphoma: Clinicopathological Characteristics and Outcome of 18 Patients from Lysa Center

A RARE CASE OF CONCURRENT PRIMARY GASTRIC AND BONE DIFFUSE LARGE B CELL LYMPHOMA.

Primary bone lymphoma (PBL) is an uncommon clinical entity and a rare non-Hodgkin's lymphoma presentation. PBL accounts for less than 5% of malignant bone tumours. Gastric lymphoma (PGL) is also rare cancer, but it is the most common site for extranodal non-Hodgkin lymphoma. We report a rare case of concurrent occurrence of bone lymphoma and gastric lymphoma. The patient presented with a slow-growing swelling around the knee joint for two years. Positron emission tomography incidentally picked up an FDG avid lesion in the fundus of the stomach. Tissue specimens of both the lesions were obtained and conformed to have diffuse large B cell lymphoma on histology and immunochemistry. He is on follow up with the oncology department and being treated with an R-CHOP regimen (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin (vincristine), and prednisone.

Genome instability and lymphoma.

Lymphoma is one of the most common malignant tumor of the hematologic system. The genome instability is not only an important molecular basis for the development of lymphoma, but also has important value in the diagnosis and prognosis of lymphoma. There are 2 types of genome instability: Microsatellite instability (MSI/MIN) at gene level and chromosomal instability at chromosome level. Through the study on genes associated with lymphoma, the unstable genes associated with lymphoma could be found, meanwhile the mechanism of its occurrence and development of lymphoma could be explored, and the important basis of molecular biology could also be provided in the field of current hot lymphoma precision medical research.

Multiple Immunoglobulin κ Gene Rearrangements within a Single Clone Unraveled by Next-Generation Sequencing–Based Clonality Assessment

Clonality assessment of the Ig heavy- and light-chain genes (IGH and IGK) using GeneScan analysis is an important supplemental assay in diagnostic testing for lymphoma. Occasionally cases with an IGK rearrangement pattern that cannot readily be assigned to a monoclonal lymphoma are encountered, whereas the occurrence of biclonal lymphomas is rare, and the result of the IGH locus of these cases is in line with monoclonality. Three such ambiguous cases were assessed for clonality using next-generation sequencing. Information on the sequences of the rearrangements, combined with knowledge of the complex organization of the IGK locus, pointed to two explanations that can attribute seemingly biclonal IGK rearrangements to a single clone. In two cases, this explanation involved inversion rearrangements on the IGK locus, whereas in the third case, the cross-reactivity of primers generated an additional clonal product. In conclusion, next-generation sequencing-based clonality assessment allows for the detection of both inversion rearrangements and the cross-reactivity of primers, and can therefore facilitate the interpretation of cases of lymphoma with complex IGK rearrangement patterns.

Hamster Polyomavirus Research: Past, Present, and Future.

Hamster polyomavirus (Mesocricetus auratus polyomavirus 1, HaPyV) was discovered as one of the first rodent polyomaviruses at the end of the 1960s in a colony of Syrian hamsters (Mesocricetus auratus) affected by skin tumors. Natural HaPyV infections have been recorded in Syrian hamster colonies due to the occurrence of skin tumors and lymphomas. HaPyV infections of Syrian hamsters represent an important and pioneering tumor model. Experimental infections of Syrian hamsters of different colonies are still serving as model systems (e.g., mesothelioma). The observed phylogenetic relationship of HaPyV to murine polyomaviruses within the genus Alphapolyomavirus, and the exclusive detection of other cricetid polyomaviruses, i.e., common vole (Microtus arvalis polyomavirus 1) and bank vole (Myodes glareolus polyomavirus 1) polyomaviruses, in the genus Betapolyomavirus, must be considered with caution, as knowledge of rodent-associated polyomaviruses is still limited. The genome of HaPyV shows the typical organization of polyomaviruses with an early and a late transcriptional region. The early region encodes three tumor (T) antigens including a middle T antigen; the late region encodes three capsid proteins. The major capsid protein VP1 of HaPyV was established as a carrier for the generation of autologous, chimeric, and mosaic virus-like particles (VLPs) with a broad range of applications, e.g., for the production of epitope-specific antibodies. Autologous VLPs have been applied for entry and maturation studies of dendritic cells. The generation of chimeric and mosaic VLPs indicated the high flexibility of the VP1 carrier protein for the insertion of foreign sequences. The generation of pseudotype VLPs of original VP1 and VP2–foreign protein fusion can further enhance the applicability of this system. Future investigations should evaluate the evolutionary origin of HaPyV, monitor its occurrence in wildlife and Syrian hamster breeding, and prove its value for the generation of potential vaccine candidates and as a gene therapy vehicle.

Comorbidities (excluding lymphoma) in Sjögren's syndrome.

The information about comorbidities (excluding lymphoma) in primary Sjögren's syndrome (pSS) is relatively scarce. Cardiovascular disease, infections, musculoskeletal conditions or malignancy are likely the most relevant comorbid conditions in pSS. Different infections (particularly oral candidal infections) and fibromyalgia are extremely frequent in the daily clinical practice. On the other hand, the incidence of cardiovascular events and cancer in pSS is low, so information about them comes from large epidemiological studies or meta-analysis. For this reason, preclinical vascular disease is investigated by different techniques, demonstrating the presence of early atherosclerosis in pSS patients. Coronary events could be slightly more frequent in pSS than in the general population. The overall risk of malignancy in pSS patients seems to be slightly increased, likely due to excess occurrence of lymphoma. An association between pSS and thyroid cancer might exist, although it should be confirmed by further investigations.

Granuloma annulare - is it a paraneoplastic condition for malignant lymphoma?

In recent years, an association between granuloma annulare and the occurrence of malignant cutaneous lymphomas in the sense of a facultative paraneoplasia has been observed several times. The aim of the present work is to provide an overview of the currently available literature on granuloma annulare as well as an analysis of its association with cutaneous lymphomas. Using the example of two patients with granuloma annulare and associated cutaneous lymphomas, we would like to sensitize clinically active dermatologists and dermatopathologists to the possible association between these two diseases. Characteristic features and clinicopathological signs are discussed, which should raise suspicion of an associated malignant lymphoma. It is recommended to rule out an underlying cutaneous and/or extracutaneous lymphoma in unusual clinical constellations (for instance distribution pattern, subjective complaints, age at first manifestation, lack of response to conventional therapy), especially in the absence of other known clinical triggers of granuloma annulare such as insect bites, trauma or varicella-zoster infections, among others. However, in individual cases the criteria mentioned here justify lymphoma screening.

Syndrome de Richter : prise en charge diagnostique et thérapeutique

Richter syndrome (RS) is defined as the occurrence of an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL) and rarely Hodgkin lymphoma (HL), in a patient with prior or concomitant chronic lymphocytic leukemia (CLL). RS is estimated to occur in 0.5-1% per year and is associated with adverse outcome. In the vast majority of patients (80%), RS is clonally related to the prior CLL. Those with unrelated RS appear to have better outcome. The therapeutic approach is based on those of de novo DLBCL or HL. However, even with modern immunochemotherapy regimens, response rate remains low. In eligible patients with related RS, a consolidation by autologous or allogeneic stem-cell transplantation must be proposed. Combinations including therapies targeting BCR or BCL2 and effective in CLL are currently being evaluated in RS. Novels immunotherapies could be promising approaches based on preliminary results.

Ocorrência de linfoma de Burkitt secundário a mieloma múltiplo em paciente tratado com protocolo CyBorD: um relato de caso

Ocorrência de linfoma de Burkitt secundário a mieloma múltiplo em paciente tratado com protocolo CyBorD: um relato de caso

Magnesium levels and outcome after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia

Low intake of magnesium has been associated with the occurrence of lymphomas and decreased magnesium levels suppress the cytotoxic function of T cells and natural killer cells in patients with “X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia” (XMEN) syndrome. These cell types are also important mediators of immune-mediated effects after allogeneic hematopoietic stem cell transplantation. Here, we show that high posttransplant magnesium levels independently associate with a lower incidence of relapse, a higher risk of acute graft-versus-host disease, and a higher non-relapse mortality in 368 patients with acute myeloid leukemia from our center. Magnesium serum levels might impact on donor-cell-mediated immune responses in acute myeloid leukemia.

EP29 A rare case of marginal zone lymphoma of the breast complicating primary Sjögren’s syndrome

Case report - IntroductionPrimary Sjögren’s patients are a higher risk of developing non-Hodgkin lymphoma (NHL) compared with patients with other autoimmune disorders and to the general population.Parotid and submandibular salivary glands are the most frequent localization of MALT lymphomas in pSS. Here we report a case of marginal zone lymphoma of the breast in a patient with long-standing primary Sjögren’s, and we will discuss the clinical and serological predictors for the development of lymphoma.Case report - Case descriptionA 79-year-old female with a 19-year history of primary Sjögren’s syndrome (anti-Ro, anti-La positive) was reviewed in the rheumatology clinic for progressive worsening of sicca symptoms. Her past medical history included recurrent pulmonary emboli, osteoporosis of the spine, asthma, microscopic colitis, Ischemic heart disease and hypothyroidism. She was a non – smoker and consumed minimal alcohol. Her past surgical history included excision of her left salivary gland, 10 years ago. She was undergoing investigation for a new left breast mass for which a biopsy revealed possible involvement by marginal zone lymphoma. A PCR was performed which was equivocal. Subsequently, she developed a right breast lump and an ultrasound scan showed a well-defined 23 x 10 mm oval hyperechoic lesion in the right upper quadrant and a 29 x 9 mm right axillary lymph node. A staging CT chest abdomen and pelvis and bone marrow sample revealed localized disease. Biopsy of breast lump was performed with PCR analysis. This revealed morphological and immunophenotypical appearances most consistent with a low-grade B –Cell lymphoma and favour a marginal zone lymphoma. The patient was reviewed by an oncologist and was treated with 24 Gy radiotherapy in 12 daily fractions and followed up by the advanced practitioner.Case report - DiscussionPrimary Sjögren’s Syndrome is an autoimmune disease characterised by lymphocytic infiltration of exocrine glands which can manifest in specific organs or as a systemic illness. Patients are at elevated risk of developing lymphoproliferative diseases including non-Hodgkin's lymphoma with a reported prevalence of 5%. On histological analysis, most patients demonstrate low-grade marginal zone B cell lymphoma with approximately 85% occurring in extranodal locations including the parotid and submandibular glands. Some patients may go on to develop high-grade lymphoma.Concerning overall disease activity, it has been recently demonstrated that a stable moderate/high disease activity, calculated either with the EULAR Sjögren’s syndrome disease activity index (ESSDAI) or with the ClinESSDAI, an ESSDAI variant excluding the biological domain, was independently associated with subsequent lymphoma occurrence.Symptomatic cryoglobulinaemic vasculitis (CV) is observed in about 3–4% of pSS patients and has been linked to the development of lymphoma. Other clinical markers of lymphoma such as palpable purpura, low levels of C4, lymphocytopenia, low levels of IgM, elevated levels of β2-microglobulinMalignant proliferation has been reported in the literature and, to the best of our knowledge, only two case reports of a marginal zone lymphoma of the breast complicating primary Sjögren’s syndrome exist.Case report - Key learning points1/ This case emphasises the need for careful clinical examination in this exceedingly rare entity.2/ Although parotid and submandibular gland are commonest extranodal site for NHL, other organs such as thyroid, ovaries and breast might be rarely be affected.3/ Clinicians should be alert if there are some clinical and serological features such as cryoglobulin and persistently low complement which usually predicts the development of lymphoma.