Bacterial infection and non-Hodgkin’s lymphoma

Abstract

One quarter of all cancers are linked to infectious diseases. The link between viral infection and cancer has been widely studied, but few reports have focused on the carcinogenic role of bacterial infection. Nonetheless, Helicobacter pylori, Chlamydia psittaci, Coxiella burnetii, Borrelia burgdorferi and Campylobacter jejuni are bacteria that can be associated with non-Hodgkin’s lymphoma (NHL), the most common haematologic malignancy. Here, we review the evidence in favour of a link between these bacterial infections and NHL. Sero-epidemiological observation makes it possible to identify a link between H. pylori, C. burnetii, B. burgdorferi infection and NHL. Helicobacter pylori, Chlamydia psittaci, Coxiella burnetii, Borrelia burgdorferi and Campylobacter jejuni could be identified in NHL tissue samples at the site of chronic inflammation, where B and T lymphocytes are attracted to participate in follicle formation. Lymphoma remissions have been observed under antimicrobial therapies supporting the carcinogenic contribution of bacteria. If the theory of causality is characterized by the lack of universal criteria for establishing a causal link between two diseases, infection and lymphoma, epidemiological, clinical, and histological evidences reported here, should lead clinicians to pay attention to these infectious agents, to detect early lymphoma transformation.     

Radioimmunotherapy of non-Hodgkin’s lymphoma: a critical appraisal

Radioimmunotherapy is a unique form of radiation therapy that uses antibodies to specifically target radionuclides for systemic cancer treatment. While chemotherapy remains the frontline treatment for non-Hodgkin’s lymphoma, two radioimmunotherapy agents are approved for use in certain follicular and transformed forms of recurrent non-Hodgkin’s lymphoma as a second- or third-line treatment option. However, there are number of clinical trials underway that will likely lead to a more expanded use of this treatment modality in the future. New agents and approaches for radioimmunotherapy are also being developed that could offer an even greater potential for this new form of therapy.     

Is Epstein-Barr virus infection associated with the pathogenesis of microscopic colitis?

BackgroundEpstein-Barr virus (EBV) has been associated with inflammation in the colon, particularly in patients with inflammatory bowel disease (IBD). Even if a relevant plasmocytosis, similar to IBD, is present in microscopic colitis (MC), the frequency of EBV infection in this setting is unknown.ObjectivesWe aimed to compare the frequency of colonic EBV infection in patients with MC, ulcerative colitis (UC), and irritable bowel syndrome (IBS).Study designThe frequency of colonic EBV infection in biopsies of 30 patients with MC, 30 patients with UC, and 30 controls with IBS was retrospectively assessed. PCR was performed to detect viral EBV DNA in colonic biopsies. In situ hybridization was also performed to identify and localize EBV-encoded small RNA1 and 2 (EBERs) within cells.ResultsThe presence of EBV DNA was detected in 27 out of 30 MC patients, in 20 out of 30 UC cases, and in none of IBS group. The frequency of EBV DNA in MC was significantly higher compared with that reported in UC (90.0% vs. 66.7%, p = 0.03). EBERs+ cells were observed in 18 out of 30 MC patients, in only 3 out of 30 UC patients (60.0% vs. 10.0%, p < 0.001), and in none of IBS group.ConclusionsEBV infection is almost always detectable in the colonic mucosa of patients with MC. Further studies are necessary to confirm this association and to clarify the role of EBV in MC and, more generally, in colonic inflammation.     

A case of primary hepatic non-Hodgkin’s lymphoma with chronic hepatitis C

We report a case of primary hepatic non-Hodgkin's lymphoma in a 67-year-old man with chronic hepatitis C. Laboratory data revealed slightly elevated liver function parameters and positive for hepatitis C virus (HCV) antibody. Abdominal ultrasonography showed hypoechoic lesions approximately 5 mm in diameter in the whole liver. Magnetic resonance imaging showed that the tumors were isointense in relationship to the liver on T(1)-weighted images but were slightly hyperintense on T(2)-weighted images. Under a clinical diagnosis of liver tumor, liver biopsy was performed. Histological examination confirmed a diagnosis of non-Hodgkin's diffuse large B-cell lymphoma, and the immunophenotype was identified to be the germinal cell type.     

Telomere size and telomerase activity in Epstein-Barr virus (EBV)-positive and EBV-negative Burkitt’s lymphoma cell lines

Summary. The telomere repeat lengths of BL cell lines were quantified by measuring terminal restriction fragment (TRF). Epstein-Barr virus (EBV)-positive Namalwa, Raji, and EB-3 cell lines have long telomeres, i.e. TRFs 10–19 kbp, whereas the Daudi cell line, producing a transformation-defective EBV mutant, has TRFs ∼2.2 kbp. EBV-negative BJAB and DG75 cell lines have short TRFs 3.9–5.4 kbp, shorter than the ∼12 kbp TRFs in PBLs. Telomerase activities of these BL cell lines are similar. TRFs of non-BL lymphoma cell lines are 2.3–5.5 kbp. Fluorescent in situ hybridization (FISH) studies of these cell lines showed remarkable heterogeneity of telomere size in chromosomes in the same BL cell. These results suggest that EBV-positive and EBV-negative BL cell lines have experienced various telomere dynamics.     

Concomitant non-Hodgkin’s lymphoma in colon and liver: report of a rare case and review of literature

A 58-year-old male patient was admitted with right upper abdominal pain. Initial hematologic evaluation revealed mildly elevated serum carcinoembryonic antigen and carbohydrate antigen (CA) 19-9 tests, while an abdominal CT-scan showed a circumferential mass along the distal ascending colon and the right flexure of colon, simultaneously a liver lesion in segment 8 is considered metastases from colorectal. colonoscopic examination revealed a circumferential growth tumor in the right flexure of colon and the colonoscopy can not reach the proximal of the tumor. We performed a right hemihepatoectomy and a right hemicolectomy associated with loco-regional lymphadenectomy. Histological examination showed diffuse large B-cell lymphomas in resected right colon as well as liver tumors. The patient received six courses of chemotherapy with CHOP-based regimens. At 14-month follow-up before this report, the patient is still alive and free of disease.     

Ofatumumab in the treatment of low-grade non-Hodgkin’s lymphomas and chronic lymphocytic leukemia

Ofatumumab is a novel anti-CD20 monoclonal antibody recently approved for the treatment of chronic lymphocytic leukemia refractory to alemtuzumab and fludarabine. Ofatumumab has also demonstrated activity in other low-grade non-Hodgkin’s lymphomas. However, the optimal time to use ofatumumab and in what patient population is debatable. This article will review some of the key clinical studies that led to the drug’s approval, current recommended usage of the drug and significant future directions.     

High prevalence of mumps in Lao People’s Democratic Republic

In the Lao People’s Democratic Republic (PDR), mumps is not a notifiable disease and mumps vaccine is currently not included in the routine childhood immunization programme. In order to assess the burden of disease, we investigated the seroprevalence of mumps-specific IgG antibodies across four provinces. In addition, we genetically characterized mumps viruses from the past 3 years from several outbreaks and single cases. Blood and/or throat swabs from suspected cases were investigated for specific IgM antibodies or viral RNA. Mumps cases occurred between March and November in 2011-2013 and 5- to 15-year-olds were most affected. Four sequences from an outbreak in the north of Lao PDR in 2011 were identical and belonged to genotype G. Eight sequences from two outbreaks and two individual cases from 2012 and 2013 belonged to genotype J. In addition, sera collected from 2379 healthy infants and school pupils aged between 9 months and 19 years and from pregnant women aged between 16 and 46 years were investigated for mumps-specific IgG. Overall, 58.2% were positive, 39.5% were negative and the remaining 2.3% were equivocal. The seropositivity increased with age, with the lowest percentage found in <1-year-old infants (9.1%) and the highest in the cohort of pregnant women (69.2%). More female subjects than male subjects were seropositive (60.4 vs. 54.9%). There were some differences between the locations. Mumps should be a notifiable disease in Lao PDR in order to get more accurate case numbers and cost estimates for public health-care, and vaccination of children and high-risk groups should be considered.     

Age-Related Characteristics of Sleep Impairments in a Model of the Preclinical Stage of Parkinson’s Disease in Rats

Neuroscience and Behavioral Physiology - Objective. To assess changes in the time characteristics of the states of sleep and waking which may serve as nonmotor signs of the initial stage of PD...     

Biomarkers of lymphoma in Sjögren’s syndrome and evaluation of the lymphoma risk in prelymphomatous conditions: Results of a multicenter study

ObjectivesTo define the biomarkers associated with lymphoproliferation in primary Sjögren’s syndrome (pSS) by distinguishing in separate groups the two best-recognized non-malignant prelymphomatous conditions in pSS, i.e., salivary gland swelling and cryoglobulinemic vasculitis (CV).MethodsA multicenter study was conducted in 5 centres. Patients fulfilled the following criteria: (1) positive AECG criteria for pSS, (2) serum cryoglobulins evaluated, and (3) lack of hepatitis C virus infection. Four groups were distinguished and analysed by multinomial analyses: (1) B-cell non-Hodgkin's lymphoma (NHL), (2) CV without lymphoma, (3) salivary swelling without NHL (SW), and (4) pSS patients without NHL or prelymphomatous conditions.ResultsSix hundred and sixty-one patients were studied. Group 1/NHL comprised 40/661 (6.1%) patients, Group 2/CV 17/661 (2.6%), Group 3/SW 180/661 (27.2%), and Group 4/pSS controls 424/661 (64.1%).Low C4 [relative-risk ratio (RRR) 8.3], cryoglobulins (RRR 6.8), anti-La antibodies (RRR 5.2), and leukopenia (RRR 3.3) were the variables distinguishing Group 1/NHL from Group 4/Controls. As concerns the subset of patients with prelymphomatous conditions, the absence of these biomarkers provided a negative predictive value for lymphoma of 98% in patients with salivary swelling (Group 3/SW). Additional follow-up studies in patients with SW confirmed the high risk of lymphoma when at least 2/4 biomarkers were positive.ConclusionsLymphoma-associated biomarkers were defined in a multicentre series of well-characterized patients with pSS, by dissecting the cohort in the pSS-associated prelymphomatous conditions. Notably, it was demonstrated for the first time that among the pSS patients with salivary swelling, only those with positive biomarkers present an increased risk of lymphoma evolution.     

Anaplastic large-cell non-Hodgkin’s lymphoma of the breast in periprosthetic localisation 32 years after treatment for primary breast cancer—a case report

Primary, as well as secondary, lymphomas of the breast are rare diseases and might, in some cases, be misdiagnosed as breast cancer on routine hematoxylin/eosin stainings. We report a case of an anaplastic large cell lymphoma in a 72-year-old woman with a history of breast cancer treated with breast-ablative surgery and a subsequent silicon implant 32 years ago. Clinically, she presented with an ulceration of the skin, which had developed within a few months. On conventional histology, the tumor cells were mimicking poorly differentiated invasive ductal carcinoma with a prominent leukocytic infiltrate. The immunoprofile of the tumor showed negativity for cytokeratins and led to the diagnosis of a CD30-positive anaplastic large cell lymphoma.     

‘Grey zones’ in the differential diagnosis of lymphoma pathology

The 2016 World Health Organization classification of lymphoid malignancies has further improved basis for pathological diagnosis and better characterization of lymphoproliferative conditions. It includes a range of new entities and expanded requirements for molecular analysis, but reliance on close integration of the clinical, pathological and molecular features still remains the cornerstone for diagnosis. Despite the advances in knowledge and refined diagnostic criteria, certain areas of lymphoma pathology remain difficult and contentious. We provide a review of some entities which continue to represent diagnostic “grey zones”, with potentially overlapping pathological, molecular or clinical features, but in most instances require specific treatments to achieve best clinical outcomes. We focus on: clarifying diagnostic ambiguity between nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte rich B-cell lymphoma, including the relevant differential diagnoses; key features and differential diagnosis of mediastinal grey zone lymphoma; characteristics of high grade B-cell lymphomas, with particular reference to their genetic features as defining diagnostic parameters; pathological overlaps of EBV-positive lymphoproliferations and their differential diagnosis with EBV-positive classic Hodgkin lymphoma.     

Pancreatitis and cholecystitis in primary acute symptomatic Epstein-Barr virus infection – Systematic review of the literature

Acute pancreatitis and acalculous cholecystitis have been occasionally reported in primary acute symptomatic Epstein-Barr virus infection. We completed a review of the literature and retained 48 scientific reports published between 1966 and 2016 for the final analysis. Acute pancreatitis was recognized in 14 and acalculous cholecystitis in 37 patients with primary acute symptomatic Epstein-Barr virus infection. In all patients, the features of acute pancreatitis or acalculous cholecystitis concurrently developed with those of primary acute symptomatic Epstein-Barr virus infection. Acute pancreatitis and acalculous cholecystitis resolved following a hospital stay of 25 days or less. Acalculous cholecystitis was associated with Gilbert-Meulengracht syndrome in two cases. In conclusion, this thorough analysis indicates that acute pancreatitis and acalculous cholecystitis are unusual but plausible complications of primary acute symptomatic Epstein-Barr virus infection. Pancreatitis and cholecystitis deserve consideration in cases with severe abdominal pain. These complications are usually rather mild and resolve spontaneously without sequelae.     

Hodgkin’s lymphoma cells exhibit high expression levels of the PICOT protein

PICOT was originally discovered as a protein kinase C (PKC) binding protein in human Jurkat T-lymphocytes in which it was found to modulate PKCθ-dependent functions. In addition, RT-PCR analysis suggested the expression of PICOT in a wide range of organs and cell types, including cells that are devoid of PKCθ. We aimed at analyzing the expression of the PICOT protein in mouse lymphoid organs, and to compare them with those of Jurkat T-lymphocytes and other cell lines. We also analyzed whether PICOT expression in T-lymphocytes is dependent on the presence of PKCθ, and whether it correlates with cell growth rate. Western blot analyses demonstrated PICOT expression in all lymphoid organs and cell lines tested. In addition, similar expression levels were observed in lymphoid organs of wild-type and PKCθ-null mice, suggesting that PICOT expression in T-lymphocytes is independent of PKCθ. However, PICOT expression levels were higher in Jurkat T-lymphocytes and other lymphoma cell lines compared to freshly isolated lymphocytes, while T-lymphocyte mitogens, such as concanavalin A, increased PICOT expression concomitantly with the induction of a faster T-lymphocyte growth rate. Finally, immunohistochemistry of freshly-isolated lymph nodes from Hodgkin’s lymphoma patients revealed significantly higher levels of PICOT in Hodgkin’s cells, compared to the normal surrounding lymphocytes. The present results show a direct correlation between PICOT expression levels and increased cell growth, both in vitro and in vivo, and suggest that immunostaining of PICOT might be useful for in situ identification of transformed cells, such as those of Hodgkin’s lymphoma.     

Polymorphisms in the repeat long regions of oncogenic and attenuated pathotypes of Marek’s disease virus 1

The nucleotide sequences of the terminal repeat long (TR_L) and internal repeat long regions (IR_L) in the genomes of 13 strains of Marek’s disease virus type 1 (MDV-1) were determined and represent the largest collection of sequencing data from a contiguous region (12.8 kb) in the serotype 1 genomes. The collection of strains used in this study has been well characterized with respect to their virulence and contains members of each pathotype (4 attenuated, 1 mildly virulent, 3 virulent, 2 very virulent and 3 very virulent plus). It has previously been reported that two loci (meq and RLORF4) in the RL regions are likely to encode virulence factors based on comparative genomic studies involving vaccine and virulent strains. Additional studies using knockout mutants have provided stronger evidence that indeed RLORF4 and meq or the overlapping genes 23 kD and RLORF6 are involved in virulence. In this report, we provide evidence that additional open reading frames (ORFs) in the RL regions differ significantly between the extremes of the pathotypes (attenuated vs. nonattenuated). A deletion of 10 base pairs has been identified in RLORF12 from two attenuated strains CVI988 BP-5, p48 and RM-1, p40; and the lower virulence strain JM/102W. A deletion of 40 bp was also identified in RLORF4 of the attenuated strain R2/23, passage 106. A 177 bp insertion within the meq loci has been identified in most of the attenuated strains examined. Interestingly, R2/23 did not contain this insertion but instead truncated proteins are predicted for the three overlapping ORFs (meq, 23 kD and RLORF6) due to a frameshift mutation. Single nucleotide polymorphisms (SNPs), which loosely partition between attenuated and nonattenuated strains, have been identified in the ORFs encoding RLORF12, RLORF8, meq, 23 kD, RLORF6, RLORF4, RLORF3 and ICP0 and three previously unidentified short ORFs: MHLS, MLHG and MPSG. Although no single nucleotide polymorphism in the RL regions could predict virulence, their overall contribution to virulence can now be examined in defined mutants containing additional insertions or deletions in ORFs, suspected of encoding virulence factors, identified by this research.     

Genetic and Antigenic Characteristics of Neisseria meningitidis Strains Isolated in the Czech Republic in 1997–1998

 Strains of Neisseria meningitidis isolated from patients and asymptomatic individuals who had been in contact with patients were investigated using four typing methods with the aim of identifying any heterogeneity and/or homogeneity among the strains. In 1993, a dramatic change in the incidence and severity of invasive meningococcal disease in the Czech Republic occurred as a consequence of the appearance of a Neisseria meningitidis strain of phenotype C : 2a : P1.5,2 and electrophoretic type ET-15, belonging to the ET-37 complex, which had not previously been identified in this country. Presented here are the results of a study of the relationships between 58 Neisseria meningitidis isolates collected between January 1997 and June 1998. Forty-nine isolates originating from patients with invasive meningococcal disease and nine from healthy contacts were analyzed using the following four methods: whole-cell enzyme immunoassay, multilocus enzyme electrophoresis, pulsed-field gel electrophoresis, and randomly amplified polymorphic DNA analysis. A high prevalence of phenotype C : 2a : P1.5,2 electrophoretic type ET-15 was confirmed among the patients' strains. Nevertheless, during the study period, they became heterogeneous. Strains isolated from healthy contacts showed greater heterogeneity in serological phenotypes and electrophoretic types from the beginning of the study, and electrophoretic type ET-15 strains were less frequent. Within the electrophoretic type ET-15 clone, strains showing the identical serological phenotype (with the exception of one isolate) were indistinguishable using randomly amplified polymorphic DNA analysis, while pulsed-field gel electrophoresis revealed heterogeneity with 12 pulsed-field gel electrophoretic types identified. The strains from the same cluster displaying the same serological phenotype were indistinguishable with any of the methods used.