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1.  Diffuse large B-cell non-Hodgkin lymphomas: the clinical relevance of histological subclassification 
British Journal of Cancer  1999;79(11-12):1770-1776.
In the REAL classification the diffuse large B-cell non-Hodgkin lymphomas (NHL) are grouped together, because subclassifications are considered to lack both reproducibility and clinical significance. Others, however, claim that patients with an immunoblastic NHL have a worse prognosis than patients with other types of diffuse large B-cell NHL. Therefore, we investigated the prognostic and clinical significance of histological subclassification of diffuse large B-cell NHL in a uniformly treated series of patients. For this retrospective study, all patients diagnosed as having an immunoblastic (IB) B-cell NHL by the Lymphoma Review Panel of the Comprehensive Cancer Center Amsterdam (CCCA) between 1984 and 1994, and treated according to the guidelines of the CCCA, were analysed. Patients with a centroblastic polymorphic subtype (CB-Poly) or centroblastic (CB) NHL by the Lymphoma Review Panel who were treated in the Netherlands Cancer Institute during the same period according to CCCA guidelines were used as reference groups. All patients' records were reviewed. Clinical parameters at presentation, kind of therapy and clinical outcome were recorded. All available histological slides were separately reviewed by two haemato-pathologists. One hundred and seventy-seven patients were included in the study: 36 patients (20.3%) with an IB NHL, 69 patients (39%) with a CB-Poly NHL and 72 patients (40.7%) with a CB NHL. The patients with an IB NHL tended to be older and presented more often with stage I or II and one extranodal site than patients with a CB and CB-Poly NHL. None of the subtypes showed a clear preference for localization in a particular site. The patients with IB or CB-Poly NHL showed a significantly worse prognosis than patients with CB NHL, with a 5-year overall survival for patients with CB NHL of 56.3% and for patients with IB or CB-Poly NHL 39.1% and 41.6% respectively. The 5-year disease free survival was 53.2% for the patients with CB, 32% for the patients with CB-Poly and 26.9% for the patients with IB NHL. A multivariate analysis showed that histological subtyping was of prognostic significance independent of the International Prognostic Index. This finding merits further exploration in prospective studies in order to judge the value of subclassification of large B-cell NHL as a guideline in therapy choice. © 1999 Cancer Research Campaign
doi:10.1038/sj.bjc.6690282
PMCID: PMC2362805  PMID: 10206291
diffuse large B-cell NHL; diffuse centroblastic NHL; immunoblastic NHL; centroblastic polymorphic subtype NHL; subclassification, prognostic significance
2.  Extranodal non-Hodgkin's lymphoma presenting as gingival mass 
Non-Hodgkin's lymphoma (NHL) commonly presents as non-tender, enlarged lymph nodes, accompanied by diffuse symptoms of fatigue and low-grade intermittent fever and it is derived predominantly from the cells of the B lymphocyte series. NHL cases occur extra-nodally and in 3% of these cases the initial presentation may be in the oral cavity. Though extra-nodal NHL of the oral cavity is a rare finding, patients with oral lesions of NHL commonly present at the dental clinic in the first instance. A careful clinical evaluation supported by histopathological and other laboratory investigations will help in identifying the disease at an early stage, resulting in better prognosis. Any delay in diagnosis has important implications on the morbidity and mortality of the condition. Due to the rarity of intraoral NHL, we present one such a case with a complaint of tumor-like mass on the gingiva of lower molar region. The lesion was clinically thought as pyogenic granuloma and later diagnosed as extra nodal NHL of the oral cavity.
doi:10.4103/0972-124X.92584
PMCID: PMC3283945  PMID: 22368372
Gingival mass; non-Hodgkin's lymphoma; pyogenic granuloma
3.  Analysis of clinical characteristics, diagnosis, treatment and prognosis of 46 patients with primary gastrointestinal non-Hodgkin lymphoma 
Molecular and Clinical Oncology  2013;2(2):259-264.
Primary gastrointestinal non-Hodgkin lymphoma (PGI NHL) is one of the most common types of extranodal lymphoma, accounting for ~30–50% of all extranodal lymphomas. The aim of the present study was to investigate the clinical characteristics, diagnosis, treatment and prognosis of patients with PGI NHL. A total of 46 patients with PGI NHL (mean age, 50 years) were enrolled in this study, with a male:female ratio of 1.3:1. The most common site of PGI NHL was the stomach (52.2%), followed by the colon (34.8%) and small intestine (8.7%). The most common symptoms of PGI NHL included abdominal pain or discomfort (91.3%), loss of appetite (65.2%) and weight loss (56.5%) and the most common pathological subtype of PGI NHL was diffuse large B-cell lymphoma (DLBCL) (78.3%). Lesions were identified in 95.7% of PGI NHL patients under preoperative endoscopic examination, whereas the diagnosis rate was only 21.7% during preoperative endoscopic biopsy. All 46 patients underwent surgical treatment and 36 also received postoperative chemotherapy or radiotherapy. The follow-up time was 6–70 months in 37 PGI NHL patients, with 1-, 3- and 5-year survival rates of 81.1, 62.16 and 50.0%, respectively. The 5-year survival rate differed significantly according to clinical stage (P=0.002) and tumor size (P=0.0017) among patients with PGI NHL. However, there was no statistically significant difference in the 5-year survival rate between patients who received surgery alone and those who received surgery plus postoperative chemotherapy or radiotherapy (P=0.1371). Furthermore, there were no statistically significant differences in gender (P=0.127), clinical stage (P=0.828), histological subtype (P=1.000) and surgical modality (P=0.509) between patients with primary gastric non-Hodgkin lymphoma (PG NHL) and those with primary intestinal non-Hodgkin lymphoma (PI NHL). In conclusion, PGI NHLs are a heterogeneous group of diseases, whereas clinical stage and tumor size were identified as adverse prognostic factors of PGI NHL. Further studies, including a larger number of patients treated with surgery alone, are required in order to elucidate the precise role of surgery combined with postoperative chemotherapy or radiotherapy in the prognosis of PGI NHL.
doi:10.3892/mco.2013.224
PMCID: PMC3917777  PMID: 24649343
non-Hodgkin lymphoma; gastrointestinal lymphoma; diagnosis; therapy; prognosis
4.  Enhanced efficacy of gemcitabine in combination with anti-CD20 monoclonal antibody against CD20+ non-Hodgkin's lymphoma cell lines in vitro and in scid mice 
BMC Cancer  2005;5:103.
Background
Despite exciting new targeted therapeutics against non-Hodgkin's lymphoma (NHL), chemotherapy remains a cornerstone of therapy. While purine nucleoside analogs have significant activity in low grade NHL, the pyrimidine nucleoside analog gemcitabine has been less extensively studied, but has important activity. Use of the anti-CD20 monoclonal antibody rituximab in combination with chemotherapy for B-NHL is becoming prevalent in clinical practice, but has not been extensively studied in pre-clinical models.
Methods
We have tested the activity of gemcitabine ± rituximab in vitro and in scid/human NHL xenograft models. We used two t(14;18)+, CD20+ follicular B cell NHL cell lines, DoHH2 a transformed NHL line and WSU-FSCCL isolated from pleural fluid of a patient with indolent NHL.
Results
Gemcitabine is cytotoxic to DoHH2 and WSU-FSCCL cells in vitro, and the IC50 is 2–3 fold lower in the presence of rituximab. Apoptosis is also enhanced in the presence of rituximab. Clearance of NHL cells from ascites in scid mice is prolonged by the combination, as compared with either agent alone. Most importantly, survival of scid mice bearing human NHL cells is significantly prolonged by the combination of gemcitabine + rituximab.
Conclusion
Based on our pre-clinical data showing prolonged survival of mice bearing human lymphoma cell line xenografts after treatment with gemcitabine + anti-CD20 antibody, this combination, expected to have non-overlapping toxicity profiles, should be explored in clinical trials.
doi:10.1186/1471-2407-5-103
PMCID: PMC1208862  PMID: 16109167
5.  Non-Hodgkin lymphoma response evaluation with MRI texture classification 
Background
To show magnetic resonance imaging (MRI) texture appearance change in non-Hodgkin lymphoma (NHL) during treatment with response controlled by quantitative volume analysis.
Methods
A total of 19 patients having NHL with an evaluable lymphoma lesion were scanned at three imaging timepoints with 1.5T device during clinical treatment evaluation. Texture characteristics of images were analyzed and classified with MaZda application and statistical tests.
Results
NHL tissue MRI texture imaged before treatment and under chemotherapy was classified within several subgroups, showing best discrimination with 96% correct classification in non-linear discriminant analysis of T2-weighted images.
Texture parameters of MRI data were successfully tested with statistical tests to assess the impact of the separability of the parameters in evaluating chemotherapy response in lymphoma tissue.
Conclusion
Texture characteristics of MRI data were classified successfully; this proved texture analysis to be potential quantitative means of representing lymphoma tissue changes during chemotherapy response monitoring.
doi:10.1186/1756-9966-28-87
PMCID: PMC2711966  PMID: 19545438
6.  Clinical features of patients with non-Hodgkin’s lymphoma metastasizing to the pituitary glands 
Oncology Letters  2013;5(5):1643-1648.
It is rare for systemic non-Hodgkin’s lymphoma (NHL) to metastasize to the hypothalamus and pituitary glands. The present study describes two patients with NHL and diabetes insipidus (DI) and 17 patients from the literature in order to analyze the clinical features of patients with NHL metastasizing to the pituitary glands. Diffuse large B cell lymphoma (DLBCL) was observed to be the most common type of NHL involving the hypothalamus-pituitary axis. A total of 11 patients (57.9%) had been diagnosed with DI (post-pituitary involvement), five (26.3%) with anterior hypopituitarism and three (15.8%) with posterior and anterior hypopituitarism. Only two cases exhibited simultaneous endocrine and lymphoma manifestations; the majority of cases (68.4%) exhibited lymphoma manifestations first. To make an etiological diagnosis of NHL with metastases to the pituitary glands, it is necessary to find that NHL exists in other regions of patient’s body. Biopsy of the sellar may have significant meaning, but this examination may difficult to perform. Chemotherapy for NHL relieves pituitary impairment symptoms and improves the overall examination results. Additionally, magnetic resonance imaging (MRI) of the pituitary gland has a certain differential diagnostic value as the T1- and T2-weighted imaging (WI) signals from patients with systemic NHL with pituitary involvement are low.
doi:10.3892/ol.2013.1266
PMCID: PMC3678777  PMID: 23760877
non-Hodgkin’s lymphoma; diabetes insipidus; anterior hypopituitarism; pituitary
7.  Immunologic and virologic predictors of AIDS-related non-Hodgkin lymphoma in the HAART era 
HIV-infected persons treated with highly active antiretroviral therapy (HAART) continue to have elevated risk for non-Hodgkin lymphoma (NHL). We conducted a retrospective cohort study of NHL among patients at an urban HIV clinic (N=3025). Proportional hazards models identified immunologic and virologic predictors of NHL. Sixty-five NHLs arose during 1989-2006. NHL incidence declined over time. Nonetheless, 51 NHLs (78%) occurred within the HAART era (1996-2006). NHL risk increased with declining CD4 count (p-trend<0.0001) and increasing HIV viral load (p-trend=0.005). In a multivariable model, NHL risk was independently associated with both current CD4 count (hazard ratios 7.7 and 3.8, respectively, for CD4 counts 0-99 and 100-249 vs. 250+ cells/mm3; p-trend<0.0001) and prior time spent with a viral load above 5.00 log10 copies/ml (hazard ratios of 3.4, 2.6, and 6.8, respectively, for 0.1-0.4, 0.5-1.4, and 1.5+ years vs. 0 years; p-trend=0.004). Although serum globulin levels were elevated compared to the general population, NHL risk was unrelated to this B-cell activation marker (p=0.39). Among HIV-infected individuals in the HAART era, NHLs are linked to immunosuppression and extended periods of uncontrolled HIV viremia. The association with high-level viremia could reflect detrimental effects on immune function related to incompletely effective HAART or direct effects on B-cells.
doi:10.1097/01.qai.0000371677.48743.8d
PMCID: PMC3078556  PMID: 20418723
non-Hodgkin lymphoma; acquired immunodeficiency syndrome; human immunodeficiency virus; immunosuppression; Epstein Barr virus; inflammation
8.  Centroblastic variant of diffuse large B-cell lymphoma: Case report and review of literature 
Diffuse large B-cell lymphoma (DLBCL) is a subtype of non-Hodgkin's lymphoma (NHL) making up about approximately 30% of all NHL. Its occurrence in the mandible is very rare. Histopathologically, five variants of DLBCL have been recognized among which centroblastic variant is the one with better prognosis. We report a case of a 55 year-old patient who presented with a painless swelling in the lower right body of the mandible since 4 months. Incisional biopsy revealed NHL like features, confirmed by immunohistochemistry using CD45, CD20, and CD3 markers to be a DLBCL of centroblastic variant. Patient was treated with chemotherapy following which the lesion regressed completely with no further recurrences. Precise histological diagnosis is crucial for the clinical management and ultimately for the survival of the patient.
doi:10.4103/0973-029X.119749
PMCID: PMC3830238  PMID: 24250090
Centroblastic variant; diffuse large B-cell lymphoma; extranodal; immunohistochemistry; non-Hodgkin's lymphoma
9.  HIV-related non-Hodgkin’s lymphoma in Calgary 
OBJECTIVE:
To determine the incidence of human immunodeficiency virus (HIV) associated non-Hodgkin’s lymphoma (NHL) in a cohort of patients from a distinct geographic region (southern Alberta). The type and location of NHL as well as how it affected the survival of these patients was examined.
PATIENTS AND METHODS:
The Southern Alberta HIV Clinic in Calgary serves all of southern Alberta, which has an estimated population of one million. The clinic has provided primary care for 1086 patients from January 1983 to August 1995. Data were obtained by reviewing the clinic’s database and patients’ charts.
RESULTS:
Over a 12-year period, 39 cases of NHL were diagnosed in a group of 1086 HIV-infected patients. Presentation of NHL was at an extranodal site in all but four cases, with the most common sites being the bowel and central nervous system. The mean CD4 count on presentation with NHL was 143.4±37.4×106/L (range 1 to 1219×106/L). Mean survival was 1.25±0.25 years with a range from 0 (diagnosed on autopsy) to 6.45 years. Patients with a CD4 count of less than 200×106/L and/or diagnosed with an AIDS-defining illness before development of NHL had significantly reduced survival (0.85 years versus 2.48 years, P<0.02 and 0.57 years versus 2.09 years, P<0.001, respectively). Patients who presented with NHL involving either nodes alone or central nervous system had significantly decreased survival (0.28 years and 0.29 years, respectively, P<0.05). Patients with NHL involving the gastrointestinal tract had a longer mean survival than those with NHL elsewhere (P<0.05). All but seven cases received therapy for NHL including chemotherapy, radiotherapy, surgery or combined therapy. Fifteen patients (47% of treated) achieved a complete response that led to improved survival (P<0.01). Patients tolerated surgery, chemotherapy and radiotherapy well and no deaths were due to NHL therapy.
CONCLUSIONS:
These data suggest that development of NHL in HIV is associated with reduced survival, and that survival is predominantly determined by CD4 count and site of involvement at the time of diagnosis of NHL.
PMCID: PMC3327386  PMID: 22514428
Human immunodeficiency virus; Non-Hodgkin’s lymphoma
10.  Hepatitis C virus-related B cell subtypes in non Hodgkin's lymphoma 
World Journal of Hepatology  2011;3(11):278-284.
AIM: To evaluate if indolent B cell-non Hodgkin’s lymphoma (B-NHL) and diffuse large B-cell lymphoma (DLBCL) in hepatitis C virus (HCV) positive patients could have different biological and clinical characteristics requiring different management strategies.
METHODS: A group of 24 HCV related B-NHL patients (11 indolent, 13 DLBCL) in whom the biological and clinical characteristics were described and confronted. Patients with DLBCL were managed with the standard of care of treatment. Patients with indolent HCV-related B-NHL were managed with antiviral treatment pegylated interferon plus ribavirin and their course observed. The outcomes of the different approaches were compared.
RESULTS: Patients with DLBCL had a shorter duration of HCV infection and a higher prevalence of HCV genotype 1 compared to patients with indolent B-NHL in which HCV genotype 2 was the more frequent genotype. Five of the 9 patients with indolent HCV-related B-NHL treated with only antiviral therapy, achieved a complete response of their onco-haematological disease (55%). Seven of the 13 DLBCL patients treated with immunochemotheraphy obtained a complete response (54%).
CONCLUSION: HCV genotypes and duration of HCV infection differed between B-NHL subtypes. Indolent lymphomas can be managed with antiviral treatment, while DLBCL is not affected by the HCV infection.
doi:10.4254/wjh.v3.i11.278
PMCID: PMC3225032  PMID: 22125661
Hepatitis C virus infection; Diffuse large B cell lymphoma; Indolent lymphoma; Pegylated interferon; Lymphomagenesis
11.  The utility of t(14;18) in understanding risk factors for non-Hodgkin lymphoma 
Characteristic chromosomal abnormalities are associated with specific histologic subtypes of non-Hodgkin lymphoma (NHL). The chromosomal translocation t(14;18)(q32;q21) is one of the most common chromosomal abnormalities in NHL, occurring in 70–90% of cases of follicular lymphoma, 20–30% of diffuse large B-cell lymphoma, and 5–10% of other less common subtypes. The t(14;18)-positive NHL may represent a homogenous group and, consequently, increase etiologic specificity in epidemiologic studies. Although the t(14;18) has important clinical ramifications, its etiologic significance remains to be determined. Two population-based, case-control studies addressed this issue by evaluating potential risk factors for t(14;18)-positive and t(14;18)-negative subgroups of NHL. Both studies found that the association between pesticide exposures and risk of NHL was largely limited to t(14;18)-positive NHL cases. However, the findings regarding cigarette smoking, family history of hematopoietic cancer, and hair dye use were not entirely consistent. These results indicate that defining subgroups of NHL according to t(14;18) status may be useful for etiologic research, particularly for exposures that are genotoxic or may contribute to the development of NHL through pathways involving the t(14;18). Studies to further evaluate these associations and delineate the effects of various exposures in other genetically-defined subgroups of NHL are warranted.
doi:10.1093/jncimonographs/lgn018
PMCID: PMC2972188  PMID: 18648007
12.  Identification of non-Hodgkin's lymphoma prognosis signatures using the CTGDR method 
Bioinformatics  2009;26(1):15-21.
Motivation: Although NHL (non-Hodgkin's lymphoma) is the fifth leading cause of cancer incidence and mortality in the USA, it remains poorly understood and is largely incurable. Biomedical studies have shown that genomic variations, measured with SNPs (single nucleotide polymorphisms) in genes, may have independent predictive power for disease-free survival in NHL patients beyond clinical measurements.
Results: We apply the CTGDR (clustering threshold gradient directed regularization) method to genetic association studies using SNPs, analyze data from an association study of NHL and identify prognosis signatures to diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL), the two most common subtypes of NHL. With the CTGDR method, we are able to account for the joint effects of multiple genes/SNPs, whereas most existing studies are single-marker based. In addition, we are able to account for the ‘gene and SNP-within-gene’ hierarchical structure and identify not only predictive genes but also predictive SNPs within identified genes. In contrast, existing studies are limited to either gene or SNP identification, but not both. We propose using resampling methods to evaluate the predictive power and reproducibility of identified genes and SNPs. Simulation study and data analysis suggest satisfactory performance of the CTGDR method.
Contact: shuangge.ma@yale.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
doi:10.1093/bioinformatics/btp604
PMCID: PMC2796812  PMID: 19850755
13.  Concurrent Infection of Hepatitis B Virus Negatively Affects the Clinical Outcome and Prognosis of Patients with Non-Hodgkin’s Lymphoma after Chemotherapy 
PLoS ONE  2013;8(7):e69400.
Hepatitis B virus (HBV) is hepatotropic and lymphotropic. HBV-infected individuals have an increased risk of developing malignant lymphoma, and the HBV infection rate in lymphoma patients is significantly higher than that in the general population. However, the exact mechanism and correlation between HBV infection and lymphoma onset and progression currently remain unclear. We retrospectively analyzed clinical data from non-Hodgkin’s lymphoma (NHL) patients with different HBV infection statuses. The results showed that the HBV infection rate was significantly higher in patients with B-cell type and late stage of NHL. The chemotherapy efficacy for NHL patients with chronic active HBV infection was significantly lower than that for the patients with chronic inactive HBV infection, the patients with HBV carriers and the patients without HBV infection. In addition, the NHL chemotherapy activated HBV replication and caused significant liver dysfunction, which could further reduce the chemotherapy efficacy. Through Kaplan-Meier survival curve and log-rank analysis, we found that the HBV infection status in NHL patients was significantly correlated with the patients’ progression-free survival (PFS) and overall survival (OS). Compared with the patients without HBV infection (PFS: 95% CI 47.915 to 55.640; OS: 95% CI 81.324 to 86.858), the PFS and OS of the patients with chronic active HBV infection were significantly shorter (PFS: 95% CI 9.424 to 42.589, P < 0.001; OS: 95% CI 42.840 to 82.259, P = 0.006). The study demonstrated that the sustained HBV replication in patients with chronic active HBV infection could be a key factor that influences the prognosis of NHL patients after chemotherapy, and thus may provide information for designing rational clinical treatments for NHL patients with different HBV infection statuses and improve the treatment efficacy and prognosis.
doi:10.1371/journal.pone.0069400
PMCID: PMC3704665  PMID: 23861969
14.  Early development of non-hodgkin lymphoma following initiation of newer class antiretroviral therapy among HIV-infected patients - implications for immune reconstitution 
Background
In the HAART era, the incidence of HIV-associated non-Hodgkin lymphoma (NHL) is decreasing. We describe cases of NHL among patients with multi-class antiretroviral resistance diagnosed rapidly after initiating newer-class antiretrovirals, and examine the immunologic and virologic factors associated with potential IRIS-mediated NHL.
Methods
During December 2006 to January 2008, eligible HIV-infected patients from two affiliated clinics accessed Expanded Access Program antiretrovirals of raltegravir, etravirine, and/or maraviroc with optimized background. A NHL case was defined as a pathologically-confirmed tissue diagnosis in a patient without prior NHL developing symptoms after starting newer-class antiretrovirals. Mean change in CD4 and log10 VL in NHL cases compared to controls was analyzed at week 12, a time point at which values were collected among all cases.
Results
Five cases occurred among 78 patients (mean incidence = 64.1/1000 patient-years). All cases received raltegravir and one received etravirine. Median symptom onset from newer-class antiretroviral initiation was 5 weeks. At baseline, the median CD4 and VL for NHL cases (n = 5) versus controls (n = 73) were 44 vs.117 cells/mm3 (p = 0.09) and 5.2 vs. 4.2 log10 (p = 0.06), respectively. The mean increase in CD4 at week 12 in NHL cases compared to controls was 13 (n = 5) vs. 74 (n = 50)(p = 0.284). Mean VL log10 reduction in NHL cases versus controls at week 12 was 2.79 (n = 5) vs. 1.94 (n = 50)(p = 0.045).
Conclusions
An unexpectedly high rate of NHL was detected among treatment-experienced patients achieving a high level of virologic response with newer-class antiretrovirals. We observed trends toward lower baseline CD4 and higher baseline VL in NHL cases, with a significantly greater decline in VL among cases by 12 weeks. HIV-related NHL can occur in the setting of immune reconstitution. Potential immunologic, virologic, and newer-class antiretroviral-specific factors associated with rapid development of NHL warrants further investigation.
doi:10.1186/1742-6405-7-44
PMCID: PMC3022662  PMID: 21156072
15.  Improved survival for non-Hodgkin lymphoma patients in New South Wales, Australia 
BMC Cancer  2010;10:231.
Background
We evaluated if the survival benefit of adding rituximab to standard chemotherapy for non-Hodgkin lymphoma (NHL) observed in clinical trials has been experienced by an Australian NHL patient population.
Methods
NHL cases diagnosed in 1985-2004 in New South Wales (NSW) were followed-up to the end of 2004. Rituximab prescription data were obtained from Medicare Australia. Using a Poisson regression model adjusted for age group, sex, NHL subtype and time period (1990-1994, 1995-1999 and 2000-2004), we estimated excess risk of death after a diagnosis of NHL. To give context to the survival trend, trends in incidence and mortality were also estimated.
Results
Compared with 1990-1994, after adjusting for age, sex and NHL subtype the relative excess risk of death was significantly lower (p < 0.0001) in 1995-1999 (0.89) and 2000-2004 (0.74). A sharp fall in mortality was observed from 2000 to 2004 (annual percentage change (APC) = -4.7, p = 0.009), while a small but significant rise in incidence was seen from 1990 to 2004 (APC = 0.5, p = 0.01). The number of times rituximab was dispensed in NSW increased rapidly from 1274 in 1999 to 9250 in 2004.
Conclusion
It is likely that some benefit of adding rituximab to the standard chemotherapy for NHL has been experienced at the population level.
doi:10.1186/1471-2407-10-231
PMCID: PMC2886045  PMID: 20497580
16.  Vaginal Lymphoma with Immune Thrombocytopenic Purpura: An Unusual Case Report 
Case Reports in Oncology  2010;3(3):397-405.
The female genital tract is rarely the initial site of presentation in lymphoma or leukemia. We report a case of non-Hodgkin's lymphoma (NHL) presenting initially in the vagina. The patient, a 75-year-old woman, had a history of immune thrombocytopenic purpura (ITP). She presented with a chief complaint of genital bleeding and introital pain. On transvaginal ultrasonography, a vaginal tumor with an irregular wall was detected, and the internal echo showed a hypoechoic and echogenic pattern. Ultrasonography and magnetic resonance imaging (MRI) suggested that the vaginal tumor was likely to be a hematoma or a hemorrhagic tumor arising from ITP. Incision and resection for a hematoma or a hemorrhagic tumor were carried out in response to genital bleeding, introital pain, and pathological diagnosis. Postoperative microscopic examination confirmed that the tumor was a vaginal NHL. The final diagnosis using the Ann Arbor staging system was high-stage (stage IV) NHL. The patient received chemotherapy, and she remains in remission for 42 months after treatment.
doi:10.1159/000289447
PMCID: PMC2992428  PMID: 21113350
Non-Hodgkin's lymphoma; Immune thrombocytopenic purpura; Vagina; Transvaginal ultrasonography; Magnetic resonance imaging
17.  Relationship between Non-Hodgkin’s lymphoma and blood levels of Epstein-Barr Virus in children in north-western Tanzania: a case control study 
BMC Pediatrics  2013;13:4.
Background
Non-Hodgkin’s Lymphomas (NHL) are common in African children, with endemic Burkitt’s lymphoma (BL) being the most common subtype. While the role of Epstein-Barr Virus (EBV) in endemic BL is known, no data are available about clinical presentations of NHL subtypes and their relationship to Human Immunodeficiency Virus (HIV) infection and Epstein Barr Virus (EBV) load in peripheral blood of children in north-western, Tanzania.
Methods
A matched case control study of NHL subtypes was performed in children under 15 years of age and their respective controls admitted to Bugando Medical Centre, Sengerema and Shirati district designated hospitals in north-western, Tanzania, between September 2010 and April 2011. Peripheral blood samples were collected on Whatman 903 filter papers and EBV DNA levels were estimated by multiplex real-time PCR. Clinical and laboratory data were collected using a structured data collection tool and analysed using chi-square, Fisher and Wilcoxon rank sum tests where appropriate. The association between NHL and detection of EBV in peripheral blood was assessed using conditional logistic regression model and presented as odds ratios (OR) and 95% confidence intervals (CI).
Results
A total of 35 NHL cases and 70 controls matched for age and sex were enrolled. Of NHLs, 32 had BL with equal distribution between jaw and abdominal tumour, 2 had large B cell lymphoma (DLBCL) and 1 had NHL-not otherwise specified (NHL-NOS). Central nervous system (CNS) presentation occurred only in 1 BL patient; 19 NHLs had stage I and II of disease. Only 1 NHL was found to be HIV-seropositive. Twenty-one of 35 (60%) NHL and 21 of 70 (30%) controls had detectable EBV in peripheral blood (OR = 4.77, 95% CI 1.71 – 13.33, p = 0.003). In addition, levels of EBV in blood were significantly higher in NHL cases than in controls (p = 0.024).
Conclusions
BL is the most common childhood NHL subtype in north-western Tanzania. NHLs are not associated with HIV infection, but are strongly associated with EBV load in peripheral blood. The findings suggest that high levels of EBV in blood might have diagnostic and prognostic relevance in African children.
doi:10.1186/1471-2431-13-4
PMCID: PMC3547779  PMID: 23294539
Non-Hodgkin’s Lymphoma; Children; HIV; EBV
18.  The comparison of the value of ct imaging and selected MRI sequences (including DWI) in the evaluation of axonal injuries 
Polish Journal of Radiology  2010;75(1):13-17.
Summary
Background:
Diffuse axonal injuries of the brain consist in the damage (overstretching or torsion) of white matter axons, as a result of the forces of energy waves, evoked in the moment of injury, together with its accelerating-retarding inertia effect. Patients with DAI are most frequently the casualties of high speed car accidents. Diffuse axonal injuries of the brain are one of the most common acute brain injuries, with lesions typically occurring in the periventricular white matter, corpus callosum, and on the borderline of the white and grey matter, subventricularly. The diagnosis of axonal injuries is difficult, as the majority of lesions found in DAI are of microscopic nature.
Material/Methods:
The material included the evaluation of 8 patients with craniocerebral injuries, normal results of brain CT (or showing slight posttraumatic lesions), and in severe neurological clinical state (continuing coma), which was all suggestive of a diffuse axonal injury. The patients were subjected to brain MRI studies within an MRI trauma protocol including FLAIR and DWI sequences, as well as sagittal T2-weighed images, which shortened the diagnostic examination time and was sufficient for the visualisation of DAI-specific lesions.
Results:
On MRI examination, seven patients were diagnosed with diffuse foci of high signal intensity, located in corpus callosum, basal ganglia, thalamus and brain stem, although the CT examination results were normal or revealing minor changes. The foci were most prominent in DWI images. DWI sequence showed a diffuse cytotoxic oedema of white matter in one case, in which the CT results were normal.
Conclusions:
The MRI examination with DWI should become a basic diagnostic tool in DAI. Due to patients’ severe condition, the diagnostic process should be shortened. This could be done with the use of some selected sequences and projections of brain MRI, including transverse DWI and FLAIR, as well as T2-weighed images in sagittal plane, which reduces the time of the examination by approx. 12–15 minutes. Correct and quick diagnosis of a diffuse axonal injury is of major therapeutic and prognostic importance.
PMCID: PMC3389848  PMID: 22802756
DAI – diffuse axonal injury; MR- DWI – diffusion weighted imaging
19.  Non-Hodgkin Lymphoma in Women: Reproductive Factors and Exogenous Hormone Use 
American Journal of Epidemiology  2008;168(3):278-288.
Few studies of reproductive hormone exposures and non-Hodgkin lymphoma (NHL) have examined NHL subtypes. Associations between reproductive hormonal factors and risk of all NHL and of two predominant subtypes, diffuse large-cell lymphoma (DLCL) (n = 233) and follicular lymphoma (n = 173), were investigated among women (n = 581) in a large, population-based, case-control study (1,591 cases, 2,515 controls). Controls (n = 836) identified by random digit dialing were frequency matched by age and county to incident NHL cases ascertained in the San Francisco Bay Area of California in 1988–1993. Adjusted unconditional logistic regression was used to obtain odds ratios. More than four pregnancies indicated a possible lower risk of all NHL (odds ratio (OR) = 0.81, 95% confidence interval (CI): 0.55, 1.2; p-trend = 0.06) and of DLCL (OR = 0.53, 95% CI: 0.31, 0.90; p-trend = 0.01). Exclusive use of menopausal hormone therapy for ≥5 years was associated with a reduced risk of all NHL (OR = 0.68, 95% CI: 0.48, 0.98) and of DLCL (OR = 0.50, 95% CI: 0.30, 0.85). Oral contraceptive use indicated a lower risk of all NHL (OR = 0.68, 95% CI: 0.49, 0.94), and perhaps DLCL (OR = 0.79, 95% CI: 0.51, 1.2), and of follicular lymphoma (OR = 0.75, 95% CI: 0.46, 1.2). Results suggest that endogenous and exogenous reproductive hormones confer different risks by NHL subtype and are associated with a reduced risk of DLCL in women.
doi:10.1093/aje/kwn119
PMCID: PMC2727261  PMID: 18550561
case-control studies; contraception; estrogens; hormone replacement therapy; lymphoma, non-Hodgkin; menopause; pregnancy; reproduction
20.  Neurolymphomatosis of Brachial Plexus in Patients with Non-Hodgkin's Lymphoma 
Neurolymphomatosis (NL) is a rare clinical disease where neoplastic cells invade the cranial nerves and peripheral nerve roots, plexus, or other nerves in patients with hematologic malignancy. Most NL cases are caused by B-cell non-Hodgkin's lymphoma (NHL). Diagnosis can be made by imaging with positron emission tomography (PET) and magnetic resonance imaging (MRI). We experienced two cases of NL involving the brachial plexus in patients with NHL. One patient, who had NHL with central nervous system (CNS) involvement, experienced complete remission after 8 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy but relapsed into NL of the brachial plexus 5 months later. The other patient, who suffered from primary central nervous system lymphoma (PCNSL), had been undergoing chemoradiotherapy but progressed to NL of the brachial plexus.
doi:10.1155/2013/492329
PMCID: PMC3844222  PMID: 24324902
21.  Lymphoid proliferations in the orbit: malignant or benign? 
Clinical, pathological, and immunological analysis of 20 patients with ocular adnexal lymphoid disease has demonstrated several parameters which are useful for distinguishing malignant from benign lesions. Patients in the fourth or fifth decade of life presenting with an acute history of pain, oedema, epiphora, double vision, and ptosis, with a mass localised in the lacrimal gland area, are more likely to have a pseudolymphoma or a chronic inflammatory lesion than a true non-Hodgkin lymphoma (NHL). It is not possible to obtain a definite diagnosis without surgical intervention, because only three out of nine patients with orbital NHL had evidence of a monoclonal B cell population in peripheral blood on admission to the Orbital Centre. Furthermore it was confirmed that the identification of the various orbital lymphoid infiltrates becomes more distinct when immunological techniques are added to the clinical and histopathological methods of investigation. Multidisciplinary cooperation leads to further improvement of diagnosis and treatment of ocular adnexal lymphoproliferative disease.
Images
PMCID: PMC1040505  PMID: 6391535
22.  A closer look at non‐Hodgkin's lymphoma cases in a national Swedish systemic lupus erythematosus cohort: a nested case‐control study 
Annals of the Rheumatic Diseases  2007;66(12):1627-1632.
Objective
To investigate risk factors for non‐Hodgkin's lymphoma (NHL) and analyse NHL subtypes and characteristics in patients with systemic lupus erythematosus (SLE).
Methods
A national SLE cohort identified through SLE discharge diagnoses in the Swedish hospital discharge register during 1964 to 1995 (n = 6438) was linked to the national cancer register. A nested case control study on SLE patients who developed NHL during this observation period was performed with SLE patients without malignancy as controls. Medical records from cases and controls were reviewed. Tissue specimens on which the lymphoma diagnosis was based were retrieved and reclassified according to the WHO classification. NHLs of the subtype diffuse large B cell lymphoma (DLBCL) were subject to additional immunohistochemical staining using antibodies against bcl‐6, CD10 and IRF‐4 for further subclassification into germinal centre (GC) or non‐GC subtypes.
Results
16 patients with SLE had NHL, and the DLBCL subtype dominated (10 cases). The 5‐year overall survival and mean age at NHL diagnosis were comparable with NHL in the general population—50% and 61 years, respectively. Cyclophosphamide or azathioprine use did not elevate lymphoma risk, but the risk was elevated if haematological or sicca symptoms, or pulmonary involvement was present in the SLE disease. Two patients had DLBCL‐GC subtype and an excellent prognosis.
Conclusions
NHL in this national SLE cohort was predominated by the aggressive DLBCL subtype. The prognosis of NHL was comparable with that of the general lymphoma population. There were no indications of treatment‐induced lymphomas. Molecular subtyping could be a helpful tool to predict prognosis also in SLE patients with DLBCL.
doi:10.1136/ard.2006.067108
PMCID: PMC2095297  PMID: 17517757
23.  Non-Hodgkin lymphoma presenting with numb chin syndrome 
BMJ Case Reports  2011;2011:bcr0120113712.
Numb chin syndrome (NCS) is a rare yet potentially ominous sensory neuropathy characterised by unilateral hypoesthesia or paraesthesia over the lower lip, chin and occasionally gingival mucosa. Recognising NCS clinically is important as this may be a subtle sign of occult malignancy progression or relapses. Current expert opinion is that patients with NCS without apparent cause should be assumed to have a malignant aetiology until proven otherwise. By far the most common non-haematologic neoplastic cause of NCS is breast cancer, while the most common haematologic neoplastic cause is non-Hodgkin lymphoma (NHL). The pathophysiology of NCS has been shown to be either direct compression of the mental nerve by tumour mass, leptomeningeal invasion or a bony lesion at mental foramen. Here we report a case of NHL presenting with NCS with no evidence of metastasis in brain parenchyma, cerebrospinal fluid or mandibular bone. Instead, diffuse dural thickening and focal lesion in clivus were identified. We propose that these may represent novel mechanisms of NCS.
doi:10.1136/bcr.01.2011.3712
PMCID: PMC3083008  PMID: 22696665
24.  Hepatitis viruses and non-Hodgkin’s lymphoma: A review 
World Journal of Virology  2012;1(6):162-173.
Non-Hodgkin’s lymphoma (NHL) is among the haematological malignancies with high prevalence worldwide, causing estimated 355 900 new cases and 191 400 deaths in 2008. High prevalence of NHL is documented in economically more developed areas while low prevalence is observed in less developed areas of the globe. A wide array of environmental factors have been reported to be either directly involved or in modifying the risk of NHL development. In addition to these factors, a number of infectious agents, chiefly viruses have also been implicated in the development of NHL. This article reviews the available literature to discuss the role of hepatitis viruses in NHL development, possible mechanisms of lymphomagenesis and also identify the areas in which further research is required to better understand this disease. A brief discussion on the clinical aspects such as classification, staging, treatment approaches have also been included in this article.
doi:10.5501/wjv.v1.i6.162
PMCID: PMC3782277  PMID: 24175222
Non-Hodgkin’s lymphoma; Hepatitis B virus; Hepatitis C virus; Hepatitis G virus; MiRNA
25.  Involvement of the ileocaecal region by non-Hodgkin's lymphoma in adults: clinical features and results of treatment. 
British Journal of Cancer  1989;60(3):366-369.
Between January 1977 and January 1988, 19 patients with non-Hodgkin's lymphoma (NHL) involving the ileocaecal region were cared for by the CRC Wessex Medical Oncology Unit. Fifteen of these patients had primary ileocaecal NHL (stages IE or IIE) and four had secondary involvement of this region (stage IV). The commonest clinical presentation was with abdominal pain and a palpable mass in the right iliac fossa. Bulky (greater than 10 cm) disease was a particularly common feature, and complete surgical removal was possible in only seven patients. All patients had intermediate (18) or high grade (one) NHL using the Working Formulation. The commonest histological subtype was diffuse large cell. Seventeen patients received postoperative therapy, comprising local radiotherapy in one and combination chemotherapy in the remaining 16. Eleven of the 19 patients remain disease-free 6-60 months from diagnosis. Because of the high incidence of bulky disease at this site, postoperative therapy may be indicated, even for patients with apparently completely excised stage I disease.
PMCID: PMC2247183  PMID: 2789943

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