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1.  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.
PMCID: PMC3917777  PMID: 24649343
non-Hodgkin lymphoma; gastrointestinal lymphoma; diagnosis; therapy; prognosis
2.  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
PMCID: PMC2362805  PMID: 10206291
diffuse large B-cell NHL; diffuse centroblastic NHL; immunoblastic NHL; centroblastic polymorphic subtype NHL; subclassification, prognostic significance
3.  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.
PMCID: PMC3678777  PMID: 23760877
non-Hodgkin’s lymphoma; diabetes insipidus; anterior hypopituitarism; pituitary
4.  Renal Involvement in Non-Hodgkin Lymphoma: Proven by Renal Biopsy 
PLoS ONE  2014;9(4):e95190.
To determine the spectrum of renal lesions in patients with kidney involvement in non-Hodgkin's lymphoma (NHL) by renal biopsy.
The clinical features and histological findings at the time of the renal biopsy were assessed for each patient.
We identified 20 patients with NHL and renal involvement, and the diagnosis of NHL was established following the kidney biopsy in 18 (90%) patients. The types of NHL include the following: chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 8), diffuse large B-cell lymphoma (n = 4), T/NK cell lymphoma (n = 3), lymphoplasmacytic lymphoma (n = 2), cutaneous T-cell lymphoma (n = 1), mucosa-associated lymphoid tissue lymphoma (n = 1) and mantle cell lymphoma (n = 1). All presented with proteinuria, and 15 patients had impaired renal function. The pathological findings included (1) membranoproliferative glomerulonephritis-like pattern in seven patients; (2) crescent glomerulonephritis in four; (3) minimal-change disease in three, and glomeruli without specific pathological abnormalities in three; (4) intraglomerular large B-cell lymphoma in one; (5) intracapillary monoclonal IgM deposits in one; (6) primary diffuse large B-cell lymphoma of the kidneys in one; and (7) lymphoma infiltration of the kidney in eight patients.
A wide spectrum of renal lesions can be observed in patients with NHL, and NHL may be first proven by renal biopsies for evaluation of kidney injury or proteinuria. Renal biopsy is necessary to establish the underlying cause of renal involvement in NHL.
PMCID: PMC3986362  PMID: 24733356
5.  Thalamic integrity underlies executive dysfunction in traumatic brain injury 
Neurology  2010;74(7):558-564.
To quantify the effects of traumatic brain injury on integrity of thalamocortical projection fibers and to evaluate whether damage to these fibers accounts for impairments in executive function in chronic traumatic brain injury.
High-resolution (voxel size: 0.78 mm × 0.78 mm × 3 mm3) diffusion tensor MRI of the thalamus was conducted on 24 patients with a history of single, closed-head traumatic brain injury (TBI) (12 each of mild TBI and moderate to severe TBI) and 12 age- and education-matched controls. Detailed neuropsychological testing with an emphasis on executive function was also conducted. Fractional anisotropy was extracted from 12 regions of interest in cortical and corpus callosum structures and 7 subcortical regions of interest (anterior, ventral anterior, ventral lateral, dorsomedial, ventral posterior lateral, ventral posterior medial, and pulvinar thalamic nuclei).
Relative to controls, patients with a history of brain injury showed reductions in fractional anisotropy in both the anterior and posterior corona radiata, forceps major, the body of the corpus callosum, and fibers identified from seed voxels in the anterior and ventral anterior thalamic nuclei. Fractional anisotropy from cortico-cortico and corpus callosum regions of interest did not account for significant variance in neuropsychological function. However, fractional anisotropy from the thalamic seed voxels did account for variance in executive function, attention, and memory.
The data provide preliminary evidence that traumatic brain injury and resulting diffuse axonal injury results in damage to the thalamic projection fibers and is of clinical relevance to cognition.
= anterior corona radiata;
= anterior thalamic nucleus;
= body of the corpus callosum;
= cortical-spinal tract;
= diffuse axonal injury;
= dorsomedial nucleus;
= diffusion tensor imaging;
= fractional anisotropy;
= forceps major;
= forceps minor;
= field of view;
= fast spin echo;
= genu of the corpus callosum;
= internal capsule;
= inferior frontal occipital fasciculus;
= loss of consciousness;
= mild TBI;
= moderate to severe TBI;
= number of excitations;
= posterior corona radiata;
= posttraumatic amnesia;
= pulvinar;
= region of interest;
= splenium of the corpus callosum;
= superior longitudinal fasciculus;
= sagittal stratum;
= traumatic brain injury;
= echo time;
= repetition time;
= ventral anterior thalamic nucleus;
= ventral lateral thalamic nucleus;
= ventral posterior lateral nucleus;
= ventral posterior medial nucleus.
PMCID: PMC2830915  PMID: 20089945
6.  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.
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.
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).
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).
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.
PMCID: PMC3547779  PMID: 23294539
Non-Hodgkin’s Lymphoma; Children; HIV; EBV
7.  Clinicopathological analysis and prognostic factors of 11 patients with primary non-Hodgkin lymphoma of the small intestine in a single institute 
Oncology Letters  2014;8(2):876-880.
The gastrointestinal (GI) tract is the most common extranodal site of involvement in non-Hodgkin lymphoma (NHL). Primary GI NHL is frequently discussed in survival analyses. Primary intestinal NHL is significantly different from primary gastric NHL with regard to its clinical features, pathological subtype, treatment and prognosis. The small intestine is involved in lymphoma less often than the large intestine. The present study aimed to analyze the clinical and pathological characteristics of primary NHL of the small intestine and its prognostic factors. A retrospective analysis was performed on clinical data from 313 cases of NHL that occurred between 1995 and 2008 in the Tri-Service General Hospital (National Defense Medical Center, Taipei, Taiwan). Among these cases, 11 cases of primary NHL of the small intestine were identified. A Cox model was used to perform the multivariate analysis. The Kaplan-Meier method was used for the survival analysis. From the 11 patients with primary NHL of the small intestine, seven patients were male (63.6%) and four patients were female (36.3%). Furthermore, nine patients (81.8%) were diagnosed with B-cell lymphoma, of which five (45.5%) were also diagnosed with diffuse large B-cell lymphoma (DLBL). Abdominal pain and/or distention were present in six (54.5%) of the patients and jejunum involvement was also observed in six (54.5%) of the 11 patients. The mean overall survival (OS) time of the 11 patients was 27.2 months and the four-year survival rate was 36.3%. The mean OS time in the patients with jejunum involvement was shorter than in those without jejunum involvement (16.9 vs. 39.6 months), although this difference was not significant (P=0.657). Surgical treatment was performed on four of the six patients with jejunum involvement due to an acute abdomen or perforation-related peritonitis. The results of the present study indicate that DLBL is the most common subtype of primary lymphoma of the small intestine, and that the site involved in NHL may affect the potential for surgery in patients with intestinal lymphoma. Furthermore, patients with primary lymphoma of the small intestine have been found to have a poor outcome compared with those with lymphoma in other regions of the GI tract. In the present study, a similar trend was observed, however, the sizes of the subgroups of primary lymphoma of the small intestine were too small for individual analysis.
PMCID: PMC4081397  PMID: 25013511
intestine; non-Hodgkin lymphoma; Taiwan
8.  Non-Hodgkin's lymphoma in systemic lupus erythematosus 
Annals of the Rheumatic Diseases  2005;64(10):1507-1509.
Objectives: To describe demographic factors, subtypes, and survival of patients with SLE who develop NHL.
Methods: A multi-site cohort of 9547 subjects with definite SLE was assembled. Subjects at each centre were linked to regional tumour registries to determine cancer cases occurring after SLE diagnosis. For the NHL cases ascertained, descriptive statistics were calculated, and NHL subtype frequency and median survival time of patients determined.
Results: 42 cases of NHL occurred in the patients with SLE during the 76 948 patient-years of observation. The median age of patients at NHL diagnosis was 57 years. Thirty six (86%) of the 42 patients developing NHL were women, reflecting the female predominance of the cohort. In the patients, aggressive histological subtypes appeared to predominate, with the most commonly identified NHL subtype being diffuse large B cell (11 out of 21 cases for which histological subtype was available). Twenty two of the patients had died a median of 1.2 years after lymphoma diagnosis.
Conclusions: These data suggest aggressive disease in patients with SLE who develop NHL. Continuing work should provide further insight into the patterns of presentation, prognosis, and aetiology of NHL in SLE.
PMCID: PMC1755239  PMID: 16162903
9.  HIV-related non-Hodgkin’s lymphoma in Calgary 
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.
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.
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.
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.  Hematological Evaluation of Primary Extra Nodal Versus Nodal NHL: A Study from North India 
Primary extra nodal lymphomas (EN-NHL) are different from primary nodal non-Hodgkin’s lymphoma (N-NHL) and are comparatively less common. Hemogram findings and bone marrow involvement is less studied and very few reports are available in the literature. The present study is a retrospective analysis of bone marrow samples evaluated for staging of non-Hodgkin’s lymphoma. The age, sex distribution, clinical features, and site of presentation, hemogram findings, pattern of bone marrow involvement and grade of reticulin fibrosis was noted. These findings were compared with the type of non-Hodgkin’s lymphoma and prognostic information was determined. A total of 647 cases of NHL, which underwent bone marrow examination for staging, over a seven year period, were retrieved and analyzed for all hematological parameters. Prevalence of EN-NHL was 23.5% (152/647), while nodal NHL comprised 76.5% (495/647) of all NHL cases. 90.1% (137/152) cases of EN-NHL were adult patients, out of which 15.3% (21/137) cases showed bone marrow infiltration as compared to 89% (441/495) adult primary nodal NHL cases, of which 39% (175/441) showed bone marrow infiltration. 9.9% (15/152) cases of EN-NHL were pediatric patients, out of which 40% (6/15) showed bone marrow infiltration, while 10.9% (54/495) of nodal NHL cases were pediatric, of which 20.3% (11/54) showed bone marrow infiltration. Hemogram findings were not found useful in predicting bone marrow infiltration in both nodal as well as EN-NHL. 100% (6/6) of pediatric patients had high grade lymphoma as compared to 48% (9/21) of adult patients, showing bone marrow infiltration in EN-NHL group. Reticulin fibrosis also did not reveal relation with grading of NHL. Prognostically EN-NHL of stomach and central nervous system were found to be better than EN-NHL of other sites, as none of these cases showed bone marrow infiltration. EN-NHL can involve various sites and the prognosis depends upon the sites of disease as well as the type of NHL. Moreover, pediatric EN-NHL cases are likely to have poorer prognosis, due to increased risk of bone marrow involvement as compared to their counterparts having primary nodal NHL. Bone marrow infiltration at times cannot be assessed reliably from hemogram findings only and a bone marrow biopsy for staging is mandatory.
PMCID: PMC3136672  PMID: 22654298
Bone marrow; Extranodal non-Hodgkin’s lymphoma; Hemogram; Reticulin
11.  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.
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.
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.
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.
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
12.  Disease patterns of pediatric non-Hodgkin lymphoma: A study from a developing area in Egypt 
Molecular and Clinical Oncology  2014;3(1):139-144.
Non-Hodgkin lymphoma (NHL) accounts for 8–10% of all childhood cancers. NHL collectively represents various lymphoid malignancies with diverse clinicopathological and biological characteristics. In this study, we aimed to describe the epidemiological and clinicopathological characteristics and treatment outcomes of pediatric NHL patients treated at the Pediatric Oncology Unit of Zagazig University Hospital and the Benha Specialized Pediatric Hospital. We conducted a cross-sectional retrospective study by reviewing the medical records of 142 patients admitted with a diagnosis of NHL over a period of 8 years (February, 2004 to February, 2012) in these two Oncology Units. The age at presentation ranged between 2 and 15 years, with a mean ± standard deviation (SD) of 6.1±2.8 years and a male:female ratio of 1.7:1. Abdominal involvement was the most common presentation (73.2%). Burkitt's lymphoma (BL) was the most common NHL subtype (69%), followed by lymphoblastic lymphoma, diffuse large B-cell lymphoma and anaplastic large-cell lymphoma, accounting for 18.3, 10.6 and 2.1% of the cases, respectively. The majority of the patients (88.7%) had been diagnosed with advanced disease (Murphy stage III/IV). Complete remission was achieved in 120 cases (84.5%). A total of 16 patients (11.3%) succumbed to the disease during the first few months and 6 patients (4.2%) remained alive following relapse. The mean follow-up duration ± SD was 34.6±25.1 months (range, 3–84 months). The 5-year overall survival (OS) and event-free survival (EFS) rates were 88.7 and 85.1%, respectively. None of the clinical, epidemiological or pathological variables exhibited a statistically significant association with the OS or EFS. In conclusion, NHL occurs at a younger age, with a higher incidence of BL and advanced-stage disease. The outcome of NHL in our two centers was satisfactory, approaching the international rates.
PMCID: PMC4251264  PMID: 25469284
pediatrics; non-Hodgkin lymphoma; Egypt; disease patterns
13.  Clinicopathologic Characteristics of T-cell Non-Hodgkin's Lymphoma: A Single Institution Experience 
Although the incidence of T-cell non-Hodgkin's lymphoma (NHL) is higher in Far East Asia than in Western countries, its incidence and clinical course in Korea are not well-defined. Therefore, we assessed the relative frequency and clinical features of T-cell NHL in Korea.
We performed a retrospetcive analysis of 586 patients with NHL.
101 (17.2%) had T-cell NHL. The most frequent subtypes of T-cell NHL were extranodal NK/T-cell lymphoma, nasal type (NASAL), peripheral T-cell lymphoma, unspecified type (PTCL-U), and anaplastic large cell lymphoma, T/null cell, primary systemic type (ALCL). The seven pathological subtypes could be classified into three prognostic subgroups. When patients with the three most frequent subtypes were grouped together, their survival was reflected in the International Prognostic Index (IPI) scores. Univariate analysis of IPI elements and other clinical features showed that clinical stage and extranodal sites were significant predictors of survival. Cox multivariate analysis showed that the number of extranodal sites was the only independent prognostic indicator.
The relative frequency of T-cell NHL seems to be decreasing in Korea, although NASAL remains frequent. Korean patients with ALCL appear to have an unfavorable prognosis. Large-scale studies are warranted for Korean patients with T-cell NHL.
PMCID: PMC2698621  PMID: 19543491
Lymphoma; T-cell; Peripheral
14.  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.
To investigate risk factors for non‐Hodgkin's lymphoma (NHL) and analyse NHL subtypes and characteristics in patients with systemic lupus erythematosus (SLE).
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.
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.
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.
PMCID: PMC2095297  PMID: 17517757
15.  Restricted Diffusion in the Splenium of the Corpus Callosum After Cardiac Arrest  
The value of MRI findings for coma prognostication is a question of great clinical and pathological relevance. We describe MRI evidence of restricted diffusion in the splenium in 5 patients with coma after cardiopulmonary resuscitation following cardiac arrest. The most common clinical presentation of corpus callosum lesions (of any cause) is altered mental status, consistent with the global importance of these extensive inter-hemispheric fibers. In our four cases with bilateral splenium restricted diffusion, none of the patients recovered consciousness. One patient with a unilateral (likely embolic) restricted diffusion lesion had excellent recovery. In contrast to unilateral ischemic callosal lesions, we believe that generalized, midline splenium restricted diffusion occurring after cardiopulmonary arrest represents Wallerian degeneration of interhemispheric neurons rather than direct ischemic damage to the white matter or axons of the callosum and thus will likely portend a poor prognosis.
PMCID: PMC2577938  PMID: 19018311
16.  Epidemiology of non‐Hodgkin lymphomas in Tyrol/Austria from 1991 to 2000 
Journal of Clinical Pathology  2006;59(1):48-55.
To analyse the entity specific incidence and disease specific survival (DSS) of non‐Hodgkin lymphomas (NHLs) in Tyrol/Austria, 1991–2000.
Data from 1307 NHLs (excluding primary cutaneous lymphomas and monoclonal gammopathies of undetermined significance) were obtained. Current status was available for all patients. Except for 29 cases of small lymphocytic (CLL/SLL), lymphoblastic leukaemia (ALL), and myeloma (MM), which were diagnosed cytologically, diagnoses were reclassified on paraffin wax embedded archival material according to new World Health Organisation criteria. Sex specific age adjusted standardised incidence rates were computed using Segi's population weighting. Annual incidence changes were calculated by weighted least square regression analysis. Survival was estimated by the Kaplan–Meier method and compared by log rank test.
NHL more frequently affected men (male/female ratio, 1.52). Mean age of occurrence was 61 and 66 years for men and women, respectively. The incidence rate of 14.3 remained constant. There was a significant increase in diffuse large B cell lymphoma (DLBCL) and decrease in CLL/SLL in men, and a decrease in MM in women. Overall DSS was 64% during the mean follow up (43 months). Age, T‐NHL, λ light chain restriction in MM, and male sex in CLL/SLL were associated with poor prognosis. In B‐NHL, DSS decreased in the following order: hairy cell leukaemia, marginal zone lymphoma, follicular lymphoma, Burkitt lymphoma, ALL, DLBCL, CLL, MM, and mantle cell lymphoma.
The incidence of NHL in Tyrol has changed in the past decade, with a significant increase in DLBCL, decrease in CLL/SLL in men, and decrease in MM in women.
PMCID: PMC1860250  PMID: 16394280
epidemiology; non‐Hodgkin lymphoma; prognosis
17.  White matter alterations differ in primary lateral sclerosis and amyotrophic lateral sclerosis 
Brain  2011;134(9):2642-2655.
Primary lateral sclerosis is a sporadic disorder characterized by slowly progressive corticospinal dysfunction. Primary lateral sclerosis differs from amyotrophic lateral sclerosis by its lack of lower motor neuron signs and long survival. Few pathological studies have been carried out on patients with primary lateral sclerosis, and the relationship between primary lateral sclerosis and amyotrophic lateral sclerosis remains uncertain. To detect in vivo structural differences between the two disorders, diffusion tensor imaging of white matter tracts was carried out in 19 patients with primary lateral sclerosis, 18 patients with amyotrophic lateral sclerosis and 19 age-matched controls. Fibre tracking was used to reconstruct the intracranial portion of the corticospinal tract and three regions of the corpus callosum: the genu, splenium and callosal fibres connecting the motor cortices. Both patient groups had reduced fractional anisotropy, a measure associated with axonal organization, and increased mean diffusivity of the reconstructed corticospinal and callosal motor fibres compared with controls, without changes in the genu or splenium. Voxelwise comparison of the whole brain white matter using tract-based spatial statistics confirmed the differences between patients and controls in the diffusion properties of the corticospinal tracts and motor fibres of the callosum. This analysis further revealed differences in the regional distribution of white matter alterations between the patient groups. In patients with amyotrophic lateral sclerosis, the greatest reduction in fractional anisotropy occurred in the distal portions of the intracranial corticospinal tract, consistent with a distal axonal degeneration. In patients with primary lateral sclerosis, the greatest loss of fractional anisotropy and mean diffusivity occurred in the subcortical white matter underlying the motor cortex, with reduced volume, suggesting tissue loss. Clinical measures of upper motor neuron dysfunction correlated with reductions in fractional anisotropy in the corticospinal tract in patients with amyotrophic lateral sclerosis and increased mean diffusivity and volume loss of the corticospinal tract in patients with primary lateral sclerosis. Changes in the diffusion properties of the motor fibres of the corpus callosum were strongly correlated with changes in corticospinal fibres in patients, but not in controls. These findings indicate that degeneration is not selective for corticospinal neurons, but affects callosal neurons within the motor cortex in motor neuron disorders.
PMCID: PMC3170531  PMID: 21798965
diffusion tensor imaging; diffusion tensor tractography; motor neuron disorders; primary lateral sclerosis; corpus callosum
18.  Body Mass Index and Non-Hodgkin's Lymphoma Survival in an Ethnically Diverse Population: The Multiethnic Cohort Study 
Obesity increases the risk of death from several malignancies including breast and colon cancer. However, for non-Hodgkin's lymphoma (NHL), the association between pre-diagnostic body mass index (BMI) and survival is unclear. We examined the association between pre-diagnostic BMI overall and NHL-specific survival in the Multiethnic Cohort (MEC) study of African Americans, Native Hawaiians, Japanese Americans, Latinos, and Caucasians.
MEC participants free of NHL at cohort entry and diagnosed with NHL during follow-up were included in the analyses (N=1348). Body mass index (BMI) was based on self-reported weight and height at cohort entry. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for pre-diagnostic BMI categories in relation to all-cause and NHL-specific mortality while adjusting for known confounders.
The mean time from cohort entry to NHL diagnosis was 7.2±3.9 years (range: 0.0–15.0 years). The mean age at NHL diagnosis was 70.6 (range 45–89) years and the mean BMI at cohort entry was 26.5±4.7 kg/m2. After a mean follow-up of 4.3±3.5 years, 679 deaths including 457 NHL-specific deaths occurred. In multivariable models, obese patients (BMI ≥ 30.0) had higher all-cause (HR = 1.55, 95%CI = 1.21 −2.00) and NHL-specific (HR = 1.84, 95%CI = 1.35 – 2.52) mortality compared to patients with high-normal BMI (22.5–24.9 kg/m2). For overweight patients (BMI 25.0 – 29.9), the respective HRs were 1.29 (95%CI = 1.05 – 1.58) and 1.47 (95%CI = 1.14 – 1.89). Stratification by NHL type suggested higher NHL-specific mortality risk for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) than for diffuse large B-cell lymphoma (DLBCL).
Pre-diagnostic obesity may be related to poorer overall and NHL-specific survival in NHL patients. Therefore, pre-diagnostic BMI may be a suitable prognostic marker for NHL patients.
PMCID: PMC4175946
19.  Common Gene Variants in the Tumor Necrosis Factor (TNF) and TNF Receptor Superfamilies and NF-kB Transcription Factors and Non-Hodgkin Lymphoma Risk 
PLoS ONE  2009;4(4):e5360.
A promoter polymorphism in the pro-inflammatory cytokine tumor necrosis factor (TNF) (TNF G-308A) is associated with increased non-Hodgkin lymphoma (NHL) risk. The protein product, TNF-α, activates the nuclear factor kappa beta (NF-κB) transcription factor, and is critical for inflammatory and apoptotic responses in cancer progression. We hypothesized that the TNF and NF-κB pathways are important for NHL and that gene variations across the pathways may alter NHL risk.
Methodology/Principal Findings
We genotyped 500 tag single nucleotide polymorphisms (SNPs) from 48 candidate gene regions (defined as 20 kb 5′, 10 kb 3′) in the TNF and TNF receptor superfamilies and the NF-κB and related transcription factors, in 1946 NHL cases and 1808 controls pooled from three independent population-based case-control studies. We obtaineded a gene region-level summary of association by computing the minimum p-value (“minP test”). We used logistic regression to compute odds ratios and 95% confidence intervals for NHL and four major NHL subtypes in relation to SNP genotypes and haplotypes. For NHL, the tail strength statistic supported an overall relationship between the TNF/NF-κB pathway and NHL (p = 0.02). We confirmed the association between TNF/LTA on chromosome 6p21.3 with NHL and found the LTA rs2844484 SNP most significantly and specifically associated with the major subtype, diffuse large B-cell lymphoma (DLBCL) (p-trend = 0.001). We also implicated for the first time, variants in NFKBIL1 on chromosome 6p21.3, associated with NHL. Other gene regions identified as statistically significantly associated with NHL included FAS, IRF4, TNFSF13B, TANK, TNFSF7 and TNFRSF13C. Accordingly, the single most significant SNPs associated with NHL were FAS rs4934436 (p-trend = 0.0024), IRF4 rs12211228 (p-trend = 0.0026), TNFSF13B rs2582869 (p-trend = 0.0055), TANK rs1921310 (p-trend = 0.0025), TNFSF7 rs16994592 (p-trend = 0.0024), and TNFRSF13C rs6002551 (p-trend = 0.0074). All associations were consistent in each study with no apparent specificity for NHL subtype.
Our results provide consistent evidence that variation in the TNF superfamily of genes and specifically within chromosome 6p21.3 impacts lymphomagenesis. Further characterization of these susceptibility loci and identification of functional variants are warranted.
PMCID: PMC2669130  PMID: 19390683
20.  Rituximab In Indolent Lymphomas 
Seminars in hematology  2010;47(2):133-142.
Indolent Non Hodgkin's lymphoma (NHL) comprises a group of incurable, generally slow growing lymphomas highly responsive to initial therapy with a relapsing and progressive course. Rituximab, an anti CD-20 antibody, has had a large impact on treatment of indolent NHL. Its effectiveness as a single agent and in conjunction with known chemotherapy regimens has made it a standard of care in the treatment of NHL. Analysis of data obtained from NHL clinical trials as well as data from the National Cancer Institute indicates that the overall survival of indolent NHL has improved since the discovery of rituximab. Given its effectiveness and tolerability, it is currently being investigated as a maintenance agent with encouraging results. This review summarizes several landmark trials utilizing rituximab as a single agent and in combination with chemotherapy for treatment of NHL. In addition, a review of the studied rituximab maintenance dosing schedules and its impact on NHL will also be presented. Overall, rituximab has changed the landscape for treatment of indolent NHL however additional research is necessary to identify the optimal dosing schedule as well as patients most likely to respond to prolonged rituximab therapy.
PMCID: PMC2848176  PMID: 20350660
21.  Quantitative fiber tracking of lateral and interhemispheric white matter systems in normal aging 
Neurobiology of aging  2008;31(3):464.
The integrity of white matter, as measured in vivo with diffusion tensor imaging (DTI), is disrupted in normal aging. A current consensus is that in adults advancing age affects anterior brain regions disproportionately more than posterior regions; however, the mainstay of studies supporting this anterior-posterior gradient is based primarily on measures of the corpus callosum. Using our quantitative fiber tracking approach, we assessed fiber tract integrity of samples of major white matter cortical, subcortical, interhemispheric, and cerebellar systems (11 bilateral and 2 callosal) on DTI data collected at 1.5 T magnet strength. Participants were 55 men (age 20-78 years) and 65 women (age 28-81 years), deemed healthy and cognitively intact following interview and behavioral testing. Fiber integrity was measured as orientational diffusion coherence (fractional anisotropy, FA) and magnitude of diffusion, which was quantified separately for longitudinal diffusivity (λL), an index of axonal length or number, and transverse diffusivity (λT), an index of myelin integrity. Aging effects were more evident in diffusivity than FA measures. Men and women, examined separately, showed similar age-related increases in longitudinal and transverse diffusivity in fibers of the internal and external capsules bilaterally and the fornix. FA was lower and diffusivity higher in anterior than posterior fibers of regional paired comparisons (genu versus splenium and frontal versus occipital forceps). Diffusivity with older age was generally greater or FA lower in the superior than inferior fiber systems (longitudinal fasciculi, cingulate bundles), with little to no evidence for age-related degradation in pontine or cerebellar systems. The most striking sex difference emerged for the corpus callosum, for which men showed significant decline in FA and increase in longitudinal and transverse diffusivity in the genu but not splenium. By contrast, in women the age effect was present in both callosal regions, albeit modestly more so in the genu than splenium. Functional meaningfulness of these age-related differences was supported by significant correlations between DTI signs of white matter degradation and poorer performance on cognitive or motor tests. This survey of multiple fiber systems throughout the brain revealed a differential pattern of age’s effect on regional FA and diffusivity and suggests mechanisms of functional degradation, attributed at least in part to compromised fiber microstructure affecting myelin and axonal morphology.
PMCID: PMC2815144  PMID: 18495300
Brain; Aging; DTI; White matter; Fiber tracking; Diffusion
22.  Serum Adiponectin As a Predictor of Childhood Non-Hodgkin's Lymphoma: A Nationwide Case-Control Study 
Journal of Clinical Oncology  2009;27(30):5049-5055.
To our knowledge, this is the first study exploring the association of childhood non-Hodgkin's lymphoma (NHL) with serum adiponectin and leptin levels in a nationwide case-control series. In addition, expression of adiponectin receptors in NHL specimens was assessed, and the association between adipokines and childhood NHL survival and prognosis was examined.
Patients and Methods
We studied 121 incident childhood (0 to 14 years) NHL cases registered in the Nationwide Registry for Childhood Hematological Malignancies (1996 to 2006) and an equal number of matched controls, for whom sociodemographic, lifestyle, prenatal characteristics, and fasting blood serums were collected. Serum adiponectin and leptin levels were determined. Immunohistochemisty for adiponectin receptors expression was performed on commercially available adult NHL specimens (n = 30) and in a subset of childhood NHL cases (n = 6) that were available. Summary statistics, multiple conditional logistic regression analyses, and survival analysis were performed.
Higher serum adiponectin, but not leptin, levels were independently associated with childhood NHL (odds ratio, 1.82; 95% CI, 1.30 to 2.56), after adjusting for obesity and established risk factors. Higher adiponectin levels at diagnosis were positively associated with relapse and poor survival, but hormone levels did not differ among NHL subtypes. Adiponectin receptors 1 and 2 were present in 90% and 57% of adult samples and in 83% and 100% of childhood NHL samples, respectively.
Elevated serum adiponectin, but not leptin, levels are independently associated with childhood NHL and poor prognosis. Adiponectin receptors are expressed in NHL, suggesting that adiponectin may represent not only a potential clinically significant diagnostic and prognostic marker but also a molecule that may be implicated in NHL pathogenesis.
PMCID: PMC2799057  PMID: 19738128
23.  Primary oral non-Hodgkin's lymphoma – A clinicopathologic study with immunohistochemical analysis 
Non-Hodgkin's lymphoma (NHL) is a group of highly diverse malignancies whose prognosis depends on the histologic type and associated factors like HIV positivity.
The aim of this study was to evaluate eight cases of NHL for their histologic type and HIV positivity, since both are major prognostic factors for NHL.
Settings and Design:
Eight cases of primary NHL of the oral cavity were evaluated for age, sex, clinical presentation, and the histologic type, along with immunohistochemistry. These cases were also evaluated for HIV positivity.
Materials and Methods:
NHL cases which were diagnosed through the dental OPD and subsequent biopsy procedure were chosen. The patient data, including age, sex, location, clinical presentation, radiographic presentation, metastasis, and histologic subtype, according to the World Health Organization (WHO) classification were tabulated. Immunohistochemical markers were used to confirm the cell type. CD20 and CD3 were used for B cell and T cell, respectively. Subsequent western blot analysis was carried out for HIV detection.
75% of the NHL was of B-cell type; of this, 83% was found to be diffuse large B-cell lymphoma, which is an aggressive variant. 62.5% of cases were found to be HIV positive.
This study emphasizes the need for HIV investigation in NHL cases and the need to determine the histologic type, both of which significantly affect the treatment outcome and prognosis.
PMCID: PMC4247555  PMID: 25452932
HIV; non-Hodgkin's lymphoma; oral cavity
24.  Functional Neuroimaging to Characterize Visual System Development in Children with Retinoblastoma 
Functional MRI and diffusion tensor imaging in children being treated for retinoblastoma showed that patterns of visual activation and diffusion parameters in associated white matter pathways reflected neural changes caused by disease and treatment.
To use functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to investigate visual system development in children being treated for retinoblastoma.
Informed consent was obtained for all participants (N = 42) in this institutional review board–approved study. Participants were imaged with a 1.5-T scanner while under propofol sedation. Diagnostic brain and orbital imaging was followed by investigational functional neuroimaging, which included fMRI during photic stimulation through closed eyelids, to measure functional activation in the visual cortex, and DTI, to evaluate diffusion parameters of white matter tracts in the corpus callosum and the periventricular optic radiations. Analysis included 115 examinations of 39 patients with a median age of 16.4 months and age range from 1.5 to 101.5 months at first evaluation.
The blood oxygen level–dependent signal was predominantly negative and located in the anterior visual cortex. Activation was affected by tumor lateralization (unilateral or bilateral), macular involvement, and retinal detachment. Patients who had undergone unilateral enucleation showed cortical dominance corresponding to the projection from the nasal hemiretina in the unaffected eye. Diffusion parameters followed a normal developmental trajectory in the optic radiations and corpus callosum, but variability was greater in the splenium than in the genu of the corpus callosum.
Longitudinal functional neuroimaging demonstrated important effects of disease and treatment. Therefore, fMRI and DTI may be useful for characterizing the impact of retinoblastoma on the developing visual system and improving the prediction of visual outcome in survivors.
PMCID: PMC3088553  PMID: 21245407
25.  Survival Patterns Among Lymphoma Patients With a Family History of Lymphoma 
Journal of Clinical Oncology  2008;26(30):4958-4965.
Genetic factors are important in the etiology and pathogenesis of chronic lymphocytic leukemia (CLL), Hodgkin's lymphoma (HL), and non-Hodgkin's lymphoma (NHL). Only a few small studies have assessed clinical characteristics and prognosis for familial patients, with inconsistent findings.
Using population-based registries from Sweden and Denmark, 7,749 patients with CLL, 7,476 patients with HL, and 25,801 patients with NHL with linkable first-degree relatives were identified. Kaplan-Meier curves were constructed to compare survival in patients with lymphoma with and without a family history of lymphoma. The risk of dying was assessed using adjusted Cox proportional hazard models.
We found 85 patients with CLL (1.10%), 95 patients with HL (1.28%), and 206 patients with NHL (0.80%) with a family history of any lymphoma. Five-year mortality was similar for patients with CLL (hazard ratio [HR], 1.28; 95% CI, 0.95 to 1.72), HL (HR, 0.78; 95% CI, 0.49 to 1.25), and NHL (HR, 0.91; 95% CI, 0.74 to 1.12) versus without a family history of any lymphoma. Mortality was also similar for patients with versus without a family history of the same lymphoma. T-cell/anaplastic lymphoma patients with a family history of NHL had poorer outcome 5-years after diagnosis (HR, 5.38; 95% CI, 1.65 to 17.52). Results were similar for 10 years of follow-up.
With the exception of T-cell/anaplastic lymphoma, survival patterns for patients with CLL, HL, and NHL with a family history of lymphoma were similar to those for sporadic patients, suggesting that most familial lymphomas do not have an altered clinical course. Our findings provide no evidence to modify therapeutic strategies for patients with CLL, HL, or NHL based solely on family history.
PMCID: PMC2652080  PMID: 18606984

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