T- and B-lymphocytes are involved in recognition of foreign antigen by the specificity of their surface T-cell receptor and immunoglobulin, generated by gene rearrangement. Each T- and B-lymphocyte carries unique rearranged TCR or immunoglobulin gene, which has been applied to detect clonal from non-clonal T- and B-cell proliferation.
The association between pure red cell aplasia (PRCA) and autoimmune haemolytic anaemia (AIHA) has rarely been reported. PRCA represents an isolated process, characterized by normochromic, normocytic anaemia, reticulocytopenia and erythroid hypoplasia in the bone marrow, and may be attributable to infection with Parvo virus B19. AIHA is a condition in which peripheral red blood cell destruction is induced by the presence of autoantibodies. However, the co-existence of these conditions is very rare, since only few cases of PRCA and AIHA associated with malignant lymphoma (ML) were reported. A case of PRCA and AIHA was detected and described, for the first time in Malaysia, in a 10-year-old child suffering from non-Hodgkin lymphoma from the Department of Haematology, Universiti Sains Malaysia. Following the induction course of chemotherapy, the patient turned anaemic, with tendency for red cell clumping, reticulocytopenia and anisocytosis. AIHA was suspected in spite of the weak Coomb reaction obtained. The bone marrow aspirate revealed the presence of giant pronormoblasts, suggesting PRCA. Serological tests for Parvo virus and other viruses were negative.
Magnetic resonance imaging is gaining importance in the diagnosis of nerve and muscular disorders. The ability of magnetic resonance imaging to delineate the different muscles and the nerve in any plane has made the differentiation between the changes of neuropathy, denervation, and nerve entrapment possible. Although findings on magnetic resonance imaging are non-specific, their use, coupled with clinical symptoms and electromyographic findings, allow an accurate diagnosis to be made without resorting to invasive biopsies.
BACKGROUND: Non-Hodgkin's lymphoma has increased in incidence in many countries, particularly in the West. Advances in diagnostic methods and the understanding of the disease over time pose a challenge to the interpretation of these trends. The aim of this study was to determine if the disease has increased in Singapore, a newly industrialized Asian country, and to examine the possible factors that may account for any observed changes.
METHODS: Data from the population-based Singapore Cancer Registry for the period 1968 to 1992 were reviewed to determine time trends based on sex and ethnic group. The Poisson regression model was fitted to the cross-tabulated data to obtain the adjusted incidence density ratios.
RESULTS: A total of 1988 cases of non-Hodgkin's lymphoma were included in the analysis. There was an overall increase in incidence among both Chinese and Malaysians. However, the rate of increase was greater in females (age-standardized rate from 1.8 per 100,000 in 1968-1972 to 4.5 per 100,000 in 1988-1992) than in males (3.2 per 100,000 to 5.9 per 100,000 in the same time periods). Between ethnic groups, Malay females were at higher overall risk compared with their Chinese counterparts (incidence density ratio 1.32; 95% confidence interval, 1.08-1.61). Although a substantial proportion of patients diagnosed with Hodgkin's disease between 1968 and 1972 were reclassified on review, using present criteria, as having non-Hodgkin's lymphoma, it is unlikely that this, and other recent changes in histologic interpretation, could have accounted for an increase of this magnitude.
CONCLUSIONS: Non-Hodgkin's lymphoma has increased in incidence among the Chinese and Malay populations in Singapore. The pattern of increase differs from that of the common cancer sites, and suggests the need to look for environmental and genetic factors that have not yet been elucidated.
We evaluated the association of two IL10 single nucleotide polymorphisms (SNPs) (rs1800896 and rs1800871) with non-Hodgkin lymphoma (NHL) risk in the three major races of the Malaysian population (Malay, Chinese and Indian; 317 cases and 330 controls). Our initial screening demonstrated that rs1800871 but not rs1800896 was significantly associated with increased NHL risk in Malays (pMalay-Rec = 0.007) and Chinese only (pChinese-Rec = 0.039). Subsequent combined analysis of the Malay and Chinese revealed significant association of rs1800871 with all (ALL) NHL subtypes (pMeta-ALL-NHL-Rec = 0.001), ALL B-cell subtypes (pMeta-ALL-B-cell-Rec = 0.003), diffuse large B-cell lymphoma (DLBCL) subtype (pMeta-DLBCL-Rec = 0.002) and ALL T-cell subtypes (pMeta-ALL-T-cell-Rec = 0.031). SNP rs1800896 showed increased risk only in follicular lymphoma (FL) (pMeta-FL-Dom = 0.0004). We also detected a male-specific association of rs1800871 with increased NHL risk (pMeta-Male-ALL-NHL-Rec = 0.006) in the combined analysis. To our knowledge, this is the first report on the association of IL10 promoter SNPs with NHL susceptibility in the three major races of Malaysia.
Large consortia efforts and genome-wide association studies (GWASs) have linked a number of genetic variants within the 6p21 chromosomal region to non-Hodgkin lymphoma (NHL). Complementing these efforts, we genotyped previously reported SNPs in the human leukocyte antigen (HLA) class I (rs6457327) and class II (rs9271100, rs2647012 and rs10484561) regions in a total of 1,145 subjects (567 NHL cases and 578 healthy controls) from two major ethnic groups in Malaysia, the Malays and the Chinese. We identified a NHL-associated (PNHL_add = 0.0008; ORNHL_add = 0.54; 95% CI = 0.37-0.77) and B-cell associated (PBcell_add = 0.0007; ORBcell_add = 0.51; 95% CI = 0.35-0.76) SNP rs2647012 in the Malaysian Malays. In silico cis-eQTL analysis of rs2647012 suggests potential regulatory function of nearby HLA class II molecules. Minor allele rs2647012-T is linked to higher expression of HLA-DQB1, rendering a protective effect to NHL risk. Our findings suggest that the HLA class II region plays an important role in NHL etiology.
Epstein-Barr virus (EBV) type B, a less potent transformer of B lymphocytes than type A, has rarely been detected in EBV-associated neoplasms except in AIDS-related lymphomas, in which about 50% of the cases contained this sub-type. In this study we analyzed the association of EBV and the distribution of virus sub-types in Asian non-Hodgkin's lymphoma (NHL) of the upper aerodigestive tract. We studied archival material of 29 NHL cases from Malaysia. B- and T-cell associated antigens were demonstrated by immunohistochemistry, and EBV early RNA EBER-1 was demonstrated using the RNA in situ hybridization technique. EBV was detected in the majority of tumour cells in 11/13 T-NHL but in only 1/16 B-NHL. EBV was sub-typed by single-step polymerase chain reaction of the EBNA-2 gene. This was successful in 9/10 cases of EBER-1-positive tumours and all contained type-A virus only. Our results showed a preponderance of T-cell lymphoma of the upper aerodigestive tract in the ethnic Chinese group of Malaysian patients, and EBV was strongly associated with T-NHL but not with B-NHL. Our results suggest that type-A EBV is the prevalent sub-type in Asian NHL of the upper aerodigestive tract, similarly to findings in Asian nasopharyngeal carcinoma.
Pharmacogenetics of methotrexate (MTX) contributes to interindividual differences in toxicity. We aimed to evaluate the impact of SNPs within the MTX pathway genes on MTX-induced toxicity and MTX plasma levels at 48 h following treatment in Asian adults with acute lymphoblastic leukemia or non-Hodgkin lymphoma.
Introduction:A unilateral enlarged tonsil always is a suspicion of carcinoma. Especially if it is with fungating ulcer-ative surface. Neoplasms in unilaterally enlarged tonsil include squamous cell carcinomas and lymphomas. Lym-phomas in oropharynx are not common specially with fungating surface. Usually lymphomas in these areas are Non-Hodgkin’s type. Case description: A 62-year-old woman was admitted in the tertiary level hospital of Kota Kinabalu, Sabah, with the complaint of sore throat, odynophagia and right neck swelling. She was treated as a case of acute tonsillitis by general practitioner without any noticeable improvement. Oral cavity examination revealed a hugely enlarged right tonsil with fungating ulcerative surface and almost obstructing the oropharynx. Trismus was seen which make the examination difficult. A non-tender right upper neck swelling was palpable. All baseline lab-oratory investigations were normal. A contrast-enhanced computed tomography (CECT) showed a heterogeneously enhancing mass at oropharynx compromising the airway, right supraclavicular lymphadenopathy. Histology of biop-sy from right tonsillar mass showed High grade B-cell lymphoma. Chemotherapy was planned. First cycle of chemo-therapy was administered, Patient was discharged home with the complete plan of chemotherapy. Conclusion: This patient was clinically suspicious of carcinoma of palatine tonsil. But later proven as high grade B-cell lymphoma. All unilateral enlarged tonsils are not always carcinoma.
Mantle cell lymphoma (MCL) is a rare, aggressive subtype of non-Hodgkin lymphoma with a poor prognosis and high recurrence rate. It seldom affects the Waldeyer's ring let alone the nasopharynx. Patients usually present at late stages of the disease leading to poor failure-free and overall survival rates. Intensive chemotherapy regimes and autologous stem cell transplantation have reported increased survival rates. We report a relapsed case of nasopharyngeal MCL, which previously occurred in the gastrointestinal tract. The patient had undergone a hemicolectomy for colon intussusception secondary to the intraluminal lymphoma mass. He was unable to complete the treatment regime for MCL due to the adverse side effects. Oropharyngeal mass was discovered during routine outpatient follow-up, which was confirmed as nasopharyngeal MCL. We discuss the prognosis, disease progression, and possible treatments.
Ocular inflammation from various causes may have similar clinical presentation thus careful clinical evaluations are mandatory particularly when the disease appear to be resistant to treatment. This paper reports a case of ocular lymphoma which was initially treated as Vogt Koyanagi Harada disease at a different centre. A 65-year-old Sudanese man complained of gradual worsening left eye vision. Careful ocular and slit lamp examination revealed a conjunctival lesion with choroidal infiltration as well as exudative retinal detachment. Computed tomography scan (CT scan) showed left eye axial proptosis, and a homogenous enhancing mass at the posterior coat of the globe. Tissue biopsy of the conjunctival lesion revealed marginal Zone B cell (MALT type), low grade, non-Hodgkin’s lymphoma. AS the ocular signs and symptoms progressed, chemotherapy was initiated. The proptosis, exudative retinal detachment, disc hyperemia and swelling improved after chemotherapy. The post treatment CT scan showed reduction of the posterior ocular coat mass. The possibility of malignant lymphoma should be considered in patients with resistant uveitis despite administration of corticosteroid. Ocular lymphoma is an indolent tumour with good prognosis. Careful ocular examination, adequate imaging studies followed by early surgical biopsy will contribute to early diagnosis.
Objective: To determine the prevalence of major depressive disorder (MDD) in hematological cancer patients and to investigate MDD with quality of life. Methods: The research, which uses a cross sectional design, has been carried out at Ampang Hospital, Kuala Lumpur. The hospital is a tertiary referral center for cancer cases that include non-Hodgkin lymphoma, acute myelogenous leukemia, acute lymphoblastic leukemia, Hodgkin lymphoma and other hematological cancers. In total, 105 patients with hematological malignancies were included in the study. This study employed the MINI International Neuropsychiatric Interview for diagnosis of MDD, the Patient Health Questionnaire (PHQ-9) for symptom severity of depression and the European Organisation for Research and Treatment of Cancer Quality Of Life questionnaire (EORTC QLQ-C30) to assess the quality of life of the respondents. Result: The response rate was 83.3%. The prevalence of MDD was 24.8% (n=26) with the majority of cases classified as moderately severe depression (38.5%). About 92.3% (n=24) of depressed hematological cancer patients were diagnosed with a current episode of MDD. The depressed patients also had significantly reduced quality of life in physical, role, emotional, cognitive and social domains (p
Neurolymphomatosis is an atypical complication of non-Hodgkin lymphoma and leukaemia involving infiltration of neurotropic neoplastic cells in the central or peripheral nervous system. A 28-year-old Malay lady with background diffuse large B-cell lymphoma stage IV presented with left homonymous hemianopia associated with cognitive function deterioration. Her best corrected visual acuity was 6/9 in both eyes. Magnetic resonance imaging (MRI) of the brain showed a lesion suggestive of secondary lymphomatous infiltration of the splenium of corpus callosum. The patient underwent chemotherapy, after which repeated MRI showed a reduction in the lesion size. Homonymous hemianopia is a rare presentation of secondary central nervous system neurolymphomatosis. A comprehensive history, physical examination, and radiological imaging are essential to establish the diagnosis in patients presenting with visual field defects.
Introduction: p16 gene plays an important role in the normal cell cycle regulation. Methylation of p16 has been reported to be one of the epigenetic events contributing to the pathogenesis of diffuse large B-cell lymphoma (DLBCL) which occurring at varying frequency. DLBCL is an aggressive and high-grade malignancy which accounts for approximately 30% of all non-Hodgkin lymphoma cases. However, little is known regarding the epigenetic alterations of p16 gene in DLBCL cases in Malaysia. Therefore, the objective of this study was to examine the status of p16 methylation in DLBCL. Methods: A total of 88 formalin-fixed paraffin-embedded DLBCL tissues retrieved from two hospitals located in the east coast of Malaysia, namely Hospital Tengku Ampuan Afzan (HTAA) Pahang and Hospital Universiti Sains Malaysia (HUSM) Kelantan, were chosen for this study. DNA specimens were isolated and subsequently subjected to bisulfite treatment prior to methylation specific-PCR. Two pairs of primers were used to amplify methylated and unmethylated regions of p16 gene. The PCR products were then separated using agarose gel electrophoresis and visualised under UV illumination. SPSS version 12.0 was utilised to perform all statistical analysis. Result: p16 methylation was detected in 65 of 88 (74%) samples. There was a significant association between p16 methylation status and patients aged >50 years old (p=0.04). Conclusion: Our study demonstrated that methylation of p16 tumor suppressor gene in our DLBCL cases is common and significantly increased among patients aged 50 years and above. Aging is known to be an important risk factor in the development of cancers and we speculate that this might be due to the increased transformation of malignant cells in aging cell population. However, this has yet to be confirmed with further research and correlate the findings with clinicopathological parameters.
Patients with advanced aggressive B-cell non-Hodgkin lymphomas (NHL) are usually treated with rituximab in combination with chemotherapy. However, disease relapse rates are high. Radiotherapy (RT) has been shown to be efficacious in treating early-stage NHL but its role in advanced stage diseases is unclear. We performed a systematic review of randomized controlled trials (RCTs) comparing chemotherapy with RT to chemotherapy alone in patients with newly diagnosed advanced aggressive NHL. We searched online databases and pooled similar outcome estimates. For time-to-event outcomes, we estimated hazard ratios (HR) for overall survival (OS) and event-free survival (EFS) using the fixed-effect model. Two RCTs involving 254 patients met inclusion criteria. The trials were single-centre RCTs with follow-up period of five and ten years. Both trials were conducted in the pre-rituximab era. Patients treated with consolidation RT had better OS (HR for mortality 0.61; 95 % CI 0.38 to 0.97) and EFS (HR for mortality 0.67; 95 % CI 0.46 to 0.98) compared to those who received no RT. There was an apparent benefit of RT on local control (OR 0.09; 95 % CI 0.04 to 0.20); although this was estimated as a dichotomous rather than time-to-event outcome. Limited evidence shows benefits of consolidation RT in advanced aggressive NHL. However, we were not able to estimate the effect size with confidence due to small number of trials and sample size. We cannot recommend routine consolidation RT in advanced aggressive NHL. More RCTs with the inclusion of rituximab and PET-CT monitoring are needed.