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Displaying publications 41 - 49 of 49 in total

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Fulltext Challenging lymphoid malignancy of primary central nervous system lymphoma: A case report

Kasinathan G, Kori AN, Hassan N

Ann Med Surg (Lond), 2020 Sep;57:307-310.
PMID: 32874561 DOI: 10.1016/j.amsu.2020.08.011

Introduction: Primary central nervous lymphoma is an aggressive disease without evidence of systemic spread with an annual incidence of 7 cases per 1,000,000 people in the United States.
Case presentation: A 68-year-old gentleman of Malay ethnicity presented with left sided weakness associated with reduced sensation for one month. The patient was healthy and denied any constitutional symptoms, joint pains, rash or seizures. There was no recent trauma. Physical examination revealed left upper and lower limb motor grade power of 3/5 with upper motor neurone weakness of the left facial nerve. He had brisk reflexes and an upgoing extensor plantar response. Brain imaging (Magnetic Resonance Imaging) showed two lesions: one occupying the right head of the caudate nucleus and the other seen at the right side of the body of the corpus callosum. Histomorphology and immunohistochemistry confirmed Diffuse Large B-Cell Lymphoma (DLBCL) of non-germinal center type. He was treated with De Angelis protocol which involves chemoradiotherapy consisting of high dose methotrexate and whole brain radiotherapy (WBRT), followed by high dose cytarabine. Brain imaging post chemoradiation showed complete remission.
Conclusion: Prompt detection with appropriate therapeutic protocol could significantly minimise the permanent neurological deficits in patients with this rare and challenging lymphoid malignancy.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse
Classifying DLBCL according cell of origin using Hans algorithm and its association with clinicopathological parameters: A single centre experience

Wn Najmiyah WAW, Azlan H, Faezahtul AH

Med J Malaysia, 2020 03;75(2):98-102.
PMID: 32281588

INTRODUCTION: In recent years, "double hit" and "double protein" involving gene rearrangement and protein expression of c-MYC and BCL2 and/or BCL6 are the most used terms to describe poor prognostic factors in diffuse large B-cell lymphoma (DLBCL). This study was to determine the frequency of double or triple protein expression by using immunohistochemistry (IHC) and comparing the result with clinicopathological features and cell of origin (COO) classification.
METHODS: We conducted a cross-sectional study by using 29 archived formalin-fixed paraffin embedded tissue blocks of DLBCL. All the samples were evaluated for the subgrouping of COO DLBCL was determined by expression of CD10, BCL6 and MUM1 based on Hans classification. In addition, expressions of c-MYC, BCL2 and BCL6 were detected by IHC.
RESULTS: Among the 29 cases, MYC, BCL2 and BCL6 proteins were detected in 72.4%, 62.1% and 62.1% of patients, respectively. Concurrent expression (c-MYC positive/BCL2 positive and/or BCL6 positive) was present in 58.6% of patients. 34.5% were categorised as germinal centre like (GCB) subgroup and 65.5% were categorised as nongerminal centre like (non-GCB) subgroup. Among the clinicopathological features, the double/triple protein expression lymphoma was significantly associated with elevated LDH level (p=0.018), IPI score (p=0.003), Ann Arbor stage (p=0.011) and complete response rate (p=0.011).
CONCLUSION: Double/triple protein lymphoma was strongly associated more adverse clinical risk factors. Thus, analyses of MYC, BCL2 and BCL6 expression by IHC represents a rapid and inexpensive approach to risk-stratify patients with DLBCL at diagnosis.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse
Microangiopathic haemolytic anaemia and thrombocytopenia due to combined vitamin B12 and folate deficiency masquerading as thrombotic thrombocytopenic purpura

Lee KT, Teoh CS, Chew TK, Goh AS

J R Coll Physicians Edinb, 2020 Jun;50(2):144-147.
PMID: 32568285 DOI: 10.4997/JRCPE.2020.213

Vitamin B12 deficiency and folate deficiency are common causes of macrocytic anaemia and both are important for many cellular processes. These deficiencies could be due to inadequate dietary intake, impaired absorption or drug ingestion. We present a case of a 47-year-old male with a history of diffuse large B-cell lymphoma (DLBCL) who was admitted for fatigue, persistent frontal headache and left upper-quadrant abdominal pain. Further investigation showed that he had pancytopenia with microangiopathic haemolytic anaemia (MAHA) and intracranial bleeding (ICB). Serum vitamin B12 and folate were later found to be low and a diagnosis of combined vitamin B12 and folate deficiency mimicking thrombotic thrombocytopenic purpura (TTP) was made. The patient responded well to vitamin B12 and folate replacement.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse
DNMT1 is associated with cell cycle and DNA replication gene sets in diffuse large B-cell lymphoma

Loo SK, Ab Hamid SS, Musa M, Wong KK

Pathol Res Pract, 2018 Jan;214(1):134-143.
PMID: 29137822 DOI: 10.1016/j.prp.2017.10.005

Dysregulation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) is associated with the pathogenesis of various types of cancer. It has been previously shown that DNMT1 is frequently expressed in diffuse large B-cell lymphoma (DLBCL), however its functions remain to be elucidated in the disease. In this study, we gene expression profiled (GEP) shRNA targeting DNMT1(shDNMT1)-treated germinal center B-cell-like DLBCL (GCB-DLBCL)-derived cell line (i.e. HT) compared with non-silencing shRNA (control shRNA)-treated HT cells. Independent gene set enrichment analysis (GSEA) performed using GEPs of shRNA-treated HT cells and primary GCB-DLBCL cases derived from two publicly-available datasets (i.e. GSE10846 and GSE31312) produced three separate lists of enriched gene sets for each gene sets collection from Molecular Signatures Database (MSigDB). Subsequent Venn analysis identified 268, 145 and six consensus gene sets from analyzing gene sets in C2 collection (curated gene sets), C5 sub-collection [gene sets from gene ontology (GO) biological process ontology] and Hallmark collection, respectively to be enriched in positive correlation with DNMT1 expression profiles in shRNA-treated HT cells, GSE10846 and GSE31312 datasets [false discovery rate (FDR) <0.05]. Cell cycle progression and DNA replication were among the significantly enriched biological processes (FDR <0.05). Expression of genes involved in the activation of cell cycle and DNA replication (e.g. CDK1, CCNA2, E2F2, PCNA, RFC5 and POLD3) were highly correlated (r>0.8) with DNMT1 expression and significantly downregulated (log fold-change cells. These results suggest the involvement of DNMT1 in the activation of cell cycle and DNA replication in DLBCL cells.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse
Fulltext A Rare Cause of Acute Kidney Injury: Primary Renal Lymphoma in a Patient with Human Immunodeficiency Virus

Mustafar R, Kamaruzaman L, Chien BH, Yahaya A, Mohd Nasir N, Mohd R, et al.

Case Rep Med, 2018;2018:8425985.
PMID: 30186328 DOI: 10.1155/2018/8425985

We reported a case of primary renal lymphoma (PRL) presented with non-oliguric acute kidney injury and bilateral kidney infiltrates in an individual with human immunodeficiency virus (HIV) disease. Acute kidney injury secondary to lymphoma infiltrates is very rare (less than 1% of hematological malignancy). A 37-year-old gentleman with underlying human immunodeficiency virus (HIV) disease was on combined antiretroviral therapy since diagnosis. He presented to our center with uremic symptoms and gross hematuria. Clinically, bilateral kidneys massively enlarged and were ballotable. Blood investigations showed hemoglobin of 3.7 g/L, urea of 65.6 mmol/L, and serum creatinine of 1630 µmol/L with hyperkalemia and metabolic acidosis. An urgent hemodialysis was initiated, and he was dependent on regular hemodialysis subsequently. Computed tomography renal scan showed diffuse nonenhancing hypodense lesion in both renal parenchyma. Diagnosis of diffuse large B cell lymphoma with germinal center type, CD20 positive, and proliferative index 95% was confirmed via renal biopsy, and there was no bone marrow infiltrates. Unfortunately, the patient succumbs prior to initiation of chemotherapy.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse
Expression of the Class II and III Beta-Tubulin in Neoplastic and Non-Neoplastic Lymphoid Tissues

Binti Yusof NS, Ameli F, Sabrina Florence Ch, Mustangin M, Abd Rahman F, Masir N

Asian Pac J Cancer Prev, 2017 04 01;18(4):1045-1050.
PMID: 28547939

Aim: Abnormal expression patterns of beta-tubulin isotypes may provide a molecular rationale for the behaviour
of lymphoma subtypes. In the present study class II and III beta-tubulin expression was assessed in non-neoplastic and
neoplastic lymphoid tissues with reference to potential utility as new tumour biomarkers. Methods and results: In this
cross-sectional study class II and III beta-tubulin expression was assessed in 304 neoplastic and 20 normal lymphoid
tissues using qualitative and semi-quantitative immunohistochemistry. Class II beta-tubulin was found to be positive in
the germinal centres, mantle zone and interfollicular regions of normal lymphoid tissues. It was also expressed in 15/15
(100%) lymphoblastic lymphomas, 229/231 (99%) mature B cell lymphomas, 22/22 (100%) T/NK-cell lymphomas and
36/36(100%) classical Hodgkin lymphomas. Class III beta-tubulin in contrast was germinal centre restricted and more
selective, being found mainly in classical Hodgkin lymphomas (34/36 (94%)). It was also expressed in 58/171(34%)
DLBCL, 11/12 (92%) mantle cell lymphomas and 6/6 (100%) Burkitt lymphomas. Other mature B cell, T/NK cell
lymphomas and precursor lymphoblastic lymphomas were usually negative. Conclusions: Class II beta-tubulin shows
ubiquitous expression in neoplastic and non-neoplastic lymphoisd tissues. In contrast, Class III beta-tubulin is germinal
centre-restricted. Its consistent expression in classical Hodgkin lymphomas may point to use in the identification of
Reed-Sternberg and Hodgkin cells. Its expression in a proportion of DLBCL, Burkitt and mantle cell lymphomas is of
interest as this may be related to their aggressiveness.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse
p16 Tumor Suppressor Gene Methylation in Diffuse Large B Cell Lymphoma: A Study of 88 Cases at Two Hospitals in the East Coast of Malaysia

Mohd Ridah LJ, A Talib N, Muhammad N, Hussain FA, Zainuddin N

Asian Pac J Cancer Prev, 2017 10 26;18(10):2781-2785.
PMID: 29072413

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.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse
Optic Nerve Infiltration in Systemic Metastatic Retinal Lymphoma (SMRL): Multimodal Imaging and Challenges in Diagnosis

Mohd Fauzi Yap MFB, Mohd Zain A, Tumain NR, Palaniappan S, Nasaruddin RA, Md Din N

Ocul Immunol Inflamm, 2020 Sep 24.
PMID: 32967510 DOI: 10.1080/09273948.2020.1800050

A 45-year-old man was diagnosed with diffuse large B-cell lymphoma stage IV which was confirmed by celiac lymph node biopsy. He subsequently completed six cycles of R-CHOP chemotherapy. Six months later, he presented with panuveitis OU with positive relative afferent pupillary defect OD. OCT revealed hyper-reflective lesions and irregularity of the retinal pigment epithelium OU. Fundus fluorescein angiogram shows hyper-auto fluorescence and granular changes on the retina. A month later, he developed swollen optic disc OD and hemorrhagic retinitis OU and treated as presumed CMV retinitis. Anti-TB was started after a positive Mantoux test. He finally consented for a vitreous biopsy which showed atypical lymphoid cells highly suggestive for vitreoretinal lymphoma and subsequently received intravitreal methotrexate OU.
CONCLUSION: Optic nerve infiltration in systemic metastatic retinal lymphoma may have initial occult signs but with profound visual loss. Ocular infections like CMV retinitis and tuberculosis may mask and delay the diagnosis in immunocompromised patients.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse
Fulltext Germline TET2 loss of function causes childhood immunodeficiency and lymphoma

Stremenova Spegarova J, Lawless D, Mohamad SMB, Engelhardt KR, Doody G, Shrimpton J, et al.

Blood, 2020 Aug 27;136(9):1055-1066.
PMID: 32518946 DOI: 10.1182/blood.2020005844

Molecular dissection of inborn errors of immunity can help to elucidate the nonredundant functions of individual genes. We studied 3 children with an immune dysregulation syndrome of susceptibility to infection, lymphadenopathy, hepatosplenomegaly, developmental delay, autoimmunity, and lymphoma of B-cell (n = 2) or T-cell (n = 1) origin. All 3 showed early autologous T-cell reconstitution following allogeneic hematopoietic stem cell transplantation. By whole-exome sequencing, we identified rare homozygous germline missense or nonsense variants in a known epigenetic regulator of gene expression: ten-eleven translocation methylcytosine dioxygenase 2 (TET2). Mutated TET2 protein was absent or enzymatically defective for 5-hydroxymethylating activity, resulting in whole-blood DNA hypermethylation. Circulating T cells showed an abnormal immunophenotype including expanded double-negative, but depleted follicular helper, T-cell compartments and impaired Fas-dependent apoptosis in 2 of 3 patients. Moreover, TET2-deficient B cells showed defective class-switch recombination. The hematopoietic potential of patient-derived induced pluripotent stem cells was skewed toward the myeloid lineage. These are the first reported cases of autosomal-recessive germline TET2 deficiency in humans, causing clinically significant immunodeficiency and an autoimmune lymphoproliferative syndrome with marked predisposition to lymphoma. This disease phenotype demonstrates the broad role of TET2 within the human immune system.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse/genetics; Lymphoma, Large B-Cell, Diffuse/pathology