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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
Pathological case of the month. Ki-1-positive anaplastic large cell lymphoma involving muscle

Menon BS, Maziah W, Samarendra M, Toha A

Arch Pediatr Adolesc Med, 2001 Mar;155(3):411-2.
PMID: 11231812
Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse/classification; Lymphoma, Large B-Cell, Diffuse/diagnosis*; Lymphoma, Large B-Cell, Diffuse/drug therapy
Impact of inadequate doses of rituximab in the treatment of diffuse large B cell lymphoma in Malaysian patients

Gan GG, Subramaniam R, Bee PC, Chin EF, Abdul-Halim H, Tai MC

Asian Pac J Cancer Prev, 2014;15(4):1703-6.
PMID: 24641394

BACKGROUND: The current standard treatment for patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) is rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP). A significant number of patients were not treated with recommended dose of rituximab due to limited financial resources in Malaysia. This study evaluates the efficacy of R-CHOP like chemotherapy in Malaysian patients with DLBCL.
MATERIALS AND METHODS: The study comprised a retrospective analysis of patients with DLBCL treated at a single centre. The outcome was compared with patients who were treated with R-CHOP like and CHOP like chemotherapy. Patients who were treated with lower dose of rituximab was subanalysed for outcome.
RESULTS: A total of 86 patients who had CHOP-like chemotherapy were included. Only 39 (45%) patients had rituximab and only 12 (29%) patients had the recommended dose. The overall response (OR) and complete response (CR) rates were 88% and 81% respectively. There was no significant difference in OR and CR in patients who had rituximab and those without rituxmab. Those with International Prognostic Index (IPI) score of ≤ 2 had significant higher CR rate, progression free survival (PFS) and overall survival (p<0.001).
CONCLUSIONS: The lack of significant improvement in CR and DFS in our patients may be due to an inadequate dose of rituximab.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse/drug therapy*; Lymphoma, Large B-Cell, Diffuse/mortality
Impact of Double Expression of C-MYC/BCL2 Protein and Cell of Origin Subtypes on the Outcome among Patients with Diffuse Large B-Cell Lymphoma: a Single Asian Center Experience

Teoh CS, Lee SY, Chiang SK, Chew TK, Goh AS

Asian Pac J Cancer Prev, 2018 May 26;19(5):1229-1236.
PMID: 29801406

Background: Diffuse large B-cell lymphoma (DLBCL) with double expression of c-MYC and BCL2 protein is
associated with dismal outcome after treatment with R-CHOP. Local data on disease burden and survival outcome in
DLBCL is limited. We investigated the prognostic values of c-MYC/BCL2 protein co-expression and cell of origin
subtypes using immunohistochemistry (IHC) and to determine their associations with multiethnic groups under
resource limited setting. Methods: This was a retrospective study which recruited 104 patients in between June 2012
and December 2015 for IHC review and analysis. Result: We demonstrated that patients with high International
Prognostic Index (IPI) (score 3-5) and co-expression of c-MYC/BCL2 protein had significant inferior overall survival
(OS) and event free survival (EFS) respectively (P<0.05). c-MYC/BCL2 protein co-expression was more common in
non-germinal center B-cell (non-GCB) (P=0.048) and contributed to adverse prognosis in this group of patients (OS,
P=0.004; EFS, P=0.005). In multivariate analysis, double-protein co-expression was a significant independent predictor
of inferior outcome after adjusted for IPI and cell of origin subtypes (OS hazard ratio [HR], 2.11; 95% CI, 1.01 to 4.04;
P=0.048; EFS HR, 2.31; 95% CI, 1.05 to 5.04; P=0.036). In addition, non-GCB subtype was more common than GCB
in Malays (60% vs 40%, P=0.106) and Chinese (81.2% vs 18.8%, P=0.042). Indians had more DLBCL without c-MYC/
BCL2 protein co-expression compared to double-protein positive cases (66.7% vs 33.3%, P=0.414). Otherwise, the
prognostic impact of ethnicity on survival outcome was insignificant (P=0.961). Conclusion: c-MYC/BCL2 protein
co-expression in non-GCB subtype constituted a unique group with extremely inferior outcome regardless of ethnicity.
Gene expression profile (GEP) may possibly provide insights into the cause of discrepancies in DLBCL subtypes and
protein expression among the multiethnic groups.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse/drug therapy; Lymphoma, Large B-Cell, Diffuse/metabolism; Lymphoma, Large B-Cell, Diffuse/mortality*; Lymphoma, Large B-Cell, Diffuse/pathology*
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
Fulltext Nasopharyngeal diffuse large B-cells lymphoma causing acute airway obstruction amid COVID-19 crisis: an anaesthetist's nightmare

Yeap TB, Teah MK, Quay YJJ, Wong MTF

BMJ Case Rep, 2021 Jan 28;14(1).
PMID: 33509897 DOI: 10.1136/bcr-2020-241008

Acute stridor is often an airway emergency. We present a valuable experience handling an elderly woman who was initially treated as COVID-19 positive during the pandemic in November 2020. She needed an urgent tracheostomy due to nasopharyngeal (NP) diffuse large B-cell lymphoma causing acute airway obstruction. Fortunately, 1 hour later, her NP swab real-time PCR test result returned as SARS-CoV-2 negative. This interesting article depicts the importance of adequate preparations when handling potentially infectious patients with anticipated difficult airway and the perioperative issues associated with it.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse/complications*; Lymphoma, Large B-Cell, Diffuse/surgery
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
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
Clinical significance of aberrant microRNAs expression in predicting disease relapse/refractoriness to treatment in diffuse large B-cell lymphoma: A meta-analysis

Ting CY, Liew SM, Price A, Gan GG, Bee-Lan Ong D, Tan SY, et al.

Crit Rev Oncol Hematol, 2019 Dec;144:102818.
PMID: 31733445 DOI: 10.1016/j.critrevonc.2019.102818

The clinical significance of aberrantly expressed microRNAs in predicting treatment response to chemotherapy in diffuse large B-cell lymphoma patients (DLBCL) remains uncertain. Feasibility of microRNA testing to predict treatment outcome was evaluated. Twenty-two types of aberrantly expressed microRNAs were associated with poor treatment response; pooled hazard ratio (HR) was 2.14 [95%CI:1.78-2.57, P

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse*
Waldeyer ring lymphoma: a case series

Teh CS, Jayalakshmi P, Chong SY

Ear Nose Throat J, 2014 Sep;93(9):E22-5.
PMID: 25255354

We encountered a patient with a tongue base lymphoma that we initially diagnosed as a lingual tonsil in view of its benign appearance. We established the correct diagnosis of Waldeyer ring lymphoma by histology. This case led us to conduct a study of all cases of Waldeyer ring lymphoma that had been treated at our center during a 10-year period. We retrospectively examined our case records and found 35 such cases. From this group, we excluded 5 cases because of incomplete data. Thus our final study group was made up of 30 patients-14 males and 16 females, aged 14 to 76 years (mean: 51.6; median 54). The primary presenting signs and symptoms were dysphagia (n = 17 [57%]), a neck mass (n = 7 [23%]), nasal symptoms (n = 5 [17%]), and pain (n = 1 [3%]). Only 4 patients (13%) had B symptoms. A total of 20 patients (67%) presented with tonsillar involvement, 8 (27%) with nasopharyngeal involvement, 1 (3%) with tongue base lymphoma, and 1 with anterior tongue involvement. Most patients (77%) presented at an early stage. Histologically, 25 patients (83%) had high-grade diffuse large B-cell lymphoma, 4 (13%) had T-cell lymphoblastic lymphoma, and 1 (3%) had follicular lymphoma. Twenty-one patients (70%) were treated with chemotherapy, 4 (13%) received adjuvant chemotherapy with either radiotherapy or surgery, 3 (10%) resorted to other forms of treatment (primarily traditional remedies), and 2 (7%) declined treatment altogether. There were 14 patients (47%) alive at the end of the study period.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse/diagnosis; Lymphoma, Large B-Cell, Diffuse/pathology
Fulltext Burkitt's lymphoma presenting with hypopituitarism: a case report and review of literature

Foo SH, Sobah SA

Endocrinol Diabetes Metab Case Rep, 2014;2014:140029.
PMID: 25045522 DOI: 10.1530/EDM-14-0029

Hypopituitarism is a rare presentation of Burkitt's lymphoma (BL). The purpose of this report is to present a case of BL presenting with panhypopituitarism and to review other case reports of lymphoma presenting with pituitary dysfunction to highlight the distinguishing features of these cases from other benign aetiologies of pituitary dysfunction such as non-functioning pituitary adenomas. We reviewed a total of 11 cases of lymphoma presenting with pituitary dysfunction published from 1998 to 2013 including the present case. The demographics, clinical presentations, laboratory features, radiological findings, histological diagnosis, treatment administered and outcomes were described. Of the total number of patients, 45.5% of the cases had diffuse large B-cell lymphoma while 27.3% had BL. Anterior pituitary dysfunction was more common than posterior pituitary dysfunction at presentation. The other common associated presenting symptoms were painful ophthalmoplegia, cranial nerve palsies and constitutional symptoms. Hypothalamic-pituitary abnormalities were often demonstrated radiologically to be associated with cavernous sinus and/or stalk involvement. All patients who completed immunochemotherapy responded haematologically. Pituitary dysfunction also improved in most cases although the recovery tended to be partial. In conclusion, a high index of suspicion of underlying malignancy, such as lymphoma, should be present in patients presenting with acute pituitary dysfunction associated with painful ophthalmoplegia, rapidly evolving neurological features, radiological features atypical of a pituitary adenoma and constitutional symptoms. An early diagnosis is essential as prompt initiation of definitive therapy will induce disease remission and recovery of pituitary dysfunction.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse
Low HIP1R mRNA and protein expression are associated with worse survival in diffuse large B-cell lymphoma patients treated with R-CHOP

Wong KK, Ch'ng ES, Loo SK, Husin A, Muruzabal MA, Møller MB, et al.

Exp Mol Pathol, 2015 Dec;99(3):537-45.
PMID: 26341140 DOI: 10.1016/j.yexmp.2015.08.019

Huntingtin-interacting protein 1-related (HIP1R) is an endocytic protein involved in receptor trafficking, including regulating cell surface expression of receptor tyrosine kinases. We have previously shown that low HIP1R protein expression was associated with poorer survival in diffuse large B-cell lymphoma (DLBCL) patients from Denmark treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). In this multicenter study, we extend these findings and validate the prognostic and subtyping utility of HIP1R expression at both transcript and protein level. Using data mining on three independent transcriptomic datasets of DLBCL, HIP1R transcript was preferentially expressed in germinal center B-cell (GCB)-like DLBCL subtype (P<0.01 in all three datasets), and lower expression was correlated with worse overall survival (OS; P<0.01) and progression-free survival (PFS; P<0.05) in a microarray-profiled DLBCL dataset. At the protein level examined by immunohistochemistry, HIP1R expression at 30% cut-off was associated with GCB-DLBCL molecular subtype (P=0.0004; n=42), and predictive of OS (P=0.0006) and PFS (P=0.0230) in de novo DLBCL patients treated with R-CHOP (n=73). Cases with high FOXP1 and low HIP1R expression frequency (FOXP1(hi)/HIP1R(lo) phenotype) exhibited poorer OS (P=0.0038) and PFS (P=0.0134). Multivariate analysis showed that HIP1R<30% or FOXP1(hi)/HIP1R(lo) subgroup of patients exhibited inferior OS and PFS (P<0.05) independently of the International Prognostic Index. We conclude that HIP1R expression is strongly indicative of survival when utilized on its own or in combination with FOXP1, and the molecule is potentially applicable for subtyping of DLBCL cases.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse/drug therapy*; Lymphoma, Large B-Cell, Diffuse/mortality
The expression of Bcl-2 by proliferating cells varies in different categories of B-cell lymphoma

Masir N, Jones M, Lee AM, Goff LK, Clear AJ, Lister A, et al.

Histopathology, 2010 Apr;56(5):617-26.
PMID: 20459572 DOI: 10.1111/j.1365-2559.2010.03524.x

To investigate the relationship between Bcl-2 protein expression and cell proliferation at single-cell level in B-cell lymphomas using double-labelling techniques.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse/metabolism; Lymphoma, Large B-Cell, Diffuse/pathology
TRPM4 expression is associated with activated B cell subtype and poor survival in diffuse large B cell lymphoma

Loo SK, Ch'ng ES, Md Salleh MS, Banham AH, Pedersen LM, Møller MB, et al.

Histopathology, 2017 Jul;71(1):98-111.
PMID: 28248435 DOI: 10.1111/his.13204

AIMS: Transient receptor potential channel melastatin 4 (TRPM4) is an ion channel that regulates influx of calcium cations (Ca2+ ). Recent studies suggest that TRPM4 is an oncoprotein, and its up-regulated transcript level has been reported in diffuse large B cell lymphoma (DLBCL). We aimed to investigate TRPM4 protein expression pattern in non-malignant tissues and DLBCL cases, and its association with clinico-demographic parameters and survival in DLBCL.
METHODS AND RESULTS: Analysis of publicly available DLBCL microarray data sets showed that TRPM4 transcripts were up-regulated in DLBCL compared to normal germinal centre B (GCB) cells, were expressed more highly in the activated B cell-like DLBCL (ABC-DLBCL) subtype and higher TRPM4 transcripts conferred worse overall survival (OS) in R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)-treated DLBCL cases (P < 0.05). Our immunohistochemical analysis showed that TRPM4 was expressed in various human tissues but not in normal B cells within lymphoid tissues (reactive tonsil, lymph node and appendix). TRPM4 protein was present in 26% (n = 49 of 189) of our cohort of R-CHOP-treated DLBCL cases and this was associated significantly with more aggressive clinical parameters, including higher lactate dehydrogenase (LDH), Eastern Cooperative Oncology Group (ECOG) scores or stage (P < 0.01 for each of the parameters) and the ABC-DLBCL subtype (P = 0.016). TRPM4 positivity conferred significantly worse OS (P = 0.004) and progression-free survival (PFS) (P = 0.005). Worse OS remained associated significantly with TRPM4 positivity in multivariate analysis, including higher International Prognostic Index (IPI) or the non-GCB DLBCL phenotype (P < 0.05).
CONCLUSIONS: TRPM4 protein expression is up-regulated in DLBCL cases compared to non-malignant B cells with preferential expression in ABC-DLBCL cases, and it confers significantly poorer DLBCL patient outcomes.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse/mortality; Lymphoma, Large B-Cell, Diffuse/pathology*
Extranodal site of diffuse large B-cell lymphoma and the risk of R-CHOP chemotherapy resistance and early relapse

Ting CY, Gan GG, Bee-Lan Ong D, Tan SY, Bee PC

Int J Clin Pract, 2020 Oct;74(10):e13594.
PMID: 32583545 DOI: 10.1111/ijcp.13594

BACKGROUND: About 20%-30% of diffuse large B-cell lymphoma (DLBCL) patients experience early disease progression despite R-CHOP chemotherapy treatment. Revised international prognostic index (R-IPI) score could risk stratify DLBCL patients but does not identify exactly which patient will be resistant to R-CHOP therapy or experience early relapse.
AIMS OF THE STUDY: To analyse pre-treatment clinical features of DLBCL patients that are predictive of R-CHOP therapy resistance and early disease relapse after R-CHOP therapy treatment.
METHODS USED TO CONDUCT THE STUDY: A total of 698 lymphoma patients were screened and 134 R-CHOP-treated DLBCL patients were included. The Lugano 2014 criteria was applied for assessment of treatment response. DLBCL patients were divided into R-CHOP resistance/early relapse group and R-CHOP sensitive/late relapse group.
RESULTS OF THE STUDY: 81 of 134 (60%) were R-CHOP sensitive/late relapse, while 53 (40%) were R-CHOP resistance/early relapse. The median follow-up period was 59 months ± standard error 3.6. Five-year overall survival rate of R-CHOP resistance/early relapse group was 2.1%, while it was 89% for RCHOP sensitive/late relapse group. Having more than one extranodal site of DLBCL disease is an independent risk factor for R-CHOP resistance/early relapse [odds ratio = 5.268 (1.888-14.702), P = .002]. The commonest extranodal sites were head and neck, gastrointestinal tract, respiratory system, vertebra and bones. Advanced age (>60 years), advanced disease stage (lll-lV), raised pre-treatment lactate dehydrogenase level, bone marrow involvement of DLBCL disease high Eastern Cooperative Oncology Group status (2-4) and high R-IPI score (3-5) showed no significant association with R-CHOP therapy resistance/early disease relapse (multivariate analysis: P > .05).
CONCLUSION AND CLINICAL IMPLICATIONS: DLBCL patients with more than one extranodal site are 5.268 times more likely to be R-CHOP therapy resistance or experience early disease relapse after R-CHOP therapy. Therefore, correlative studies are warranted in DLBCL patients with more than one extranodal site of disease to explore possible underlying mechanisms of chemoresistance.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse/drug therapy*; Lymphoma, Large B-Cell, Diffuse/physiopathology*
Comparison of protein-based cell-of-origin classification to the Lymph2Cx RNA assay in a cohort of diffuse large B-cell lymphomas in Malaysia

Phang KC, Akhter A, Tizen NMS, Rahman FA, Zahratul Azma R, Elyamany G, et al.

J Clin Pathol, 2018 Mar;71(3):215-220.
PMID: 28775174 DOI: 10.1136/jclinpath-2017-204548

AIMS: The cell of origin (COO) based molecular characterisation into germinal centre B-cell-like (GCB) and activated B-cell-like (ABC) subtypes are central to the pathogenesis and clinical course in diffuse large B-cell lymphoma (DLBCL). Globally, clinical laboratories employ pragmatic but less than ideal immunohistochemical (IHC) assay for COO classification. Novel RNA-based platforms using routine pathology samples are emerging as new gold standard and offer unique opportunities for assay standardisation for laboratories across the world. We evaluated our IHC protocols against RNA-based technologies to determine concordance; additionally, we gauged the impact of preanalytical variation on the performance of Lymph2Cx assay.
METHODS: Diagnostic biopsies (n=104) were examined for COO classification, employing automated RNA digital quantification assay (Lymph2Cx). Results were equated against IHC-based COO categorisation. Assay performance was assessed through its impact on overall survival (OS).
RESULTS: 96 (92%) informative samples were labelled as GCB (38/96; 40%) and non-GCB (58/96; 60%) by IHC evaluation. Lymph2Cx catalogued 36/96 (37%) samples as GCB, 45/96 (47%) as ABC and 15/96 (16%) as unclassified. Lymph2Cx being reference, IHC protocol revealed sensitivity of 81% for ABC and 75% for GCB categorisation and positive predictive value of 81% versus 82%, respectively. Lymph2Cx-based COO classification performed superior to Hans algorithm in predicting OS (log rank test, p=0.017 vs p=0.212).
CONCLUSIONS: Our report show that current IHC-based protocols for COO classification of DLBCL at UKM Malaysia are in line with previously reported results and marked variation in preanalytical factors do not critically impact Lymph2Cx assay quality.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse/classification*; Lymphoma, Large B-Cell, Diffuse/diagnosis; Lymphoma, Large B-Cell, Diffuse/pathology
Diffuse large B-cell lymphoma in Southeast Asian cohort: expression patterns of B-cell receptor (BCR) repertoire and its linkage with molecular subtypes and response to R-CHOP therapy

Masir N, Akhter A, Roshan TM, Florence CS, Abdul-Rahman F, Tumian NR, et al.

J Clin Pathol, 2019 Sep;72(9):630-635.
PMID: 31189540 DOI: 10.1136/jclinpath-2019-205837

AIMS: Heightened B-cell receptor (BCR) activity in diffuse large B-cell lymphoma (DLBCL) is well established, and a subset of patients with relapsed DLBCL can benefit from BCR-targeted therapies. Universal outreach of such emerging therapies mandates forming a global landscape of BCR molecular signalling in DLBCL, including Southeast Asia.
METHODS: 79 patients with DLBCL (nodal, 59% and extranodal, 41%) treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy were selected. Expression levels of BCR and linked signalling pathway molecules were inter-related with Lymph2Cx-based cell of origin (COO) types and overall survival (OS).
RESULTS: Activated B-cell (ABC) type DLBCL constituted 49% (39/79) compared with germinal centre B-cell (GCB) type DLBCL (29/79; 37%) and revealed poor prognosis (p=0.013). In ABC-DLBCL, high BTK expression exerted poor response to R-CHOP, while OS in ABC-DLBCL with low BTK expression was similar to GCB-DLBCL subtype (p=0.004). High LYN expression coupled with a poor OS for ABC-DLBCL as well as GCB-DLBCL subtypes (p=0.001). Furthermore, high coexpression of BTK/LYN (BTKhigh/LYNhigh) showed poor OS (p=0.019), which linked with upregulation of several genes associated with BCR repertoire and nuclear factor-kappa B pathway (p<0.01). In multivariate analysis, high BTK and LYN expression retained prognostic significance against established clinical predictive factors such as age, International Prognostic Index and COO (p<0.05).
CONCLUSIONS: Our data provide a clear association between high BCR activity in DLBCL and response to therapy in a distinct population. Molecular data provided here will pave the pathway for the provision of promising novel-targeted therapies to patients with DLBCL in Southeast Asia.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse/drug therapy*; Lymphoma, Large B-Cell, Diffuse/ethnology; Lymphoma, Large B-Cell, Diffuse/genetics; Lymphoma, Large B-Cell, Diffuse/mortality
High frequency of germinal centre derivation in diffuse large B cell lymphoma from Asian patients

Shia AK, Gan GG, Jairaman S, Peh SC

J Clin Pathol, 2005 Sep;58(9):962-7.
PMID: 16126878

Recent reports have divided diffuse large B cell lymphoma (DLBCL) into germinal centre B cell-like and activated B cell-like subgroups with implicated differences in prognosis.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse/genetics; Lymphoma, Large B-Cell, Diffuse/immunology; Lymphoma, Large B-Cell, Diffuse/pathology*
Fulltext Role of the Nasogastric Tube and Lingzhi (Ganoderma lucidum) in Palliative Care

Wang X, Huang Y, Radha Krishna L, Puvanendran R

J Pain Symptom Manage, 2016 Apr;51(4):794-799.
PMID: 26891608 DOI: 10.1016/j.jpainsymman.2015.11.028

Decision-making on behalf of an incapacitated patient at the end of life is a complex process, particularly in family-centric societies. The situation is more complex when attempts are made to accommodate Eastern concepts of end-of-life care with more conventional Western approaches. In this case report of an incapacitated 74-year-old Singaporean man of Malay descent with relapsed Stage 4 diffuse large B cell lymphoma who was without an established lasting power of attorney, we highlight the difficult deliberations that ensue when the patient's family, acting as his proxy, elected to administer lingzhi through his nasogastric tube (NGT). Focusing on the questions pertaining to end-of-life decision-making in Asia, we consider the issues surrounding the use of NGT and lingzhi in palliative care (PC) and the implementation of NGT for administering lingzhi in a PC setting, particularly in light of a dearth of data on such treatment measures among PC patients.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse/therapy

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