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Microscopic studies on postmortem vermiform appendix of the adult males of Bangladesh

Bakar SM, Shamim M, Salam A, Sultana SA

Ir J Med Sci, 2016 Feb;185(1):249-57.
PMID: 25894278 DOI: 10.1007/s11845-015-1287-4

BACKGROUND: The anatomy of the vermiform appendix shows variations in its macroscopic dimensions and microscopic features, some of which have potentials of influencing the clinical aspects of the appendix.
AIM: The aim of this study was to find out some microscopic features of appendix and evaluate the correlation between the microscopic features of the appendix and the age of the subjects and to determine whether these findings should influence the clinical implications of appendix.
METHODS: In this cross-sectional observational study, thirty adult males' (age from 18 to 67 years) postmortem appendices and adnexa from Bangladeshi victims of road traffic accidents were sectioned at the base, midzone and tip stained with H+E stain and examined under microscope. Measurements were taken at the base, at the midzone and at the tip of the appendix, and the mean of the three measurements was considered as the overall value.
RESULTS: The overall number of mucosal glands in a section ranged from 42.33 to 130.00 and the number of the germinal centres varied between 2.33 and 10.00. The overall luminal diameter ranged between 1764.58 and 3208.33 µm. The overall luminal diameter in more than 52 % of cases was between 2700.00 and 3299.99 µm with a median value of 2750 µm.
CONCLUSION: The overall number of mucosal glands showed a tendency towards a positive correlation with age. The overall luminal diameter and the overall number of germinal centres showed a tendency towards a negative correlation with the age. However, none of the tendencies of correlation reached statistically any significant level.

Matched MeSH terms: Germinal Center/pathology*
Unrecognised IgG4 association in progressively transformed germinal centers of lymph nodes with subsequent full-blown IgG4-related chronic fibrosing pancreatitis: A case report

Son HJ, Lee H, Kim JH, Yu IK, Han HY

Malays J Pathol, 2018 Apr;40(1):73-78.
PMID: 29704388

Progressively transformed germinal centers (PTGC) is a benign process characterised by a morphological variant of reactive follicular hyperplasia in lymph nodes. It was recently shown that some cases of PTGC are associated with IgG4-related disease (IgG4-RD) or increased IgG4 plasma cells. Five years ago, a 57-year-old woman presented with enlargement of multiple lymph nodes in the left parotid, submandibular, and neck areas, pathologically diagnosed as PTGC after excisional biopsy. Since then, she has experienced numbness in her extremities, especially the left shoulder and arm, pruritus on the left side of the face and intermittent facial palsy, for which she has been receiving regular symptomatic treatment. Recently the patient developed diabetes mellitus (approximately seven months ago). In routine follow-up scans, a mass was detected in left kidney and magnetic resonance imaging of the abdomen prior to surgery revealed a slightly enhanced bulky mass replacing the pancreatic tail and uncinate process. The mass in left kidney was diagnosed as clear cell renal cell carcinoma, and the pathological features of the pancreatic lesion were those of IgG4-related chronic fibrosing pancreatitis. Retrograde examination of the neck lymph node diagnosed as PTGC showed increased deposition of IgG4-positive plasma cells.

Matched MeSH terms: Germinal Center/pathology*
Fulltext Epstein-Barr virus, the germinal centre and the development of Hodgkin's lymphoma

Mohamed G, Vrzalikova K, Cader FZ, Vockerodt M, Nagy E, Flodr P, et al.

J Gen Virol, 2014 Sep;95(Pt 9):1861-1869.
PMID: 24893782 DOI: 10.1099/vir.0.066712-0

The relationship between Epstein-Barr virus (EBV) and the germinal centre (GC) of the asymptomatic host remains an enigma. The occasional appearance of EBV-positive germinal centres in some patients, particularly those with a history of immunosuppression, suggests that EBV numbers in the GC are subject to immune control. The relationship, if any, between lymphoid hyperplasia with EBV-positive germinal centres and subsequent or concurrent lymphomagenesis remains to be clarified. As far as the development of EBV-associated Hodgkin's lymphoma is concerned, the suppression of virus replication, mediated by LMP1 on the one hand, and the loss of B-cell receptor signalling on the other, appears to be an important pathogenic mechanism. A further important emerging concept is that alterations in the microenvironment of the EBV-infected B-cell may be important for lymphomagenesis.

Matched MeSH terms: Germinal Center/immunology*; Germinal Center/virology*
Association of circulatory Tfh-like cells with neutralizing antibody responses among chronic HIV-1 subtype C infected long-term nonprogressors and progressors

Swathirajan CR, Nandagopal P, Vignesh R, Srikrishnan AK, Goyal R, Qureshi H, et al.

Pathog Dis, 2019 06 01;77(4).
PMID: 31505637 DOI: 10.1093/femspd/ftz044

HIV-1 vaccine functioning relies on successful induction of broadly neutralizing antibodies (bNAbs). CXCR3- circulatory T-follicular helper (cTfh) cells are necessary for inducing B-cells for generating bNAbs. Recent studies have suggested that CXCR3+ Tfh cells might also influence bNAb production. Plasma samples from 34 ART-Naïve HIV-1 infected individuals [long-term nonprogressors (LTNP)-19; Progressors-13] were tested against a heterologous virus panel (n = 11) from subtypes A, B, C, G, AC, BC and AE. Frequencies of CXCR3+ and CXCR3- cTfh-like cells in peripheral circulation were studied using flow cytometry. LTNP showed significantly lower CXCR3+ and higher CXCR3- cTfh-like cell frequencies, while neutralization breadth was observed to be broader in progressors. A positive correlation was observed between bNAb breadth and potency with CXCR3+PD-1+ cTfh-like cells in LTNP. Based on neutralization breadth, 9 HIV-1 infected individuals were classified as 'top neutralizers' and 23 as 'low neutralizers' and they did not show any correlations with CXCR3+ and CXCR3- cTfh-like cells. These preliminary data suggest that CXCR3+ similar to CXCR3- might possess significant functional properties for driving B-cells to produce bNAbs. Hence, an HIV vaccine which is capable of optimal induction of CXCR3+ cTfh cells at germinal centers might confer superior protection against HIV.

Matched MeSH terms: Germinal Center
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: Germinal Center/metabolism*; Germinal Center/pathology
DNMT1 is predictive of survival and associated with Ki-67 expression in R-CHOP-treated diffuse large B-cell lymphomas

Loo SK, Ch'ng ES, Lawrie CH, Muruzabal MA, Gaafar A, Pomposo MP, et al.

Pathology, 2017 Dec;49(7):731-739.
PMID: 29074044 DOI: 10.1016/j.pathol.2017.08.009

DNMT1 is a target of approved anti-cancer drugs including decitabine. However, the prognostic value of DNMT1 protein expression in R-CHOP-treated diffuse large B-cell lymphomas (DLBCLs) remains unexplored. Here we showed that DNMT1 was expressed in the majority of DLBCL cases (n = 209/230, 90.9%) with higher expression in germinal centre B-cell-like (GCB)-DLBCL subtype. Low and negative DNMT1 expression (20% cut-off, n = 33/230, 14.3%) was predictive of worse overall survival (OS; p < 0.001) and progression-free survival (PFS; p < 0.001). Nonetheless, of the 209 DNMT1 positive patients, 33% and 42% did not achieve 5-year OS and PFS, respectively, indicating that DNMT1 positive patients showed considerably heterogeneous outcomes. Moreover, DNMT1 was frequently expressed in mitotic cells and significantly correlated with Ki-67 or BCL6 expression (r = 0.60 or 0.44, respectively; p < 0.001). We demonstrate that DNMT1 is predictive of DLBCL patients' survival, and suggest that DNMT1 could be a DLBCL therapeutic target due to its significant association with Ki-67.

Matched MeSH terms: Germinal Center/pathology
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: Germinal Center/pathology
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: Germinal Center
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

Matched MeSH terms: Germinal Center
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: Germinal Center
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: Germinal Center
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: Germinal Center/pathology*

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