• Humans
• Lymphoma, Large B-Cell, Diffuse/metabolism
• Lymphoma, Large B-Cell, Diffuse/pathology
• Lymphoma, Large B-Cell, Diffuse/mortality
• Lymphoma, Large B-Cell, Diffuse/diagnosis
• Male
• Female
• Middle Aged
• Interferon Regulatory Factors/metabolism
• Interferon Regulatory Factors/genetics
• Proto-Oncogene Proteins c-bcl-6/metabolism
• Proto-Oncogene Proteins c-bcl-6/genetics
• Proto-Oncogene Proteins c-myc/metabolism
• Proto-Oncogene Proteins c-myc/genetics
• Neprilysin/metabolism
• Adult
• Aged
• Ki-67 Antigen/metabolism
• Herpesvirus 4, Human
• Biomarkers, Tumor/metabolism
• Prognosis
• Epstein-Barr Virus Infections
• Aged, 80 and over
• Doxorubicin/therapeutic use
• Immunohistochemistry
• Gene Expression Regulation, Neoplastic
• Vincristine/therapeutic use
• Clinical Relevance

• Bone
• diffuse
• large B-cell
• lymphoma
• nasal
• non-Hodgkin
• palate

• DLBCL
• GCB
• diffuse large B-cell lymphoma (DLBCL)
• large B-cell lymphoma (LBCL)
• non-GCB
• pleomorphic mantle cell lymphoma (MCL)

Treatment response in diffuse large B-cell lymphoma (DLBCL) is heterogenous. The Hans algorithm (using 30% cut-offs for CD10, BCL6, and MUM1 protein expression) has been the most favored method to categorize DLBCL into germinal center B-cell (GCB) and non-GCB subtypes in order to predict prognosis. However, the algorithm’s ability to prognosticate is not always consistent.

This retrospective cohort study was conducted on DLBCL patients receiving R-CHOP therapy at Dr. Cipto Mangunkusumo Hospital, Jakarta from 2014 to 2017. We aimed to compare the prognostic value of Hans algorithm as well as the protein levels of CD10, BCL6, MUM1, and Ki67 at different cut-offs. Ninety-two patients were classified based on Hans algorithm and various proteins at different cut-off values were analyzed with regard to event-free survival at 24 months using survival analysis. The cut-off values were then compared using receiver operating characteristic curves.

A significant survival difference was observed with MUM1 expression cut-off of 50% or more (log rank p = 0.035). CD10, BCL6, Ki67, and Hans algorithm showed AUCs below or near 0.5 (0.405, 0.436, 0.498, and 0.413, respectively), whereas MUM1 showed an AUC of 0.835, in predicting events within 24 months. MUM-1 cut-off of 70.5% yielded an optimal trade-off for sensitivity and specificity.

MUM1 expression of 50% or more can help predict prognosis in DLBCL patients receiving R-CHOP therapy and can be considered as for use as a single marker to predict prognosis.

Diffuse large B-cell lymphoma, which accounts for about approximately 30% to 40% of non-Hodgkin's lymphomas, is the most common type and is a class of aggressive B-cell lymphomas. However, diffuse large B-cell lymphomas primary to the adrenal gland are rare.

A 73-year-old man was admitted with abdominal pain and fatigue. After admission, enhanced adrenal computed tomography indicated irregular masses on both adrenal glands, with the larger one on the left side, approximately 8.0 cm × 4.3 cm in size. The boundary was irregular, and surrounding tissues were compressed. No obvious enhancement was observed in the arterial phase. Resection of the left adrenal gland was performed. Pathological diagnosis revealed diffuse large B-cell lymphoma. After surgery, the patient received R-CHOP immunochemotherapy. During the fourth immunochemotherapy, patient condition deteriorated, and he eventually died of respiratory failure.

R-CHOP is the conventional immunochemotherapy for primary adrenal diffuse large B-cell lymphoma. Surgery is mainly used to diagnose the disease. Hence, the ideal treatment plan remains to be confirmed.

• Large B-cell lymphoma
• Adrenal glands
• Immunochemotherapy
• Surgical procedures
• Case report

Primary bone marrow diffuse large B-cell lymphoma is an exceedingly rare form of non-Hodgkin lymphoma. It may demonstrate a leukemic presentation, and a proportion of cases have CD5 expression. The prognostic implications of this CD5-positivity remain unknown. Here, we present a 78-year-old man who presented with circulating peripheral blood lymphoma cells and a hypercellular marrow involved by diffuse large B-cell lymphoma, germinal center B-cell subtype. The patient responded favorably to six cycles of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) and intrathecal methotrexate. He unfortunately relapsed in several enlarged inguinal lymph nodes and succumbed to the lymphoma approximately one year after diagnosis, demonstrating the particularly aggressive clinical course of his disease.

• Indonesia
• diffuse
• large B-cell
• lymphoma
• survival rate

• DLBCL
• R-CHOP
• diagnosis
• precision medicine
• prognosis

CD10, BCL6, and MUM1 are commonly used immunohistochemical stains for classifying diffuse large B-cell lymphoma (DLBCL), which is useful in predicting outcome. Conflicting reports of the prognostic value of other markers such as BCL2, CD23, and Ki67 proliferation index have been reported. Our objective was to correlate these immunostains and Hans classification with response to therapy and overall survival.

A retrospective study of patients diagnosed with DLBCL from 2008–2014 at a tertiary-care cancer hospital. The slides with the IHC stains were reviewed by two independent pathologists. The clinical outcomes––assessed independently––were response to therapy and overall survival. The treatment response evaluation was based on the new Lugano classification. Statistical analyses were conducted using the Fisher’s exact test and Kaplan–Meier survival curves. Significance was set at P < 0.05.

Forty-one patients were included in the study with a known Hans classification, available clinical data, and at least 5-year follow-up. CD10 immunostain was reported in all patients, whereas CD23 was the least reported in only four patients. No significant association was observed between CD10, BCL6, MUM1, BCL2, and both Response to therapy and overall survival. Owing to few cases reported CD23 immunostain, further analysis of association is not reported. High Ki67 proliferative index of >80% was statistically significantly associated with shorter overall survival and not statistically significant associated with no response to therapy. Hans classification subtypes were not predictive in regard to therapy response.

High Ki67 expression (>80%) was associated with shorter overall survival in DLBCL. Hans classification subtypes were not predictive.

• Activated B-cell (ABC)
• B-lymphocytes
• BCL2
• BCL6
• CD10
• CD23
• Ki67
• MUM1
• cell-of-origin classification
• diffuse large B-cell lymphoma (DLBCL)
• germinal center B-cell (GCB)
• immunohistochemistry
• overall survival
• therapy response

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL), accounting for about 40% of all cases of NHL. Analysis of the tumor microenvironment is an important aspect of the assessment of the progression of DLBCL. In this review article, we analyzed the role of different cellular components of the tumor microenvironment, including mast cells, macrophages, and lymphocytes, in the tumor progression of DLBCL. We examined several approaches to confront the available pieces of evidence, whereby three key points emerged. DLBCL is a disease of malignant B cells spreading and accumulating both at nodal and at extranodal sites. In patients with both nodal and extranodal lesions, the subsequent induction of a cancer-friendly environment appears pivotal. The DLBCL cell interaction with mature stromal cells and vessels confers tumor protection and inhibition of immune response while delivering nutrients and oxygen supply. Single cells may also reside and survive in protected niches in the nodal and extranodal sites as a source for residual disease and relapse. This review aims to molecularly and functionally recapitulate the DLBCL–milieu crosstalk, to relate niche and pathological angiogenic constitution and interaction factors to DLBCL progression.

• DLBCL
• angiogenesis
• cell adhesion mediated drug resistance
• tumor microenvironment
• tumor progression

• 1 CSRD VA

• B-cell antigen receptor
• Diffuse large B-cell lymphoma
• Janus kinase
• P53 pathway
• Wnt/β- catenin
• nuclear factor-κB
• phosphatidylinositol-3-kinase.

Standard treatment with a thiotepa-based regimen in countries with a limited resource is less feasible. Aims of the study were to evaluate the treatment outcome, and identify the prognostic factors in patients with primary central nervous system lymphoma (PCNSL).

We conducted a retrospective study of 43 patients diagnosed with PCNSL, DLBCL subtype, who were treated with either HDMTX-based regimen, whole brain radiotherapy (WBRT), or both between 2010 and 2017.

There were 43 patients with a median age of 65 years (range 34–89 years). Protein expression of CD10, Bcl6, MUM1, Bcl2 and MYC were found in 19, 86, 91, 91 and 23%, respectively. Both germinal center B cell (GCB) and double-expressor (MYC+/Bcl2+) lymphomas were found in 21%. Multiple brain lesions and maximum tumor diameter (MTD) ≥5 cm were seen in 27 and 10 patients, respectively. Chemotherapy combined with WBRT, chemotherapy and WBRT were given to 20, 14 and 9 patients, respectively. Overall complete remission (CR) rate was 55.8%. Those receiving a combined-modality therapy had a higher CR rate than those treated with either chemotherapy (75% versus 36%, p = 0.036) or WBRT (75% versus 44%, p = 0.109). Median follow-up time was 17 months, and a 7-year overall survival (OS) was 40%. Features associated with a prolonged OS were an ECOG score ≤ 2 (p = 0.001), multiple brain lesions (p = 0.010), multiple area of brain involvement (p = 0.023), MTD < 5 cm (p = 0.004), GCB subtype (p = 0.003) and positive CD10 staining (p = 0.007). Expression of Bcl2 protein was associated with a significantly worse OS in the non-GCB DLBCL patients.

The factors affecting treatment outcomes in PCNSL were cell of origin of DLBCL, lesion characteristics, patients’ status and treatment regimen.

• CD10
• Chemotherapy plus WBRT
• GCB lymphoma
• Non GCB lymphomas
• PCNSL

Diffuse large B-cell lymphoma (DLBCL) is classified into germinal center-like (GCB) and non-germinal center-like (non-GCB) cell-of-origin groups, entities driven by different oncogenic pathways with different clinical outcomes. DLBCL classification by immunohistochemistry (IHC)-based decision tree algorithms is a simpler reported technique than gene expression profiling (GEP). There is a significant discrepancy between IHC-decision tree algorithms when they are compared to GEP.

To address these inconsistencies, we applied the machine learning approach considering the same combinations of antibodies as in IHC-decision tree algorithms. Immunohistochemistry data from a public DLBCL database was used to perform comparisons among IHC-decision tree algorithms, and the machine learning structures based on Bayesian, Bayesian simple, Naïve Bayesian, artificial neural networks, and support vector machine to show the best diagnostic model. We implemented the linear discriminant analysis over the complete database, detecting a higher influence of BCL6 antibody for GCB classification and MUM1 for non-GCB classification.

The classifier with the highest metrics was the four antibody-based Perfecto–Villela (PV) algorithm with 0.94 accuracy, 0.93 specificity, and 0.95 sensitivity, with a perfect agreement with GEP (κ = 0.88, P < 0.001). After training, a sample of 49 Mexican-mestizo DLBCL patient data was classified by COO for the first time in a testing trial.

Harnessing all the available immunohistochemical data without reliance on the order of examination or cut-off value, we conclude that our PV machine learning algorithm outperforms Hans and other IHC-decision tree algorithms currently in use and represents an affordable and time-saving alternative for DLBCL cell-of-origin identification.

The online version of this article (10.1186/s12967-019-1951-y) contains supplementary material, which is available to authorized users.

• COO identification
• DLBCL
• IHC algorithm
• Linear discriminant analysis
• Machine learning

• Asia
• BCL2 and BCL6 gene rearrangements
• c-Myc
• diffuse large B-cell lymphoma
• diffuse large B-cell lymphoma with CD5 protein expression
• diffuse large B-cell lymphoma with positive EBER expression
• non-germinal center B-cell subtype

• diffuse large B-cell lymphoma
• international prognostic index
• non-Hodgkin lymphoma