Primary diffuse large B-cell lymphoma of the Central Nervous System
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) in the United States and worldwide, accounting for about 22 percent of newly diagnosed cases of B-cell NHL in the United States. More than 18,000 people are diagnosed with DLBCL each year.
DLBCL is an aggressive (fast-growing) NHL that affects B-lymphocytes. Lymphocytes are one type of white blood cell. B-cells are lymphocytes that make antibodies to fight infections and are an important part of the lymphatic system.
Although it can occur in childhood, the occurrence of DLBCL generally increases with age, and most patients are over the age of 60 at diagnosis.
DLBCL can develop in the lymph nodes or in “extranodal sites” (areas outside the lymph nodes) such as the gastrointestinal tract, testes, thyroid, skin, breast, bone, brain, or essentially any organ of the body. It may be localized (in one spot) or generalized (spread throughout the body). Despite being an aggressive lymphoma, DLBCL is considered potentially curable.
see also spinal B cell lymphoma.
The B-cell lymphomas are types of lymphoma affecting B cells.
Epidemiology
Diffuse Large B-cell Lymphoma (DLBCL) is the most common form of Non Hodgkin lymphoma (NHL), accounting for 25-30 percent of cases in the United States. Extranodal sites are involved in approximately 40% of cases of DLBCL 1).
The majority of Primary central nervous system lymphomas (PCNSL) (95%) are considered diffuse large B cell lymphomas (DLBCLs).
B-cell lymphomas include both Hodgkin lymphomas and most non-Hodgkin lymphomas. They are typically divided into low and high grade, typically corresponding to indolent (slow-growing) lymphomas and aggressive lymphomas, respectively. As a generalisation, indolent lymphomas respond to treatment and are kept under control (in remission) with long-term survival of many years, but are not cured. Aggressive lymphomas usually require intensive treatments, with some having a good prospect for a permanent cure.
DLBCLs are characterized as high grade and most of them are CD20 positive while the minority of PCNSL consists of types such as Burkitt lymphomas, Burkitt-like lymphomas and lymphoblastic lymphomas
Clinical features
Clinically heterogeneous
Outcome
40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease.
Alizadeh et al. proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumours. Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumours of DLBCL patients, apparently reflecting the variation in tumour proliferation rate, host response and differentiation state of the tumour. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal centre B cells ('germinal centre B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'). Patients with germinal centre B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumours on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer 2).
Case series
2016
Patients were consecutive PCNSL cases treated in Leon Berard Cancer Centre, Lyon, France, from 1985 to 2011. Histology was diffuse large B cell lymphoma in 94%. Patients were treated by methotrexate (92%) and cytarabine (63%) based-chemotherapy followed by radiotherapy for 108 patients (51%). Clinical records were reviewed for details at relapse and relationship to planned imaging. The imaging follow-up strategy was performed according to each treating physicians.
Among 209 PCNSL patients, 127 complete response patients entered in post-treatment observation and 63 (50%) subsequently relapsed. Among the 125 evaluable patients, the majority of relapses (N = 49, 80%) was asymptomatic and identified before the planned brain imaging. Surveillance imaging detected relapses before symptoms in 12 patients who entered in post-therapy observation (10%). The median number of brain imaging during the follow-up was 7 (0-13). A total of 819 MRI/CT-scan were performed leading to the detection of 12 asymptomatic relapses. The one year OS rates were 41% and 58% for symptomatic and non-symptomatic relapses, respectively (P = 0.21).
The majority of PCNSL relapses occurred outside planned follow-up with no difference in patient outcome between symptomatic and asymptomatic relapses. The role of brain imaging for the detection of relapses in the follow-up of PCNSL patients remains to be clarified 3).