Diffuse large B cell lymphoma
Encyclopedia
Diffuse large B-cell lymphoma (DLBL, DLBCL, or DLCL) is a type of aggressive non-Hodgkin lymphoma
. It accounts for approximately 40% of lymphomas among adults. The median age at diagnosis is 70 years, but it also occurs in children and young adults. As with most non-Hodgkin lymphomas, there is a male predominance, although primary cutaneous diffuse large B cell lymphoma is more common in women . Of all cancers involving the same class of blood cell
, 31% of cases are DLBL.
Chromosome anomalies are:
s, seen in Hodgkin lymphoma.
. An expanded protocol, called CHOP-R, has improved survival and rates of complete responses for DLBL patients, particularly elderly patients. R-CHOP is a combination of one monoclonal antibody, 3 chemotherapy drugs, and one steroid: rituximab
(Rituxan), cyclophosphamide
(Cytoxan) doxorubicin
(Hydroxydaunorubicin), vincristine
(Oncovin), and prednisone
. Chemotherapy
is most often administered intravenously and is most effective when it is administered multiple times over a period of months (e.g. every 3 weeks, over 8–10 months). For someone who will be receiving chemotherapy it is suggested they have a PICC (Peripherally inserted central catheter
) in their arm near the elbow, and the catheter will extend through one of the large veins to within centimeters of the heart. Radiation
is another common treatment and is most effective if done prior to the chemotherapy, or as the last treatment after chemotherapy has been completed.
Non-Hodgkin lymphoma
The non-Hodgkin lymphomas are a diverse group of blood cancers that include any kind of lymphoma except Hodgkin's lymphomas. Types of NHL vary significantly in their severity, from indolent to very aggressive....
. It accounts for approximately 40% of lymphomas among adults. The median age at diagnosis is 70 years, but it also occurs in children and young adults. As with most non-Hodgkin lymphomas, there is a male predominance, although primary cutaneous diffuse large B cell lymphoma is more common in women . Of all cancers involving the same class of blood cell
Lymphoproliferative disorders
Lymphoproliferative disorders refer to several conditions in which lymphocytes are produced in excessive quantities. They typically occur in patients who have compromised immune systems...
, 31% of cases are DLBL.
Classification
Two or three major subtypes of DLBL have been identified based on their genetic activity:- activated (ABC-DLBCL), with a pattern of genetic expression that is similar to healthy, activated B cells, and
- germinal center (GCB DLBCLGCB DLBCLGene expression profiling has revealed that Diffuse Large B-Cell Lymphoma is composed of at least 3 different sub-groups, each having distinct oncogenic mechanisms that respond differently to therapies...
), with a pattern of genetic expression that is similar to germinal centerGerminal centerGerminal centers are sites within lymph nodes where mature B lymphocytes rapidly proliferate, differentiate, mutate their antibodies , and class switch their antibodies during a normal immune response to an infection...
B cells and a chromosomal translocationChromosomal translocationIn genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer. It is detected on...
involving the gene bcl-2. This type has a relatively favorable prognosis. - primary mediastinal B-cell lymphomaPrimary mediastinal B-cell lymphomaPrimary mediastinal B-cell lymphoma, abbreviated PMBL, is a type of lymphoma that rises in the mediastinum and predominantly affects young adults.It is similar to diffuse large B-cell lymphoma; however, generally has a significantly better prognosis....
(PMBL) Where the cancer is found in the thymus gland and lymph nodes behind the sternum (mediastinumMediastinumThe mediastinum is a non-delineated group of structures in the thorax, surrounded by loose connective tissue. It is the central compartment of the thoracic cavity...
), the area between the lungs, in the middle of the chest.
Chromosome anomalies are:
- t(14;18)(q32;q21) with BCL2-rearrangement.
- t(3;Var)(q27;Var) with BCL6BCL6B-cell lymphoma 6 protein is a protein that in humans is encoded by the BCL6 gene.- Function :The protein encoded by this gene is an evolutionarily conserved zinc finger transcription factor and contains an N-terminal POZ/BTB domain...
-rearrangement. These are common chromosomal translocations. - t(8;14)(q24;q32) with MYCMycMyc is a regulator gene that codes for a transcription factor. In the human genome, Myc is located on chromosome 8 and is believed to regulate expression of 15% of all genes through binding on Enhancer Box sequences and recruiting histone acetyltransferases...
rearrangements. - A combination of MYCMycMyc is a regulator gene that codes for a transcription factor. In the human genome, Myc is located on chromosome 8 and is believed to regulate expression of 15% of all genes through binding on Enhancer Box sequences and recruiting histone acetyltransferases...
, BCL6BCL6B-cell lymphoma 6 protein is a protein that in humans is encoded by the BCL6 gene.- Function :The protein encoded by this gene is an evolutionarily conserved zinc finger transcription factor and contains an N-terminal POZ/BTB domain...
and/or BCL2 rearrangements, (in the so-called "double hit" or "triple hit" diffuse large B-cell lymphomas). - Other less characteristic anomalies.
Histomorphology
DLBCLs consists of cells that are 4-5 times the diameter of a small lymphocytes and typically have marked cell-to-cell variation in size and shape. Their cytoplasm is typically basophilic and moderate in abundance. Nucleoli can be small but conspicuous to large and prominent and may be peripheral and/or central. Large bizarre cells can occasionally mimic Reed-Sternberg cellReed-Sternberg cell
Reed–Sternberg cells are different giant cells found with light microscopy in biopsies from individuals with Hodgkin's lymphoma primarily due to EBV, and certain other disorders...
s, seen in Hodgkin lymphoma.
Treatment
Standard treatment is CHOPCHOP
CHOP is the acronym for a chemotherapy regimen used in the treatment of non-Hodgkin lymphoma. CHOP consists of:* Cyclophosphamide, an alkylating agent which damages DNA by binding to it and causing cross-links...
. An expanded protocol, called CHOP-R, has improved survival and rates of complete responses for DLBL patients, particularly elderly patients. R-CHOP is a combination of one monoclonal antibody, 3 chemotherapy drugs, and one steroid: rituximab
Rituximab
Rituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...
(Rituxan), cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
(Cytoxan) doxorubicin
Doxorubicin
Doxorubicin INN is a drug used in cancer chemotherapy. It is an anthracycline antibiotic, closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA....
(Hydroxydaunorubicin), vincristine
Vincristine
Vincristine , formally known as leurocristine, sometimes abbreviated "VCR", is a vinca alkaloid from the Catharanthus roseus , formerly Vinca rosea and hence its name. It is a mitotic inhibitor, and is used in cancer chemotherapy.-Mechanism:Tubulin is a structural protein that polymerizes to...
(Oncovin), and prednisone
Prednisone
Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...
. Chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
is most often administered intravenously and is most effective when it is administered multiple times over a period of months (e.g. every 3 weeks, over 8–10 months). For someone who will be receiving chemotherapy it is suggested they have a PICC (Peripherally inserted central catheter
Peripherally inserted central catheter
A peripherally inserted central catheter is a form of intravenous access that can be used for a prolonged period of time...
) in their arm near the elbow, and the catheter will extend through one of the large veins to within centimeters of the heart. Radiation
Radiation
In physics, radiation is a process in which energetic particles or energetic waves travel through a medium or space. There are two distinct types of radiation; ionizing and non-ionizing...
is another common treatment and is most effective if done prior to the chemotherapy, or as the last treatment after chemotherapy has been completed.
Prognosis
The germinal-center subtype has the best prognosis, with 60% of treated patients surviving more than five years.See also
- Primary mediastinal B-cell lymphomaPrimary mediastinal B-cell lymphomaPrimary mediastinal B-cell lymphoma, abbreviated PMBL, is a type of lymphoma that rises in the mediastinum and predominantly affects young adults.It is similar to diffuse large B-cell lymphoma; however, generally has a significantly better prognosis....
- a type of large B-cell lymphoma similar to DLBCL, that arises in the mediastinumMediastinumThe mediastinum is a non-delineated group of structures in the thorax, surrounded by loose connective tissue. It is the central compartment of the thoracic cavity...
of young adults.