Symptoms and Diagnosis
The risk factors for DLBCL are not known at present although underlying immunodeficiency and EBV infection could be involved. Diffuse large B cell lymphoma occurs mainly in older people, the average age being 65.
Often the first sign of DLBCL is a painless swelling in the neck, armpit or groin due to enlarged lymph nodes (nodal DLBCL). However, in 40% of cases, disease is first seen in the intestine, skin, bone, brain or spinal cord (extranodal DLBCL).
Some patients experience a loss of appetite, fatigue, night sweats, raised temperature and weight loss.
Diagnosis of diffuse large B cell lymphoma requires examination of the lymph node tissue (histology/biopsy). An enlarged lymph node (or part of it) is removed and examined microscopically. Immunophenotyping can be useful to classify the type of DLBCL. DLBCL is subdivided on the basis of morphological, biological and clinical characteristics. However, many DLBCL are difficult to classify and are referred to as ‘DLBCL-not otherwise specified’ (NOS).
Biopsies may also be taken from other sites such as the bone marrow. Additional procedures such as blood tests and x-rays may also be used to reach a diagnosis and assess how far it has spread to various organs in the body. Common sites to spread include the liver, lungs or bones.
The standard treatment for primary nodal DLBCL is a combination of chemotherapy agents (cyclophosphamide, doxorubicin, vincristine and prednisone) known as ‘CHOP’ in combination with the chimeric CD20 monoclonal antibody rituximab. Although many patients benefit from this treatment, the disease is still fatal in around 40% of cases.
The chance of successful treatment is partially associated with localization of the tumor, stage of the disease, serum lactate dehydrogenase levels, age and the general health of the patient. These factors are combined to give a score, the international prognostic index (IPI), which classifies patients as low or high risk. However, the predicted response to therapy can have limited clinical relevance.
If initial treatment fails or relapse occurs, the prognosis is poor. At this stage, high-dose chemotherapy, radio-immunotherapy or stem cell transplantation are the only remaining options.
Studies have shown that lymphoma cells require continuous expression of anti-apoptotic proteins or mutated apoptosis-inducing proteins to survive, and can be killed with agents that target these proteins. Several apoptosis targeting therapies are currently undergoing clinical trials in diffuse large B cell lymphoma patients. Hopefully such therapies will be effective in DLBCL that do not respond to chemotherapy, providing hope for patients who are incurable by current treatments.
Molecular targeted therapies for diffuse large B-cell lymphoma based on apoptosis profiles by S.Cillessen, C.Meijer, M.Notoya, G.Ossenkoppele, J Oudejans. The Journal of Pathology, 2010, Vol 220, P509–520
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