Last updated on May 18, 2019 at 10:56
Burkitt lymphoma (BL) is an aggressive, mature non-Hodgkin B cell lymphoma. A lymphoma is always present; leukaemia is uncommon but may occur. Three subtypes exist, each of which have different etiology and clinical manifestations.
Endemic Burkitt lymphoma is associated with EBV infection and is most commonly seen in children and young adults in equatorial Africa and South America. The lymphoma is typically located in the head and neck area.
Sporadic Burkitt lymphoma is associated with EBV in only 30% of cases. It can occur anywhere in the world but is most commonly seen in western countries. It mostly affects children and young adults, and the typical manifestation is a lymphoma in the abdomen, forming an abdominal mass.
Immunocompromised-related Burkitt lymphoma is associated with HIV/AIDS and other immunocompromised states. EBV infection is present in around 30% of cases. It has no typical manifestation.
All three forms of BL are highly associated with translocations of the C-MYC gene, which is located on chromosome 8. The most common translocations are:
- t(8;14) with IgH/MYC – most common
- t(2;8) with IgK/MYC
- t(8;22) with IgL/MYC
The tumor cells have very high rate of proliferation, and apoptosis is widespread. This causes the “starry sky” pattern on histology.
Burkitt lymphoma is one of the fastest-growing neoplasms, but most patients can be cured with aggressive chemotherapy.
Diffuse large B-cell lymphoma
Diffuse large B-cell lymphoma (DLBCL) is an aggressive, mature non-Hodgkin B-cell lymphoma. It’s the most common non-Hodgkin lymphoma. It mostly affects older adults in the 60-70 years range. Immunodeficiency is a strong risk factor, especially together with EBV.
DLBCL forms rapidly growing tumors. Approximately 60% of them are extranodal. Extranodal tumors are usually found in the CNS, GI tract, mediastinum or skin.
The name comes from that the tumor cells are very large on histology. The tumors show a diffuse “blastic” infiltrate.
There is no one gene or translocation that is always implicated in DLBCL, however one or more of the three genes Myc, BCL2 and BCL6 are commonly mutated or translocated. The more of these genes that are mutated, the worse the prognosis.
DLBCL may be primary or de novo, in which case it is sporadic, or secondary, where it occurred as a Richter transformation from chronic lymphocytic leukaemia (CLL), follicular lymphoma (FL) or marginal zone lymphoma (MZL). The secondary cases have worse prognosis than the primary ones.
Without treatment is DLBCL rapidly fatal. With intensive chemotherapy and anti-CD20 immunotherapy is complete remission achieved in most patients.
Plasma cell neoplasms
Plasma cell neoplasms or plasma cell dyscrasias are mature non-Hodgkin B-cell lymphomas that belongs to the “other” group. Because these tumor cells are plasma cells they usually produce immunoglobulins, either complete or just fragments of them. Because the neoplasm originates from one plasma cell is the proliferation monoclonal, which in practice means that all the tumor cells produce the exact same immunoglobulin, which accumulated in the serum.
Diagnosis is based on the presence of these monoclonal immunoglobulins in the serum, where they’re known as “M proteins”. Parts of these immunoglobulins can also be detected in the urine, where they’re known as Bence-Jones proteins. Bence-Jones proteins are often immunoglobulin light chain proteins.
Due to the presence of large amounts of a monoclonal immunoglobulin in the serum these disorders can also be called monoclonal gammopathies. Plasma cell neoplasms are most common in middle-aged and elderly persons. It’s more common in males and black people.
AL amyloidosis can occur in these diseases due to the high level of immunoglobulin light chains in the blood.
There are four important plasma cell dyscrasias:
- Plasma cell myeloma (multiple myeloma)
- Solitary plasmacytoma
- Monoclonal gammopathy of unknown significance (MGUS)
- Lymphoplasmacytic lymphoma
Plasma cell myeloma or multiple myeloma is the most important of these three. The word “myeloma” means “malignant tumor of the bone marrow” and is not related to the myeloid cell line. It’s one of the most common lymphoid neoplasms.
Plasma cell myeloma infiltrates the bone marrow of many bones in the body and frequently produces lytic lesions anywhere in the skeletal system. The lytic lesions appear as cytokines produced by the tumor cells promote osteoclast activity. The symptoms of plasma cell myeloma can be remembered with the mnemonic CRAB:
- Hypercalcaemia – due to osteolysis
- Renal failure – as the tubules are damages as they reabsorb M and Bence-Jones protein
- Anaemia – due to the infiltrated bone marrow
- Bone lesions – localized osteolytic lesions
Patients with plasma cell myeloma become immunosuppressed as the cancer interferes with the normal function of plasma cells. This increases the risk of bacterial infections.
Plasma cell myeloma has a poor prognosis; the average survival after diagnosis is 2 years.
Solitary plasmacytoma is an early stage of plasma cell myeloma, where there are yet no systemic symptoms. It occurs as a solitary mass of clonal plasma cells that are similar to those of plasma cell myeloma. They may occur in bone or extraosseously, most frequently in the upper respiratory tract. Those that are extraosseous have better prognosis, as they are cured by local resection.
They usually progress to plasma cell myeloma within 10 years.
Monoclonal gammopathy of unknown significance (MGUS) is an asymptomatic monoclonal gammopathy, meaning that there are M proteins in the blood. MGUS can be found in 1-3% of healthy adults over 50. <10% of the bone marrow is occupied by plasma cells. There is no organ damage, lymphoma or leukaemia.
MGUS is not a cancer, but it progresses to plasma cell myeloma eventually. After 10 years have 12% of cases progressed, after 20 years the number is 25%.
Lymphoplasmacytic lymphoma or Waldenström macroglobulinaemia is special in that not only plasma cells but also plasmacytoid lymphocytes are proliferating. The levels of M protein in the blood is elevated.
28. Indolent B cell lymphomas (FL, CLL, MCL, MZL)
30. Hodgkin lymphoma