Non-Hodgkin lymphoma is a type of lymphoma that primarily involves (B/T) .
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A 6-year-old girl is brought to the emergency department because of nausea, vomiting, diarrhea, and muscle cramps. Mother of the patient reports that her daughter has not urinated in the past 24 hours. She is currently undergoing treatment for non-Hodgkin lymphoma. Which of the following is the most likely diagnosis?
Content Reviewers:Rishi Desai, MD, MPH, Tanner Marshall, MS, Tanner Marshall, MS, Tanner Marshall, MS, Miguel Quintana, MD
The term non-Hodgkin lymphoma, sometimes called NHL, can be broken down. Lymph- refers to lymphocytes and oma- refers to a tumor.
The naive B cells then leave the bone marrow and circulate in the blood and eventually settle down in lymph nodes.
Humans have hundreds of lymph nodes, scattered throughout the body, and they’re considered secondary lymphoid organs.
Plasma cells release antibodies or immunoglobulins.
Antibodies bind to pathogens like viruses and bacteria, to help destroy or remove them.
In fact, the combination of surface proteins that are on an immune cell works a bit like an ID card.
Now, a B cell is activated when it encounters an antigen that binds just perfectly to its surface immunoglobulin.
These proliferating centroblasts form a germinal center, located in the center of the follicle of the lymph node.
These centroblasts have a rearrangement of their immunoglobulin genes, and some of them undergo a class switch where they change from producing IgM antibodies to producing IgG or IgA antibodies.
Within the germinal center, centroblasts mature into centrocytes; and the centrocytes that make antibody with high affinity for the antigen, differentiate into either plasma cells which go to the medulla or memory B-cells which circulate in the blood and reside in lymph nodes, spleen, and mucosa-associated lymphoid tissue, also called MALT.
Now, T-cell development starts in the thymus from precursors that arise in the bone marrow.
Mature T-cells circulate in the blood and are found in the paracortex of the lymph nodes.
In non Hodgkin lymphoma, there is usually a genetic mutation in a lymphocyte - either a B cell or a T cell. When something like that happens, cells are supposed to undergo apoptosis - or programmed cell death, but instead the lymphocyte starts to divide uncontrollably - becoming a neoplastic cell.
Usually, lymphomas develop in lymph nodes and they’re called nodal lymphomas.
Lymphomas can happen anywhere in the body, though, and when they develop in other tissues or organs - like the stomach or skin - they’re called extranodal lymphomas.
Lymphoma cells can also get into the blood and can spread to other parts of the body.
If lymphoma cells get into the gastrointestinal tract they can grow and cause bowel obstruction. If they go to the bone marrow, they can crowd out normal bone marrow progenitor cells and decrease the number of healthy red blood cells, white blood cells and platelets. If they go to the spinal cord they can cause spinal cord compression.
And there are various types of B cell lymphomas and an important feature is how quickly each one grows- they can be indolent or slow to grow, aggressive, or highly aggressive.
The first type of B cell lymphoma is a diffuse large B cell lymphoma, this type is the most common and it’s an aggressive lymphoma.
A second type of B cell lymphoma is a follicular lymphoma, and it’s an indolent lymphoma.
One known mechanism for how a follicular lymphoma develops, is a chromosomal translocation between chromosome 14 and chromosome 18.
In the translocation, the two chromosomes swap large pieces of chromosome with each other. As a result the BCL2 gene from chromosome 18 is placed after the immunoglobulin heavy chain promoter on chromosome 14, and that results in overexpression of bcl-2.
Bcl-2 normally blocks cell death, or apoptosis, so overexpression of the bcl-2 gene prevents the cell from dying.
A third type of B cell lymphoma is Burkitt lymphoma, and it’s a highly aggressive lymphoma.
Burkitt lymphoma can also result from a chromosomal translocation. In this case, the Myc gene is translocated from chromosome 8 where it ends up adjacent to IgH promoter on chromosome 14 and again that upregulates its expression.