Non-Hodgkin lymphomas
How each non-Hodgkin lymphoma mirrors a stage of normal B-cell or T-cell development in the lymph node, how translocations such as t(14;18), t(11;14) and MYC drive them, and why some grow over years and others over weeks.
By the end, you can
- Relate the zones of a normal lymph node and the stages of B-cell maturation to the lymphomas that arise from each.
- Explain how translocations involving BCL2, cyclin D1 and MYC, chronic antigen stimulation and immunodeficiency lead to lymphoma.
- Describe the gross and microscopic appearance of lymphoma and the features of follicular, mantle cell, marginal zone, diffuse large B-cell and Burkitt lymphoma.
- Contrast indolent and aggressive lymphomas, and outline the main T-cell and NK-cell lymphomas.
- Explain the findings of lymphoma and what grading and staging measure.
- Recognise the classic biopsy appearances, classifications, staging and tests of non-Hodgkin lymphoma, and explain how anti-CD20 antibodies, chemotherapy, radiotherapy, CAR T cells and H. pylori eradication act on the clone.
What it is
Non-Hodgkin lymphomas are malignant clonal proliferations of B cells, T cells or natural killer (NK) cells that form masses in lymph nodes and other lymphoid tissues; the term covers every lymphoma except Hodgkin lymphoma. Each type resembles a stage of normal lymphocyte development (its cell of origin), and types range from indolent (slow-growing, such as follicular lymphoma) to aggressive (such as diffuse large B-cell and Burkitt lymphoma).
6 types to tell apart
- Follicular lymphoma
- Germinal centre B cells with t(14;18) and BCL2; indolent, but can transform.
- Mantle cell lymphoma
- Naive mantle zone B cells with t(11;14) and cyclin D1; CD5-positive; usually aggressive.
- Marginal zone lymphoma
- Memory B cells driven by chronic antigen, including extranodal MALT lymphoma of the stomach.
- Diffuse large B-cell lymphoma
- The commonest type: sheets of large B cells, arising anew or from an indolent lymphoma.
- Burkitt lymphoma
- Germinal centre B cells driven by MYC translocation; among the fastest-growing human tumours.
- T-cell and NK-cell lymphomas
- Less common, often aggressive; they arise in the paracortex or in tissues such as skin and gut.
US spelling: centre → center.
Normal function
Lymph node zones and B-cell maturation
A lymph node filters lymph arriving through its . The outer holds of B cells, the beneath is the T cell zone, and hold plasma cells beside sinuses that drain to the hilum. The same lymphocytes recirculate through the spleen, the tonsils, the mucosa-associated lymphoid tissue (MALT) of the gut and the marrow.
B cells are made in the marrow, where each builds a unique antibody gene by cutting and rejoining its DNA (V(D)J recombination). Naive B cells settle in follicles and form the mantle zone around active ones. A B cell that meets its antigen with T-cell help enters a germinal centre: dividing centroblasts mutate their antibody genes (somatic hypermutation) and switch antibody class, then smaller centrocytes are tested against the antigen. Germinal centre cells switch off the survival protein BCL2, so cells that fail selection die by apoptosis.
Survivors leave as memory B cells, many settling in the marginal zone outside the mantle (prominent in the spleen and MALT), or as antibody-secreting plasma cells. T cells mature in the thymus and work in the paracortex and in tissues. Each stage can give rise to a lymphoma that keeps its parent cell’s appearance, markers and home.
Underlying change · Step 1 of 5
A lymphocyte clone and its translocation
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Underlying change · Step 2 of 5
The cell of origin: a map of B-cell lymphomas
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 3 of 5
Effacement and indolent versus aggressive growth
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 4 of 5
T-cell and NK-cell lymphomas
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Consequences · Step 5 of 5
Effects, grading and staging
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Symptoms and signs
Symptoms, signs and findings
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Exam detail
Exam detail
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Treatment
How treatment works
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Recap
Recap
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Self-check
Check your understanding
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .