29th May 2023

Non-Hodgkin’s lymphoma

Overview

Non-Hodgkin’s lymphoma (NHL) is an umbrella term for all other forms of lymphoma and comprises a phenotypically disparate group of diseases, which all arise from a malignant lymphoid proliferation. There are more than 30 different types of NHL.

NHL can be divided in a number of ways, most commonly into high or low grade. They can also be divided into B- or T-cell lymphomas. In the UK, 9 out of 10 lymphomas are B-cell in origin.

High-grade lymphomas grow quickly and cause significant morbidity. They do however tend to be more sensitive to chemotherapy and this offers the possibility of a cure. Low-grade lymphomas tend to behave quite indolently, and some may never need treatment. If treatment is given, it is with the aim to produce a period of remission, with relapse at some point in the future likely. Low grade lymphoma may occasionally transform into a high-grade phenotype.

There is a huge variety in how NHL can present with almost any symptoms possible.

• Progressive painless lymphadenopathy is the most common feature
• Compression of surrounding structures is frequent, particularly with high grade lymphomas:
  • Renal/ureteric obstruction
  • Bowel obstruction
  • SVC obstruction
• ‘B’ symptoms are common (drenching night sweats, fevers, >10% weight loss in a 6-month period)
• Hepatomegaly and/or splenomegaly
• Cytopenias if bone marrow involvement
• Extranodal involvement can affect almost anywhere including CNS disease
• Skin involvement is most commonly seen in T-cell lymphoma

Subtypes of NHL

Examples of high-grade lymphoma:

• Diffuse large B cell lymphoma (DLBCL) – most common (40%) type of NHL
• Burkitt’s lymphoma
• Mantle cell lymphoma
• Post-transplant lymphoproliferative disorder (PTLD)
• Primary CNS lymphoma
• Enteropathy associated T cell lymphoma (EATL)
• Peripheral T cell lymphoma NOS
• Anaplastic large cell lymphoma

Examples of low-grade lymphoma:

• Follicular lymphoma
• CLL/Small lymphocytic lymphoma
• Lymphoplasmacytic lymphoma (LPL)
• Marginal zone lymphoma including MALT lymphoma
• Hairy cell leukaemia
• Mycosis fungoides

Many types of NHL are closely linked with infectious/inflammatory conditions and immunodeficiency syndromes.

PTLD is an umbrella term for a spectrum of lymphoproliferative disorders occurring due to immunosuppression following both solid organ and stem cell transplant. It is uncommon but well recognised. It is often, but not always, related to uncontrolled EBV-infected B-lymphocyte proliferation, which is normally controlled by cytotoxic T-lymphocytes (depleted with immunosuppressive therapy). It progresses through several stages, with initial stages showing more of a reactive hyperplasia before evolving into full blown lymphoma, with appearances and behaviour similar to DLBCL or Burkitt’s. In the early stages, a simple reduction of immunosuppression may result in complete remission, but later stages often need treatment with chemotherapy.
In a similar fashion, some forms of lymphoma which are strongly linked with infection e.g. gastric MALT lymphoma and H. pylori will sometimes regress spontaneously with the resolution of infection.

Treatment

There are large numbers of treatment regimes for NHL which are beyond the scope of MRCP. However, it is worth knowing about R-CHOP for DLBCL (and several other lymphoma types). This regimen consists of:

R – rituximab (anti-CD20 MAb expressed on B-cells)

C – cyclophosphamide

H – doxorubicin

O – vincristine

P – prednisolone

Many lymphoma regimens are based around a combination of steroids, conventional chemotherapy, and immunotherapy. Radiotherapy often plays a role, either as an adjunct in bulky disease or as a curative option in localised disease.

NHL is staged according to the Lugano system like with Hodgkin’s lymphoma.