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They may sound similar, but Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) are two distinct types of lymphoma, each with unique disease characteristics. In this issue of HealthNews, we look at some of the key differences between them.

Lymphoma is a type of blood cancer that begins in the lymphatic system—a network of vessels, nodes, and ducts throughout the body that is part of our immune system. It occurs when lymphocytes (a type of white blood cell in our immune system that helps fight infection) grow and multiply uncontrollably.

In Singapore, lymphoma is the 5th most common cancer in both males and females¹. It is also the 7th and 8th most common cause of cancer deaths in Singaporean males and females respectively.

Lymphoma can be classified into two main types: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). HL, NHL and their subtypes each have their own unique disease characteristics, so it is important to know the differences between them.

What is Hodgkin lymphoma?

HL commonly originates from B-lymphocytes (i.e. B-cells). It often starts in the lymph nodes of the upper part of the body, including the neck, chest and underarms².

HL tends to spread in a predictable, orderly manner from one group of lymph nodes to the next (i.e. contiguous spread).

HL can be divided into two main subtypes:

• Classical HL (cHL)

  cHL is the most common subtype of HL, accounting for more than 9 in 10 cases of HL in developed countries³. It is characterised by Hodgkin and Reed-Sternberg cells, which are large, abnormal lymphocytes that may contain more than one nucleus⁴.

  cHL can be further divided into four subtypes:

  • Nodular sclerosis HL (NSCHL)
  • Mixed cellularity HL (MCCHL)
  • Lymphocyte-rich HL
  • Lymphocyte-depleted HL
• Nodular lymphocyte-predominant HL (NLPHL)

  NLPHL affects approximately 5% of patients with HL⁵. It is characterised by lymphocyte-predominant cells (known as popcorn cells). This type of HL is slow-growing and treated differently from cHL.

What is non-Hodgkin lymphoma?

NHL can begin anywhere in the body where lymphatic tissues are present, including organs such as the stomach, intestines or skin. It commonly originates from B-lymphocytes (i.e. B-cells). In rare cases, it may also originate from T-lymphocytes (i.e. T-cells) or natural killer (NK) cells.

NHL is a heterogeneous disease that can be divided into over 60 subtypes, based on the cell type (B-cell, T-cell, or NK cell), location (nodal or extranodal), and tumour grade. B-cell lymphomas are the most common subtype of NHL, making up about 85% of NHL cases⁶.

NHL may occur in a single lymph node or multiple sites in the body (i.e. non-contiguous spread). NHL subtypes can be grouped based on the rate of disease progression:

• Indolent lymphomas, which are slow-growing e.g. Follicular Lymphoma (FL)
• Aggressive lymphomas, which are fast-growing, and usually need to be treated right away e.g. Diffuse Large B-cell Lymphoma (DLBCL)

Differences between HL and NHL

The following table illustrates some key differences between HL and NHL:

Besides the key differences illustrated above, HL and NHL can generally be distinguished by the presence of Hodgkin and Reed-Sternberg cells, which make up a small part of the tumour in patients with HL, and increase in number as the disease progresses. Reed-Sternberg cells may also be seen infrequently in B-cell and T-cell NHL with comparable morphology and immunophenotype⁹.

Doctors may determine the patient's specific subtype of lymphoma by examining the lymphoma cells under a microscope, alongside other diagnostic tests.

Are symptoms similar or different for HL and NHL?

In general, HL and NHL share common symptoms, such as:

• Fever
• Unexplained weight loss
• Night sweats
• Anaemia or reduced red blood cell count
• Painless swelling of the lymph nodes in the neck, armpit, or groin
• Itching of the skin all over the body
• Persistent fatigue
• Coughing, difficulty breathing, and chest pain
• Pain in the abdomen

With both HL and NHL, the first symptoms to appear are often fever, unexplained weight loss, and night sweats. HL patients may also experience inflammatory symptoms, such as lymph node pain, when drinking alcohol.

Treating HL and NHL

In general, HL and NHL can be managed with a wide array of treatment modalities^10-11:

• Chemotherapy uses chemical drugs to destroy cancer cells. It is usually given as first-line treatment for HL and NHL, and may be administered alone or in combination with other therapies for improved patient outcomes.
• Radiation therapy uses high-energy rays such as X-rays to kill cancer cells. It is usually used as first-line treatment for localised NHL, or in combination with chemotherapy for advanced or aggressive NHL. For cHL, radiation therapy is often given after chemotherapy, especially in cases of large or bulky tumours.
• Immunotherapy harnesses the patient's own immune system to destroy cancer cells. They include monoclonal antibodies and immune checkpoint inhibitors, which may be used in the treatment of both HL and NHL.
• Stem cell transplantation (SCT), also known as bone marrow transplantation, involves replacing damaged bone marrow with healthy stem cells. It is usually reserved as second-line treatment when patients have relapsed or refractory disease that does not respond to standard treatment.
• Chimeric Antigen Receptor (CAR) T-cell Therapy is a recent development that involves genetically engineering a patient's T-cells to destroy cancer cells. This type of immunotherapy has shown promising outcomes in the treatment of lymphoma, with an overall success rate of 60-80% in achieving remission¹². Lymphoma patients currently eligible to receive CAR T-cell Therapy include:
  • Adults with relapsed or refractory DLBCL who have not benefitted from at least two types of standard treatment.
  • Adults with relapsed or refractory FL who have not benefitted from at least two types of standard treatment.

The treatment aims and approaches for both HL and NHL depend on the disease subtype, characteristics of the disease, extent of the disease, as well as the patient's general health. It is thus important to get the correct diagnosis and staging to determine the most appropriate treatment for the patient.

¹Singapore Cancer Registry Annual Report 2020
²'What is Hodgkin Lymphoma?', American Cancer Society, 2023
³'What is Hodgkin Lymphoma?', American Cancer Society, 2023
⁴'Reed-Sternberg cell', National Cancer Institute Dictionary of Cancer Terms, 2023
⁵https://www.ncbi.nlm.nih.gov/books/NBK499969/
⁶'Types of B-cell Lymphoma', American Cancer Society, 2023
⁷'Hodgkin Lymphoma Risk Factors', American Cancer Society, 2023
⁸'Non-Hodgkin Lymphoma Risk Factors', American Cancer Society, 2023
⁹Yadav G, Singh A, Jain M, Kushwaha R, Verma SP. Reed Sternberg-Like Cells in Non-Hodgkin Lymphoma: A Diagnostic Challenge. Discoveries (Craiova). 2022 Sep 30;10(3):e155. doi: 10.15190/d.2022.14. PMID: 36540090; PMCID: PMC9754675.
¹⁰'Treating Hodgkin Lymphoma', American Cancer Society, 2023
¹¹'Treating Non-Hodgkin Lymphoma', American Cancer Society, 2023
¹²https://ashpublications.org/bloodadvances/article/4/21/5414/