30. Hodgkin lymphoma

Hodgkin lymphoma

Introduction

Hodgkin lymphoma (HL) is a distinctive group of B-cell lymphoid neoplasms that are characterized by the presence of a special cell type called Reed-Sternberg cell (RS cells). It’s also characterised by the fact that the tumour consists of mostly inflammatory, responsive cells, and just a few cancerous cells. Actually, for this reason, HL has sometimes been called Hodgkin disease rather than lymphoma. The RS cells originate from mature germinal centre B-cells and cells express CD15 and CD30.

Unlike most non-Hodgkin lymphomas, Hodgkin lymphomas arise in a single lymph node and typically spreads to other lymph nodes in that region. For example, it is frequent that only the cervical lymph nodes are affected, or only the mediastinal lymph nodes, but rarely more regions at the same time.

Hodgkin lymphoma is highly treatable and curable, even when disseminated.

Etiology

Hodgkin lymphoma is associated with EBV infection in many cases, as well as immunodeficiency and autoimmune diseases.

Pathomechanism

During the normal immune response will germinal centre B cell undergo somatic hypermutation (= affinity maturation) to develop more specific antibodies against a pathogen. In this process many of these B-cells fail to mutate their immunoglobulin heavy chain gene correctly and therefore die by apoptosis. The pathogenesis of Hodgkin lymphoma may involve a germinal centre B cell that fails to mutate its heavy chain gene and therefore should die of apoptosis, but something stops the apoptosis. EBV proteins may be the cause of this anti-apoptotic activity.

Classification

There are five subtypes of HL, four of which are considered “classic Hodgkin lymphoma”:

• Classic Hodgkin lymphoma (95% of cases)
  • Nodular sclerosis HL – most frequent subtype
  • Mixed cellularity HL
  • Lymphocyte predominant HL
  • Lymphocyte depletion HL – least frequent subtype
• Nodular lymphocyte predominant HL (5% of cases)

Clinical features

It frequently presents with painless cervical, axillary or mediastinal lymphadenomegaly. “B symptoms” are rare but may occur.

Classical Hodgkin lymphoma

Classical Hodgkin lymphoma (cHL) occurs in two different age peaks: around 15-30 years and above 55. cHL was the first curable lymphoma, and now 80-90% of cases are cured.

Most subtypes of cHL have good prognosis, except for the lymphocyte depletion type, which luckily is the rarest type. The 5-year survival rate is close to 100% for stage I and II, and around 50% for stage IV classical Hodgkin lymphoma.

Nodular sclerosis HL is the most frequent subtype, accounting for 50-70% of all cases of cHL. It most frequently affects mediastinal lymph nodes of patients in the 15-30 year range.

Nodular lymphocyte predominant Hodgkin lymphoma

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) accounts for only 5% of Hodgkin lymphomas. The cell type in this case is a variant Reed-Sternberg cell that is called L&H cell or popcorn cell. This cell expresses CD20 but not CD30 or CD15.

NLPHL usually affects children or adults between 30-40 years. It tends to recur but generally has a very good prognosis. 50% of NLPHL involves a translocation of the BCL6 gene.

Hodgkin lymphoma vs non-Hodgkin lymphoma

The reason the lymphoid neoplasms are classified this way is because these two types have different characteristics. They are summed up in the table below:

Hodgkin lymphoma	Non-Hodgkin lymphoma
Often localized to a single lymph node region, cervical, axillary or mediastinal	Often localized to multiple lymph node regions
Extranodal involvement uncommon	Extranodal involvement common
Originate from B-cells	Originate from B, T or NK cells
Mostly affects adolescents and young adults	Mostly affects older adults (>55)
Very good prognosis	Prognosis depends on subtype
Very few cancer cells surrounded by inflammatory cells	Only cancer cells
Less common	More common
Main symptom is painless lymphadenomegaly and B symptoms