Hodgkin's lymphoma

The aetiology of HL remains unclear but is likely to be multi-factorial. Furthermore, it may vary with age at presentation, geographic location, and histological sub-type. The presentation of HL (i.e., fevers, night sweats, lymphadenopathy) suggests an infectious aetiology. Indeed, the malignant Reed-Sternberg cells harbour Epstein-Barr virus (EBV) antigens in a significant proportion of cases (20% to 40%).[9][10] The demonstration that a history of mononucleosis is a risk factor for developing EBV-positive HL further supports this hypothesis.[11] Whether the association between EBV and HL is causal has not been conclusively demonstrated. Furthermore, not all cases of HL are related to EBV or infectious mononucleosis.

There is evidence of a familial predisposition to HL, but this is uncommon (approximately 5% of cases are believed to be familial).[12][13][14] If a monozygotic twin is diagnosed with HL, the risk of the second twin developing HL is nearly 100 times greater than that of the general population.[15] The risk among dizygotic twins is lower (approximately 7 times greater than the general population).[16] First-degree relatives of patients with HL are approximately 3 times more likely to develop the disease than the general population.[17][18]

The pathogenesis of HL remains unclear, although several mechanisms have been postulated. Pathogenesis is likely to be different in patients with Epstein-Barr virus (EBV)-positive disease compared with those with EBV-negative disease.

HL is a B-cell malignancy, and immunoglobulin expression is typically absent despite gene re-arrangements and somatic hyper-mutation.[19] Surface immunoglobulin (B-cell receptors) is required for B-cell maturation and survival.[20][21] In EBV-positive disease, it is thought that viral proteins (LMP1, LMP2A, EBNA1) allow infected, abnormal B cells to evade apoptosis and/or replicate in an uncontrolled manner by mimicking constitutively active cellular receptors that are essential for B-cell growth, survival, and evasion of apoptosis.[22][23]

The 5th edition of the World Health Organization Classification of haematolymphoid tumours: lymphoid neoplasms[1]

Classical HL (95% of cases).[2]

Within this category:
- Nodular sclerosis (70%)
- Mixed cellularity (25%)
- Lymphocyte-rich (5%)
- Lymphocyte-depleted (<1%).

Nodular lymphocyte-predominant HL (NLPHL; 5% of cases).

The International Consensus Classification of mature lymphoid neoplasms: a report from the Clinical Advisory Committee[3]

The International Consensus Classification (ICC) of mature lymphoid neoplasms Clinical Advisory Committee has reclassified NLPHL as ‘nodular lymphocyte predominant B-cell lymphoma’. The ICC highlighted biological and clinical differences between NLPHL and classical HL and the close relationship of NLPHL to T-cell/histiocyte-rich large B-cell lymphoma.[3]

The 5th edition of the World Health Organization Classification of haematolymphoid tumours retains the existing terminology and position of NLPHL as a subtype of Hodgkin's lymphoma. However, the WHO recognises ‘nodular lymphocyte predominant B-cell lymphoma’ as an acceptable term, with definitive adoption of these changes under consideration.[1]

Aetiology

Pathophysiology

Classification