Hodgkins lymphoma

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Hodgkins lymphoma (Hodgkin's lymphoma, Hodgkin's disease, Hodgkin lymphoma, HL) is a type of monoclonal lymphoma classically characterised by the presence of Reed-Sternberg cells, but more accurately by the presence of the Lewisx trisaccharide, also known as the CD15 antigen, as a diagnostic marker on such cells.

Nodular lymphocyte predominant Hodgkin's lymphoma (5% of "Hodgkin's" lymphoma) is often regarded separately due to its different phenotype and more favourable clinical behaviour.

Contents

History

First described by Thomas Hodgkin in 1832[1]. The original description was not a microscopic one, although microscopes were available at that time. Instead it was based on the gross appearances of the spleen and lymph nodes. Historical material was available on 3 cases in Hodgkin's original series. Modern analysis of these 3 cases, still retained at the Gordon Museum at Guy's Hospital in London, shows that two were Hodgkin's lymphomas, while another was a non-Hodgkin's lymphoma[2][3]) it became one of the first malignancies to have high cure rates with radiotherapy and classic cell division blocking chemotherapy.

Classification terminology has evolved from Jackson and Parker in 1944 three type paragranuloma, granuloma, and sarcoma to lymphocyte predominance (LP), nodular sclerosis (NS), mixed cellularity (MC), and lymphocyte depletion (LD) subtypes based on the 1966 Lukes and Butler terminology[4].

Epidemiology

About 11% of all lymphomas with an age-standardized rate of 1 per 100,000, with lowest incidence in the Far East and highest in Near East and Italy. In the developed world, it is the commonest neoplasm of adolescents (overwhelmingly most in this age group are of the NS histological subtype) and has another peak in incidence in those over 60 years (most are MC subtype).

Pathology

Reed-Sternberg cell (binucleate) and Hodgkin cell in classic Hodgkin's lymphoma. Note the mixed cellularity
Reed-Sternberg cell (binucleate) and Hodgkin cell in classic Hodgkin's lymphoma. Note the mixed cellularity

It is almost always derived from (post-)germinal centre B cells. Classical Hodgkin's lymphoma has a small number of mononuclear Hodgkin (H) cells and bi/multi-nucleated Reed-Sternberg (RS) cells in an extensive inflammatory background making up about 85% of the abnormal cells.

Hodgkin's lymphoma, unlike other B-cell lymphomas has an almost complete absence of B-cell markers from the H and RS cells, e.g. CD19, CD20 (may be weak) and CD79b and the up-regulation of B-cell lineage inappropriate genes. OCT2 and BOB1 are co-transcription factors involved in immunoglobulin production - these are typically inactivated in cHL. The Hodgkin/Reed-Sternberg cells, collectively known as HRS cells, are typically CD15, CD30 and MUM1 positive.

Nodular lymphocyte-predominant Hodgkin's lymphoma, in contrast, is typically positive for pan-B cell markers, but negative for CD15, CD30 and MUM1.

20-40% of classical Hodgkins lymphoma is associated with the presence of Epstein-Barr virus genome in the malignant cells[5]. Familial Hodgkins lymphoma is associated with both EBV positivity and HLA class I haplotypes. Gene studies have produced prognostic markers.

Clinical

Classical Hodgkins lymphoma presents in adolescents and young adults as persistent painless firm lymphadenopathy, usually of the upper body.

In the immunocompromised, e.g. those with HIV infection, it often presents as extranodal disease and with B symptoms. Rarely, it may present with para-neoplastic syndromes of which the classic symptoms were pruritus and alcohol-induced pain.

Treatment

First line

Despite massive improvements in survival and decreased toxicity the optimal treatment remains controversial[6]. Radiotherapy alone may be an option in some presentations. Consolidative radiotherapy has more long term side-effects than chemotherapy (it increases rates of secondary cancers, cardiovascular disease, and stroke two to seven-fold at 25 years) and some are advocating chemotherapy alone.

Chemotherapy regimes with good response have been reasonably well defined:

Treatment is usually assessed after 2 cycles of chemotherapy using 18-FDG PET. The metabolic response on PET is assessed using the Deauville score. ~80% of patients will have a good response (PET negative) with a favourable prognosis such that there is some evidence that dropping bleomycin from ABVD in this group produces similar outcomes. In contrast, PET-positive patients have a poorer prognosis and may benefit from escalation to eBEACOPP.

Relapse

Other treatments:

  • Rituximab
  • Brentuximab vedotin , an anti-CD30 monoclonal antibody has an increasing role in refractory/relapsed disease.

References

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