HODGKIN LYMPHOMA

HODGKIN LYMPHOMA
The histological hallmark of Hodgkin lymphoma (HL) is the presence of Reed-Sternberg cells, which are large malignant lymphoid cells of B-cell origin (Fig. 24.30). They are often only present in small numbers but are surrounded by large numbers of reactive normal T cells, plasma cells and eosinophils. The WHO classification is based on histology and is shown in Box 24.51. Nodular lymphocyte¬
24.50 EPIDEMIOLOGY AND AETIOLOGY OF
HODGKIN LYMPHOMA I
Incidence
v Approximately 4 new cases/100 000 population/year
Sex ratio
v Slight male excess (1.5:1)
Age I
i
v Median age 31 years; first peak at 20-35 years and second at
50-70 years
Aetiology
0 Unknown. More common in patients from well-educated
backgrounds and small families. Three times more likely with a
past history of infectious mononucleosis but no causal link to
Epstein-Barr virus infection proven
 
Fig. 24.30 Hodgkin lymphoma showing typical Reed-Sternberg cell,
24.51 WHO PATHOLOGICAL CLASSIFICATION AND INCIDENCE OF HODGKIN LYMPHOMA (HL)
predominant HL is slow-growing, localised and rarely Classical HL is divided into four histological subtypes from the appearance of the Reed-Sternberg cells and surrounding reactive cells. The nodular sclerosing type accounts for the initial peak in young patients and is more comm women. Mixed cellulariy is more common in the e peak. Lymphocyte-rich HL usually presents in Lymphocyte-depleted HL is rare and probably repr large cell or anaplastic non-Hodgkin lymphoma.
fatal. on in lderly men. esents
Clinical features There is painless rubbery lymphadenopathy, usually in the neck or supraclavicular fossae; the lymph nodes fluctuate in size. Young patients with nodular scle disease may have large mediastinal masses whic surprisingly asymptomatic but may cause dry coug some breathlessness. Isolated subdiaphragmatic nodes
in less than 10% at diagnosis. Hepatosplenomegaly present but does not alwavs indicate disease. Spr contiguous from one node to the next and extr disease, such as bone, brain or skin involvement. is ra
may rosing h are h and occur
may be ead is anodal re.
Investigations Treatment of HL depends upon the stage at present therefore investigations aim not only to diagnose lymp but also to determine the extent of disease (Box 24.52 ation;
homa ).
he n,
r~
~ Full blood count may be completely normal. A normochromic, normocytic anaemia may be presen together with lymphopenia. is a bad prognostic fact An eosinophilia or a neutrophilia may be present. • ESR may be raised.
• Renal function tests are required to ensure function normal prior to treatment.
• Liver,functiou may be abnormal in the absence of disease or reflect hepatic infiltration. :1n obstructiv pattern may be caused by nodes at the porta hepatis
• LDH measurements, as raised lewel~ are an adverse prognostic factor.
t and, or.
is
e
 
24.52 CLINICAL STAGES OF HODGKIN LYMPHOMA
(ANN ARBOR CLASSIFICATION)
Stage Definition
I Involvement of a single lymph node region (I) or
 extralymphatic site (IA+_)
II Involvement of two or more lymph node regions (II) or an
 extralymphatic site and lymph node regions on the same
 side of (above or below) the diaphragm (IIE)
III Involvement of lymph node regions on both sides of t
 diaphragm with (IIIE) or without (III) localised
 extralymphatic involvement or involvement of the spleen
 (Ills) or both (IIISo
I IV Diffuse involvement of one or more extralymphatic
I tissues, e.g. liver or bone marrow
A No systemic symptoms
B Weight loss, drenching sweats
The lymphatic structures are defined as the lymph nodes, splee n
thymus, Waldeyer s ring, appendix and Peyer s patches.
 
 Type Histology Incidence
 Nodular lymphocyte-  5%
 predominant HL  
 Classical HL Nodular sclerosing 70%
  Mixed cellularity 20%
  Lymphocyte-rich 5%
  Lymphocyte-depleted Rare   
 
Fig. 24.31 CT-guided percutaneous needle biopsy of retroperitoneal nodes involved by lymphoma.
• Chest X-ray may show a mediastinal mass.
• CT scan of chest and abdomen to permit staging. Bulky disease (greater than 10 cm in a single node mass) is an adverse prognostic feature.
• Lymph node biopsy may be undertaken surgically or by percutaneous needle biopsy under radiological guidance (Fig. 24.31).
Management
Treatment options include radiotherapy. chemotherapy or a combination of the two (Box 24.53).
24.54 THE ChIVPP REGIMEN FOR -
HODGKIN LYMPHOMA
Drug Dose
Chlorambucil 6 Mg/M2 (up to 10 mg total) days 1-14 orally
Vinblastine 6 Mg/M2 (up to 10 mg total) days 1 and 8 i.v.
Procarbazine 100 Mg/M2 days 1-14 orally
Prednisolone 40 mg/m2 days 1-14 orally
80% of patients will respond to this combination therapy, with drugs delivered on an outpatient basis every 3-4 weeks for a total of 6-8 cycles. Treatment response is assessed clinically and by repeat CT.
This type of chemotherapy carries a high risk of inducing permanent infertility in men; adequate counselling and sperm storage must be offered at diagnosis. The risk of infertility is lower for women but advice about obtaining ovarian tissue before starting treatment should be given as appropriate. Premature menopause may result from treatment and hormone replacement therapy should be discussed with the patient. Corticosteroids can cause avascular necrosis of bone, particularly the femoral head. Myelodysplasia and acute leukaemia can occur 5-10 years after alkylating therapy but the incidence is less than 5%.
Combined modality therapy
Radiotherapy may be given to the original sites of bulky disease after treatment by chemotherapy to reduce the risk of relapse. This form of treatment carries the greatest risk of long-term complications.
 
Radiotherapy
Good results are obtained in localised stage IA or stage IIA disease with no adverse prognostic features. Careful planning is required to limit the doses delivered to normal tissues. Fertility is usually preserved after radiotherapy. Women receiving breast irradiation during the treatment of chest disease have an increased risk of breast cancer and should be placed on a screening programme. Patients continuing to smoke after lung irradiation are at particular risk of lung cancer.
Chemotherapy
All other patients are treated initially with chemotherapy. The regimen in Box 24.54 is widely used in the UK. Over
24.53 THERAPEUTIC GUIDELINES FOR 91
HODGKIN LYMPHOMA
Indications for radiotherapy
• Stage I disease
• Stage IIA disease with three or fewer areas involved
• After chemotherapy to sites where there was originally bulk
disease
• To lesions causing serious pressure problems
Indications for chemotherapy
• All patients with B symptoms
• Stage II disease with more than three areas involved
• Stages III and IV disease
Prognosis
Over 90% of patients with stage IA disease are cured by radiotherapy alone. Patients with stage IIA disease have a reduced cure rate from radiotherapy. Approximately 70% of patients treated with chemotherapy are cured. The 15% of patients who fail to respond to initial chemotherapy have a poor prognosis but some may achieve long-term survival after high-dose chemotherapy and autologous stem cell rescue. Patients relapsing after local radiotherapy have a good cure rate after subsequent chemotherapy but with an increased risk of long-term toxicity. Those relapsing within a year of initial chemotherapy have a good salvage rate with high-dose therapy and autologous stem cell rescue. Patients relapsing after 1 year may obtain long-term survival with further chemotherapy.