NHL has a current incidence of 17 per 100,000 and this has been increasing over the past 50 years.1 The aetiology is unknown in most cases. Some subtypes are associated with infectious agents (for example, Epstein-Barr virus) and an increased incidence is seen in association with immune defects, such as HIV/AIDS.
Pathology and clinical features
Eighty-five per cent of cases of NHL are B-cell derived and the remaining 15% are T-cell derived. NHL is currently classified according to histological subtype using the WHO classification (see boxes 1a,1b).2
Accurate diagnosis is important because different subtypes will be treated with different treatment regimens. For many years, NHL has been subdivided into low- and high-grade disease. In general, high-grade lymphomas are aggressive, highly proliferative and, if not treated, rapidly fatal, but can be cured with chemotherapeutic regimens. Low-grade lymphomas are relatively indolent and patients can survive with them for many years. However, low-grade lymphomas are not usually considered curable.
The prime feature is lymphadenopathy occurring at any site, most commonly the neck, axilla, or inguinal region. There is often more than one lymph node region involved. Other symptoms, sometimes called B symptoms, include night sweats, weight loss greater than 10% of body weight and anorexia.
The features of bone marrow involvement include anaemia, thrombocytopenia and leucopaenia. Other presentations include an abdominal mass (the second most common extranodal site after the bone marrow), skin involvement (especially in T-cell lymphomas) and the CNS. CNS symptoms may indicate a primary CNS lymphoma. Spinal cord compression and hyperviscosity symptoms (due to Waldenstrom’s macroglobulinaemia) are other possible presentations.
Diagnosis and staging
A whole lymph node biopsy is preferred for diagnosis, although needle core biopsies are increasingly being used. The diagnosis of lymphoma is becoming ever more complicated and a number of investigations need to be carried out. These include microscopy, immunological investigation by immunohistochemistry, cytogenetic analysis, fluorescent in-situ hybridisation, and molecular genetic analysis. A bone marrow aspiration and trephine biopsy are important for staging but can also be useful in diagnosis. Other laboratory investigations include an FBC and lactate dehydrogenase (LDH). The LDH level is used as a prognostic marker and is elevated in more rapidly proliferating and extensive disease. HIV testing is always performed and immunoglobins are assessed (lymphoproliferative disorders account for 4% of all cases of monoclonal gammopathy of undetermined significance). A uric acid test will assist in the prevention or management of tumour lysis syndrome.
Imaging techniques include a CT scan of the thorax, abdomen and pelvis, which is normally required to assess the patient’s stage (Figure 1). MRI scanning is only required in special circumstances, for example in presentations of spinal cord compression. PET scanning is being investigated in clinical trials to assess response to treatment and to stratify treatment. Its exact role in routine practice has yet to be established.
Staging of the disease is based on the Ann Arbor Staging System (see Box 2). Although this was initially designed for use in Hodgkin’s lymphoma, it is also used in NHL.
The most commonly used prognostic index is the International Prognostic Index, which is used for aggressive NHL. It assesses adverse patient-related factors (age and performance status) and tumour-related factors (staging, LDH level and the number of extranodal sites). The presence of no or one adverse factors is associated with a five-year overall survival of more than 70%, compared with less than 30% for four or five factors. More recently a prognostic index has been developed for follicular lymphoma, the Follicular Lymphoma International Prognostic Index.