The term non-Hodgkin’s lymphoma encompasses many different histological subtypes. The basic subdivision into high and low grade (Kiel classification) reflects the rate at which the cells are dividing. Ironically, high-grade lymphomas (those in which the cells are dividing quickly) are potentially curable, whereas low-grade lymphomas are generally considered to be incurable with conventional therapy, although patients may live for a number of years and respond to treatment several times. A further subdivision is made on the basis of B- or T-cell origin. Most NHLs are of B-cell phenotype although T-cell tumours are increasingly being recognized. Several different histological groupings have been suggested; the two most widely used at present are the Kiel classification and the ‘Working Formulation’. The latter (which looks much simpler) is not really a histological classification but an attempt to group together diseases which behave in a relatively similar way, to allow comparison between treatment results.
Most patients present with peripheral lymph node enlargement, with or without systemic symptoms. Patients with low-grade lymphoma often have bone marrow infiltration and may have symptoms of anaemia, recurrent infections or bleeding. In addition to peripheral lymphadenopathy, NHLs frequently also involve mediastinal, intra-abdominal and pelvic lymph nodes with resulting symptoms. In contrast, they may involve only an extranodal site, e.g. part of the gastrointestinal tract 24.
FULL BLOOD COUNT AND ESR – anaemia; an elevated wee or thrombocytopenia would be suggestive of bone marrow infiltration.
UREA AND ELECTROLYTES – patients may, for example, have renal impairment as a consequence of ureteric obstruction, secondary to intra-abdominal or pelvic lymph node enlargement.
LIVER BIOCHEMISTRY may be abnormal if there is hepatic involvement.
CHEST X-RAY. CT SCANS of chest, abdomen and pelvis.
BONE MARROW ASPIRATE AND TREPHINE BIOPSY.
LYMPH NODE BIOPSY (or Trucut needle biopsy in the case of surgically inaccessible nodes) .
Treatment will depend on the extent and distribution of disease as well as on histological subtype. Patients with stage I disease can be cured with radiotherapy alone (or radiotherapy plus chemotherapy); those with more extensive involvement require systemic therapy.
Repeated remissions can usually be achieved with relatively simple treatment, e.g. the allcylating agent chlorambucil. More intensive treatment has thus far not been shown to improve survival. The response rate at presentation, first and second recurrence is approximately 75%, with a median survival of 9 years. With such conventional therapy, the disease remains incurable, and new approaches such as IFN and the use of myeloablative therapy with allogeneic or autologous BMT are therefore being investigated. Low-grade B-cell diffuse lymphomas (generally either lymphoplasmacytoid or centrocytic) The majority of patients present with advanced disease, the bone marrow frequently being involved. In the small proportion of patients who present with localized disease, the site may be extranodal, most frequently the gastrointestinal tract. The prognosis for patients with low-grade B-cell diffuse lymphoma is worse than that of patients with equivalent stage follicular lymphoma, with a median survival of 3.5 years, fewer than 20% surviving more than 5 years.
Low-grade T-cell lymphoma
These tumours are less common than their B-cell counterparts and are part of a spectrum of disease known as ‘peripheral T-cell lymphomas’. Patients present with enlargement of a peripheral lymph node which, on biopsy and immunophenotyping, is found to be of T-cell origin. Remissions can be achieved with relatively simple treatment, e.g. chlorambucil, but are usually short-lived and therefore more intensive treatment is generally used. However, with current conventional treatment, recurrence is virtually inevitable.
High-grade lymphomas are more commonly of B-cell, rather than T-cell, origin. Some patients with localized (stage I disease) can be cured with local radiotherapy with or without chemotherapy, or chemotherapy alone. However, the majority present with more advanced disease, chemotherapy being usually given with curative intent. Achievement of a CR is a prerequisite for cure.
Treatment usually comprises an anthracycline, e.g. doxorubicin given with cyclophosphamide, vincristine (oncovin) and prednisolone (CHOP). Variations on a theme of CHOP have since been tried but thus far none has been shown to be definitively superior in terms of survival. Three factors correlate with survival: advanced disease (stage III and IV), a high serum lactate dehydrogenase (LDH) and poor performance status (an estimate of the person’s general state of health) are all associated with a poor prognosis.
With modern combination chemotherapy, 60-70% of patients respond to treatment and about one-third overall are cured. The treatment is inevitably myelosuppressive and therefore, particularly in older patients, the main problem is potentially fatal infection as a consequence of neutropenia. Recurrent high-grade lymphoma has a grave prognosis. However, a proportion of patients who respond to further chemotherapy at recurrence can still be cured with myeloablative therapy supported by autologous BMT or peripheral blood progenitor cells.
Burkitt’s lymphoma was first described by Dennis Burkitt in children in West Africa who presented with a specific syndrome comprising a lesion in the jaw, extranodal abdominal involvement and ovarian tumours. This specific type of lymphoma is found in areas of Africa where there is a high incidence of the Epstein Barr virus EBV) and in areas where malaria is common. Most patients have EBV antibodies in the serum. The tumour can be treated with both radiation and chemotherapy and associated with a chromosome change, most commonly.