Aetiology

The cause of the majority of cases of NHL is obscure. However, specific chromosomal translocations are closely associated with particular histological types. Thus, the majority of Burkitt’s lymphoma cases demonstrate the t(8;14) abnormality in which the MYC oncogene on chromosome 8 is moved next to the immunoglobulin heavy chain region on chromosome 14. Almost 90% of follicular low-grade lymphomas are characterised by t(14;18) where the BCL2 gene on chromosome 18 is moved to the immunoglobulin heavy chain region. This leads to excessive expression of BCL2, an oncogene known to inhibit apoptosis (programmed cell death). It is likely that such chromosome rearrangements require further events – perhaps co-expression of a second proto-oncogene or antigenic stimulus – to produce the clonal malignant cell. Possible triggering antigens include Helicobacter pylori in gastric MALT lymphoma and hepatitis C in marginal zone lymphoma. The aggressive extranodal lymphomas seen in AIDS are likely to result from a combination of immunosuppression (due to the HIV virus), deregulation of a proto-oncogene (MYC) and secondary viral infection (Epstein–Barr virus). Similar tumours may follow organ transplantation.

Classification

This is complex and ever-changing with a real risk of ‘heart-sink’ for the uninitiated. In simplest terms NHL can be divided into ‘high-grade’ and ‘low-grade’ types. High-grade tumours are composed of large poorly differentiated lymphoid cells. They have an aggressive clinical course but are often curable. Low-grade tumours are composed of smaller, better differentiated cells. They are more indolent clinically but have a tendency to repeatedly relapse.

The current WHO classification avoids the overly simplistic high-grade/low-grade split and divides lymphomas into more specific subtypes based on clinical features, morphology, immunophenotype, karyotype and molecular characteristics. In addition to NHL and Hodgkin’s lymphoma the WHO scheme contains a number of other lymphoid neoplasms occurring mainly at extranodal sites that are discussed elsewhere (e.g. myeloma, hairy cell leukaemia). Some of the major entities are shown in Table 30.1.

Clinical presentation

NHL is essentially a disease of lymph nodes but it has a more diverse presentation than Hodgkin’s lymphoma with more irregular spread and a higher incidence of extranodal involvement. It may be an indolent disorder, perhaps requiring no immediate treatment, or an aggressive, rapidly fatal malignancy.

Diagnosis and staging

Diagnosis depends on obtaining a tissue biopsy, usually a lymph node, for histological examination (Fig 30.2). Immunophenotyping is used to identify the degree of maturation of the malignant cell and determine whether it is of B- or T-cell origin. B-cell antigenic ‘markers’ include CD19, 20 and 22 and T-cell markers CD2, 3, 5 and 7. Gene rearrangement studies also aid identification. B-cell lymphomas have their immunoglobulin genes clonally rearranged while in T-cell lymphomas there is clonal rearrangement of the T-cell receptor genes. Molecular techniques (see p. 100) are being increasingly used to detect chromosome abnormalities and to derive prognostic information.

The staging system is similar to that used in Hodgkin’s lymphoma. Patients are staged with CT scanning (Fig 30.3), MRI or PET, and a bone marrow aspirate and trephine. However, in NHL the stage plays a more modest role in management than in Hodgkin’s lymphoma. The histological type of the tumour is more closely related to the likely clinical course and other factors impinge upon prognosis. An international prognostic index (IPI), based on age, stage, bulk of disease, performance status and serum lactate dehydrogenase (LDH) level, is commonly used (see Appendix III).

Management and prognosis

Only some of the commoner NHL subtypes will be discussed.