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Lymphomas are neoplasms of T, B or natural killer (NK) lymphoid cells and their precursors. Although having different characteristics from their normal counterparts, the neoplastic cells of many lymphomas have the features of lymphoid cells at a particular stage of differentiation. In addition, lymphoma cells can have the characteristics of lymphocytes that normally reside in a particular organ or tissue. Neoplastic lymphocytes tend to ‘home’ to the tissues and specific locations where their normal counterparts reside. Lymphomas arise as a result of a series of mutations in a single lymphoid cell. Usually, this is a cell already committed to the B, T or NK lineage although rarely the mutation is in a pluripotent myeloid-lymphoid stem cell or in a common lymphoid stem cell. In the former case, exemplified by the 8p11 syndrome (FGFR1 rearranged), patients can have a B-cell precursor or T-cell precursor leukaemia/lymphoma during one phase of the disease and an acute or chronic myeloid leukaemia during another phase [1]. In the latter instance, exemplified by mixed lineage acute leukaemia (designated mixed phenotype acute leukaemia in the WHO classification), neoplastic cells express various combinations of B-lineage, T-lineage and myeloid markers on cells of the same clone [2]. Lymphomas differ from lymphoid leukaemias in that the predominant disease manifestations are in lymphoid organs or tissues whereas in lymphoid leukaemias, the predominant manifestations are in the bone marrow and the blood.

The mutations leading to lymphoma are very variable. Invariably, they involve oncogenes and often there is also loss of function of tumour suppressor genes. It is the nature of the molecular events that is the crucial factor determining the nature of the lymphoma. Sometimes, these molecular changes are the result of major chromosomal rearrangements, such as a translocation or inversion, and can be predicted by standard cytogenetic analysis [3].

An understanding of the normal immune system necessarily underpins an understanding of the nature of lymphoma.

The normal immune system

The immune system includes lymph nodes, spleen and thymus and, in addition, lymphoid cells in many other organs, including particularly the bone marrow, the liver, the gastrointestinal tract, the upper and lower respiratory tracts and the genitourinary system. Mucosa-associated lymphoid tissue (MALT) includes (1) discrete lymphoid structures such as the appendix, Peyer’s patches in the submucosa of the intestine, and the tonsils and adenoids (collectively referred to as Waldeyer’s ring) in the pharynx and (2) lymphocytes in the submucosa of various organs that do not form any macroscopically recognizable structure. The various components of the immune system are interconnected by lymphatic channels and by the blood stream. In addition to lymphoid cells and certain plasma proteins, the normal immune system includes other cells with phagocytic and antigen-presenting function, including neutrophils, monocytes, macrophages and dendritic cells [4]. The immune system has both innate and adaptive components, and both of these ...

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