Introduction to the lymphoproliferative disorders

Lymphoproliferative disorders occur when the normal mechanisms of control of proliferation of lymphocytes break down, resulting in autonomous, uncontrolled proliferation of lymphoid cells and typically leading to lymphocytosis and/or lymphadenopathy, and sometimes to involvement of extranodal sites, e.g. bone marrow.

Causes of lymphoproliferative disorder

These include (1) malignant—clonal in nature, resulting from the uncontrolled proliferation of a single transformed cell, e.g. lymphoma; (2) nonmalignant—polyclonal lymphoproliferative disorders may result from conditions including (a) infections—lymphocytosis is commonly caused by viral infections, e.g. Epsitein–Barr virus (EBV); lymphadenopathy is a common feature of a very wide variety of infections, (b) reactive—conditions such as systemic lupous erythematosus (SLE) and sarcoidosis frequently cause lymphadenopathy.

Clinical approach

Distinguishing among the lymphoproliferative disorders clinically and pathologically is not always easy.

Clinical assessment—when eliciting the history of a patient with suspected lymphoproliferation, particular note should be taken of their general health, the type and duration of any constitutional symptoms, and any episodes of recent infection/exposure to drugs/travel. Thorough examination of all lymph node sites is required, as is careful examination of the oropharynx, tonsils, skin, spleen, and liver.

Investigation—whenever a lymphoproliferative disorder is suspected, the key initial investigation is the full blood count and examination of the blood film, sometimes augmented by immunocytochemistry and flow cytometry. Depending on clinical context, other investigations may include (1) serological studies for viral pathogens; (2) serological studies for rheumatological disease; (3) imaging for mediastinal and intra-abdominal lymphadenopathy; (4) bone marrow examination; and—if no diagnosis is apparent—(5) lymph node biopsy. However, there are many pitfalls in morphological interpretation of lymph node histology, which is a matter for the specialist, who will often draw on supplementary information from flow cytometry, cytogenetics, and immunoglobulin/TCR gene rearrangement studies to demonstrate the clonal nature of malignant disease and provide data with prognostic and therapeutic significance, or to identify the presence of specific viruses such as EBV and human herpes virus 8.