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Current Issues in Cancer Current Issues in Cancer Non-Hodgkin's lymphoma-. I: characterisation and treatment BMJ: first published as 10.1136/bmj.304.6843.1682 on 27 June 1992. Downloaded from Susan E O'Reilly, Joseph M Connors This is the eighth in a series of The non-Hodgkin's lymphomas are a heterogeneous providing increasing insight into the molecular artic es examining recent collection of lymphoproliferative malignancies whose biological origin of lymphomas and have shown that developments in cancer clinical behaviour, prognosis, and management vary the follicular (nodular) lymphomas are almost exclu- widely according to histological subtype, stage, and sively ofB cell origin and that lymphoblastic lymphoma bulk of disease. They are the seventh most commonly and mycosis fungoides typically arise from T cells. diagnosed malignancy. Typically patients present with Diffuse lymphomas may arise from B or T cells or may localised or generalised lymphadenopathy. Common be of indeterminate origin. We have used the working presenting findings are haematological cytopenias, formulation terminology throughout this review (table drenching night sweats, unexplained fevers, or weight I). loss greater than 10% of baseline (B symptoms); Developmentsinimmunology, monoclonal antibody hepatosplenomegaly, abdominal masses, or compres- probes, cytogenetics, and characterisation ofoncogenes sion of internal organs such as the gastrointestinal and growth factors will continue to expand our under- tract, blood vessels, airways, spinal cord, ureters, or standing of lymphomas. And these added insights into bile ducts; or localised tumours of parenchymal or lymphoma classification may eventually translate into visceral organs. Nevertheless, lymphoma may mimic improved treatments. Nevertheless, despite the virtually any other neoplasm. increasing sophistication of the molecular biologists Until about 25 years ago, most patients with non- and pathologists most clinical decisions are based on Hodgkin's lymphomas died of their disease. Although light microscopy. An experienced haematopathologist radiotherapy, single drug chemotherapy, and cortico- can regularly and reproducibly distinguish between steroid treatments were useful in palliating these follicular (nodular) and diffuse lymph node disease and patients, they were rarely curative. The advent of between small and large lymphocytes. It is usually effective combination chemotherapy regimens, initially relatively straightforward to distinguish the uncommon developed for Hodgkin's disease and subsequently special lymphomas: small non-cleaved cell (Burkitt's applied to non-Hodgkin's lymphomas, resulted in the and non-Burkitt's) and T cell lymphoblastic lym- cure of advanced tumours in a few patients with phomas. In addition, haematopathologists can lymphoma.' Similarly, improvements in histological discriminate between the true lymphomas and subclassification, diagnostic radiology, radiation lymphoma-like conditions such as sarcoidosis, syphilis, therapy, and general supportive care, especially in pseudolymphomas, and lymphadenopathy related to treating infectious complications of lymphomas, have HIV, as well as rare conditions such as lymphomatoid all contributed to a better understanding of the nature http://www.bmj.com/ of lymphomas and clearer planning of management of these disorders. More recently, developments in molecular biology of oncogenesis have begun to reveal Box 1- Staging procedures for malignant the aetiological events in their development.2 lymphomas Mandatory procedures Histological classification History and physical examination Biopsy of diagnostic tissue Optimal management ofnon-Hodgkin's lymphomas Laboratory profile: on 25 September 2021 by guest. Protected copyright. must be based on a clear understanding of the cell Complete blood count, liver and renal function pathology, the staging, and clinical course of the tests, serum calcium concentration, serum protein various subtypes. A more detailed understanding electrophoresis of the prognostic factors influencing the course of Chest radiographs lymphomas is also helpful in planning treatment. Computed tomography of abdomen and pelvis Bone marrow aspiration and biopsy Several different histological classifications are used Upper gastrointestinal series, small bowel follow throughout the world, resulting in confusion and through for all ear, nose, and throat lymphomas (in difficulty in comparing data from different centres. 20% of such lymphomas there is gastrointestinal The working formulation for classifying lymphomas disease) provides a comprehensive system which focuses on Ear, nose, and throat examination (to visualise British Columbia Cancer reproducing characteristics identifiable by light micro- Waldeyer's ring, nasopharynx) in all gastrointestinal Agency, Vancouver BC, scopy. It combines the most reproducible histological lymphomas Canada V5Z 4E6 features in several classification schemes into a system Optional procedures Susan E O'Reilly, medical allocating the lymphomas to 10 different subtypes, and oncologist Lymphangiography (only ifresult will alter treatment) it also provides a cross reference to other systems.3 In Cytology of cerebrospinal fluid in high risk patients: Joseph M Connors, medical the working formulation lymphomas are assigned to oncologist Small non-cleaved and lymphoblastic tumours three categories-low, intermediate, and high grade- Large cell tumour with marrow or sinus disease based on the natural course Correspondence to: Dr of these diseases, as Patients with neurological abnormalities O'Reilly. modified by the best treatment available in the '60s Cytology of pleural or peritoneal effusions and '70s. Computed tomography or radiography ofsymptomatic The working formulation does not take into account sites Series edited by: Dr G M the more detailed information now available on Bone scanning (if pain present) Mead. immunological which is based on Laparotomy recommended for: phenotyping, specific Diagnosis of abdominal mass cell membrane and cytoplasmic antigen testing and Resection of gastrointestinal lymphoma BMJ7 1992;304: 1682-6 various DNA probe information. Such techniques are 1682 BMJ VOLUME 304 27 JUNE 1992 lymphoma. Although the extent and duration of staging investigations may have to be modified in Box 2-Ann Arbor staging classification urgent situations or in frail patients, all other patients for Hodgkin's disease should undergo the mandatory procedures and any Stage I clinically indicated optional procedures listed in box 1. The most commonly used staging system is that of the Single lymph node region affected or single extra- BMJ: first published as 10.1136/bmj.304.6843.1682 on 27 June 1992. Downloaded from lymphatic organ or site Ann Arbor Conference (box 2).6 This system was StageII originally devised for Hodgkin's disease, a slowly Two or more lymph node regions affected on the same progressive disease that tends to advance in an orderly side ofthe diaphragm with or without localised disease fashion to contiguous, usually nodal structures. in extralymphatic site (IIIE) Malignant lymphomas, on the other hand, usually Stage III occur in elderly people, often progress early to distant Lymph node regions affected on both sides of the nodal or extranodal sites, and may evolve rapidly. diaphragm with or without localised disease of an Therefore, the Ann Arbor staging system is not as extralymphatic organ or site (IIIE) or spleen (IIIS), or useful a predictor of treatment outcome in malignant both (IIISE) lymphoma as in Hodgkin's disease. As a consequence, Stage IV a simple staging system based on anatomic extent of Diffuse or disseminated disease in one or more extra- disease, tumour bulk, and constitutional symptoms is lymphatic organs, with or without associated lymph adequate for initial clinical decision making. This node disease system is based on the Ann Arbor staging system plus Subtype A-Asymptomatic information about the patient's age and bulk of disease Subtype B -Patient has constitutional symptoms: (box 3) and applies to a wide range of presentations of Fever, night sweats, or weight loss > 10% of lymphoma. baseline Once a pathologist has reviewed a biopsy specimen from a lymph node or extranodal site affected by lymphoma and clinical staging has been completed as granulomatosis, angioimmunoblastic lymphadeno- described above, patients can be classified for treatment pathy, Wegener's granulomatosis, and lethal midline according to histology, extent of disease, and age. granuloma. Table II gives guidelines for an overall approach to The prognostic and therapeutic implications of more management. recently defined entities such as intermediate cell lymphoma and its follicular variant, mantle zone lymphoma,4 and peripheral T cell lymphoma (the Low grade lymphomas commonest non-cutaneous T cell lymphoma)5 are About 40% of lymphomas encountered in North unclear at present and await more complete description America and western Europe are low grade. Box 4 and analysis. With current treatment techniques shows their characteristics. These lymphomas typically pathologists need only separate the lymphomas into present insidiously, often with progressive lympha- three main therapeutic groups -low grade, aggressive denopathy, which may wax and wane or with cyto- (comprising the large cell lymphomas and immuno- penias, hepatosplenomegaly, or compression of blastic lymphoma), and a special category (Burkitt's ureters, veins, or bile ducts. Patients usually do not and non-Burkitt's small non-cleaved cell lymphoma
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