NON-HODGKINS LYMPHOMA EPIDEMIOLOGY AND ETIOLOGY Epidemiology 1.

Each year, approximately 31,700 patients in the United states are diagnosed as having nonHodgkins lymphoma (NHL), and about 16,500 patients die of the disease 2. Peak incidence occurs after age 50 years, much later than that for Hodgkins disease 3. The incidence is slightly higher in males (1.4:1) Etiology 1. A viral etiology for at least some lymphomas has been suggested by epidemiologic, cell culture, and immunologic investigations. 2. Demonstration of the translocation of the c-myconcogene into the immunoglobulin gene locus in burkitts lymphoma has provided a major breakthrough in the study of malignant transformation of lymphoid cells. 3. An increased risk of NHL in persons exposed to agricultural herbicides, particularly of the phenoxyacetic acid group, has been reported Detection And Diagnosis Clinical Detection Symptoms and sign of NHL are similar to those in Hodgkins disease expect for the following generalizations 1. Unlike Hodgkins disease, noncontiguous spread is the rule in NHL, and the mediastinum is often spared. More frequently. Early involvement of oropharyngeal lymphoid tissue, skin, the GI tract, and bone is frequent 2. In children, initial intra-abdominal manifestations are common, unlike Hodgkins disease 3. Leukemic transformation with a high peripheral lymphocyte count occurs in about 13% of patients with lymphocytic lymphoma 4. Autoimmune anemia with positive antiglobulin (combs) tes accurs in a significant minority of NHL patiens Diagnostic 1. Surgical biopsy establishes the diagnosis a. Although histology continues to be the primary decision-making criteria, immunophenotyping, and enzymatic and cytogenetic studies should supplement morphologic analysis b. The most suspicious node should be selected for excisional biopsy c. Aspiration of bone marrow effusions may provide the diagnoses

2. The remainder of the required ANS suggested diagnostic and are similliat Classification Histopathology NHL are a divers group of diseases that differ with regard to histology, natural history, and response to therapy. This heterogeneity has led to several histopathologic classifications, which in turn have contributed to difficulty in interpreting study results. These studies have revealed that all NHL s of follicular type are of B-cell origin ; the so called histiocytic lymphoma is almost always a lymphocytic malignancy, usually of B-cell type, but occasionally of T-cell origin ; mixed lymphoma are wholly of lymphocytic origin; Burkitts lymphomas demonstrate a surface marker pattern ; and immunoglobulin gene rearrangement is characteristic of B-cell origin. The distinction between malignant lymphoma and benign lymphadenopathy can sometimes be difficult . Monoclonality on immunophenotyping and gene rearrangement in such patients are the criteria used to diagnose a neoplastic process Anatomic staging Although the staging system is the same as that used for Hodgkins disease, a report with long-term follow-up of 1,153 patients has shown that the stage of the disease is less predictive of outcome compared with Hodgkins disease. Staging Work-up Because of the noncontiguous spread of NHL, the majority of patients will manifest stage III or IV disease 1. Recommended procedur. In addition to lymph node biopsy, the following procedures are recommended a. Complete physical examination (including pelvic examination for women) b. Complete blood cell counts, including differential white blood cell and reticulocyte counts c. Direct coombs (antiglobulin) test. Autoimmune hemolytic anemia is significantly more frequent in NHL than in Hodgkins disease d. Blood chemistry analysis (including alkaline phosphatase, albumin, globulin, immunoglobulin, uric acid, creatine) e. Bone marrow biopsy f. Chest x-ray (posteroanterior and lateral) g. CT is useful in detecting upper retroperitoneal and mesenteric nodes and liver involvement. 2. Procedures appropriate under selected circumstances : a. Additional radiographic procedures ; 1. Whole-chest tomography or MRI if any abnormality is noted or suspected on routine chest x-ray.

2. Bilateral lower-extremity lymphogram continues to be the optimal procedure for the evaluation of para-aortic lymph nodes, performed in institutions adept at this procedure. 3. Head or spinal CT or MRI for neurologic signs or symptoms. 4. Bone scan and plain bone radiographs for patients with symptomatic areas 5. Gallium whole body scans and liver spleen scans are at times appropriate. b. Exploratory laparotomy and splenectomy should be considered if therapeutic decisions depend on the identitifications of infradiaphragmatic involvement, such as for selected patients with stage I large cell lymphoma. PRINCIPLES OF TREATMENT Surgery 1. The primary role of surgery is in establishing diagnosis 2. Resection of extranodal GI primaries may rarely be curative, although additional treatment for microresidual or macroresidual disease is generally indicated 3. Splenectomie may be rarely beneficial for hypersplenism 4. Laparatomy may be rarely considered in carefully selected patiens, especially in younger patiens with apparently localized NHL, for whom radiation therapy is to encompass all disease with cure as the goal. Radiation Therapy The role of radiation therapy in the management of NHL has progressively decreased as chemotherapeutic regimens have become more effective. The complications of radiotherapy for NHL are similar to those that occur in the treatment of Hodgkins disease. 1. Favorable histology or low-grade NHL (Nodular lymphocytic well-differentiated, nodular poorly-differentiated lymphocytic, nodular mixed, diffuse lymphocytic well differentiated) lymphocytic , nodular mixed, diffused lymphocytic well-differentiated) a. Stage I-II disease ; Following extensive staging, only 10% to 30% of patients with lowgrade lymphoma will have localized disease, and most of these patients have follicular (nodular) subtypes. b. Stage III-IV low-grade lymphoma : Patients with advanced-stage low-grade lymphomas are heterogeneous in their disease characteristics, and several possible treatment strategies can be considered . 2. Unfavorable histology (intermediate-and high-grade) NHL nodular histiocytic, diffuse histiocytic, diffuse lymphocytic poorly-differentiated, diffuse mixed, and including diffuse and large cell subtypes according to the working formulation a. Stage I-II unfavorable NHL b. Stage III-IV unfavorable NHL

3. Extranodal NHL : Patients with extranodal NHL with out associated nodal involvement, or with only regional involvement (stage IE or IIE) are generally treated similarly to other patients with early-stage NHL. However, selected extranodal sites require some individualization of therapy. a. Waldeyers ring b. Other head and neck sites c. GI tract d. Bone e. Thyroid f. Skin g. CNS

RESULTS AND PROGNOSIS Results of Chemotherapy 1. Indolent lymphomas : Survival for stage I disease at 10 years is 83%. Survival curves for stages II, III, and IV disease do not differ significantly. Although a substantial proportion of patients with advanced stage are alive at 7 years, the majority of them are not disease free. 2. Aggressive lymphomas : A CR rate of 50%, and survival at 13 years of 30% with CHOP therapy .