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Asymptomatic patients can be monitored for evidence of disease progression without immediate need for chemotherapy.[9,30,31] Prognostic factors associated with symptoms requiring therapy include the following: The management of lymphoplasmacytic lymphoma is similar to that of other low-grade lymphomas, especially diffuse, small lymphocytic lymphoma/chronic lymphocytic leukemia.[30,32-34] If the viscosity relative to water is greater than four, the patient may have manifestations of hyperviscosity.Plasmapheresis is useful for temporary, acute symptoms (such as retinopathy, congestive heart failure, and central nervous system [CNS] dysfunction) but should be combined with chemotherapy for prolonged control of the disease.If the clinical pattern of relapse suggests that the disease is behaving in a more aggressive manner, a biopsy should be performed, if feasible.[23] Documentation of conversion to a more aggressive histology requires an appropriate change to a therapy applicable to that histologic type.[24] Rapid growth or discordant growth between various disease sites may indicate a histologic conversion.[23] The risk of histologic transformation was 30% by 10 years in a retrospective review of 325 patients from diagnosis between 19.[25] In this series, high-risk factors for subsequent histologic transformation were advanced stage, high-risk FLIPI, and expectant management.The 5-year OS rate was more than 50% for patients who had biopsy-proven, aggressive-histology transformation in several multicenter cohort studies employing rituximab plus anthracycline or platinum-based chemotherapy, or similar therapy followed by autologous or allogeneic stem cell transplantation (ASCT).[23,26,27] In a prospective nonrandomized study, at a median follow-up of 6.8 years, 379 (14%) of 2,652 patients subsequently transformed to a more aggressive histology after an initial diagnosis of follicular lymphoma.[28][Level of evidence: 3iii Div] The median OS after subsequent transformation was 5 years; however, among 47 patients with evidence of transformation in conjunction with follicular lymphoma at the time of initial diagnosis, the OS was no worse than that of the other nontransformed patients (5-year OS, 88%; 95% confidence interval [CI], 74%–95%).Rearrangement of the Despite the advanced stage, the median survival ranges from 8 to 15 years, leading to the designation of being indolent.[5-7] Patients with advanced-stage follicular lymphoma are not cured with current therapeutic options.The rate of relapse is fairly consistent over time, even in patients who have achieved complete responses to treatment.[8] Watchful waiting, i.e., the deferring of treatment until the patient becomes symptomatic, is an option for patients with advanced-stage follicular lymphoma.[9,10] An international index for follicular lymphoma (i.e., the Follicular Lymphoma International Prognostic Index [FLIPI]) [11-13] identified five significant risk factors prognostic of overall survival (OS): Patients with none or one risk factor have an 85% 10-year survival rate, while three or more risk factors confer a 40% 10-year survival rate.[11] In a revised FLIPI-2, an elevated beta-2-microglobulin and lymph node size of more than 6 cm are proposed prognostic factors instead of serum LDH and the number of nodal areas.[14] Although the FLIPI and FLIPI-2 indices can predict progression-free survival (PFS) and OS, the scores cannot be used to establish the need for therapy, nor can they be used to predict response to therapy.[11,14] The primary use of FLIPI or FLIPI-2 is to assure a balance of prognostic factors or to define entry requirements in randomized clinical trials.

Although lymph node biopsies are recommended whenever possible, sometimes immunophenotypic data are sufficient to allow diagnosis of lymphoma when fine-needle aspiration cytology is preferred.[1,2] Historically, uniform treatment of patients with non-Hodgkin lymphoma (NHL) has been hampered by the lack of a uniform classification system.As a result, the Working Formulation has become outdated and less useful to clinicians and pathologists.Thus, European and American pathologists have proposed a new classification, the Revised European American Lymphoma (REAL) classification.[5-8] Since 1995, members of the European and American Hematopathology societies have been collaborating on a new World Health Organization (WHO) classification, which represents an updated version of the REAL system.[9,10] The WHO modification of the REAL classification recognizes three major categories of lymphoid malignancies based on morphology and cell lineage: B-cell neoplasms, T-cell/natural killer (NK)-cell neoplasms, and Hodgkin lymphoma (HL).In 1982, results of a consensus study were published as the Working Formulation.[3] The Working Formulation combined results from six major classification systems into one classification.This allowed comparison of studies from different institutions and countries.

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Indolent NHL types have a relatively good prognosis with a median survival as long as 20 years, but they usually are not curable in advanced clinical stages.[3] Early-stage (stage I and stage II) indolent NHL can be effectively treated with radiation therapy alone.