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Lymphoma – Non-Hodgkin Lymphoma, Classification, Staging and Prognostic Factors

    Non-Hodgkin lymphoma (NHL) results from a clonal expansion of B cells (85%) or T cells and/or natural killer (NK) cells (15%). NHL are grouped into categories of indolent, aggressive, or highly aggressive, based on their biology and natural history. Indolent NHLs are considered incurable (except for the few patients with stage I disease [disease confined to one lymph node group] that can be eradicated by radiotherapy.

    The median survival of patients with indolent NHL (most who present themselves with advanced disease) is 7 to 10 years. Patients with aggressive or highly aggressive NHL are potentially curable with combination chemotherapy. Immunophenotyping of these malignant cells is routinely performed in the diagnosis of NHL. All B-cell-derived NHLs are CD-19* and CD-20*. Characteristic cytogenetic markers may be found in patients with some forms of NHL, and the differential diagnosis of NHL can be narrowed by using a panel of monoclonal antibodies and genetic markers.

B-Cell Neoplasms

  • Low-grade lymphoma: This type is characterized by painless, slowly progressive peripheral lymphadenopathy, which may regress spontaneously. In advanced disease, malignant transformation may occur to intermediate- or high-grade lymphoma.
  • Intermediate- and high-grade lymphoma: This type has a variable clinical presentation but is usually accompanied by lymphadenopathy. In more than one-third of patients, extranodal disease is present, with B symptoms.
  • Diffuse Large B Cell Lymphoma: The most common type of lymphoma, with an increased incidence in HIV positive patients, and higher risk of CNS involvement. [Lumbar puncture is performed when neurologic signs and symptoms are present, in HIV-related lymphoma, primary CNS lymphoma, testicular lymphoma and paranasal sinus involvement.] It is essential that molecular testing is done on tissue specimens to ensure appropriate diagnosis.
  • Burkitt lymphoma: Large abdominal masses may result in presenting signs of and symptoms of bowel obstruction or obstructive hydronephropathy.
  • Primary CNS lymphoma: CNS lymphomas are high-grade B-cell lymphomas, often seen in immunodeficient patients.

    Patients with NHL who have the same stage of disease according to the Ann Arbor staging system, may have very different clinical outcomes. The International Prognostic Index (IPI) was developed as a predictive model of outcome for patients with diffuse large cell lymphoma. The index is based on five pre-treatment characteristics found to be independent predictors of death. The age-adjusted IPI was derived for patients younger than 60 years. For these patients, the age-adjusted factors are performance status, serum lactate dehydrogenase concentration, number of extranodal sites and stage.

    Risk categories and corresponding survival rates are provided below. The IPI was modified to be applied to follicular lymphoma and is referred to as the Follicular Lymphoma IPI (FLIPI). This index also includes five independent factors consisting of a number of extranodal sites, serum lactate dehydrogenase concentration, age, stage, and hemoglbin concentration, which replaces performance status in this scheme:

Prognostic indices for non-Hodgkin Lymphoma

    Patients with high-risk IPI scores are destined to have a poorer prognosis. Aggressive treatment such as high-dose chemotherapy with hematopoietic cell support ,as part of front-line therapy to improve the outcome of such patients, is being tested in trials. The National Cancer Center Network guidelines recommend that these patients be considered for clinical trials (preferred) evaluating new approaches, or standard cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (R-CHOP).

    Similarly, patients with follicular lymphoma with a high-risk FLIPI score are candidates for clinical trials, or treatment with standard regimens such as R-CVP (cyclophosphamide, vincristine, prednisone, rituximab) or R-CHOP. There are no data from randomized, prospective trials using these prognostic indices to guide therapeutic decisions. In the future, prognostication will be further refined with the use of DNA micro-array technology, which shows which genes are over- and/or under-expressed in a given tumour.