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What are the differences between aggressive lymphomas and indolent lymphomas?

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Key concept

One method to segregate hematological malignancies, including lymphomas, is the evolution time that the disease takes to clinically progress. Indolent lymphomas are those which evolve over years, whereas aggressive lymphomas do so over months. Indolent lymphomas are also known as low grade and aggressive lymphomas as high grade.1

Clinical scenario

A 65-year-old man develops enlarged cervical lymph nodes. He is completely asymptomatic. One year and a half later, he becomes anemic and develops additional enlarged lymph nodes in the axilla. An excisional biopsy is made, and he is diagnosed with follicular lymphoma, an indolent type of lymphoma.

Action item
  • When facing a diagnosis of lymphoma, always obtain the grade of the tumor as estimated by the pathologist based on the Ki-67 immunohistochemistry of the disease


The proportion of proliferating cells correlates with the immunostaining biopsy sections to determine the percentage of Ki-67 antibody–positive cells. In general, it can be said that indolent lymphomas have a Ki-67 of ≤30%, aggressive lymphomas between 30% and 75%, and highly aggressive lymphomas >75% Ki-67.2 Ki-67 is a monoclonal antibody that reacts selectively with a nuclear antigen that is present only in proliferating cells in the G1, S, and G2 phase but is absent in the G0 phase (resting cells).

  • Ki-67 and MIB-1 monoclonal antibodies bind different epitopes of the same proliferation-related antigen. Ki-67 and MIB-1 can be used on fixed sections.3 MIB-1 can be used on formalin-fixed paraffin-embedded sections, after heat-mediated antigen retrieval. For this reason, it has essentially replaced Ki-67 in clinical use

  1. Gascoyne RD, Thieblemont C, Freedman AS. Hematopathology approaches to diagnosis and prognosis of indolent B-cell lymphomas. Hematology Am Soc Hematol Educ Program 2005:299-306.

  2. Ali AE, Morgen EK, Geddie WR, et al. Classifying B-cell non-Hodgkin lymphoma by using MIB-1 proliferative index in fine needle aspirates. Cancer Cytopathol 2010;118:166-72.

  3. Banklfalvi A, Simon R, Brandt B, et al. Comparative methodological analysis of erbB-2/Her-2 gene dosage, chromosomal copy number and protein overexpression in breast carcinoma tissues for diagnostic use. Histopathology 2000;37:411-19.

How do I know which patients benefit from rituximab?

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Key concept

B cell lymphomas represent 85% of all NHL diagnoses. B cells express a surface protein, CD20, that participates in the regulation of intracellular calcium, the cell cycle, and apoptosis. Because this protein is not shed, modulated, or internalized, it represents an ideal target for the use of monoclonal targeted therapy.1

Clinical scenario

A 72-year-old man was essentially asymptomatic when admitted to a hospital with severe abdominal pain. A CT of the abdomen was performed followed by a mesenteric biopsy that confirmed the diagnosis of diffuse large B cell lymphoma, germinal center subtype. His Ki-67 level was 40%. After completion of the initial staging process, the ...

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