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ASH Image Bank (2001); doi:10.1182/ashimagebank-2001-100221
Copyright © 2001 by the American Society of Hematology.
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Full Case Study

Lymphocyte differentiation: postulated cell of origin of some lymphoid neoplasms

Nancy Lee Harris, M.D.

Massachusetts General Hospital



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  		Figure 1. Lymphocyte differentiation: postulated cell of origin of some lymphoid neoplasms.

 

   Diagnosis
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 Diagnosis
 
Neoplasms that correspond to proliferating stages of either antigen-independent or antigen-dependent differentiation are likely to be aggressive, while those that correspond to naive or mature effector stages are likely to be indolent. Neoplasms of precursor cells tend to be more common in children, while those of antigen-dependent effector and memory cells tend to be more common in adults. Neoplasms often follow homing patterns of their normal counterparts: thus, neoplasms of bone marrow precursor cells are often acute leukemias; those of germinal center cells occur in follicular areas of lymph nodes and other tissues, those of memory cells are often found in sites of antigenic stimuation, such as the gastrointestinal tract.

T-cell neoplasms: The tumor that corresponds to the stages of T-cell differentiation in the thymic cortex is precursor T lymphoblastic lymphoma/leukemia; the variety of immunophenotypes and antigen receptor gene rearrangements found in precursor T-cell neoplasia correspond to the variety of stages of intrathymic T-cell differentiation. Some cases of T-cell prolymphocytic leukemia (PLL) and peripheral T cell lymphoma may correspond to naive T cells. Most cases of peripheral T-cell lymphoma are thought to correspond to stages of antigen-dependent T-cell differentation - for example, mycosis fungoides corresponds to a mature, effector CD4+ cell, hepatosplenic gd T-cell lymphoma to a splenic gd T cell, T-cell large granular lymphocyte leukemia (LGL) to a mature effector CD8+ cell - however, the relationship between neoplastic and normal T cells is not nearly as well understood as in the B-cell system.  The systemic symptoms such as fever, skin rashes and hemophagocytic syndromes associated with some peripheral T-cell lymphomas may be a consequence of cytokine production by the neoplastic T cells. 

B-cell neoplasms: Neoplasms of precursor B cells usually involve bone marrow and peripheral blood, and are known as common or precursor B acute lymphoblastic leukemia; rarely, they present as solid tumors (precursor B lymphoblastic lymphoma). Two neoplasms appear to correspond to naive CD5 positive B cells: a subset of B-cell chronic lymphocytic leukemia and mantle cell lymphoma. The corresponding neoplasm to the IgM-producing plasma cell of the early primary immune response may be lymphoplasmacytic lymphoma (immunocytoma), or Waldenstrom's macroglobulinemia. Burkitt's lymphoma may correspond to the early SIgM+ B blast. Follicular lymphomas are tumors of germinal center B cells, in which centrocytes fail to undergo apoptosis because they have a chromosomal rearrangement, t(14;18), that prevents the normal switching off of the BCL2 gene. Most large B-cell lymphomas are thought to derive from germinal center and post-germinal center activated B cells - centroblasts and immunoblasts. Extranodal, nodal, and splenic marginal zone lymphomas and about 50% of B-CLL/SLL appear to correspond to memory B-cells of either marginal zone or circulating type, respectively.


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Related ASH-SAP Chapter:space logo
Chapter 12: Lymphoproliferative disorders

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Copyright © 2001 by the American Society of Hematology.