Hodgkin Lymphoma Non-Hodgkin Lymphoma

More often localized to a single axial group of nodes (cervical, mediastinal, para-aortic) More frequent involvement of multiple peripheral nodes

Orderly spread by contiguity Noncontiguous spread

Mesenteric nodes and Waldeyer ring rarely involved Waldeyer ring and mesenteric nodes commonly involved

Extranodal involvement uncommon Extranodal involvement common

myeloid series (erythrocytes, granulocytes, monocytes, and platelets). These diseases primarily involve the bone marrow and to a lesser degree the secondary hematopoietic organs (the

spleen, liver, and lymph nodes) and present with altered hematopoiesis. Three broad categories of myeloid neoplasia exist:

• Acute myelogenous leukemias, characterized by the accumulation of immature myeloid forms in the bone marrow and the suppression of normal hematopoiesis

• Myelodysplastic syndromes, associated with ineffective hematopoiesis and associated cytopenias

• Chronic myeloproliferative disorders, usually associated with an increased production of terminally differentiated myeloid cells

The pathogenesis of myeloid neoplasms is best understood in the context of normal hematopoiesis, which (you will remember from Chapter 13 ) involves a hierarchy of hematopoietic

progenitor cells. At the top of the hierarchy sits the pluripotent stem cell, which gives rise to multipotent progenitor cells committed to lymphoid or myeloid differentiation. The latter in

turn produce more committed progenitors, which eventually give rise to terminally differentiated cells of a single type (e.g., erythrocyte, monocyte). In addition to giving rise to committed

daughter cells, hematopoietic progenitor cells must also replicate themselves without differentiating (or else they would eventually disappear), a process known as self-renewal.

Normal hematopoiesis is finely tuned by homeostatic feedback mechanisms involving cytokines and growth factors that modulate the marrow output of red cells, granulocytes, and

platelets. These mechanisms are deranged in marrows involved by myeloid neoplasms, which "escape" from normal homeostatic controls on growth and survival, and suppress the function

of residual normal stem cells. The specific manifestations of the different myeloid neoplasms are further influenced by (1) the position of the transformed cell within the hierarchy of

progenitors and (2) the effect of the transforming events on differentiation programs, which may be blocked or preferentially shunted toward one lineage at the expense of others. We will

return to these themes as each type of myeloid neoplasm is discussed.

Given that all myeloid neoplasms originate from a transformed hematopoietic progenitor cell, it should come as no surprise that divisions between these neoplasms are sometimes blurred.

Myeloid neoplasms, like other malignancies, tend to evolve over time to more aggressive forms of disease.

In particular, both the myelodysplastic syndromes and the chronic myeloproliferative disorders often "transform" to acute myelogenous leukemias. In the specific case of one of the

myeloproliferative disorders, chronic myelogenous leukemia, transformation to acute lymphoblastic leukemia/lymphoma is also seen, indicating a likely origin from a transformed

pluripotent stem cell.

Date: 2016-04-22; view: 915