CLL/SLL is an indolent, slowly growing tumor in which increased tumor cell survival appears to be more important than tumor cell proliferation per se. In line with this idea, CLL/SLL cells contain high levels of BCL2, a protein that inhibits apoptosis (Chapters 1 and 6). One mechanism of BCL2 overexpression appears to be chromosomal deletions that lead to the loss of genes encoding micro-RNAs that are negative regulators of BCL2. Also of critical importance are signals generated by surface immunoglobulin (the so-called B cell receptor, or BCR). BCR signals flow through an intermediary called Bruton tyrosine kinase (BTK) that ultimately contributes to the expression of genes that promote the survival of CLL/SLL cells.
CLL/SLL also causes immune dysregulation, particularly of normal B cells. Through unclear mechanisms, the accumulation of CLL/SLL cells suppresses normal B cell function, often resulting in hypogammaglobulinemia. Paradoxically, approximately 15% of patients develop auto-antibodies against their own red cells or platelets. When present, the autoantibodies are made by nonmalignant bystander B cells, indicating that CLL/SLL cells somehow impair immune tolerance.
MORPHOLOGYInvolvedlymphnodesareeffacedbysheetsofsmalllymphocytesandbyscatteredill-definedfocioflarger,activelydividingcells(
Fig.12.15A ).Thepredominantcellsaresmall,restinglymphocyteswithdark,round nuclei,andscantycytoplasm(Fig.
12.15B ).Thefociofmitoticallyactivecellsarecalledproliferation centers, whicharepathognomonicforCLL/SLL.Inadditiontothelymphnodes,thebonemarrow,spleen,andliverareinvolvedinalmostallcases.Inmostpatientsthereisanabsolutelymphocytosis featuringsmall,mature-lookinglymphocytes.Thesecirculatingcellsarefragileandduringthepreparationofsmearsmanyaredisrupted,producingcharacteristicsmudge cells. Variablenumbersoflargeractivatedlymphocytesalsoareusuallypresentinbloodsmears.
Immunophenotype and Genetics. CLL/SLL is a neoplasm of mature B cells expressing the CD20 and surface immunoglobulins. The tumor cells also express CD5. This http://ebooksmedicine.net
Fig. 12.15 Smalllymphocyticlymphoma/chroniclymphocyticleukemia—lymphnode.(A)Low-powerviewshowsdiffuseeffacementofnodalarchitecture.(B)Athighpower,amajorityofthetumorcellshavetheappearanceofsmall,roundlymphocytes.A“prolymphocyte,”alargercellwithacentrallyplacednucleolus,alsoispresentinthisfield(arrow).(A,Courtesy of Dr. José Hernandez, Department of Pathology, University of Texas Southwestern Medical School, Dallas,Texas.) is a helpful diagnostic clue, since among B cell lymphomas only CLL/SLL and mantle cell lymphoma (discussed later) commonly express CD5. Approximately 50% of tumors have karyotypic abnormalities, the most common of which are trisomy 12 and deletions involving portions of chromosomes 11, 13, and 17. Unlike in other B cell neoplasms, chromosomal translocations are rare.