ANALYSIS OF IMMUNOGLOBULIN GENES IN SPLENIC MARGINAL ZONE LYMPHOMA SUGGESTS ONGOING MUTATION

Splenic marginal zone lymphoma (SMZL) is a lo ic grade primary splenic B cell lymphoma, originally thought to be related to splenic marginal zone B cells. Later studies showed that SMZL sometimes may be accompa nied by villous lymphocytes in the peripheral blood, a condition previ ously characterized as splenic lypmphoma with villous lymphocytes (SLV L). The relationship between SMZL and splenic marginal zone B cells ha s recently been called into question. We report four further cases of SMZL, two of which were associated with villous lymphocytes in the per ipheral blood. In addition to immuno-phenotypical analysis, we have st udied the IgV(H) genes in each case, because the extent and patterns o f their mutation can indicate the normal B cell counterpart of lymphom as. The IgV(H) genes in the four cases of SMZL studied are mutated, wh ich is consistent with their origin from postfollicular marginal zone B cells. Evidence of ongoing mutation was also observed. This contrast s with a study showing that blood-borne tumor cells in SLVL show no si gn of ongoing mutation. It is possible that the ongoing mutations in t he cases studied here are acquired in a splenic microenvironment, such as that found in the follicle center. HUM PATHOL 29:585-593. Copyrigh t (C) 1998 by W.B. Saunders Company.