Follicular lymphoma-like B cells of uncertain significance (in situ follicular lymphoma) may infrequently progress, but precedes follicular lymphoma, is associated with other overt lymphomas and mimics follicular lymphoma in flow cytometric studies

In situ follicular lymphoma, more recently known as follicular lymphoma-like B cells of uncertain/undetermined significance is well accepted. However, the morphological criteria have evolved since it was first described and data are limited and conflicting regarding its clinical implications and whether the extent of involvement predicts an association with overt lymphoma. It is also unknown how often it will be identified by flow cytometric studies and how often it precedes overt follicular lymphomas. A multiparameter study of 31 biopsies with follicular lymphoma-like B cells of uncertain significance and 4 'benign' lymph node biopsies that preceded an overt follicular lymphoma was, therefore, performed. Fifty-two percent of biopsies with follicular lymphoma-like B cells were associated with a prior or concurrent lymphoma but only 6% subsequently developed lymphoma (median follow up 26 months). Neither the number, proportion or density of BCL2(+) germinal centers were associated with overt follicular lymphoma/diffuse large B-cell lymphoma. Flow cytometric studies identified follicular lymphoma-like B cells in 8 of 15 evaluable cases. The proportion but not the absolute number of BCL2(+) germinal centers was associated with the likelihood of positive flow cytometric studies (P<0.01). All 4 'benign' biopsies that preceded an overt follicular lymphoma demonstrated follicular lymphoma-like B cells. Thus, although few patients with follicular lymphoma-like B cells of uncertain significance progress within the follow-up period, it at least precedes many follicular lymphomas. The extent of involvement does not predict the occurrence of prior or concurrent lymphomas. Flow cytometric studies demonstrating follicular lymphoma-like B cells must not be over-interpreted as they may only reflect follicular lymphoma-like B cells.