Variability of immunoglobulin expression in follicular lymphoma. An immunohistologic and molecular genetic study.

Immunohistochemical and molecular genetic studies were performed on tissues involved by follicular lymphomas that at some point in their course showed a lack of detectable surface or cytoplasmic immunoglobulins (Ig). The variable nature of Ig expression in these lymphomas was evidenced by three tumors biopsied from two different sites that showed an Ig-negative phenotype in one biopsy versus an Ig-positive phenotype in the other. The B lineage derivation of Ig-negative follicular lymphomas was confirmed by the presence of Ig heavy and light chain gene rearrangements in eight of eight lymphomas tested. In a way similar to Ig-expressing follicular lymphomas, the Ig-negative tumors were characterized by bcl-2 gene rearrangements (seven of eight) and overexpression of the Bcl-2 protein (eight out of nine). In two of the three lymphomas with Ig-positive and Ig-negative tumor cell populations, the clonal relationship of the Ig-expressing and nonexpressing cells was established by demonstration of identical t(14; 18) DNA rearrangements. The findings demonstrated that the variability of Ig expression in follicular lymphomas reflects the phenotypic heterogeneity of these tumors and is not a manifestation of separate clonal origins.