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Blood, 15 March 2002, Vol. 99, No. 6, pp. 2192-2198
NEOPLASIA
Tumor cell dissemination in follicular lymphoma
Sabine Oeschger,
Andreas Bräuninger,
Ralf Küppers, and
Martin-Leo Hansmann
From the Senckenberg Department of Pathology,
University of Frankfurt, Frankfurt/Main, and the Institute for
Genetics, University of Cologne, Cologne, Germany.
The derivation of follicular lymphomas (FLs) from germinal centers
is not only supported by their morphologic appearance with a nodular
growth pattern and a germinal center-like cellular composition, but
also by the presence of ongoing somatic hypermutation (a germinal center B cell-specific process) during their clonal expansion. The
intraclonal sequence diversity of the tumor cells and their follicular
growth pattern allows one to analyze lymphoma cell dissemination and
the way the tumor "metastasizes" to distinct follicles. In the
present study, we analyzed individual follicles of 3 FLs by
micromanipulation of single cells from individual lymphoma follicles
and amplification of immunoglobulin V region genes. Genealogical trees
for the VH and the VL gene rearrangements were
constructed to analyze the clonal relationship among individual cells
of 3 distinct follicles of each case. In all 3 cases there is evidence
that distinct tumor follicles are founded by many tumor cells,
suggesting that there is extensive migration of the tumor cells among
follicles. The observation that the tumor cells of FLs retain their
follicular growth patterns despite this cellular migration supports the
idea that they depend on the follicular microenvironment for their
clonal expansion.
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