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Follicular Lymphomas Contain a Clonally Linked But Phenotypically
Distinct Neoplastic B-Cell Population in the Interfollicular Zone
Ahmet Dogan,
Ming-Qing Du,
Antonella Aiello,
Tim C. Diss,
Hong-Tao Ye,
Lang-Xing Pan, and
Peter G. Isaacson
From the Department of Histopathology, UCL Medical School, London, UK
and the Divisione di Anatomia Patologica, Instituto Nazionale Tumori,
Milano, Italy.
Follicular lymphomas are thought to arise from the follicle center B
cells and are characterized by follicular structures that recapitulate
many features of normal secondary lymphoid follicles. The neoplastic B
cells of follicular lymphoma reside not only in follicles but also in
the interfollicular zone in which they form a diffuse infiltrate. We
have investigated the frequency, extent, and biological characteristics
of this interfollicular component in 30 cases of follicular lymphoma.
An interfollicular B-cell infiltrate of variable extent (minimal,
moderate, or prominent) was present in all cases. Morphologically
interfollicular neoplastic B cells were small centrocyte-like cells
with lower grade cytology and lower proliferation fraction compared
with the neoplastic follicles. The neoplastic phenotype of these cells
(CD20+, light chain restricted) was confirmed in 18 cases. Clonal identity between the follicular and interfollicular
components was shown in five cases using microdissection and PCR
amplification of immunoglobulin heavy chain genes. Analysis of Ig heavy
chain gene sequences showed identical variants of tumor subclones in
both follicular and interfollicular compartments, indicating active
tumor cell traffic between the two. In six cases in which frozen tissue
was available, the immunophenotype of follicular and interfollicular
tumor cells were compared using immunohistochemistry. Activation
markers such as CD10, CD38, and CD95 and T-cell costimulatory molecules
CD80 and CD86, which were expressed by neoplastic follicles, were
either downregulated or absent in the interfollicular component in most
of the cases. The low-grade cytological features, low proliferation
fraction, and downregulation of activation markers in the
interfollicular neoplastic B cells suggests that these are resting
cells analogous to memory B cells of normal lymphoid tissues. The
presence of such a resting tumor cell subpopulation in the majority of
follicular lymphomas may partly account for the remarkable resistance
to therapy of this disease.
Blood, Vol. 91 No. 12 (June 15), 1998:
pp. 4708-4714
© 1998 by The American Society of Hematology.
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