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Hum
Pathol. 2006 Feb;37(2):152-9. Epub
2006 Jan 10.
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The proliferation center
microenvironment and prognostic markers in chronic
lymphocytic leukemia/small lymphocytic lymphoma.
Soma LA,
Craig FE, Swerdlow SH.
Division of Hematopathology,
University of Pittsburgh School of Medicine, PA
15213-2582, USA.
Prognostication in chronic
lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
based, in part, on ZAP-70 and CD38 expression, and
to a lesser extent, on MUM1/IRF4 expression, is
currently of great interest. The more aggressive
type of CLL/SLL is reportedly characterized by
neoplastic cells that are more responsive to B-cell
signaling with proliferation centers (PCs), a
potentially important site of neoplastic cell
stimulation. To study the relationship of these
markers to each other and to the pattern of PCs,
immunohistochemical stains for ZAP-70 and MUM1/IRF4
were performed and the PC patterns assessed (where
possible) in 29 tissue biopsies with CLL/SLL. CD38
expression was assessed in 18 cases using flow
cytometry. Ten evaluable cases had a typical PC
pattern and 16 an atypical pattern with larger or
more confluent PCs and/or more numerous
paraimmunoblasts/transformed cells. ZAP-70 was
positive in 14 of 28 cases, including 3 with
atypical PCs and enhanced PC staining. All 29 cases
showed MUM1/IRF4 expression in PCs. Seven cases,
none with atypical PC, also showed uniform
positivity throughout, 14 showed weaker staining of
surrounding lymphocytes, and 8 had PC staining only.
CD38 was positive in 14 of 18 cases. The only
significant association identified was between
uniform MUM1/IRF4 positivity and typical PCs (P =
.004). These findings highlight the complex
interrelationship of prognostic markers in CLL/SLL
and demonstrate potentially important
microenvironmental variations in their expression.
They support the hypothesis that PCs are a site for
B-cell receptor signaling, which helps explain
reported site-dependent antigenic variation in CLL/SLL,
and suggest that PC morphology may correlate with
other biological features.
PMID: 16426914 [PubMed - indexed for
MEDLINE]