The World Health Organization (WHO) classification
of Hodgkin lymphoma (HL) distinguishes two
types: Classical Hodgkin lymphoma (CHL) and nodular
lymphocyte predominant Hodgkin lymphoma (NLPHL).
Both groups have in common that they mostly derive
from B cells with rare classical cases originating from T
cells. They differ in their histomorphology, immunophenotype,
and clinical behavior. One of the subtypes of
CHL, designated as lymphocyte-rich classical Hodgkin
lymphoma (LRCHL), shares some morphological features
with NLPHL. The transcription factors BSAP, BOB.1,
Oct2 and MUM I are sequentially expressed in normal Bcell
development In order to investigate the relationship
between the CHL subgroups and NLPHL, we examined
the protein expression of these transcription factors using
immunohistochemistry in 15 reactive processes and 4
different subtypes of 58 HL cases. Our findings underline
the B-cell origin of HL, without evidence, that reactive
processes like progressively transformed germinal centers
(PTGCs) are precursor lesions of HL. Furthermore, they
demonstrate that LRCHL is distinct from NLPHL and that
it is closely related to the mixed cellularity CHL (MCHL)
in respect of BSAP, BOB.1, and Oct2 expression. It
therefore occupies an intermediate position between
MCHL and NLPHL. Based on MUM1 staining, LRCHL
exhibits a more mature phenotype than NLPHL.
Keywords Hodgkin lymphoma • Transcription factors •
BSAP/Pax5 Oct2 BOB.I/OBF1 MUMUIRF4
Both authors, S.A. Steimle-Grauer and M. Tinguely, contributed
equally to this work.
S.A. Steimle-Grauer () • M. Tinguely • L. Seada • C. Fellbaum •
M.-L. Hansmarm
Senckenbereisches Institute of Pathology,
Johann Wolfgang Goethe-University of Frankfurt,
Theodor-Stern-Kai 7. 60596 Frankfurt am Main, Germany
e-mail: Steimle-Grauer@em.uni-frankfurt.de
Tel.: A-49-69-63015761
Fax: +49-69-63015241
Introduction
Hodgkin lymphoma (HL) is one of the most common
lymphomas in the Western world. Its cellular origin has
been a controversial issue for years. Single-cell analyses
of Hodgkin and Reed Sternberg (HRS) cells revealed a
majority of about 98% of classical Hodgkin lymphoma
(CHL) as being derived from B cells and only about 2%
from T cells [6, 12, 29, 43]. In recent years, intensive
research has confirmed the division into two main groups,
the CHL and the rare nodular lymphocyte predominant
Hodgkin lymphoma (NLPHL). They are distinguished by
their different morphology as well as by their immunophenotype.
The malignant lymphocytic and histiocytic
(L&H) cells in NLPHL express B-cell associated
molecules as CD20, CD79a, J-chain and immunoglobulins,
but lack CD30 and CD15. In contrast, the FIRS cells
in CHL typically express CD30 and often CD15 but, in
most instances, are devoid of CD20, CD79a, I-chain and
immunoglobulins [41, 52]. Genotypically, all HLs contain
rearranged immunoglobulin genes; however, both types
have different patterns [5, 19, 22, 23, 26, 27].
In 1995, four cases of a variant of classical Hodgkin's
disease were described as follicular Hodgkin's disease
[2]. Recently, this variant of CHL, which morphologically
resembled NLPHL in terms of nodular growth and
lymphocyte richness, and CHL in terms of the immunophenotype,
was designated as the common nodular
variant of lymphocyte-rich classical Hodgkin lymphoma
(LRCHL). The nodules in LRCHL, predominantly consisting
of B cells, differ from those in NLPHL in that they
represent expanded mantle zones with atrophic germinal
centers (GCs) [1, 13]. Single-cell analyses for immunoglobulin
gene rearrangements of LRCHL revealed that its
tumor cells are derived from antigen experienced B cells
with a mutation pattern similar to that of CHL
(Brauninger et al. unpublished observations).
To gain new insights into the cellular origin and the
maturation stage of HL, we first examined the localization
of the tumor cells in HL, focusing on LRCHL and
NLPHL. Thereafter, B-cell specific activator |
