Clonal cytogenetic abnormalities in the plasma cell
variant of Castleman disease
Kaaren K. Reichard
, Sheldon Robinett
, M. Kathryn Foucar
Department of Pathology, University of New Mexico, Albuquerque, NM, USA;
TriCore Reference Laboratories,
Albuquerque, NM, USA
Castleman disease (CD) is widely regarded as a non-neoplastic process, yet clonal cytogenetic
abnormalities have been rarely reported and are restricted to the hyalineevascular variant. It
remains unclear whether this reﬂects true rarity in such tumors - the fact that such cases are
not routinely submitted for cytogenetic studies, or that suspension culture techniques are errone-
ously used rather than in situ cultures. We report a localized plasma cell variant of CD (PC-CD)
with clonal abnormalities. A human immunodeﬁciency virusenegative 35-year-old man sought
care for vague abdominal pain and was found to have an isolated 6-cm mesenteric mass. PC-
CD was diagnosed by integrating clinical, laboratory, morphologic, and immunophenotypic
studies. Flow cytometric, immunohistochemical, and molecular IGH@ gene rearrangement
studies were all negative for a clonal B or plasma cell population. A cytogenetic in situ culture
analysis revealed an abnormal karyotype: 46,XY,add(6)(p23),add(7)(p15),del(7)
(p15),add(9)(q22)/46,XY,inv(9)(p13q22)/46,XY,À3,þr/46,XY. A cytogenetic suspen-
sion culture showed a normal karyotype. On the basis of the morphologic and immunophenotypic
features, these genetic changes are attributed to the non-lymphoid cells, most probably of
stromal, dendritic, or endothelial origin. Because the pathogenesis of PC-CD is not thought to
typically involve the proliferation of these cell types, this is a new and unexpected ﬁnding and
may provide pathogenetic insight.
Keywords Castleman disease, cytogenetics, plasma cell variant, clonal abnormality
ª 2011 Elsevier Inc. All rights reserved.
Castleman disease (CD) is one of the more common causes of
non-neoplastic lymphadenopathy. Currently, CD comprises
four variants (hyalineevascular, plasma cell, human herpes-
virus 8 [HHV8] associated, and multicentric) with heteroge-
neous clinical presentations and prognosis (1). In the
hyalineevascular subtype (HV-CD), occasional cases will
manifest signiﬁcant follicular dendritic cell (FDC) prolifera-
tions, FDC tumors, vascular tumors, and abnormal collections
of plasmacytoid dendritic cells (2e7). Clonal cytogenetic
abnormalities have been reported in both the myoid and
dendritic components of HV-CD cases (7e9). These ﬁndings
have prompted investigators to consider such stromal over-
growths as part of the histogenesis of CD.
The plasma cell variant of CD (PC-CD) may occur in
a localized form but is more commonly multicentric.
Morphologically, normal lymph node architecture is retained
with variable follicular hyperplasia and prominent interfollicular
plasmacytosis. In contrast to HV-CD, or a marked stromal and
dendritic cell proliferation have not been emphasized in the
published literature. The pathogenesis of localized PC-CD is
not well understood, although HHV8 infection and increased
levels of interleukin-6 (IL-6) seem to each play a role. To our
knowledge, clonal cytogenetic abnormalities have not been
reported in localized PC-CD.
Materials and methods
The surgical sample was collected fresh with a portion
submitted for ﬂow cytometry, cytogenetics, routine
morphology, and immunohistochemistry.
We examined the sample using six-color ﬂow cytometry with
antibodies against CD3, CD4, CD5, CD7, CD8, CD19, CD20,
Received February 25, 2011; received in revised form March 30,
2011; accepted April 11, 2011.
* Corresponding author.
E-mail address: firstname.lastname@example.org
2210-7762/$ - see front matter ª 2011 Elsevier Inc. All rights reserved.
Cancer Genetics 204 (2011) 323e327