Baylor University Medical Center Proceedings January 2014, Volume 27, Number 1 | Page 31

a

b

c

Figure 1. Lymph node biopsy results showing features of Castleman’s disease. (a) A germinal center with a penetrating blood vessel. H&E ×200. (b) Collection of
plasmablasts encroaching on the germinal center, forming a “microlymphoma.” GC indicates germinal center; PB, plasmablasts. H&E ×500. (c) HHV-8 staining in
plasmablasts surrounding the germinal center. In situ hybridization ×20.

previously pathologic lymph nodes were normal in size. A
PET scan done after completion of chemotherapy showed no
residual disease. The patient continues retroviral therapy, and
his HIV load is now undetectable. He is also being treated
with abacavir/lamivudine for hepatitis B. A follow-up HHV-8
DNA by polymerase chain reaction was <1000 copies/mL. An
IL-6 level was not repeated.
DISCUSSION
MCD is a rare, aggressive lymphoproliferative disorder that
has a poor prognosis usually requiring systemic chemotherapy
(1–4). MCD is commonly associated with HHV-8, an oncogenic herpesvirus, and is most often seen in immunosuppressed
individuals infected by HIV type 1 (5). The pathologic features of MCD strongly suggest a chronic antigen stimulation
response, and HHV-8 has been found in virtually all cases of
HIV-related MCD (6). The presentation is usually nonspecific, resulting in an extensive differential diagnosis that often
results in a delay of the diagnosis. The diagnosis is established
on the clinical presentation of a lymphoproliferative disorder
with evidence of multisystem involvement and the classic histopathology on a lymph node biopsy as described in the case
presentation. Those with MCD may develop lesions described
previously as microlymphomas composed of plasmablasts. The
plasmablasts typically reveal lambda light chain restriction but
do not harbor somatic mutations in the rearranged immunoglobulin genes. With disease progression, frank plasmablastic
lymphomas may develop (7, 8). It is interesting that these lymphomas are monoclonal, although the immunoglobulin genes
remain unmutated (8). Compared with HIV-infected patients
without MCD, those with MCD have a 15-fold increased risk
of non-Hodgkin lymphomas, with the most common subtype
of MCD being HHV-8–positive plasmablastic lymphoma.
It has long been recognized that the features of MCD
strongly suggest a secondary antigen proliferation response. It
has been hypothesized that an infectious agent could be the triggering antigen for the introduction of a pathological process via
abnormal IL-6 production, unregulated by a defective immune
January 2014

system (9, 10). The IL-6 level in our case was elevated. HIV
itself is highly replicated in lymphoid tissue and could play a
role in the persistent B-cell activation (11). The IL-6 signaling
pathway may play an important role in driving HHV-8-infected
naive B cells to differentiate into plasmablasts (12). HHV-8
enco