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extremities, face, and genitalia and are typically multifocal, with the appearance of
papules, patches, plaques, or nodules. Patch lesions correspond to the earliest
stage, whereas other forms are characteristic of more advanced disease. However,
these clinical manifestations do not necessarily reflect the progression of KS
because different lesion forms can appear simultaneously. KS lesions are also
found in the oral cavity and internal organs (gastrointestinal tract, lungs, and
lymph nodes) [ 68 ]. Diagnostic confirmation of KS is done through immunohisto-
chemistry for LANA detection in biopsies.
7.2.3.2 Primary Effusion Lymphoma and Multicentric Castleman’s
DiseasePrimary effusion lymphoma (PEL) is a rare tumor associated with KSHV infection,
and it is also known as body cavity-based lymphoma (BCBL). The incidence of this
tumor is very low, even in populations with high KSHV seroprevalence (3% of
AIDS-related lymphomas and 0.4% of all AIDS-unrelated diffuse large cell NHLs)
[ 38 ]. PEL is commonly found as lymphomatous effusions in body cavities. Although
it is more common in HIV-positive males, HIV-negative men and women can also
develop PEL [ 69 ]. Diagnostic criteria for PEL have been proposed, including immu-
noblastic anaplastic large cell morphology, null cell phenotype, and B-cell genotype
[ 70 ]. The PEL cell is assumed and confirmed at a preterminal stage of B-cell dif-
ferentiation. Multiple copies of the KSHV genome can be found in PEL cells, rang-
ing from 40 to 80 copies per cell, and the viral particles of KSHV can be isolated
from cells derived from PEL, which makes it a useful tool to study the virology of
KSHV. It also boosts the serologic assays in the clinical diagnosis. Similar to KS,
KSHV infection is necessary but not sufficient for the development of PEL. EBV
infection may be also involved in the development of this disease because both viral
genomes are found in many types of PEL [ 38 ].
Patients with Castleman’s disease usually have multiple enlarged lymph nodes,hence the name multicentric Castleman’s disease (MCD). Approximately 90% of
patients with MCD have the plasma cell-type morphology. The association
between KSHV infection and MCD was established shortly after the discovery of
KSHV [ 71 ]. Both PEL and MCD can originate from KSHV-infected preterminal
B cells, although cells in MCD do not undergo the GC reaction, whereas those in
PEL do [ 38 ]. The symptoms of MCD include fever, malaise, wasting, hypoalbu-
minemia, cytopenia, and hyponatremia. The systemic symptoms in MCD are
related to the excess production of cytokines (both IL-6 and vIL-6). Lytic anti-
gens can be detected in MCD, indicating that abundant lytic viral replication
occurs; this makes it a feature of MCD by comparison with other KSHV-related
diseases [ 72 ].
S. Li et al.