e12 Arch Pathol Lab Med—Vol 128, January 2004
Pathologic Quiz Case
—Juskevicius & Vnencak-Jones
Pathologic Quiz Case
A 17-Year-Old Renal Transplant Patient With Persistent Fever,
Pancytopenia, and Axillary Lymphadenopathy
Ridas Juskevicius, MD; Cindy Vnencak-Jones, PhD
17-year-old adolescent boy with end-stage renal dis-
ease due to focal segmental glomerulosclerosis un-
derwent a second kidney transplant because of the chronic
rejection and loss of the ﬁrst allograft that he had received
11 years previously. The patient was on several immuno-
suppressive drugs including FK506 and prednisone. Lab-
oratory studies perioperatively demonstrated pancytope-
nia, and on the second postoperative day, the patient be-
gan to display temperature spikes that reached as high as
398C. The postoperative graft function was excellent. On
physical examination, the patient was found to have left
axillary lymphadenopathy, which was later conﬁrmed by
computerized tomography scanning. Computerized to-
mography scanning did not demonstrate any other ab-
normalities. Results of aggressive workups for infectious
disease, including blood and urine cultures, cytomegalo-
virus analysis, and polymerase chain reactions for par-
vovirus B-19, herpesviruses 6, 7, and 8, and hepatitis se-
rologic studies, were negative. The patient continued to
experience temperature spikes despite the discontinuation
of some of the immunosuppressive drugs that initially
were thought to be the cause of his persistent fever. A
biopsy of the axillary lymph node was performed.
The excised lymph node measured 2 cm in its greatest
dimension and showed a grossly unremarkable cut sur-
face. A microscopic examination of the hematoxylin-eo-
sin–stained sections demonstrated conﬂuent nodular areas
containing proliferation of the vessels of various sizes and
Accepted for publication August 21, 2003.
From the Department of Pathology, Vanderbilt University Medical
Center, Nashville, Tenn.
Corresponding author: Cindy Vnencak-Jones, PhD, Department of
Pathology, Vanderbilt University Medical Center, 4605 The Vanderbilt
Clinic, Nashville, TN 37232 (e-mail: cindy.vnancak-jones@vanderbilt.
shapes in the background of the intact lymph node archi-
tecture (Figures 1 and 2). The plump endothelial cells lin-
ing the lymphatic vessels showed variable size, abundant
pale cytoplasm, and vesicular nuclei with occasionally
prominent nucleoli. Many areas had solid clusters of the
plump endothelial cells without visible vascular lumens
(Figure 3). Rare mitotic ﬁgures, numerous neutrophils,
and extravasated erythrocytes were present. Interstitial ar-
eas contained abundant amphophilic granular and amor-
phous material (Figure 3, insert) that, on Warthin-Starry–
stained sections, showed the presence of the small rod-
shaped structures consistent with bacilli. Granulomata
were not present, and special acid-fast bacilli and Gomori
methenamine silver stains were negative. DNA was ex-
tracted from ten 10-mm-thick sections of the parafﬁn-em-
bedded lymph node, and varying amounts of template
DNA were ampliﬁed in a multiplex polymerase chain re-
action (tubes 1, 3, 5, and 7). One primer pair was speciﬁc
for the 16S ribosomal RNA genes of Bartonella henselae,and
a second primer pair, speciﬁc for exon 10 of the cystic
ﬁbrosis transmembrane conductance regulator (CFTR)
gene, was used as a quality control locus to verify suc-
cessful ampliﬁcation of patient DNA.
included multiple negative controls interspersed between
patient samples (tubes 2, 4, and 6), normal human DNA
(tube 8), and B henselae DNA (tube 9). Amplicons were
subjected to electrophoresis on a 2% agarose gel (Figure
4, bottom) and characterized using DNA marker frag-
ments of known sizes (tube 10). Amplicons generated
from the host CFTR gene are fragments 98 base pair (bp)
in length, while those generated from B henselae DNA are
153 bp. The sensitivity and speciﬁcity of the assay was
increased by Southern blotting and hybridization with a
P-labeled probe (Figure 4, top) speciﬁc for B henselae.
What is your diagnosis?
Arch Pathol Lab Med—Vol 128, January 2004
Pathologic Quiz Case
—Juskevicius & Vnencak-Jones e13
e14 Arch Pathol Lab Med—Vol 128, January 2004
Pathologic Quiz Case
—Juskevicius & Vnencak-Jones
Pathologic Diagnosis: Bacillary Angiomatosis of the
Lymph Node in the Renal Transplant Recipient
Bacillary angiomatosis of the lymph node can be de-
ﬁned as a tumorlike proliferation of the small blood ves-
sels and is one of the manifestations of infection by Bhen-
Bartonella henselae is a small, curved, motile gram-
negative bacillus that is difﬁcult to culture and frequently
requires molecular methods for identiﬁcation and specia-
tion. The reservoir of B henselae is a domestic cat and cat
ﬂea, and the organism is transmitted to humans by direct
contact with the cat that has long-term bacteremia. Cat
ﬂeas can transmit B henselae between cats, but transmis-
sion to humans by ﬂeas from cats has not been proven.
Bartonella quintana is a related organism that causes trench
fever, which is characterized by cycling fever and is trans-
mitted among humans by the human body louse. An in-
fection by B quintana can also manifest as vasoproliferative
lesions histologically indistinguishable from the lesions of
bacillary angiomatosis caused by B henselae. However, the
distribution of the lesions may be inﬂuenced by different
species of Bartonella; subcutaneous and bone involvement
is strongly associated with B quintana, with lymph node
involvement being almost exclusively associated with B
It appears that the status of the host immune system is
a critical determinant of the clinical and pathologic man-
ifestation of the B henselae infection. In the immunocom-
petent host, it manifests as cat scratch disease with pro-
longed regional lymphadenopathy that, histologically, is
characterized by necrotizing granulomata. Also, otherwise
healthy cat scratch disease patients do not have a signiﬁ-
cant bacteremic phase. Recurrent fever with bacteremia
and bacillary angiomatosis as a manifestation of B henselae
infection almost exclusively occurs in human immunode-
ﬁciency virus–infected/acquired immunodeﬁciency syn-
drome patients, typically with CD4 lymphocyte counts
less than 100 cells/mm
. Only rare cases have been re-
ported in immunosuppressed transplant recipients and
cancer chemotherapy patients.
Bacillary angiomatosis is a potentially systemic disease
with wide range of documented tissue involvement (brain,
lymph node, bone marrow, skeletal muscle, conjunctiva,
and mucosal surfaces of the gastrointestinal and respira-
tory tract). Skin involvement is the most frequent and is
best described occurring as single or multiple lesions. In-
volvement of the liver and spleen can manifest as bacillary
Pathologic ﬁndings in most tissues are similar and con-
sist of the proliferation of small vessels lined by plump
endothelial cells that demonstrate variable atypia in the
background of mucinous and ﬁbrotic stroma. This stroma
contains variable numbers of neutrophils and aggregates
of bacteria that, on hematoxylin-eosin–stained tissue sec-
tions, have the appearance of purple-to-amphophilic gran-
The main differential diagnosis to consider is Kaposi
sarcoma, which morphologically may resemble bacillary
angiomatosis and also occurs in immunocompromised in-
dividuals, especially human immunodeﬁciency virus–
positive persons. The vessels in Kaposi sarcoma are cleft-
like, the endothelial cells are spindled shaped, and there
are no aggregates of bacteria present.
It is not entirely clear why an infection by the same
species of Bartonella causes different clinical and histo-
pathologic manifestations between immunocompetent and
immunosuppressed patients. These differences cannot be
explained solely by differences in the status of the host
immune system. The difference in virulence among the
pathogenetic genotypes of B henselae and their geographic
distribution may play a role, but this remains to be proven.
Also, it has been proposed that a speciﬁc Bartonella factor
causing endothelial proliferation is expressed or activated
in persons with defective cellular immunity.
This case illustrates the utility of conﬁrming the pres-
ence of B henselae in formalin-ﬁxed, parafﬁn-embedded
tissue. The production of signiﬁcant amounts of 153-bp
amplicons visualized on the ethidium bromide–stained
gel (Figure 4, bottom) speciﬁc to B henselae DNA from the
patient specimen (Figure 4, top) correlates with the abun-
dant amphophilic granular and amorphous material seen
on hematoxylin-eosin–stained sections (Figure 3). Early
diagnosis of bacillary angiomatosis is essential, since ef-
fective antibiotic therapy including erythromycin, azith-
romycin, or doxycycline is available, and unrecognized
disease may lead to a fatal outcome.
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