Pathologic quiz case: a 17-year-old renal transplant patient with persistent fever, pancytopenia, and axillary lymphadenopathy. Bacillary angiomatosis of the lymph node in the renal transplant recipient

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e12 Arch Pathol Lab Med—Vol 128, January 2004
Pathologic Quiz Case
—Juskevicius & Vnencak-Jones
Residents’ Pages
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.
Control reactions
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-
ular clusters.
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.
1. Anderson B, Sims K, Regnery R, et al. Detection of Rochalimaea henselae
DNA in specimens from cat-scratch disease patients by using polymerase chain
J Clin Microbiol.
2. Kerem BS, Rommens JM, Buchanan JA, et al. Identification of the cystic
fibrosis gene: genetic analysis.
3. Scott MA, McCurley TL, Vnencak-Jones CL, et al. Cat scratch disease: de-
tection of Bartonella henselae DNA in archival biopsies from patients with clin-
ically, serologically and histologically defined disease.
Am J Pathol.
4. Koehler JE, Sanchez MA, Garrido CS, et al. Molecular epidemiology of Bar-
tonella infections in patients with bacillary angiomatosis-peliosis.
N Engl J Med.
5. Karem KL, Paddock CD, Regnery RL. Bartonella henselae, B. quintana, and
B. bacilliformis: historical pathogens of emerging significance.
Microbes Infect.
6. Ioachim HL, Ratech H. Bacillary angiomatosis of lymph nodes. In: Ioachim
HL, Ratech H, eds.
Ioachim’s Lymph Node Pathology.
3rd ed. Philadelphia, Pa:
Lippincott Williams & Wilkins; 2002:120–123.
7. Cline MS, Cummings OW, Goldman M, et al. Bacillary angiomatosis in a
renal transplant recipient.
8. Conrad DA. Treatment of cat-scratch disease.
Curr Opin Pediatr.
    • "Borrelia burgdorferi infection (Lyme disease) has been described in the literature in transplant recipients, including 1 kidney transplant recipient [14] , 1 heart transplant recipient (with car- ditis) [15], and 1 allogeneic hematopoietic stem cell transplant recipient [16]. Bartonella henselae infection has been described after heart [9] and kidney transplantation10111213, with variations in the manifestation of infection that include hemophagocytosis [137], closely associated acute allograft rejection [10], peliosis hepatis [138], peliosis hepatitis and hepatorenal syndrome [139], pulmonary nodules [140], and osteomyelitis [141] . Brucella species infection has been reported after kidney trans- plantation [21, 22] and as a donor-derived infection during HSCT [23], mostly in areas of endemicity. "
    [Show abstract] [Hide abstract] ABSTRACT: Numerous reports exist of the transmission of zoonoses to humans during and after solid-organ and hematopoietic stem cell transplantation. Donor-derived infections of numerous etiologies, including West Nile virus infection, Chagas disease, toxoplasmosis, rabies, lymphocytic choriomeningitis virus infection, and infection due to Brucella species have been reported. Most zoonoses occur as a primary infection after transplantation, and immunocompromised patients are more likely to experience significant morbidity and mortality from these infections. Risks of zoonotic infection in the posttransplantation period could be reduced by patient education. Increased recognition of the risks of zoonoses, as well as the advent of molecular biolog-based testing, will potentially augment diagnostic aptitude. Documented zoonotic infection as it affects transplantation will be the primary focus of this review.
    Article · Apr 2007
    • "Both of our cases showed that awareness of a possible Bartonella infection in the post-transplant setting followed by diagnosis and adequate treatment is associated with a good outcome. The clinical presentation for bartonellosis should be considered in patients with fever, malaise, lymphadenopathy, skin lesions, and an elevated alkaline phosphatase in the context of contact with a cat or kitten141516171819. In the early 90s, the gram-negative bacterium B. henselae was first shown to be a causative agent of BA, peliosis hepatis, and bacteremia. "
    [Show abstract] [Hide abstract] ABSTRACT: Bartonella henselae has not only been identified as the causative agent of cat scratch disease, but it is also associated with other significant infectious syndromes in the immunocompromised population. We describe two cases of B. henselae associated diseases in liver transplant recipients who both had contact with cats. The first recipient developed localized skin manifestation of bacillary angiomatosis in association with granulomatous hepatitis. He tested positive for Immunoglobulin G (IgG) antibodies against B. henselae. The second patient developed axillary lymphadenopathy, with biopsy showing necrotizing granulomatous inflammation and polymerase chain reaction studies were positive for B. henselae DNA. Her serology for bartonellosis showed a fourfold rise in antibody titers during her hospitalization. Both patients responded to treatment with Azithromycin in combination with Doxycycline. These were the only cases within a series of 467 consecutive liver transplants performed in 402 patients performed during a 4-year period. Although bartonellosis is a rare infection in liver transplantation recipients, it should always be included in the differential diagnosis of patients presenting with fever, central nervous system (CNS) symptoms, skin lesions, lymphadenopathy, and hepatitis especially if prior contact with cats is reported.
    Article · Sep 2006
    • "Histopathologically, cutaneous BA is characterized by a tumorlike growth pattern with proliferation of capillaries having protuberant epitheloid endothelial cells [127, 193]. In transplant patients, various clinical manifestations or pathological lesions have been reported, such as pulmonary nodules [34] or sternal abscess [32], disseminated infection with granulomatous hepatitis [112], acute organ rejection [66], bacillary peliosis [2] and bacillary angiomatosis [118] . A case of hemophagocytic syndrome in a transplant patient was recently associated with B. henselae infection [119]. "
    [Show abstract] [Hide abstract] ABSTRACT: Within the last 15 years, several bacteria of the genus Bartonella were recognized as zoonotic agents in humans and isolated from various mammalian reservoirs. Based on either isolation of the bacterium or PCR testing, eight Bartonella species or subspecies have been recognized as zoonotic agents, including B. henselae, B. elizabethae, B. grahamii, B. vinsonii subsp. arupensis, B. vinsonii subsp. berkhoffii, B. grahamii, B. washoensis and more recently B. koehlerae. The present manuscript reviews the factors associated with the emergence of these zoonotic pathogens, including better diagnostic tools and methods to identify these fastidious bacteria, host immunosuppression (caused by infectious agents, cancer, aging or induced by immunosuppressive drugs), the interaction of co-infection by several infectious agents that may enhanced the pathogenecity of these bacteria, increased outdoor activity leading to exposure to wildlife reservoirs or vectors, poverty and low income associated with infestation by various ectoparasites, such as body lice and finally the dispersal of Bartonellae around the world. Furthermore, a description of the main epidemiological and clinical features of zoonotic Bartonellae is given. Finally, the main means for diagnosis, treatment and prevention of these diseases are presented.
    Full-text · Article · May 2005
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