Nephrol Dial Transplant (2004) 19: 984-987
Nephrol Dial Transplant Vol. 19 No. 4 © ERA-EDTA 2004; all rights reserved
Case Report
Wegener's granulomatosis presenting as multiple bilateral renal masses
Nelson Leung1,
Steven R. Ytterberg2,
Michael L. Blute3,
Donna J. Lager4,
Ulrich Specks5 and
Fernando C. Fervenza1
1Division of Nephrology and 2Division of Rheumatology, 5Pulmonary and Critical Care Medicine, 3Department of Internal Medicine, Department of Urology and 4Department of Pathology, Mayo Clinic Rochester, Rochester, Minnesota, USA
Correspondence and offprint requests to: Dr F. C. Fervenza, Division of Nephrology, Ei-S24, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN 55905, USA. Email: fervenza.fernando{at}mayo.edu
Keywords: anti-neutrophil cytoplasm antibody; granulomatous inflammation; renal masses; vasculitis; Wegener's granulomatosis
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Introduction
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Wegener's granulomatosis (WG) is a systemic disease characterized
pathologically by necrotizing granulomatous inflammation of
the respiratory tract and generalized vasculitis involving medium-
and small-sized vessels. Kidney involvement is usually manifested
as a focal segmental necrotizing glomerulonephritis, with crescents
[
1]. Anti-neutrophil cytoplasm antibody (ANCA) testing has provided
a very useful diagnostic aid. The majority of patients with
WG have antibodies towards proteinase 3 (PR3-ANCA) (>70%),
but antibodies towards myeloperoxidase (MPO-ANCA) is seen in
20% of cases. A few patients (<10% of cases) are ANCA negative.
Occasionally, the disease may present as a single renal mass
[
2,
3]. However, WG presenting as bilateral renal masses in a
patient who is ANCA negative is unusual and illustrates the
diagnostic dilemma presented by such a case. Recognition of
these limited forms of WG is crucial in order to ensure early
diagnosis and treatment.
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Case
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A 66-year-old male presented in March 2001 with a 2 month history
of fever, night sweats, lower extremity weakness and pain. He
had been well until September 2000 when, following a skiing
accident, he was found to be hypertensive and was started on
a combination of atenolol and hydrochlorothiazide. In January
2001 he began to notice increased fatigue, lower extremity pain
and weakness. He also developed upper respiratory tract symptoms
with a dry cough. He was placed on a sequential course of amoxycillin,
cephalexin and doxycycline with no improvement. In addition
to these symptoms, a month prior to the clinic visit, the patient
began experiencing nightly fevers with drenching night sweats.
Blood tests showed anaemia, leukocytosis, thrombocytosis and
elevated sedimentation rate (76 mm/1 h). He was admitted to
his local hospital for work-up of fever of unknown origin. An
ENT evaluation showed no polyps or ulceration in the nasal cavity
and posterior rhinoscopy was normal. A head computerized tomography
(CT) scan showed opacity of the left sphenoid sinus as well
as the left ethmoid and maxillary sinus, together with marked
thickening of the mucosa of the sphenoid and maxillary sinus.
He was started on a course of azithromycin. Blood tests showed
that his ANA was negative, serum creatinine was 1.0 mg/dl and
urinalysis was normal. Bone marrow biopsy examination showed
normal cellularity with a M:E ratio of 3:1. Tests for ANCA showed
that he had a positive p-ANCA. Anti-myeloperoxidase (MPO) and
anti-proteinase 3 (PR3) antibody titres were unavailable. Because
of a concern for systemic vasculitis, he was referred to the
Mayo Clinic for further evaluation. When seen at our institution,
he complained of weight loss of >20 lbs over the last 6 months,
increasing headaches and abdominal pain mainly over the left
flank for the previous 10 days. On physical exam his temperature
was 36.1°C, blood pressure was 145/80 mmHg and pulse rate
was 89. Apart from some punctuate lesions on his back, which
resembled the start of a vesicular rash, the remainder of the
physical examination, including a complete ENT exam, was unremarkable.
Laboratory evaluation showed haemoglobin 12.6 g/dl, white cell
count 11.2
x 10
9/l, platelets 184
x 10
9/l, sedimentation rate
54 mm/1 h, serum creatinine 1.2 mg/dl and a normal urinalysis.
Also normal were the results of bilateral temporal artery biopsies,
renal ultrasound and an abdominal angiogram that included the
renal arteries, performed to evaluate the abdominal pain. ANCA
serology was positive with a p-ANCA pattern and an anti-MPO
of 60.3 EU/ml, together with an elevated C-reactive protein
of 10.9 mg/dl. A diagnosis of systemic vasculitis was entertained
and he was started on oral prednisone 60 mg daily, which resulted
in prompt relief of his symptoms. Prednisone was gradually tapered
and completely discontinued at the end of October 2001. In January
2003, 22 months after the initial presentation, the patient
returned complaining that his night sweats had returned and
he was experiencing progressive fatigue, but no return of the
abdominal pain. His sinus symptoms had improved, but he had,
however, developed peripheral oedema and leg pain, mostly in
the calves, without a clear relationship with exercise. Laboratory
evaluation again showed a normal serum creatinine and an entirely
normal urinalysis. He had a mildly elevated C-reactive protein,
but with a normal sedimentation rate and negative assays for
MPO and PR3-ANCA. Chest X-ray, Doppler studies of the legs as
well as an echocardiogram were all reported as normal. In the
process of evaluating the cause of his oedema, a CT scan of
the abdomen and pelvis was performed, which showed multiple
bilateral renal masses, 2–3 cm in size (
Figure 1). To
further characterize these masses, the patient underwent renal
ultrasound and excretory urogram, which showed the masses to
be solid. Fine needle aspiration of the renal masses was suspicious
for lymphoma, but this was not confirmed on the tissue specimen,
which was reported as fibrotic with a mixed reactive inflammatory
cell infiltrate. The patient then underwent bilateral surgical
exploration of the renal masses. Pathological examination of
the surgical specimens submitted from both kidneys showed similar
morphological alterations. Much of the renal parenchyma was
replaced by numerous, confluent small necrotizing granulomas
with central collections of neutrophils and cellular debris
(
Figure 2). There was also an associated mixed interstitial
inflammatory cell infiltrate. No infectious organisms, including
acid-fast bacilli, were detected on Gomori–methenamine
silver (GMS) or auramine–rhodamine stains. The glomeruli
appeared normal and no necrotizing glomerular lesions were identified.
No arteritis was observed. These pathological findings were
consistent with the diagnosis of WG. Based on these results,
the patient was started on a combination of prednisone 60 mg
daily and oral methotrexate 25 mg weekly, together with single-strength
trimethoprim–sulphamethoxazole daily. This resulted in
prompt symptomatic improvement. Prednisone dose was tapered
to 10 mg daily at 6 months while methotrexate was continued
at the same dose. Six months after the beginning of treatment,
a repeat CT of the abdomen showed that the renal masses had
decreased in size with no evidence of new masses (
Figure 2).
During the same period, several MPO and PR3 assays remained
negative.
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Fig. 2. (A) Necrotizing granuloma with central necrosis and neutrophils surrounded by histiocytes and a mixed inflammatory cell infiltrate (H&E, 200x). (B) Higher magnification of granuloma with central necrosis and a neutrophilic infiltrate (H&E, 400x).
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Discussion
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WG is a systemic disease characterized pathologically by the
presence of necrotizing granulomatous lesions of the upper and
lower respiratory tracts and a generalized vasculitis of small
to medium-sized vessels, often associated with a glomerulonephritis
[
4]. Kidney involvement is common, but extrarenal manifestations
usually precede renal disease by many months [
5,
6]. Renal pathology
usually reveals a focal segmental necrotizing glomerulonephritis,
with or without crescents, and rarely accompanied by necrotizing
granulomas [
1]. However, the overall clinical picture varies
considerably, with forms of the disease limited to the lungs
not being uncommon [
7]. A few cases of WG presenting as crescentic
glomerulonephritis, without respiratory tract involvement, have
also been recognized [
8]. Rarely, a solitary renal mass, which
pathological examination reveals to be WG, has been described
[
2,
3,
9–
12]. However, in only two of these cases was a
renal mass the sole initial manifestation of the disease [
2,
3].
Even rarer, WG can present as multiple renal masses. We found
only one previously reported case in which multiple renal masses
were the initial manifestation of WG [
13]. This case was similar
to ours in the fact that renal function was not affected and
needle biopsies of the masses were non-diagnostic. In contrast
to our case, however, the previously described patient was ANCA
positive, which helped in making a presumptive diagnosis of
WG. The discovery of serum IgG antibodies against cytoplasmic
components of neutrophils and monocytes (ANCA) and of its association
with WG has provided a useful diagnostic tool for the patient
with this disease. ANCA are present in >90% of patients with
active systemic WG and are highly specific [
14]. However, ANCA
sensitivity is lower in patients with active localized disease,
as demonstrated by our case. Therefore, a negative c-ANCA test
result does not exclude a diagnosis of WG. Treatment with prednisone
and cyclophosphamide has significantly improved survival of
WG, although relapse rates remain high and side effects of treatment
are not trivial [
6]. In patients with normal renal function,
an alternative treatment using prednisone combined with low-dose
weekly methotrexate has been shown to be equally effective in
inducing remission, while reducing the number of side effects
[
15]. Although urogenital tuberculosis may show a similar presentation
on CT, multiple renal biopsy sections failed to be stained for
acid-fast bacilli. In addition, the fact that the patient improved
while on high-dose prednisone and methotrexate argues against
this diagnosis.
In summary, we present a case of WG in which multiple bilateral renal masses were the major clinical findings. This form of presentation is rare, but emphasizes the importance of considering WG in the differential diagnosis when dealing with tumour-like lesions of the kidney.
Conflict of interest statement. None declared.
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Received for publication: 14.10.03
Accepted in revised form: 25.11.03
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