Keywords
Wegener granulomatosis - granulomatosis with polyangiitis - immunosuppressive therapy
Introduction
Wegener granulomatosis (WG) now known as granulomatosis with polyangiitis (GPA) was
first described by Friedrich Wegener in 1936. It has characteristics of necrotizing
granulomatous inflammation and pauci-immune vasculitis in small- to medium-sized blood
vessels. Involvement of the kidney is common, which presents as proteinuria, hematuria
(microscopic), and hypertension.[1]
[2] A very rare presentation of GPA is solitary renal mass or multiple renal masses.
Differential diagnoses are renal tumors, abscesses, and lymphomas. Solitary renal
mass is rarely a presenting feature of GPA and is reported in only eight cases to
date. Treatment is cyclophosphamide, azathioprine, rituximab, and glucocorticoids.
Most patients were diagnosed after nephrectomy; however, we suspected GPA and managed
conservatively with rituximab, and steroids after diagnosing with ultrasound-guided
biopsy. This article aims to present this rare entity and review the literature.
Case Summary
A 27-year-old female presented with mild flank pain, loss of appetite, and low-grade
fever for 3 months. On examination, her vitals were as follows: pulse was 84/min,
blood pressure 108/70, and a lump was palpable in the right lumbar region extending
into the right hypochondrium and umbilical regions. Investigations revealed hemoglobin
9.5 g/dL, urea 25 mg/dL, creatinine 0.8 mg/dL, total leucocyte count 10,300, C-reactive
protein (CRP) 127 mg/L, and erythrocyte sedimentation rate 57 mm, and urine culture
was sterile.
Ultrasound kidney, ureter, and bladder showed a heterogeneous hypoechoic mass of size
8.6 × 7.8 × 5.2 involving the lower and mid pole of the right kidney that was displacing
the pelvic calyceal system. Contrast-enhanced computed tomography (CT) scan was suggestive
of an ill-defined mass 8.6 × 7.8 × 5.2 cm in the lower and mid pole displacing the
pelvicalyceal system toward the upper pole, with minimal internal vascularity. Mass
had unclear borders and was infiltrating perinephric fat and duodenum. Contrast enhancement
of mass was 50 to 60 Hounsfield unit, which was as low compared to normal kidney parenchyma.
The heterogeneous perinephric fat stranding was seen. Multiple lymph nodes were enlarged
predominantly paraaortic, and aortocaval, the largest measuring 28 × 32 mm ([Figs. 1],[2],[3]).
Fig. 1 Axial contrast-enhanced computed tomography scan showing ill-defined heterogeneous
mass occupying in mid and lower pole of the right kidney with perinephric stranding.
Fig. 2 Coronal sections of the contrast-enhanced computed tomography abdomen show heterogenous
mass mid and lower pole with ill-defined margins, perinephric stranding, and involving
duodenum.
Fig. 3 Urography films of contrast-enhanced computed tomography abdomen showing heterogenous
mass mid and lower pole with ill-defined margins. For Peer Review pushing calyces
away without involving them.
Since the radiological features were unlikely of renal cell carcinoma (RCC), an ultrasound-guided
biopsy was planned to rule out RCC, renal abscess, lymphomas, or tuberculosis. Biopsy
revealed inflammatory infiltrate with foci of neutrophilic micro-abscess, epithelioid
cells granuloma, and multinucleated giant cells spread among lymphocytes and plasma
cells along with neutrophils. The inflammatory infiltrates comprised patchy foci of
neutrophilic microabscesses, occasionally scattered epithelioid cells with epithelioid
cell granuloma ([Figs. 4] and [5]).
Fig. 4 Histopathology showing areas of necrosis with a collection of neutrophils (orange
arrow), few epithelioid cell granulomas (blue arrow), and occasional giant cells (green
arrow) (400X, hematoxylin and eosin).
Fig. 5 Histopathology showing areas of necrosis with a collection of neutrophils, few epithelioid
cell granulomas, and occasional giant cells (400X, hematoxylin and eosin).
Cytoplasmic–antineutrophil cytoplasmic antibody was 1:290 with strongly positive anti-PR3,
suggesting WG. On systemic examination, she had sinusitis with no involvement of respiratory
tract, lungs, eyes, ear, and skin. She was prescribed azathioprine and steroids (prednisolone
60 mg). She was counselled regarding the disease and prednisolone 60 mg was started
with weekly tapering of steroids (5mg/week till the 5 mg dose was achieved. Prednisolone
5 mg continued for 1 year. Azathioprine 50 mg twice daily was started; however, she
developed abdominal pain, diarrhea, and vomiting after 2 weeks. Azathioprine was stopped
and rituximab was started 1 g weekly for 4 weeks then 500 mg every 6 months. On follow-up,
symptomatic resolution was seen with a resolution of renal mass at 6 months, and her
full blood count, renal function, and CRP returned to normal.
Discussion
WG is necrotizing granulomatous vasculitis of unknown etiology involving the respiratory
tract, lungs, skin, eyes, kidneys, etc. It has varied presentations ranging from mild-to-severe
illness. It is small-to-medium vessel vasculitis with necrotizing granulomatous inflammatory
nodules involving the respiratory tract, and kidneys. GPA initially involves the kidney
in 20% of cases, although subsequent involvement is seen in 80% of cases. Ocular manifestations
of WG are seen in 50 to 60 % of cases. It may occur secondary to granulomatous sinusitis
or due to focal vasculitis in the form of nasolacrimal duct obstruction, proptosis,
conjunctivitis, episcleritis, scleritis, corneoscleral ulceration, uveitis, and optic
neuritis. Kidney involvement is seen as microhematuria, proteinuria, and renal failure.
Microscopically, it is seen as patchy necrotizing glomerulonephritis.[1]
[2]
Renal mass is a rare presentation of GPA and its clinical and radiologic manifestations
are similar to a renal abscess, tumor, or an inflammatory process.[3]
Maguire et al reported one patient had renal mass out of 31 patients presenting with
GPA.[4]
Frigui et al[5] et al in a review of literature reported renal involvement as renal mass in 13 patients.
He concluded that imaging alone cannot differentiate between renal tumors and mass
due to WG. Villa-Forte et al[6] reported a case of simultaneous development of RCC and GPA renal lesions and proposed
renal biopsy to confirm the diagnosis of suspected GPA and repetition of imaging studies
to determine the resolution of mass lesions after appropriate treatment. He reported
renal lesions in a WG along with RCC.
GPA presenting with solitary renal mass is seen in only eight case reports. Three
patients were diagnosed with GPA after nephrectomy for renal mass and one after partial
nephrectomy for renal mass. Four patients were diagnosed with percutaneous biopsy
and managed conservatively.[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
Pathologic analysis of the masses in these cases revealed them to be inflammatory
masses or pseudo tumors or RCC. It is prudent to differentiate RCC from the inflammatory
mass. Taking a meticulous history and physical examination and high clinical suspicion
is of great importance to prevent unnecessary interventions and delay treatment.
Yamamoto et al reported 24 cases of renal mass in GPA with solitary lesions seen in
62%, (13/21), both kidneys having multiple masses in 28.5% (6/21), and unilateral
kidneys having multiple masses. The finding was confirmed with a CT scan in 15 patients.
The most common finding was hypovascular mass with undemarcated margins. Other investigations
that can help differentiate could be magnetic resonance imaging and positron emission
tomography scans. Other sites involved were seen in 50 % of cases including the upper
respiratory tract, ears, and lungs.
Immunosuppressive therapy, that is, primarily azathioprine, cyclophosphamide, rituximab,
and steroids, has markedly improved survival and remission rates in GPA patients.
However, the therapy with cyclophosphamide is associated with significantly increased
side effects and risk of urinary bladder cancer development. Rituximab and azathioprine
are fewer toxic alternatives to cyclophosphamide.
In our case, a history of fever, arthralgia, flank pain, and atypical features on
CT scan like hypovascular mass with indistinct borders, peritumoral stranding, and
lymphadenopathy were crucial for diagnosis. Ultrasound-guided biopsy clinched the
diagnosis. In addition, antineutrophil cytoplasmic antibodies and anti-PR3 antibodies
were positive. She was prescribed steroids and rituximab and she responded dramatically.
Renal biopsy, although paramount, should not delay treatment if other features suggest
GPA. Diagnosis of WG is critical as surgery could be detrimental in these patients
with delay in treatment.
Conclusions
In case of hypovascular renal mass in young patients with suggestive history, a clinician
should keep GPA in mind as early diagnosis can make a difference. Medical treatment
with steroids and rituximab is effective in inducing remission and maintenance.
