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British Journal of Radiology (2007) 80, e230-e233
© 2007 British Institute of Radiology
doi: 10.1259/bjr/42250860
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Case report

Granulomatous renal masses following intravesical bacillus Calmette–Guérin therapy: the central unaffected calyx sign

A T Senés 1 L Badet, MD, PhD 2 D Lyonnet, MD 1,3 and O Rouvière, MD, PhD 1,3,4

1 Hospices Civils de Lyon, Department of Urinary and Vascular Radiology, Hôpital Edouard Herriot, Lyon, F-69437, France, 2 Hospices Civils de Lyon, Department of Urology, Hôpital Edouard Herriot, Lyon, F-69437, France, 3 Université de Lyon, Lyon, F-69003, France; Université de Lyon 1, Faculté de Médecine Lyon Nord, Lyon, F-69003, France, 4 Inserm, U556, Lyon, F-69424, France

Correspondence: Dr Olivier Rouvière, Department of Genitourinary and Vascular Radiology, Hôpital E. Herriot, 5 place d'Arsonval, 69437 Lyon Cedex 03, France. E-mail: Olivier.rouviere{at}netcourrier.com


   Abstract
Top
 Abstract
Introduction
 Case report
 Discussion
 References
 
A 67-year-old man with a history of melanoma, treated surgically 7 years before, was referred for vomiting and right flank pain after three intravesical instillations of bacillus Calmette–Guérin (BCG) for superficial bladder cancer. A CT scan showed a mass on the right kidney, with a normal calyx in its centre. Percutaneous biopsy, obtained because of melanoma history, showed granulomatous reaction caused by BCG infection. The renal mass disappeared after 9 months of anti-tuberculous treatment. The presence of an unaffected calyx in the centre of the renal mass is an interesting finding for both teaching purposes — it clearly illustrates the pathogeny of the disease, with the bacillus invading the renal parenchyma through the papilla — and diagnostic purposes — a malignant tumour is likely to displace or destroy neighbouring calyces rather than leaving them unaffected. However, the diagnostic value of this sign remains to be determined by further research.


   Introduction
Top
 Abstract
 Introduction
Case report
 Discussion
 References
 
Intravesical instillations of bacillus Calmette–Guérin (BCG) have been shown to be effective in the treatment and prophylaxis of recurrent superficial tumours (Ta-T1) and carcinoma in situ of the bladder. Complications from BCG therapy are for the most part minor. Short-term symptoms of cystitis are almost expected. Mild haematuria, low-grade fever and myalgias are common and usually of limited duration. Serious systemic complications (including fever of 40°C, severe malaise, hepatic dysfunction and granuloma formation in the liver and lungs) are rare; life-threatening BCG sepsis has been reported in only 0.4% of patients [1].

The development of a granulomatous renal mass is another potentially serious side effect, occurring in approximately 0.1% of patients [1]. The mechanism of renal granuloma formation following intravesical BCG therapy (vesicoureteral reflux vs systemic spread) remains unclear and controversial. Although CT scans have been obtained in many of the reported cases [2–6], little is known about the appearance of these renal granulomas on CT images. It is particularly unclear whether or not CT could discriminate renal granulomas from primary or secondary malignant masses.

We report here a case of post-BCG renal granuloma containing an unaffected calyx in its centre. We think that this previously unreported "central unaffected calyx sign" could be useful for diagnostic purposes and might also help illustrate the mechanism of renal parenchyma invasion.


   Case report
Top
 Abstract
 Introduction
 Case report
Discussion
 References
 
A 67-year-old man with a history of cutaneous melanoma surgically removed 7 years before was hospitalized for gross haematuria. Cystoscopy showed two bladder polyps. Transurethral resection revealed poorly differentiated (grade 3) pT1 transitional cell carcinomas.

The patient was started on intravesical BCG (Immucyst, Connaught strain; Aventis Pasteur, Lyon, France). He underwent three weekly sessions without complications; however, the fourth session had to be postponed because of the occurrence of gross haematuria and right flank pain, without fever. Cystoscopy showed cystitis and a mild stenosis of the right ureteral meatus. Ultrasound showed a 4 cm solid mass of the right kidney (Figure 1Go). A contrast-enhanced CT of the abdomen confirmed the presence of a slightly hypervascular solid mass (mean attenuation of +65 Hounsfield units (HU) on arterial phase images and +75 HU on excretory phase images) on the convexity of the right kidney. Three smaller masses, with the same appearance, were also seen on the same kidney. On excretory phase images, a normal calyx could be seen in the centre of the largest mass (Figure 2Go). The relationship between the three other masses and the calyces could not be determined clearly because of the small size of the masses (<3 cm), the obliquity of the calyces and the relatively large thickness of the slices (5 mm). An excretory urogram confirmed that all of the calyces, including the one that was in the centre of the largest mass, had a normal appearance, with no displacement, no distortion and no filling defect (Figure 3Go).


Figure 1
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  		Figure 1. Sonogram showing a solid mass on the right kidney(black arrow).

 

Figure 2
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  		Figure 2. Axial contrast-enhanced CT images showing a slightly hypervascular solid mass on the right kidney (a: arrowhead, arterial phase imaging) with a normal calyx in its centre (b: arrow, excretory-phase imaging).

 

Figure 3
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  		Figure 3. Excretory urogram of the right kidney. The calyx included in the mass shows neither distortion nor displacement(arrow).

 
Because of the history of melanoma, an ultrasound-guided 18-gauge needle biopsy of the largest mass was obtained. It showed necrotizing granulomatous inflammation.

BCG instillations were discontinued and the patient was treated with isoniazid, rifampine and ethambutol for 9 months. A CT examination obtained at the end of the treatment period showed the total disappearance of the four masses, which had been replaced by localized areas of parenchymal atrophy (Figure 4Go).


Figure 4
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  		Figure 4. Axial contrast-enhanced CT images, obtained at the same slice level as Figure 2Go, after 9 months of treatment with isoniazid, rifampine and ethambutol (a: arterial phase imaging; b: excretory-phase imaging). The granulomatous mass has completely disappeared and has been replaced by a focal area of parenchymal atrophy (arrows).

 

   Discussion
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 Abstract
 Introduction
 Case report
 Discussion
References
 
Theoretically, there are two mechanisms for renal abscess formation after intravesical BCG instillations.

The most obvious one is a direct seeding of the upper urinary tract owing to vesicoureteral reflux. This was the most likely route of inoculation in most of the published cases that were reported in patients with documented vesicoureteral reflux or an ipsilateral indwelling JJ stent [3–7]. However, iatrogenic reflux occurs in 20–40% of patients after repeated transurethral resection of superficial bladder tumours [8–11] and in up to 70% of patients after resection of polyps in the vicinity of a ureteral ostium [12, 13]. In contrast, renal complications of BCG therapy are rare, even if their incidence may be underestimated because of asymptomatic cases [14]. Direct BCG instillation in the renal collecting system gave contradictory results. Mukamel et al [15] obtained no renal complication in pigs 1–3 months after treatment. In humans, one group of researchers obtained renal granulomas in 4 out of 16 patients [16]; another group reported no complications in 10 patients [17]. Nevertheless, vesicoureteral reflux is not considered a contraindication to intravesical BCG therapy [1]. Whether or not patients with known reflux should receive prophylactic anti-tuberculous treatment remains unclear [3, 4, 18–22].

The other possible route of inoculation is haematogenous dissemination. Systematic dissemination with granulomas in distant organs such as the lungs, liver, muscles or subcutaneous tissue is a well-known complication of BCG therapy [1, 20, 22–25]. In such cases, the portal of entry in the bloodstream may be a fresh bleeding wound in the urethra or bladder, or a severely inflamed urothelium, and it is recommended to wait for at least 1–2 weeks after tumour resection before proceeding with BCG instillations [1, 22, 23, 26, 27]. Systemic immune reaction to antigenic components of the vaccine, with deposition of immune complexes, could also explain the renal lesions, especially in the few reported cases with acute renal failure, interstitial fibrosis and/or glomerular nephropathy [18, 26].

Whatever the mechanism of renal involvement, renal granulomas can usually be successfully treated with anti-tuberculous drugs, as well as steroids.

On CT, renal granulomas appear as hypovascular solid masses [2–6] that raise the possibility of a malignant event, and an imaging-guided biopsy is necessary before beginning anti-tuberculous treatment. In our case, a normal calyx was visible at CT in the centre of one of the renal masses. This calyx showed no distortion and no displacement. To the best of our knowledge, this "central unaffected calyx sign" has not been reported before. It is interesting in two ways.

Firstly, it strongly suggests that the renal parenchyma has been invaded in an isotropic way through the papilla, and therefore that vesicoureteral reflux is the most likely route of invasion.

Secondly, this finding could be useful for diagnostic purposes. A malignant tumour is indeed likely to displace or destroy neighbouring calyces rather than leaving them unaffected. Imaging features of renal tuberculosis (caused by Mycobacterium tuberculosis) are also different. M. tuberculosis is believed to spread haematogeneously in the glomerular and peritubular capillary bed from a pulmonary site of primary infection, leading to granuloma formation in the renal cortex first [28, 29]. Enlarging granulomas invade the medulla and tend to displace and distort calices, just as malignant tumours [30, 31]. Irregularity of the caliceal contour, hydrocalycosis or hydronephrosis due to strictures, and urinary tract calcifications can also be seen as a result of the secondary spread of the bacilli into the collecting system [28–30].

Whether the "central unaffected calyx sign" is pathognomonic of BCG renal infection due to vesicoureteral reflux remains to be determined. This sign might be seen in other cases of tumour-like pyelonephritis with infection of the renal parenchyma through the papilla. It is also likely that in our patient, who had a history of melanoma, the biopsy could not have been avoided on the basis of this sign only. However, we encourage radiologists to prospectively look for this sign in order to further evaluate its diagnostic signification.

It is important to note that there are some technical requirements to clearly seeing this "central unaffected calyx sign", and this might explain that it has been overlooked in previously reported cases of BCG renal infection. Firstly, excretory phase images, with good filling of the renal collecting system, need to be obtained. Secondly, unless the calyx is nearly horizontal (as in our case), thin overlapping sections and high-quality multiplanar reformations might be necessary.

Received for publication June 1, 2006. Revision received August 16, 2006. Accepted for publication August 24, 2006.


   References
Top
 Abstract
 Introduction
 Case report
 Discussion
 References
 

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