British Journal of Radiology (2007) 80, e305-e309
© 2007 British Institute of Radiology
doi: 10.1259/bjr/36850585
Polycystic kidneys: a cautionary story
R J Currie, MA, MRCS
1
S J Freeman, MRCP, FRCR
1
F McCormick, FRCPath
2 and
R J S McGonigle, MD, FRCP
3
Departments of 1 Radiology, 2 Pathology and 3 Renal Medicine, Derriford Hospital, Plymouth PL6 8DH, UK
Correspondence: Dr Simon Freeman, Consultant Radiologist, X-Ray West, Level 6, Derriford Hospital, Plymouth PL6 8DH, UK. E-mail: simon.freeman{at}phnt.swest.nhs.uk
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Abstract
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We describe the imaging appearances of a patient with bilateral, synchronous, multiloculated renal cell carcinoma with a predominantly cystic nature. The patient had progressive chronic renal failure. He was initially erroneously diagnosed as having autosomal dominant polycystic kidney disease (ADPKD) on the basis of the imaging findings. We believe this to be the first report describing bilateral synchronous renal carcinomas replacing the renal parenchyma imitating ADPKD.
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Case report
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A 50-year-old man complaining of recurrent right upper quadrant abdominal pain was referred for specialist nephrological review following an abnormal ultrasound examination of the kidneys. He had presented some 15 years earlier with accelerated hypertension at which time his serum creatinine level had been 250 µmol l–1. Over the ensuing years, his blood pressure had been well controlled on a powerful combination of antihypertensive drugs, with his renal function slowly deteriorating and reaching a serum creatinine concentration of 450 µmol l–1. An ultrasound study of the abdomen performed when the patient was aged 40 was reported to have shown normal-sized kidneys (renal length: right 9.3 cm, left 10.3 cm) with increased cortical echogenicity relative to the medullary pyramids consistent with "parenchymal renal disease" but no evidence of renal cysts. The cause of renal failure had been attributed to hypertensive nephrosclerosis; renal biopsy had not been performed. The patient had no other significant past medical history and there was no family history of renal disease.
At review, the serum creatinine had risen to 600 µmol l–1 and estimated creatinine clearance was <10 ml min–1. Physical examination was unremarkable. The ultrasound examination showed that both kidneys were enlarged, both measuring approximately 14 cm in length, and the renal parenchyma was almost entirely replaced by cysts of varying sizes (Figure 1
). Although most of the cysts were simple in appearance, several were noted to show moderate complexity comprising septation (Figure 2) and some soft tissue elements. There was a single simple cyst in the liver but no cysts in the spleen or pancreas.
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Figure 1. Ultrasound images of the right(a) and left (b) kidneys showing multiple cysts of varying size.
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Figure 2. Ultrasound image of the left kidney showing an anterior cyst containing a thickened septation.
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A provisional diagnosis of autosomal dominant polycystic kidney disease (ADPKD) was made on the basis of the patient's renal failure and the sonographic appearance of the kidneys; however, in view of the complexity of several of the renal cysts, further evaluation of the kidneys with CT was undertaken. This examination confirmed that the kidneys were largely replaced by cysts, some of which showed complexity, with several high-density and septated cysts identified (Figure 3). Although most of the cysts did not show evidence of enhancement following intravenous contrast medium administration, a definite enhancing nodule was seen in an upper pole cyst in the right kidney, representing a Bosniak category IV cyst (Figure 4). The renal veins and inferior vena cava were patent and there was no evidence of regional lymphadenopathy or distant metastases. An MRI examination also demonstrated enlarged multicystic kidneys, some cysts showing evidence of haemorrhage (Figure 5); the enhancing nodule in the same right upper pole cyst as seen on CT was also demonstrated but not as clearly as on the CT examination. On the basis of these findings, it was felt that a right upper pole cystic renal cell carcinoma, arising from a polycystic kidney, could not be excluded. The patient was advised to undergo right nephrectomy.
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Figure 3. Unenhanced(a) and post-intravenous contrast medium (b) CT images showing bilateral renal enlargement owing to multiple cysts.
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Figure 4. Intravenous contrast medium-enhanced CT image through the upper pole of the right kidney showing an enhancing soft tissue nodule arising from an upper pole cyst (arrow). (The complex mass seen at the upper pole of the left kidney showed no evidence of enhancement following contrast.)
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Figure 5. Coronal(a) and axial (b) short tau inversion recovery (STIR) MRI images through the kidneys showing that the renal parenchyma is almost entirely replaced by cysts. There are several low-signal cysts representing haemorrhagic cysts containing blood products.
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Pathological examination of the right nephrectomy revealed virtual replacement of the kidney by a multifocal, multiloculated partly solid, partly cystic tumour with focal haemorrhage. Microscopically, this was a multiloculated Fuhrman Grade 2 papillary (chromophil) renal cell carcinoma (Figure 6a). A small amount of normal renal parenchyma containing tubules and glomeruli was identified between the cysts. Local excision appeared complete (Stage pT2).
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Figure 6. (a) Right kidney: solid area of papillary renal cell carcinoma composed of papillae covered by malignant epithelial cells with abundant eosinophilic cytoplasm (H&E section). (b) Left kidney: branching papillae of papillary renal cell carcinoma protruding into the surrounding cystic space (H&E section).
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In view of the histological findings of the right kidney, a left nephrectomy was performed 4 months later when the patient was deemed fit for further major surgery.
The pathology of the left nephrectomy specimen was similar to the right. There was a mulitloculated partly solid, partly cystic papillary renal cell carcinoma, Fuhrman Grade 2 (stage pT2) (Figure 6b
), replacing the kidney with no definite benign tissue identified. Local excision appeared complete. In both kidneys a mixture of Type 1 and Type 2 papillary renal cell carcinomas was identified but the predominant morphology was Type 1 in each kidney. These tumours were characterized by cells with small ovoid nuclei with inconspicuous nucleoli but with plentiful, mainly eosinophilic, cytoplasm. Some of the cysts had a benign appearance being lined by attenuated simple epithelium.
Post-operatively, the patient has been established on continuous ambulatory peritoneal dialysis and remains well apart from minor complications relating to dialysis. He has been re-established on the renal transplant waiting list.
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Discussion
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Cystic renal disease comprises a mixture of inherited, developmental and acquired abnormalities. Simple renal cysts are a frequent incidental finding in middle-aged and elderly patients, the prevalence increasing with age such that over 20% of individuals aged above 70 years have at least one renal cyst and 9% will have bilateral cysts [1]. Multiple bilateral renal cysts in middle age or the presence of renal cysts in young adults is, however, an uncommon finding and should raise the possibility of hereditary cystic kidney disease, particularly when there is a positive family history or acquired renal cystic disease in patients with renal failure.
ADPKD is the most common hereditary kidney disease with a prevalence of 1:400 to 1:1000 in white populations [2]. It is characterized by the development of multiple renal cysts, often leading to renal failure in the fifth or sixth decade, accounting for 3–10% of patients on maintenance dialysis, although as many as 50% of patients with ADPKD never require renal replacement therapy [3]. In 85% of cases the underlying gene abnormality is located on chromosome 16 (PKD1); the remaining cases are almost all due to a defect in chromosome 4 (PKD2) [2], which tends to be a less severe form of the disease. Although most patients with this condition will have a family history of ADPKD, new mutations account for up to 3.6% of cases, thus family history is not always positive [2]. Hepatic cysts are also usually present in patients with ADPKD but do not usually affect hepatic function. Cysts may also be present in the spleen, pancreas, ovaries and testes [3]. Imaging studies typically show bilateral renal enlargement with multiple renal cysts of varying sizes establishing the diagnosis with virtual certainty in a patient with a positive family history. Ultrasound can be used to diagnose ADPKD in affected families; the presence of two renal cysts (unilateral or bilateral) in individuals younger than 30 years, two cysts in each kidney in individuals aged 30–59 years and at least four cysts in each kidney in those aged 60 or above is regarded as sufficient to establish the diagnosis [4]. Because of the milder clinical course of disease associated with PKD2, ADPKD is only excluded with certainty when the ultrasound study is negative for cysts at or above the age of 30 [5]. Diagnosis is, however, more problematic when multiple renal cysts are discovered in an adult patient with a negative family history. It is now considered that ADPKD does not carry an increased incidence of renal cell carcinoma [2].
Multiple renal cysts may also be a feature of other inherited renal diseases. Tuberous sclerosis (TS) is an autosomal dominant disease with an incidence of approximately 1:10000 but with a much higher spontaneous mutation rate than ADPKD. It is characterized by the development of hamartomas in the skin, brain and viscera; in the kidney, cysts and angiomyolipomas develop and end-stage renal failure occurs in 5–15% [3]. Von Hippel–Lindau (VHL) disease is also an autosomal dominant condition that has a prevalence of approximately 1:35000. It can also result in the development of multiple renal cysts in addition to haemangioblastomas of the central nervous system, angiomas of the retina, cystic lesions of the pancreas, phaeochromocytomas and epidydimal cystadenomas [3]. Unlike ADPKD, VHL and to a lesser extent TS are associated with an increased incidence of renal cell carcinoma; the frequency of renal cancer is estimated at 28–45% for VHL and 1–2% for TS [6]. Confusion with ADPKD is, however, unlikely because of the other renal and extrarenal features of these conditions.
A number of other hereditary renal cell cancer syndromes are now recognized that predispose to multiple bilateral renal cancers [6, 7]. A particular consideration in this patient would be hereditary papillary renal cancer syndrome, an autosomal dominant disorder due to a mutation of the gene at 7q31.3. Unlike many other hereditary renal cancer syndromes, this disorder is not associated with extrarenal manifestations. In this condition, however, tumours are of a specific cell type (Type 1 papillary carcinoma) and cysts are unusual, and, in combination with a negative family history, this effectively excludes the diagnosis in this patient.
Acquired cystic kidney disease (ACKD) was first described by Dunnill et al [8] in 1977 who reported on a post-mortem series of 30 patients who had been maintained on haemodialysis; 14 of these patients were found to have bilateral cystic kidneys. This condition is characterized by the development of multiple renal cysts, usually in patients on maintenance peritoneal or haemodialysis. It is recognized that ACKD develops as a result of sustained uraemia and may therefore occasionally be present before dialysis is started; it is reported to be present in 8–13% of patients with end-stage renal disease not on dialysis [9]. ACKD is diagnosed by the presence of at least three to five cysts in each kidney in a patient with chronic renal failure not attributable to ADPKD. Unlike ADPKD, the kidneys are usually small and the cysts are also usually small (>0.5 cm); occasionally, however, ACKD can produce large cystic kidneys indistinguishable on imaging studies from those in ADPKD [10]. ACKD is associated with an increased incidence of renal cell carcinoma, estimated to be 12–18 times greater than that in the general population [11]. Most of these tumours, however, appear to be small and of low malignant potential. The incidence of invasive or metastatic renal carcinoma in patients on dialysis is probably only three to six times greater than that in the general population [9].
Diagnosis of renal cell carcinoma in polycystic kidneys is frequently difficult on imaging studies because of the anatomical distortion produced by the cysts and also the complexity produced by cyst haemorrhage or infection; enhancement of a renal mass of more than 20 HU on CT is usually taken as a significant finding indicating a probable tumour. [12] MR can also be helpful in these patients because of its multiplanar imaging capacity and ability to detect blood products in complex haemorrhagic cysts [9].
In this patient, the ultrasound study showed bilateral enlarged and mulitcystic kidneys and was interpreted as representing ADPKD. Although the number of cysts present fulfilled the sonographic criteria for ADPKD for an individual aged 50 at risk for this disease [4], there was no positive family history and this would therefore have made this diagnosis much less likely. Additionally, an ultrasound study (that was not available at the time of the diagnosis of ADPKD) showed no renal cysts when the patient was 40 years of age, excluding ADPKD as the cause of this patient's cystic kidneys. Instead, this patient had developed synchronous bilateral multifocal renal carcinoma with a large cystic element diffusely replacing the renal parenchyma, mimicking ADPKD. We are unaware of any similar cases in the literature. It is possible that this patient had developed renal failure-associated ACKD, accounting for the multiplicity of cysts and increasing the risk of multifocal tumour.
In summary, although ADPKD is one of the most common causes of enlarged polycystic kidneys associated with renal failure, it should be diagnosed with caution in patients without a positive family history, and consideration should be given to the other hereditary and non-hereditary causes of multiple renal cysts. We believe this to be the first report describing bilateral synchronous renal carcinomas replacing the renal parenchyma imitating ADPKD.
Received for publication May 15, 2006.
Revision received September 5, 2006.
Accepted for publication September 21, 2006.
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References
|
|---|
- Ravine D, Gibson RN, Donlan J, Sheffield LJ. An ultrasound renal cyst prevalence survey: specificity data for inherited renal cystic diseases. Am J Kidney Dis 1993;22:803–7.[Medline]
- Pirson Y, Chauveau D, Devuyst O. Autosomal-dominant polycystic kidney disease. In: Davidson AM, Cameron JS, Grünfield JP, Ponticelli C, Ritz E, Winearls CG, et al, editors. Oxford textbook of clinical nephrology, 3rd edn. Oxford: Oxford University Press, 2005
- Choyke PL. Inherited cystic diseases of the kidney. Radiol Clin N Am 1996;34:925–46.[Medline]
- Ravine D, Gibson RN, Walker RG, Sheffield LJ, Kincaid-Smith P, Danks DM. Evaluation of ultrasonographic diagnostic criteria for autosomal dominant polycystic kidney disease. Lancet 1994;343:824–7.[CrossRef][Medline]
- Nicolau C, Torra R, Badenas C, Vilana R, Bianchi L, Gilabert R, et al. Autosomal dominant polycystic kidney disease types 1 and 2: assessment of US sensitivity for diagnosis. Radiology 1999;213:273–6.[Abstract/Free Full Text]
- Choyke PL, Glenn GM, Walther MM, Zbar B, Linehan WM. Hereditary renal cancers. Radiology 2003;226:33–46.[Abstract/Free Full Text]
- Choyke PL. Imaging of hereditary renal cancer. Radiol Clin N Am 2003;41:1037–51.[CrossRef][Medline]
- Dunnill MS, Millard PR, Oliver D. Acquired cystic disease of the kidneys: a hazard of long-term intermittent maintenance haemodialysis. J Clin Path 1977;30:868–77.[Abstract/Free Full Text]
- Levine E. Acquired cystic kidney disease. Radiol Clin N Am 1996;34:947–64.[Medline]
- Neureiter D, Frank H, Kunzendorf U, Waldherr R, Amann K. Dialysis-associated acquired cystic kidney disease imitating autosomal dominant polycystic kidney disease in a patient receiving long-term peritoneal dialysis. Nephrol Dial Transplant 2002;17:500–3.[Free Full Text]
- Kawamura K, Ikeda R, Suzuki K. [Acquired renal cystic disease]. Hinyokika Kiyo 2000;46:651–6.[Medline]
- Karashima A, Goldman SM, Sandler CM. The indeterminate renal mass. Radiol Clin N Am 1996;34:997–1015.[Medline]
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Abstract
Case report
