An asymptomatic patient with multiple solid renal masses: errors in diagnosis

Caterina Canavese1, Laura Rizzo2, Paolo Aveta3, Federico Cesarani4, Giuseppe Isolato4, Giancarlo Anselmetti2, Giorgio Passarino5, Ottavio Davini2, Donatella Pacchioni5, Paola Cassoni5, Daniela Bergamo6 and Piero Stratta1

1 Transplantation and Nephrology, Department of Nephro-Urology, Amedeo Avogadro University, Maggiore Hospital, Novara, 2 Radiodiagnostic Unit, Molinette Hospital, Torino, Departments of Internal Medicine, Sections of 3 Urology, 4 Radiology, 6 Nephrology, and 5 Biomedical Science and Human Oncology, Section of Pathology, University of Torino, Torino, Italy

Correspondence and offprint requests to: Caterina Canavese, Transplantation and Nephrology, Department of Nephro-Urology, Amedeo Avogadro University, Ospedale Maggiore della Carità, Corso Mazzini 18, 28100 Novara, Italy. Email: ccanavese{at}hotmail.com

Keywords: biopsy; computed tomography; magnetic resonance imaging; oncocytoma; renal carcinoma; xanthogranulomatous pyelonephritis



   First step: suspecting renal carcinoma
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 First step: suspecting renal...
 Second step: choice of...
 Third step: histological...
 Fourth step: prostatectomy to...
 Fifth step: toward a...
 Sixth step: surgical diagnosis...
 Discussion
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A 63-year-old man was referred to us in December 1997 from an out-patient clinic for further work-up and treatment of a ‘presumed bilateral renal carcinoma’.

At admission, the patient had no symptoms except for a vague suprapubic discomfort with occasional dysuria, both of which had started several weeks earlier. He had a history of similar symptoms 7 years earlier (1990). At that time, he had dysuria for several weeks before seeking medical consultation, which resulted in a presumed diagnosis of prostatitis.

His intravenous urogram then was normal, except for a double pelvis in the left kidney, and his ultrasound examination had revealed a small prostatic adenoma. His symptoms had disappeared completely after a short course of rifampicin. No further examinations were carried out as his symptoms did not reappear until November 1997, when ultrasonography showed a prostatic adenoma and, incidentally, an area of increased echogenicity at the upper pole of the right kidney. A computed tomographic (CT) scan disclosed multiple solid areas in both kidneys, leading us to diagnose a malignancy [1–3].

The physical examination on admission revealed a healthy appearing individual with a blood pressure of 144/85 mmHg. Laboratory tests provided the following results: white blood cell count 4760/mm3, with 58.6% of neutrophils; slightly increased erythrocyte sedimentation rate (ESR; 13 mm/h, normal <10), C-reactive protein <3.5 mg/dl (normal <5); normal blood urea nitrogen (BUN; 30 mg/dl), creatinine (1.0 mg/dl), urea (46 ml/min) and creatinine clearance (98 ml/min). Urinalysis was negative for protein, blood and nitrites. The microscopic examination of the urine showed hyaline casts and a few red and white blood cells. Urine cultures yielded no growths of common organisms or acid-fast bacilli. Cultures from the urethral meatus and of semen were also negative for many pathogens, including Chlamydia, Gardenella, Mycoplasma and Ureoplasma urealyticum.



   Second step: choice of biopsy as diagnostic tool
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 First step: suspecting renal...
 Second step: choice of...
 Third step: histological...
 Fourth step: prostatectomy to...
 Fifth step: toward a...
 Sixth step: surgical diagnosis...
 Discussion
 Teaching point
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Ultrasonography, CT scan and magnetic resonance imaging (MRI) yielded considerably discrepant results. Ultrasonography revealed only one isoechogenic area, in the centre of the right kidney (Figure 1, A1), whereas the CT scan showed multiple irregular solid areas bilaterally (Figure 1, A2). The MRI confirmed the bilateral presence of multiple irregular nodular areas, with well-defined inhomogeneous hyperintensity in the renal cortex visualized on non-enhanced T1-weighted images (Figure 1, A3).



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Fig. 1. (A) 1997. (A1) Ultrasonic examination showing an isoechogenic area surrounded by a thin hypoechogenic halo in the upper pole of the right kidney (arrow). (A2) Axial contrast-enhanced abdominal CT scan demonstrates dishomogeneous, hypodense bilateral renal lesions (arrows) showing mainly peripheral contrast enhancement. (A3) T1-weighted MRI without contrast shows dishomogeneous hyperintensity of the lesions in both kidneys (arrows). (A4) A fine needle (gauge 20), CT-guided percutaneous biopsy was performed of the upper pole of the right kidney (arrow). (B) 2001. MRI images—coronal plane, T2-weighted, without contrast agent. On the right kidney, one lesion is evident at the upper pole where a biopsy had been performed 4 years earlier (arrow in B1). On the left kidney, one nodular lesion is shown at the lower pole (arrow in B2).

 
A renal perfusion scan showed bilateral functioning kidneys with areas in the upper pole of each kidney which, although not fully functional, showed no signs of obstruction. Therefore, we biopsied the upper pole of the right kidney under CT visualization (Figure 1, A4).



   Third step: histological diagnosis of xanthogranulomatous pyelonephritis
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The biopsy specimen of the nodular lesion at the upper pole of the right kidney did not disclose any atypical or malignant cells. The renal parenchyma appeared to have been completely replaced by chronic inflammatory tissue made up of a large amount of amorphous hyaline material along with collagen and areas of fibrosis and calcifications. On the basis of these findings, a diagnosis of an advanced form of xanthogranulomatous pyelonephritis was made, supported by the fact that foamy, lipid-laden macrophages were absent, replaced by chronic inflammatory elements.

Xanthogranulomatous pyelonephritis may be the result of chronic renal infection and obstruction [4–6]. Since the only element which might have caused recurrent infection ascending to the renal parenchyma was the noxa, in this case prostatitis, we speculated that an undiagnosed vescico-ureteral reflux could have caused an infection to ascend from subclinical prostate infections and over time led to the bilateral focal xanthogranulomatosis pyelonephritis.



   Fourth step: prostatectomy to remove a trigger for infection
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The patient underwent cystography, which excluded vescico-ureteral reflux. Some hours later, the patient had fever, leukocytosis and an acute urinary obstruction that led to an increase in his serum creatinine to 2 mg/dl. This episode advanced the prostatectomy, already planned, intended to obviate future obstructions that would worsen the kidney disease. Microscopic examination of the excised prostate revealed benign hyperplasia: several small and large nodular aggregations and even glands that had dilated into cysts, as well as fibrous and muscular proliferations of the stroma.

It was speculated that previous subclinical prostatitis (along with the only clinically documented episode 7 years earlier) may have led to subacute processes inside the renal parenchyma. We thought that a form of ‘healing’ had taken place over time, forming the chronic inflammatory tissue, ‘scarred areas’, in both kidneys. The patient was discharged with the pathological diagnosis of xanthogranulomatous pyelonephritis, and was to have strict follow-up and periodic radiological examinations.



   Fifth step: toward a surgical confirmation of the previous diagnosis
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At the beginning of 2001, the patient had a repeat MRI, at a time when he had no clinical symptoms and had stable renal function (serum creatinine 1.2 mg/dl and creatinine clearance of 90 ml/min). The MRI confirmed the presence in the right and left kidneys of two solid masses whose dimensions and appearance were identical to those found 4 years earlier (Figure 1B).

We reasoned that, if the diagnosis of xanthogranulomatous pyelonephritis were right, the solid renal masses should have been anachronous, some lesions older and some more recent, and also that the removal of the infected prostate ‘identified’ as the original locus of the ascending pyelonephritis should have allowed a partial regression of the solid masses, of at least the most recent and florid one, the one logically most susceptible to some form of ‘healing’.

The fact that this had not taken place not only fed the seeds of the diagnostic doubts that had never been completely dispelled, but also gave rise to second thoughts: the foci had silhouettes that went beyond the contours of the kidneys and showed mild contrast enhancement and central ‘scars’.

A team decision was made to perform a surgical biopsy of the two lesions in the left kidney.



   Sixth step: surgical diagnosis of oncocytoma
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The patient had a surgical exploration of the left kidney via a loin incision. Two well-encapsulated ruddy masses, of 3.3 and 3 cm, were found in the lower and upper poles. They were well circumscribed, had cut surfaces of a uniform mahogany-brown colour, and had no foci of necrosis. As frozen sections suggested an initial diagnosis of a renal oncocytoma, a conservative enucleation was adopted, and both masses were carefully enucleated.

The definitive histological examination showed the masses to be composed of oncocytes—large cells with granular eosinophilic cytoplasm and abundant mitochondria (Figure 2). The final diagnosis was renal oncocytoma.



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Fig. 2. Histological features of the renal oncocytic lesions obtained by surgical removal of the upper and lower polar masses of the left kidney. In the intraoperative frozen section, an intense eosinophilic lesion was evident both at low (A) and high magnifications (B). In (B), it is also possible to recognize cell components: a large, eosinophilic cytoplasm and central nucleus. Histological examination of the surgical specimen confirmed the pattern already observed during intraoperative frozen section examination. In addition, a certain nuclear pleomorphism was present (arrowheads) (C). At low magnification, the neoplastic eosinophilic area (outlined by arrowheads) is surrounded by sclerotic renal parenchyma, the result of previous inflammation (D).

 
At discharge, the patient's a serum creatinine was 1.6 mg/dl and his creatinine clearance 67 ml/min. Two years later (in 2003), the patient's repeat MRI showed substantial stability of the previous picture. At the time of this report, he is in excellent health, with no evidence of any clinical problems, a serum creatinine stable at 1.6 mg/dl, and creatinine clearance at 69 ml/min.



   Discussion
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 First step: suspecting renal...
 Second step: choice of...
 Third step: histological...
 Fourth step: prostatectomy to...
 Fifth step: toward a...
 Sixth step: surgical diagnosis...
 Discussion
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The neoplasm this patient had posed a difficult diagnostic challenge. Renal oncocytoma is a solid epithelial tumour thought to arise from the proximal convoluted tubules of the kidneys. It is rare; bilateral multicentric renal oncocytomas are even more rare. This disease, often misdiagnosed as a malignant tumour, generally has a benign course [7–10].

The results of the histological examination of larger samples of renal tissue obtained from our patient by surgical excision demonstrated that his true diagnosis had eluded us for 4 years. It was only the last, and most invasive, procedure that provided the correct diagnosis.

In conclusion, we report an uncommon case of renal oncocytoma, which highlights the difficulties of making a correct diagnosis even with the available modern diagnostic modalities. In this case, two diagnostic errors were made: a wrong initial hypothesis of malignant renal carcinoma was made followed by a wrong diagnosis of bilateral xanthogranulomatosis.

Although our patient has histologically proven multifocal left renal oncoytoma and biopsy-proven right chronic pyelonephritis (the left renal lesions are identical to the right one on MRI), our final diagnosis was bilateral multifocal renal onococytoma, with a putative diagnosis of pyelonephritis based on tissue located in a marginal portion of a tumour (also present in the right kidney). A sampling error during the fine needle biopsy had led us to miss the principal diagnosis.

Several important points are raised by this case. (i) in the evaluation of patients with multiple renal solid masses, watchful management is not advocated, because urological imaging modalities do not provide specific diagnoses; (iii) clinical thinking is important when interpreting the results of pathological investigation and radiological findings; (iii) a benign tumour is one that is non-cancerous. While not immediately life-threatening, many tumours classified as benign may grow; finding them is to be regarded as fortuitous, something to be evaluated and treated with nephron-sparing surgery at an early stage.



   Teaching point
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 First step: suspecting renal...
 Second step: choice of...
 Third step: histological...
 Fourth step: prostatectomy to...
 Fifth step: toward a...
 Sixth step: surgical diagnosis...
 Discussion
 Teaching point
 References
 
The lesson of this case is that a probabilistic approach to clinical decision making can be of little help in patients with bilateral solid renal masses.

  1. In patients who have evidence of multiple bilateral renal masses, renal oncocytoma should be in the differential diagnosis.
  2. The combined use of ultrasound, CT and MRI may help identify such lesions, and should today permit diagnostic certitude pre-operatively, so that conservative, rather than radical, surgery can be employed, especially in the face of an early or incidental diagnosis (often the most common situation at present).
  3. This diagnosis needs histological evidence obtained through the surgical exploration of the kidney, as clinical history may be non-contributory and radiological images insufficient to provide definite diagnostic criteria.
  4. Lastly, radiologically guided biopsy, though a useful technique in many situations, may be insufficient and may even lead to the wrong diagnosis in others.

Conflict of interest statement. None declared.



   References
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 First step: suspecting renal...
 Second step: choice of...
 Third step: histological...
 Fourth step: prostatectomy to...
 Fifth step: toward a...
 Sixth step: surgical diagnosis...
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 References
 

  1. Elmore JM, Kadesky KT, Koeneman KS, Sagalowsky AI. Reassessment of the 1997 TNM classification system for renal cell carcinoma. Cancer 2003; 98: 2329–2334[CrossRef][ISI][Medline]
  2. Motzer RJ, Bande NHr, David M. Nanu DM. Renal-cell carcinoma. N Engl J Med 1993: 335: 865–875[CrossRef]
  3. Semelka RC, Shoenut JP, Magro CM, Kroeker MA, MacMahon R, Greenberg HM. Renal cancer staging: comparison of contrast-enhanced CT and gadolinium-enhancing fat-suppressed spin-echo and gradient-echo MR imaging. J Magn Reson Imaging 1993; 3: 597–602[Medline]
  4. Nataluk EA, McCullough DL, Scharling EO. Xantho-granulomatous pyelonephritis, the gatekeeper's dilemma: a contemporary look at an old problem. Urology 1995; 45: 377–380[CrossRef][ISI][Medline]
  5. Perez LM, Thrasher JB, Anderson EE. Successful management of bilateral xanthogranulomatous pyelonephritis in bilateral partial nephrectomy. J Urol 1993; 149: 100–102[ISI][Medline]
  6. Ozcan H, Akyar S, Atasoy C. An unusual manifestation of xantho-granulomatous pyelonephritis: bilateral focal solid masses. Am J Radiol 1995; 165: 1552–1553[ISI][Medline]
  7. Morra MN, Das S. Renal oncocytoma: a review of histogenesis, histopathology, diagnosis and treatment. J Urol 1993; 150: 295–302[ISI][Medline]
  8. Katz DS, Gharagozloo AM, Peebles TR, Oliphant M. Renal oncocytomatosis. Am J Kidney Dis 1996; 27: 579–582[ISI][Medline]
  9. Dechet CB, Bostwick DG, Blute ML, Bryant SC, Zincke H. Renal oncocytoma: multifocality, bilateralism, metachronous tumor development and coexistent renal cell carcinoma. J Urol 1999; 162: 40–42[CrossRef][ISI][Medline]
  10. De Carli P, Vidiri A, Lamanna L, Cantiani R. Renal oncocytoma: image diagnostics and therapeutic aspects. J Exp Clin Cancer Res 2000; 19: 287–290[ISI][Medline]
Received for publication: 5. 8.04
Accepted in revised form: 12. 4.05





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