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Article of the Week: Accuracy of ultrasonography for renal stone detection and size determination: is it good enough for management decisions?

Every week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video discussing the paper.

If you only have time to read one article this week, it should be this one.

Accuracy of ultrasonography for renal stone detection and size determination: is it good enough for management decisions?

Vishnu Ganesan*,, Shubha De*, Daniel Greene*, Fabio Cesar Miranda Torricelli* and Manoj Monga*

 

*Glickman Urological Kidney Institute, and Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, USA

 

Abstract

Objectives

To determine the sensitivity and specificity of ultrasonography (US) for detecting renal calculi and to assess the accuracy of US for determining the size of calculi and how this can affect counselling decisions.

Materials and Methods

We retrospectively identified all patients at our institution with a diagnosis of nephrolithiasis who underwent US followed by non-contrast computed tomography (CT) within 60 days. Data on patient characteristics, stone size (maximum axial diameter) and stone location were collected. The sensitivity, specificity and size accuracy of US was determined using CT as the standard.

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Results

A total of 552 US and CT examinations met the inclusion criteria. Overall, the sensitivity and specificity of US was 54 and 91%, respectively. There was a significant association between sensitivity of US and stone size (P < 0.001), but not with stone location (P = 0.58). US significantly overestimated the size of stones in the 0–10 mm range (P < 0.001). Assuming patients with stones 0–4 mm in size will be selected for observation and those with stones ≥5 mm could be counselled on the alternative of intervention, we found that in 14% (54/384) of cases where CT would suggest observation, US would lead to a recommendation for intervention. By contrast, when CT results would suggest intervention as management, US would suggest observation in 39% (65/168) of cases. An average of 22% (119/552) of patients could be inappropriately counselled. Stones classified as 5–10 mm according to US had the highest probability (43% [41/96]) of having their management recommendation changed when CT was performed. The use of plain abdominal film of kidney, ureter and bladder and US increases sensitivity (78%), but 37% (13/35) of patients may still be counselled inappropriately to undergo observation.

Conclusions

Using US to guide clinical decision-making for residual or asymptomatic calculi is limited by low sensitivity and inability to size the stone accurately. As a result, one in five patients may be inappropriately counselled when using US alone.

Editorial: Ultrasonography vs computed tomography for stone size

In this edition of the BJUI Ganesan et al. [1] report a retrospective analysis of 552 ultrasonography (US) examinations that were followed by a non-contrast CT within 60 days in 486 patients collected over an 18-year period (1995–2012). The sensitivity of US for stone detection was 54% and its specificity was 91% when compared to CT, and sensitivity was positively associated with stone size (increasing from 73% for stones of 0–4 mm to 77% for 5–10 mm, and 89% for >10 mm; P < 0.001), but not with intra-renal location of stones (P = 0.58). US overestimated the size of stones that were <10 mm (P < 0.001), and had a tendency to underestimate size for those >10 mm (P = 0.05).

Stones were grouped into three size categories, based on clinical relevance to stone management: ≤4 mm (where observation would likely be recommended), 5–10 mm (where shockwave lithotripsy [SWL] would be chosen) or >10 mm where an endoscopic approach would be undertaken). Using these thresholds, 39% of cases would have been misassigned to observation and 14% of patients would have been inappropriately advised to undergo active treatment.

One may question the use of CT as the ‘gold standard’, as CT is also prone to sizing inaccuracy. Nevertheless, the headline findings that the inaccuracies inherent in US diagnosis and sizing may compromise clinical management are important. Other authors have made similar observations: in a literature review, Ray et al. [2] reported that US sensitivity was 45% for the detection of renal and ureteric calculi, with specificity up to 94% for ureteric stones and 88% for renal stones and that US overestimated stone size by a mean of 1.9 mm over CT, especially with stones of <5 mm. Similarly, Sternberg et al. [3] showed that the largest stone diameter was over-estimated by an average of 2.2 mm with US, and that errors increased with reducing stone size, rising from a 3% difference in stones >10 mm to 27% for those of 5–10 mm, and an 85% difference in stones ≤5 mm.

It is well established that, whilst having the advantage of no radiation dose, that US is a ‘user dependent’ study but there are also inherent limitations of US compared to CT for stone imaging. CT is capable of much finer spatial resolution, whilst US is prey to more diagnostic confounders. Reflectivity arising from sinus fat or the edges of the papillae may be mistaken for small calculi. For size, it can be difficult to delineate stone edges with the same precision as with CT. The sensitivity of US for stone detection can be improved by adjusting the imaging modalities between ray line (the conventional form of US), spatial compound and harmonic imaging (the most accurate stone size modality). Techniques such as increasing the gain and the transducer-to-stone depth and identifying ‘twinkle artefact’ using colour Doppler have also been used to improve stone detection [4].

However, manoeuvres to improve sensitivity of US may also compromise size measurement. An in vitro study has shown that each 2 cm increase in depth setting increases the size overestimation of stones by ~22% [5]. Using calcium oxalate monohydrate stones, the same group have shown that measuring the posterior acoustic shadow provided a more precise assessment of stone size than measurement of the stone itself [4]. Interestingly, the accuracy of stone width measurement was worse with greater transducer-to-stone depth, but measurement of the shadow width was independent of depth, and all US modalities (ray line, spatial compound, and harmonic imaging) performed similarly for shadow size. Shadow measurement was accurate to within 1 mm of the stone size [4], and similar findings have been shown in vivo, where 73% of the stone measurements and 85% of the shadow measurements were within 2 mm of the size on CT [6].

Unfortunately, not all stones cast an acoustic shadow, particularly the smaller ones, which are most likely to be over-sized. May et al. [6] showed that 89% of stones >5 mm, but only 53% of stones <5 mm demonstrated a posterior acoustic shadow. However, this may provide a further value for US-based clinical decision making, as stones that do not shadow are most likely <5 mm and are small enough to pass spontaneously, and therefore to be managed conservatively.

It is also important to be aware that CT stone measurements are also prone to error and inter-observer variability. Comparing in vitro CT measurements of stones in a ‘kidney sized potato model’, Eisner et al. [7] have shown that the most accurate measurements were obtained using magnified ‘bone window’ settings, which showed a mean 0.13 mm difference compared to a ‘gold standard’ measurement using callipers. This study also included a comparison of size estimate for spontaneously passed ureteric stones (thus a true reference standard) demonstrating that magnified ‘bone window’ measurements were equivalent to digital calliper measurements (the mean underestimation vs digital callipers was only 0.3 mm, P = 0.4), while measurements using magnified soft tissue windows were statistically different (mean underestimation 1.4 mm, P = 0.001) [7].

With its safety and accessibility, US should be the ideal modality for postoperative follow-up, both for assessment of stone recurrence, monitoring for enlargement of residual fragments, and for identifying the rare but important finding of ‘silent obstruction’, with the potential to lose renal function. However, given the ‘real-life’ data reported in this edition of the BJUI [1], and particularly the findings that 22% of patients might have been managed inappropriately when using US for decision making alone, increasing to 43% of patients who had stones between 5 and 10 mm on US, the authors have concluded that patients monitored by US might benefit from an additional CT if intervention is being considered, particularly for stones in the 5–10 mm range by US measurement.

Given the key importance of stone size to the outcome of interventions for stone disease, accurate imaging should translate into improved decision making and patient counselling and allow fairer inter-surgeon and departmental comparisons. Until the best US protocol and settings have been established, we recommend that, when US is used for diagnosis or follow-up, careful optimisation of the settings is crucial. Colour Doppler for ‘twinkle artefact’, and a high gain setting can be used to reduce the risk of missing stones, combined with removing all filtering and compressing the grey scale range to enhance the posterior shadowing. Harmonic imaging (which is now available on most commercial machines) is more accurate than cross beam or compound beams (that are used for standard renal US settings). When decisions need to be made, particularly those based on stone size, CT of the kidneys, ureters and bladder remains invaluable, from which the longest stone diameter should be measured, using magnified images and the ‘bone window’ setting. Current methods for accurate estimation of stone volume are impractical or imprecise. Manual segmentation can be accurate but is laborious, whilst standard semi-ellipsoid formulae cannot account for the wide variety of stone shapes seen in practice. Further studies devoted to simplifying stone volume estimation are necessary. There is also the wider challenge of how best to report stone imaging data. The key variables are stone size, density and location; and the morphology of the collecting system. Agreement between the various stakeholders – sonographers, radiologists and endourologists – over imaging standards and a minimal data set for stone imaging would improve management.

Daron Smith* and Uday Patel

 

*Institute of Urology, University College Hospital, and Department of Radiology, St Georges Hospital, London, UK

 

References

 

 

2 Ray AA, Ghiculete D, Pace KT, Honey RJ. Limitations to ultrasound in the detection and measurement of urinary tract calculi. Urology 2010; 76: 295300

 

3 Sternberg KM, Eisner B, Larson T, Hernandez N, Han J, Pais VMUltrasonography signicantly overestimates stone size when compared to low-dose, noncontrast computed tomography. Urology 2016; 95: 6771

 

4 Dunmire B, Harper JD, Cunitz BW et al. Use of the acoustic shadow width to determine kidney stone size with ultrasound. J Urol 2016; 195: 1717

 

5 Dunmire B, Lee FC, Hsi RS et al. Tools to improve the accuracy of kidney stone sizing with ultrasound. J Endourol 2015; 29: 14752

 

6 May PC, Haider Y, Dunmire B et al. Stone-mode ultrasound for determining renal stone size. J Endourol 2016; 30: 95862

 

 

Video: Accuracy of ultrasonography for renal stone detection and size determination: is it good enough for management decisions?

Accuracy of ultrasonography for renal stone detection and size determination: is it good enough for management decisions?

 

Abstract

Objectives

To determine the sensitivity and specificity of ultrasonography (US) for detecting renal calculi and to assess the accuracy of US for determining the size of calculi and how this can affect counselling decisions.

Materials and Methods

We retrospectively identified all patients at our institution with a diagnosis of nephrolithiasis who underwent US followed by non-contrast computed tomography (CT) within 60 days. Data on patient characteristics, stone size (maximum axial diameter) and stone location were collected. The sensitivity, specificity and size accuracy of US was determined using CT as the standard.

Results

A total of 552 US and CT examinations met the inclusion criteria. Overall, the sensitivity and specificity of US was 54 and 91%, respectively. There was a significant association between sensitivity of US and stone size (P < 0.001), but not with stone location (P = 0.58). US significantly overestimated the size of stones in the 0–10 mm range (P < 0.001). Assuming patients with stones 0–4 mm in size will be selected for observation and those with stones ≥5 mm could be counselled on the alternative of intervention, we found that in 14% (54/384) of cases where CT would suggest observation, US would lead to a recommendation for intervention. By contrast, when CT results would suggest intervention as management, US would suggest observation in 39% (65/168) of cases. An average of 22% (119/552) of patients could be inappropriately counselled. Stones classified as 5–10 mm according to US had the highest probability (43% [41/96]) of having their management recommendation changed when CT was performed. The use of plain abdominal film of kidney, ureter and bladder and US increases sensitivity (78%), but 37% (13/35) of patients may still be counselled inappropriately to undergo observation.

Conclusions

Using US to guide clinical decision-making for residual or asymptomatic calculi is limited by low sensitivity and inability to size the stone accurately. As a result, one in five patients may be inappropriately counselled when using US alone.

Infographic: The origins of urinary stone disease: upstream mineral formations initiate downstream Randall’s plaque

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Figure 1 The medullo-papillary complex. A total of 8–12 paraboloid complexes are contained within each human kidney. Each complex can be separated into three zones (Zones 1–3) distinguished by distinct segments of the loop of Henle. There are short- and long-looped nephrons and vessels. Owing to the paraboloid geometry of the medullo-papillary complex, shorter looped nephrons and vessels are contained in the periphery, and the longest looped nephrons and vessels are located centrally. Non-fenestrated descending vasa recta are surrounded by layers of smooth muscle, in contrast to the ascending vasa recta comprised of fenestrated endothelium. Within Zone 3, a transition occurs where pericytes replace smooth muscle.

bju13555-fig-0002

Figure 2 Spatial relationships and size distributions of the tubules and vessels within the medullo-papillary complex. From Zone 1 to Zone 2, the ascending and descending vasa recta become organised into vascular bundles (dotted line) and interbundle regions. In Zone 3, the descending thin limbs join the vascular bundles (light dotted line), and these are separate from collecting duct clusters. Collecting ducts grow larger in diameter towards Zone 3 and coalesce to form the 6–12 ducts of Bellini. These anatomically specific compartments contribute to radial and axial concentration gradients along the course of the complex.

bju13555-fig-0003

Figure 3 Medullo-papillary function is characterised by pressure and chemical gradients. Pressure gradients are present from Zone 1 to Zone 3. Due to the paraboloid form of the complex, larger diameter vasa recta are located centrally within the vascular bundles and have higher pressure gradients and flow rates than in the peripherally located vasa recta. Poiseuille’s law relates flow rate as proportional to pressure and radius to the fourth power, and inversely proportional to fluid viscosity and tube length. Within each tube, velocity of fluid is highest at the centerline, but decreases near the wall due to resistance. Over time, within a concentrated fluid, solutes are expected to accumulate along the walls. From Zone 1 to Zone 3, an increasing osmolarity gradient, contributed by primarily sodium salts and urea, generates the urine concentrating ability through countercurrent exchange. Areas vulnerable to hypoxic injury include the tip of the Zone 3, and Zone 2 because of the metabolically active thick ascending limbs and their relative physical separation from the descending vasa recta.

bju13555-fig-0004

Figure 4 Biomineralisation of the medullo-papillary complex leading to Randall’s plaque. Over time, lower pressure gradients in the peripheral tubules relative to the centrally located tubules lead to intratubular mineralisation within Zones 1 and 2. The functional volume of the complex gradually decreases, and at a certain threshold, the change in pressure gradient drives a mechanoresponsive switch that leads to interstitial mineralisation in Zone 3. The accumulation of biominerals in the interstitial space eventually becomes endoscopically visible as Randall’s plaque, the foundation for a future urinary tract stone.

 

Abstract

Objectives

To describe a new hypothesis for the initial events leading to urinary stones. A biomechanical perspective on Randall’s plaque formation through form and function relationships is applied to functional units within the kidney, we have termed the ‘medullo-papillary complex’ – a dynamic relationship between intratubular and interstitial mineral aggregates.

Methods

A complete MEDLINE search was performed to examine the existing literature on the anatomical and physiological relationships in the renal medulla and papilla. Sectioned human renal medulla with papilla from radical nephrectomy specimens were imaged using a high resolution micro X-ray computed tomography. The location, distribution, and density of mineral aggregates within the medullo-papillary complex were identified.

Results

Mineral aggregates were seen proximally in all specimens within the outer medulla of the medullary complex and were intratubular. Distal interstitial mineralisation at the papillary tip corresponding to Randall’s plaque was not seen until a threshold of proximal mineralisation was observed. Mineral density measurements suggest varied chemical compositions between the proximal intratubular (330 mg/cm3) and distal interstitial (270 mg/cm3) deposits. A review of the literature revealed distinct anatomical compartments and gradients across the medullo-papillary complex that supports the empirical observations that proximal mineralisation triggers distal Randall’s plaque formation.

Conclusion

The early stone event is initiated by intratubular mineralisation of the renal medullary tissue leading to the interstitial mineralisation that is observed as Randall’s plaque. We base this novel hypothesis on a multiscale biomechanics perspective involving form and function relationships, and empirical observations. Additional studies are needed to validate this hypothesis.

Ryan S. Hsi*, Krishna Ramaswamy*, Sunita P. Ho† and Marshall L. Stoller*

 

*Department of Urology, and Division of Biomaterials and Bioengineering, Department of Preventive and Restorative Dental Sciences, School of Dentistry, University of California San Francisco, San Francisco, CA, USA

 

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Article of the Week: Identifying predictors of renal function decline after surgery

Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Preoperative predictors of renal function decline after radical nephroureterectomy for upper tract urothelial carcinoma

Matthew Kaag, Landon Trost*, R. Houston Thompson*, Ricardo Favaretto†, Vanessa Elliott, Shahrokh F. Shariat‡, Alexandra Maschino†, Emily Vertosick†, Jay D. Raman and Guido Dalbagni†

Penn State Hershey Medical Center, Hershey, PA, *Mayo Clinic, Rochester, MN, †Memorial Sloan-Kettering Cancer Center, New York, NY, USA, and ‡Medical University of Vienna, Vienna, Austria

OBJECTIVES

To model renal function after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). To identify predictors of renal function decline after surgery, thereby allowing the identification of patients likely to be ineligible for cisplatin-based chemotherapy in the adjuvant setting.

PATIENTS AND METHODS

We retrospectively identified 374 patients treated with RNU for UTUC at three centres between 1995 and 2010. Estimated glomerular filtration rate (eGFR) was calculated using Chronic Kidney Disease Epidemiology Collaboration equation before RNU and at early (1–5 months after RNU) and late (>5 months) time points after RNU. Only patients deemed eligible for cisplatin-based chemotherapy before RNU (preoperative glomerular filtration rate [GFR] ≥60 mL/min/1.73 m2) were included. Multivariable analysis identified the preoperative predictors of eGFR after RNU at early postoperative and late postoperative time points.

RESULTS
A total of 163 patients had an eligible early post-RNU eGFR measurement and 172 had an eligible late eGFR measurement. The median eGFR declined by 32% and did not show a significant trend toward recovery over time (P = 0.4). On multivariable analysis preoperative eGFR and patient age were significantly associated with early and late postoperative eGFR, while Charlson comorbidity index score was significantly associated with late postoperative eGFR alone.
 

CONCLUSIONS
In patients with normal preoperative eGFR (≥60 mL/min/1.73 m2), renal function decreases by one-third after RNU and does not show evidence of recovery over time. Elderly patients and those with pre-RNU eGFR closer to 60 mL/min/1.73 m2 (lower eGFR in the present cohort) are more likely to be ineligible for adjuvant cisplatin-based chemotherapy regimens because of renal function loss after RNU.

 

 

Editorial: ‘Discontent is the first necessity of progress’, Thomas A. Edison

This study from Kaag et al. [1] investigates predictors of renal functional decline after radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC). They evaluate early (2 months) and late (6 months) predictors of renal functional decline, finding that on a multivariable model only age at surgery and preoperative renal function were independently associated with early postoperative function. This is an intuitive finding whereby we expect older patients and those with lower renal function to have a more dramatic decrease in renal function after RNU.

Age, preoperative renal function, and Charlson score were associated with late functional recovery. The latter is a counterintuitive finding, as higher Charlson score was associated with less decrease in renal function. Charlson comorbidity was not significant on univariate analyses. Why it would become significant on multivariate is unclear. Whether it is an artifact related to study methodology or is a real phenomenon will require further study.

Unquestionably, this study [1] adds to the growing discontent of our current management of UTUC. The authors cogently discuss the issues related to better risk stratification as a natural consequence of instituting a neoadjuvant chemotherapy paradigm in those with high-risk disease. Multiple retrospective studies have failed to show a benefit of adjuvant chemotherapy, whereas now we have a matched-cohort study showing significant rates of downstaging and complete remission [2], and as well significantly improved 5-year survival, with institution of a neoadjuvant paradigm [3]. One cannot view the dismal outcomes of this disease without being discontent and wishing for progress. We need to continue getting out the message to not only urologists who reflexively institute RNU in patients with a risk-unstratified upper tract filling defect, but as well many medical oncologists who can only function based on guidance from level I data, which for this disease, will be a long time coming.

Surena F. Matin

Department of Urology, MD Anderson Cancer Center, Houston, TX, USA

References

1 Kaag M, Trost L, Thompson RH et al. Pre-operative predictors of renal function decline following radical nephroureterectomy for upper tract urothelial carcinoma. BJU Int 2014; 114: 674–9

2 Matin SF, Margulis V, Kamat A et al. Incidence of downstaging and complete remission after neoadjuvant chemotherapy for high-risk upper tract transitional cell carcinoma. Cancer 2010; 116: 3127–34

3 Porten S, Siefker-Radtke AO, Xiao L et al. Neoadjuvant chemotherapy improves survival of patients with upper tract urothelial carcinoma. Cancer 2014; 120: 1794–9

Step-by-Step: Ultra-mini percutaneous nephrolithotomy (UMP): one more armamentarium

Ultra-mini percutaneous nephrolithotomy (UMP): one more armamentarium

Janak Desai and Ronak Solanki

Department of Urology, Samved Hospital, Ahmedabad, India

OBJECTIVE

• To describe our newly developed technique for the removal of renal stones, which we have called ultra-mini percutaneous nephrolithotomy (UMP).

METHODS

• UMP was performed in 62 patients using a 3.5-F ultra-thin telescope and specially designed inner and outer sheaths. A standard puncture was made and the tract was dilated up to 13 F.

• The outer sheath was introduced into the pelvicalyceal system and the stone was disintegrated with a 365-μ holmium laser fibre, introduced through the inner sheath.

• Stone fragments were evacuated using the specially designed sheath by creating an eddy current of saline; the fragments then came out automatically.

RESULTS

• The mean calculus size was 16.8 mm. Four of the 62 patients were children, three had a solitary kidney and two were obese.

• UMP was feasible in all cases with a mean (sd) 1.4 (1.0) gm/dL haemoglobin decrease and a mean hospital stay of 1.2 (0.8) days. The stone-free rate at 1 month was 86.66%.

• In two patients intraoperative bleeding obscured vision, requiring conversion to mini-percutaneous nephrolithotomy. There was one postoperative complication of hydrothorax, but there were no other postoperative complications and no auxiliary procedures were required.

CONCLUSIONS

• UMP is a very safe and effective method of removing renal calculi up to 20 mm. The use of consumables and disposables is minimal and the patient recovery was fast.

• Further clinical studies and direct comparison with other available techniques are required to define the place of UMP in the treatment of low-bulk and medium-bulk renal urolithiasis. It may be particularly useful for lower calyx calculi and paediatric cases.

Papillary Renal Cell Carcinoma and Clear Cell Renal Cell Carcinoma Arising in a Single Kidney

We report a case of clear cell RCC and papillary RCC arising in the same kidney.

Authors: Tait, Laura; Coleman, Pamela; Ahaghotu, Chiledum
Corresponding Author: Tait, Laura Department of Surgery-Division of Urology, Howard University Hospital Washington, DC

 

Introduction
Renal cell carcinoma (RCC) is responsible for 80 percent of all primary renal neoplasms and approximately 65,000 Americans are diagnosed with RCC each year (1). Clear cell RCC comprises a majority of all RCC tumors diagnosed histologically. They arise from the proximal tubule and macroscopically appearsolid or cystic (2). Clear cell RCC occurs most commonly as a sporadic disease. Papillary RCC are diagnosed in 10 to 15 percent of patients with RCC (3, 4, 5, 6). As with clear cell cancers, papillary RCCs originate from the proximal tubule, but they are morphologically and genetically distinct malignancies. Papillary carcinomas are frequently multifocal and bilateral, and commonly present as small, early stage tumors (7). For localized disease, radical nephrectomy has been the most widely used approach and remains the preferred procedure for cases suggestive of renal malignancy. The diagnosis of clear cell RCC has been established by identifying distinct morphological and histologic features of this tumor following nephrectomy. These unique qualities include neoplastic cells with clear cytoplasm in an acinar growth pattern. These findings separate it from papillary RCC in which psammoma bodies and a strong positive staining for CK7 are characteristic. This case is unique in that there were no prior available reports describing two RCC tumors of separate origin found within a single kidney. We report a case of clear cell RCC and papillary RCC arising in the same kidney.

Case report
A 55-year-old African American male presented to his PCP with a two-week history of hematuria. The patient’s past medical history included hypertension, hepatitis c, and a hernia repair. He was referred to urology and a computed tomography scan demonstrateda complex heterogenous cyst within the right kidney with characteristics suggestive of malignancy and the presence of a left pelvic kidney. Right nephrectomy was performed. Two renal tumors were noted upon gross examination. The main tumor mass was a well-circumscribed, lobulated, homogeneous yellow tumor at the inferior pole of the kidney measuring 4.2×4.0x3.6 cm and demonstrated microscopic invasion of the renal sinus. The satellite tumor was found to be compressing the renal parenchyma at the inferior pole and was a 0.6 cm, firm, well-circumscribed nodule with homogeneous, tan/grey cut surface with characteristic hilar vessel wall invasion. Renal tumor tissues obtained at operation wasfixed in formalin and embedded in paraffin. The specimens were serially sectioned using three-micrometer thick cuts. The sections were stained with hematoxylin-eosin and immunohistochemical studies were undertaken. CK7 staining was performed with the satellite papillary renal cell carcinoma showing strong positive staining. CK7 staining was negative within the main tumor mass. The pathology results provide evidence that clear cell RCC and papillary RCC can simultaneously arise within a single kidney.

Pathology
Macroscopically, the kidney showed no gross abnormalities. The tumor measuring 4.2 x 4.0 x 3.6 cm and the tumor measuring 0.6 cm were observed in the inferior pole. The cut surface of the main tumor showed a yellowish color while the satellite tumor had a tan/grey cut surface appearance. At the posterior/inferior pole it was noted that the renal capsule was expanded by a gelatinous blood clot. The cut surface is shown (Fig. 1).

Microscopically, the main tumor located at the inferior pole showed a proliferation of neoplastic cells with clear cytoplasm and an acinar growth pattern. The nuclear characteristics were a Fuhrman nuclear grade 4 (Fig. 2). Given this tumor’s microscopic characteristics, a diagnosis of clear cell carcinoma was made.

The satellite tumor showed a proliferation of neoplastic cells with foamy macrophages and psammoma bodies (Fig. 3). This satellite tumor also demonstrated strong positive staining for CK7, a well-known tumor marker for papillary renal cell carcinoma. Based on the microscopic and immunohistologic findings, a diagnosis of papillary renal cell carcinoma was made.

Discussion
This case report describes a unique finding of clear cell and papillary RCC within a single kidney. The pathology of this conditionis described to illustrate how both tumors were morphologically different from one another. This particular anomaly has not been previously described in the literature.
The risk factors for RCC have been well-documented and include smoking, hypertension, occupational exposure to toxic compounds, obesity, acquired cystic disease of the kidney, analgesic abuse nephropathy, and genetic predisposition (8,9). These documented findings are similar to our case report in that the patient had a history of hypertension. The literature suggests that hypertension predisposes to the development of RCC. Although our patient had high blood pressure for many years, the incidence of RCC seems to be independent of anti-hypertensive medications. Therefore, hypertension may have played a role in the development of clear cell and papillary RCC seen in this patient.
Another risk factor our patient had for developing RCC waschronic hepatitis c infection. An epidemiologic study of over 67,000 patients found that chronic infection with the hepatitis C virus was associated with a significantly increased risk of RCC (10). This risk factor combined with hypertension may have put our patient at increased risk for RCC.
Although no clear cell RCC and papillary RCC have been found simultaneously before, a coexisting RCC can be identified in 10 to 32 percent of patients with oncocytoma (11). This evidence demonstrates that two unique RCC tumors can exist in a single kidney. Our findings of two RCC within the same kidney is consistent with past evidence of simultaneous tumors but are new in that none have reported clear cell and papillary RCC. Therefore, in our case, we were able to determine the possible risk factors predisposing our patient to RCC and report the new discovery of two RCC tumors within the same kidney.

Conclusions
We present a unique example of clear cell and papillary RCC within the same kidney. Histology of the tissues at the time of nephrectomy confirmed the diagnosis of two distinct renal tumors. Risk factors for RCC seen in this patient include hypertension and chronic hepatitis c. Although there are reports of oncomytoma and coexisting RCC, there have been no observed findings of clear cell and papillary RCC simultaneously.

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References
1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012; 62:10.
2. Presti JC Jr, Rao PH, Chen Q, et al. Histopathological, cytogenetic, and molecular characterization of renal cortical tumors. Cancer Res 1991; 51:1544.
3. Tannenbaum M. Ultrastructural pathology of human renal cell tumors.PatholAnnu 1971; 6:249.
4. Thoenes W, Störkel S, Rumpelt HJ. Histopathology and classification of renal cell tumors (adenomas, oncocytomas and carcinomas).The basic cytological and histopathological elements and their use for diagnostics.Pathol Res Pract 1986; 181:125.
5. Störkel S, van den Berg E. Morphological classification of renal cancer. World J Urol 1995; 13:153.
6. Patard JJ, Leray E, Rioux-Leclercq N, et al. Prognostic value of histologic subtypes in renal cell carcinoma: a multicenter experience. J ClinOncol 2005; 23:2763.
7. Beck SD, Patel MI, Snyder ME, et al. Effect of papillary and chromophobe cell type on disease-free survival after nephrectomy for renal cell carcinoma. Ann SurgOncol 2004; 11:71.
8. Mandel JS, McLaughlin JK, Schlehofer B, et al. International renal-cell cancer study. IV. Occupation. Int J Cancer 1995; 61:601.
9. Wolk A, Gridley G, Niwa S, et al. International renal cell cancer study. VII. Role of diet. Int J Cancer 1996; 65:67.
10. Gordon SC, Moonka D, Brown KA, et al. Risk for renal cell carcinoma in chronic hepatitis C infection. Cancer Epidemiol Biomarkers Prev 2010; 19:1066.
11. Chao DH, Zisman A, Pantuck AJ, et al. Changing concepts in the management of renal oncocytoma. Urology 2002; 59:635.

 

Date added to bjui.org: 12/12/2012

DOI: 10.1002/BJUIw-2012-060-web

 

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