CT and MRI imaging features and long-term follow-up of adult Wilms’ tumor

Abstract

Background

Only few previous case reports have been found focusing on the imaging findings of adult Wilms’ tumor (WT).

Purpose

To characterize multislice computed tomography (MSCT), magnetic resonance imaging (MRI) characteristics, and follow-up results of adult WT.

Material and Methods

Sixteen patients with WT were studied retrospectively. MSCT and MRI were undertaken to investigate the tumor characteristics.

Results

Tumors (mean diameter, 13.1 ± 4.5 cm) exhibited an expansible appearance and disrupted the reniform contour (16/16), cystic components (16/16), curvilinear calcification (1/16), poorly marginated (2/16), hemorrhage (16/16), displacement of renal pelvis or calyx (13/16), and had lymph node or distal metastases (5/16). Attenuation of WT was less or equal compared to renal parenchyma on unenhanced CT (P > 0.05), while tumor enhancement after administration of a contrast agent was lower than that of normal renal parenchyma (P < 0.05). WT was isointense on T1-weighted (T1W) imaging, isointense or hypointense on T2-weighted (T2W) imaging. Tumor enhancement was less than normal renal cortex in all phases (P < 0.05). The number of tumor stages (grades I, II, III, and IV) was two, three, six, and five cases, respectively. Follow-up time was in the range of 19–123 months; six patients died within 3 years, six patients died within 5 years after the initial diagnosis, with the remaining patients still alive.

Conclusion

Adult WT tends to be a large tumor, isointense or hypointense on T2W imaging with enhancement less than normal renal parenchyma in all phases. The long-term follow-up results demonstrated the poor prognosis of the tumor.

Keywords

Wilms’ tumor adult follow-up therapy computed tomography (CT)magnetic resonance imaging (MRI)

Introduction

Wilms’ tumor (WT) is one of the commonest malignant tumors of childhood. Ninety-eight percent of cases occur in individuals aged less than 10 years, only 2% of reported cases have been adults (1). Most WTs in children are of low stage, have a favorable histology, and are associated with an excellent prognosis. A favorable outcome can be expected even among most neoplasms with small foci of anaplasia. However, most WTs in adults have a poor prognosis, and about two-thirds of patients die of their disease within 3 years of diagnosis in China (2). In routine clinical work, the rate of correct imaging diagnosis of WTs in adults by imaging is low. This is likely due to both a low incidence and a low level of awareness.

Although adult WTs have been relatively well described in pathology studies (3,4), imaging data are scanty. However, patients with adult WT have a different prognosis from other renal cell carcinoma (RCC) subtypes. A close collaboration between radiologists and oncological surgeons is essential to optimize imaging both for initial diagnosis, staging, and preoperative workup, as well as for follow-up during and after treatment. Furthermore, international protocols provide guidelines for imaging workup that allow an inter-institutional comparison for not only research, but also for second opinion statements as well as multi-center therapy evaluation (5). Therefore, an accurate diagnosing is important for guiding clinical treatment.

Material and Methods

Patients

This study was approved by the Institutional Research Ethics Committee. A search of pathology records and PACS system identified 16 patients (computed tomography [CT], n = 16; CT and magnetic resonance imaging [MRI], n = 13) with adult WTs who were hospitalized at Subei People’s Hospital, Yangzhou, PR China between 2001 and 2014. Details of the patients’ age, gender, tumor size, surgery or biopsy confirmation, metastasis, clinical symptoms, follow-up, and therapy were recorded.

CT and MRI technique

CT was performed with one of two clinical scanners: a 16-MSCT scanner, or a 64-MSCT scanner (GE Healthcare, Milwaukee, WI, USA). Scanning parameters were: 120 kVp; 200–300 mAs; section thickness, 3 mm; collimation, 0.6–2.5 mm; pitch, 1.0–1.4; reconstruction interval, 50%; field of view (FOV), 33 cm; rotation time, 0.5 s; reconstruction kernel, B40. Images were obtained with a renal mass protocol that included unenhanced images followed by nephrographic phase images 120 s after i.v. administration of non-ionic contrast medium (Iohexol 350 mgI/mL, Omnipaque, GE Healthcare, Cork, Ireland) at 3–4 mL/s and volume of 1.5 mL/kg followed by a 20-mL saline flush.

MR examination was performed with either a 1.5 T or a 3.0 T MR scanner (Vision or Symphony, Siemens Medical Solutions, Iselin, NJ, USA; or Excite Twin Speed, GE Healthcare, Waukesha, WI, USA). All sequences were acquired with anterior and posterior saturation bands. Axial T1-weighted (T1W) and T2-weighted (T2W) MR images were obtained during breath-hold. The transverse planes covered the entire area of the kidneys. The following sequences were obtained: (i) coronal T2W half Fourier single-shot fast spin-echo; (ii) axial dual-echo T1W in-phase and opposed-phase gradient-echo; and (iii) coronal and sagittal three-dimensional (3D) frequency-selective fat-saturated T1W spoiled gradient-echo. Coronal 3D T1W gradient-echo acquisitions were obtained dynamically in the cortical, medullary, and delayed phases after administration of a bolus of 0.1 mmol/kg gadolinium-DTPA (Magnevist; Berlex Laboratories, Wayne, NJ, USA) at a rate of 2 mL/s followed by a 20-mL saline ﬂush. The ﬁrst pass was timed to the cortical phase by using a test bolus of 2 mL of contrast agent, and the nephrographic phase was initiated 20 s after the cortical phase. The timing bolus was administered following the initial precontrast phase acquisition.

Pathologic examination

Pathological specimens were observed by light microscopy and immunohistochemical analysis. All renal tumors were confirmed to be WT by pathology and immunohistology.

Imaging and statistical analysis

Imaging characteristics were retrospectively analyzed by two genitourinary radiologists with more than 10 years of experience each. The evaluated parameters included tumor calcification, cystic components, and hemorrhage. Retroperitoneal lymph nodes or distal metastasis, perinephric stranding, hydronephrosis, and renal tissue invasion were also documented.

The presence of an expansile or infiltrative pattern of growth was assessed, as well as which pattern predominated in each case. Expansile growth was characterized by well-marginated bulging tumor margins that displace normal parenchyma, whereas infiltrative growth on CT or MRI was characterized by poorly marginated borders between the tumor and normal renal parenchyma.

The tumor percentage signal intensity (SI) and tumor-to-cortex enhancement index change were assessed. Percentage SI changes were calculated for the tumor and the renal cortex on enhanced phase images as follows: ([SI_post—Sipre]/Sipre) × 100, where SIpost is the SI of the ROI on the contrast-enhanced phase images and SIpre is the SI of the ROI on the image obtained before administration of the contrast agent. The relative enhancement of the tumor with respect to the renal cortex in the same patient (tumor-to-cortex enhancement index) was calculated for cortical, medullary, and delayed phase images as the percentage SI change of the tumor divided by the percentage SI change of the renal cortex.

Statistical analyses were undertaken using SPSS 17.0 statistical software (SPSS Inc, Chicago, IL, USA). Numeric data were expressed as mean ± standard deviation and categorical data were expressed as percentages. Evaluated characteristics were compared using analysis of variance (ANOVA) or independent-samples t test. P values < 0.05 were considered statistically significant.

Results

Clinical, CT, and MRI appearances in adult WT

The study included 16 patients (8 men, 8 women) with WT. The mean age at diagnosis was 32.7 ± 11.8 years (age range, 18–57 years). Presenting symptoms of WT included flank pain (n = 6), hematuria (n = 13), and palpable mass (n = 12).

Sixteen patients with WT (mean diameter, 13.1 ± 4.5 cm) exhibited an expansible appearance and disrupted the reniform contour (16/16, Figs 1 –3), cystic components (16/16), poorly marginated (2/16), hemorrhage (16/16, Fig. 2b), calcification (1/16, Fig. 3a), displacement of renal pelvis or calyx (13/16), invasion into renal vein, inferior vena cava or ureter (3/16), and had lymph node or distal metastases (5/16). Attenuation of WT was less or equal compared to renal cortex or medulla on unenhanced CT (35.9 ± 4.7 vs. 38.7 ± 3.9 or 33.1 ± 4.6, P = 0.073) (Table 1). On dynamic contrast-enhanced CT scan, the CT attenuation of WT was less than normal renal cortex and medulla during all phases (P = 0.000, 0.000, 0.000, respectively, Table 1).

Fig. 1.

WT of right kidney in a 57-year-old-man. (a) Unenhanced CT scan showed a clearly marginated mass (diameter, 6 cm), exhibited an expansible appearance and disrupted the reniform contour. (b) Contrast-enhanced CT scan showed mild enhancement which was less than that of the cortex in the cortical phase, and the blood vessel within the tumor was noted (white arrow).

Fig. 2.

WT of right kidney in a 24-year-old-man. (a) Unenhanced CT scan showed a clearly marginated mass (diameter, 12 cm), exhibited an expansible appearance together with cystic components (black arrow) and hemorrhage (white arrows). (b, c) The hemorrhage within tumors was hyperintense on T1W imaging (b, arrow), hypointense on T2W imaging (c, arrow). (d) Contrast-enhanced MR scan showed mild heterogeneous enhancement (arrow).

Fig. 3.

WT of left kidney in a 27-year-old-woman. (a) Unenhanced CT scan showed a clearly marginated hypodense mass (diameter, 13 cm), exhibited an expansible appearance together with curvilinear calcifications (white arrow) and cystic components (black arrow). (b) Contrast-enhanced CT scan showed mild heterogeneous enhancement which was less than that of the cortex in the cortical phase. The tumor distorted and displaced the collecting system and the blood vessel within the tumor was shown (white arrow). (c) The WT was hypointense on T2W imaging (arrow).

Table 1.

The CT values of adults with Wilms’ tumor (n = 16), normal renal cortex, and medulla.

Phase	Renal cortex	Renal medulla	WT	P value
Unenhanced	37.9 ± 3.3	32.6 ± 4.1	34.7 ± 3.9	0.073
Cortical	181.3 ± 8.9	76.2 ± 5.1	69.3 ± 7.1	0.000
Medullary	213.2 ± 10.2	108.1 ± 6.9	78.3 ± 6.3	0.000
Delayed	99.6 ± 9.1	90.7 ± 6.0	68.3 ± 5.1	0.000

WT was isointense on T1W imaging, isointense or hypointense on T2W imaging. The hemorrhage within tumors was hyperintense on T1W imaging, hypointense on T2W imaging (Figs 2c and 3c). On cortical, medullary, and delayed phases, WTs showed less signal intensity changes ([127.1 ± 8.3]%, [156.6 ± 11.8]% and [138.6 ± 11.1]% than the renal cortex [296.6 ± 40.3]%, [258.3 ± 51.2]% and [230.3 ± 31.7]%, respectively, P = 0.000). The tumor-to-cortex enhancement index during the cortical, medullary, and delayed phases was 0.49 ± 0.19, 0.69 ± 0.31, and 0.56 ± 0.23, respectively. WT enhanced less than renal cortex during all phases.

Therapy and follow-up

In this study, the number of the patients with tumor stages (grades I, II, III, and IV) was two, three, six, and five cases, respectively. All of the 16 patients with WTs underwent radical nephrectomy, radiotherapy, or chemotherapy and were followed up in 19–123 months (Table 2). Six patients died within 3 years, six patients died within 5 years after the initial diagnosis, with the remaining patients still alive (Table 2).

Table 2.

General and follow-up data of adults with Wilms’ tumor (n = 16).

Patient no.	Age (years)	Gender	Clinical presentation	Max dimension (cm)	Therapy	Follow-up (months)	Relapse	Outcome
1	18	M	Hematuria, mass	10	S + R + C	89	No	NED
2	24	M	Hematuria, mass	12	S + R + C	111	No	NED
3	27	F	Hematuria, mass	13	S + R + C	14	Yes	Died
4	33	F	Pain, mass	17	S + R	19	Yes	Died
5	35	F	Hematuria, mass	16	S + C	23	Yes	Died
6	57	M	Hematuria, pain	6	S + R + C	47	Yes	Died
7	19	F	Mass, pain	11	S + C	38	No	Died
8	26	F	Hematuria, mass	9	S + R + C	56	Yes	Died
9	37	M	Hematuria, mass	23	S + R + C	49	No	Died
10	41	M	Hematuria, mass	15	S + R	29	Yes	NED
11	21	F	Mass, pain	9	S + C	39	No	Died
12	31	F	Hematuria, pain	21	S + R	42	Yes	Died
13	19	M	Hematuria, mass	13	S + R + C	31	Yes	Died
14	39	M	Hematuria, mass	11	S + R + C	27	Yes	Died
15	51	F	Hematuria, pain	9	S + C	123	No	NED
16	45	M	Hematuria, mass	15	S + R + C	33	Yes	Died

C, chemotherapy; F, female; M, male; NED, no evidence of disease; R, radiotherapy; S, surgery.

Microscopic findings

Microscopic analysis indicated that the blastemal cells of WT are small, closely packed, and mitotically active rounded or oval cells with scant cytoplasm, and overlapping nuclei containing evenly distributed, slightly coarse chromatin, and small nucleoli. Hemorrhage, or hemosiderin deposition were found in all 16 cases. Immunochemistry staining demonstrated vimentin, neuron specific enolase (NSE), WT-1 in 13 cases (+++), 13 cases (++), and 15 cases (++), respectively.

Discussion

WT is one of the commonest malignant tumors of childhood. It appears mainly in the first 5 years of life. Pediatric WTs are typically large (average diameter, 12 cm) and spherical. On CT scan, pediatric WT appears heterogeneous and attenuation is usually slightly lower than the uninvolved kidney on unenhanced scans. On MR scan, tumor demonstrates a heterogeneous hypointense signal on T1W sequences and heterogeneous hypo- or isointense signal relative to renal cortex with hyperintense necrotic or cystic areas on T2W sequences (5).

Incidental examples of adult WT have been described in the literature (about 2% of all described cases) (6,7). Kilton (8) have applied six rigid diagnostic criteria for adult WT, which still remain in use: (i) primary renal neoplasm; (ii) primary blastematous spindle- or round-cell component; (iii) formation of abortive or embryonal, tubular epithelial, or glomeruloid structure; (iv) no areas of tumor diagnostic of renal cell carcinoma; (v) pictorial confirmation of histology; and (vi) age >15 years. According to these strict diagnostic criteria, only about 300 cases of adult WT have been reported in the English literature to date.

Most RCCs grow by radial expansion with displacement of the normal parenchyma, focal bulging of the renal contour, and pseudocapsule formation (9,10). Infiltrative growth was a less common pattern (11), which differ from those of cortical clear cell RCCs (12), the most common subtype, exhibit an expansible appearance with exophytic growth that disrupts the reniform contour (13). WTs exhibited an expansible appearance that disrupted the reniform contour (14). In our study, 16 patients with WTs had an expansible appearance that disrupted the reniform contour.

In our MR cases, isointense or hypointense signal on T2W imaging were observed, which was thought to be due to hemosiderin deposition (15,16). This is in distinction to many renal tumors that are hyperintense on T2W imaging, such as clear cell RCCs (17), some cystic renal tumors, and cysts. Larger clear cell RCCs tend to have a heterogeneous, hyperintense signal on T2W MRI, separating them from WT (18,19).

Perlman (20) reported that calcification within the tumors often suggested RCC subtypes. RCCs >3 cm often contain intratumoral necrosis, hemorrhage, cystic components, and calcifications, and are usually of the clear cell variety. In our study, there was evidence of calcification in only one patient, which was curvilinear compared with the stippled calcification seen in neuroblastoma.

In our study, enhancement was lower in WTs than in renal cortex in all phases. This enhancement pattern is atypical of hypervascular tumors such as clear cell RCCs, renal medullary carcinomas, renal angiomyolipomas, and renal angiomas. For example, the degree of enhancement of clear cell RCC is commonly similar or higher than renal cortex (21). Therefore, one may distinguish between WTs and tumors with hypervascularity on the basis of differences in enhancement.

In common with WTs, collecting duct carcinomas, chromophobe RCCs, and renal lymphomas are hypovascular compared to renal parenchyma on enhanced CT imaging. Medullary involvement and an inﬁltrative appearance are common ﬁndings on CT imaging and may suggest the diagnosis of collecting duct carcinomas (22). Papillary RCCs may be multifocal and bilateral, and tend to be less than 2 cm in size at diagnosis (23,24).

Lymph node or distal metastasis was noted in five cases and inferior vena cava or ureter in three cases of WT. Others have reported metastasis associated with this tumor occurring in adult (25). However, pediatric WT extension of tumor thrombus into the renal vein and inferior vena cava has been reported in up to 10% of cases, with possible extension into the right atrium. In comparison, clear cell RCC is associated with renal vein infiltration (26).

Information regarding the clinical behavior of adult WT is limited due to the rare incidence (27). Although the clinical course of these patients are rather indolent, routine follow-up is still mandatory (28). The correct distinction of WTs from other tumors can lead to better understanding of their clinicopathologic differences, which should aid in developing individualized management plans (29).

The present study had certain limitations. First, a small number of patients were included owing to the rarity of adult WT; and second, 81% (13/16) of patients with adult WT were diagnosed by pathology. Therefore, further multicenter cooperation on the radiological diagnosis of adult WT is required.

In conclusion, adult WT is a rare subtype of renal tumor with special pathologic features. Imaging features of adult WT include a large tumor, isointense or hypointense on T2W imaging with enhancement less than the normal renal parenchyma in all phases.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors received National Natural Science Foundation of China: 81401384.

References

Kaste

Brady

Yee

. Is routine pelvic surveillance imaging necessary in patients with Wilms tumor? Cancer 2013; 119: 182–188.

Küpeli

Bilici

. Preoperative chemotherapy with doxorubicin in Wilms tumor. J Pediatr Hematol Oncol 2012; 34: e106–e109.

Huang

Shen

. Multimodal therapy for adult Wilms’ tumour: an experience from one centre. Clin Transl Oncol 2011; 13: 672–676.

Schenk

Gunther

Schrader

. Childhood kidney tumors the relevance of imaging. Radiologe 2005; 45: 1112–1123.

Riccabona

. Imaging of renal tumours in infancy and childhood. Eur Radiol 2003; 13: L116–L129.

Lall

Pritchard-Jones

Walker

. Wilms’ tumor with intracaval thrombus in the UK Children’ s Cancer Study Group UKW3 trial. J Pediatr Surg 2006; 41: 382–387.

Slovis TL (ed). The ALARA (as low as reasonably achievable) concept in pediatric CT intelligent dose reduction. Multidisciplinary conference organized by the Society of. Pediatr Radiol 2002;32:217–213.

Kilton

Matthews

Cohen

. Adult Wilms tumor: a report of prolonged survival and review of literature. J Urol 1980; 124: 1–5.

Barnacle

McHugh

. Limitations with the response evaluation criteria in solid tumors (RECIST) guidance in disseminated pediatric malignancy. Pediatr Blood Cancer 2006; 46: 127–134.

10.

Grundy

Hutton

Middleton

. Outcome of patients with stage III or inoperable WT treated on the second United Kingdom WT protocol (UKWT2); a United Kingdom Children’s Cancer Study Group (UKCCSG) study. Pediatr Blood Cancer 2004; 42: 311–319.

11.

Brisse

. The radiologic contribution to surgical aspects of kidney tumors in children. JBR-BTR 2005; 88: 250–253.

12.

Brisse

Schleiermacher

Helfre

. Preoperative Wilms tumor rupture: a retrospective study of 57 patients. Cancer 2008; 113: 202–213.

13.

Vujanić

Kelsey

Mitchell

. The role of biopsy in the diagnosis of renal tumors of childhood: results of the UKCCSG Wilms tumor study 3. Med Pediatr Oncol 2003; 40: 18–22.

14.

Grundy

Perlman

Rosen

. Current issues in Wilms tumor management. Curr Probl Cancer 2005; 29: 223–260.

15.

Owens

Veys

Pritchard

. Role of chest computed tomography at diagnosis in the management of Wilms’ tumor: a study by the United Kingdom Children’s Cancer Study Group. J Clin Oncol 2002; 20: 2768–2773.

16.

Ehrlich

Hamilton

Grundy

. The value of surgery in directing therapy for patients with Wilms’ tumor with pulmonary disease. A report from the National Wilms’ Tumor Study Group (National Wilms’ Tumor Study 5). J Pediatr Surg 2006; 41: 162–167.

17.

Green

Grigoriev

Nan

. Congestive heart failure after treatment for Wilms’ tumor: a report from the National Wilms’ Tumor Study group. J Clin Oncol 2001; 19: 1926–1934.

18.

Coppes

Arnold

Beckwith

. Factors affecting the risk of contralateral Wilms tumor development: a report from the National Wilms Tumor Study Group. Cancer 1999; 85: 1616–1625.

19.

Bergeron

Iliescu

Thiesse

. Does nephroblastomatosis influence the natural history and relapse rate in Wilms’ tumour? A single centre experience over 11 years. Eur J Cancer 2001; 37: 385–391.

20.

Perlman

Grundy

Anderson

. WT1 mutation and 11P15 loss of heterozygosity predict relapse in very low-risk Wilms tumors treated with surgery alone: a children’s oncology group study. J Clin Oncol 2011; 29: 698–703.

21.

Wright

Green

Daw

. Late effects of treatment for Wilms tumor. Pediatr Hematol Oncol 2009; 26: 407–413.

22.

Kalapurakal

Breslow

. Intraoperative spillage of favorable histology Wilms tumor cells: inﬂuence of irradiation and chemotherapy regimens on abdominal recurrence. A report from the National Wilms Tumor Study Group. Int J Radiat Oncol Biol Phys 2010; 76: 201–206.

23.

Koizumi

Mizusawa

Oguchi

. Adult Wilms’ tumor mimicking adrenal tumor: case report. Hinyokika Kiyo 2008; 54: 603–606.

24.

Daw

Gregoric

Rodman

. Renal function after ifosfamide, carboplatin and etoposide (ICE) chemotherapy, nephrectomy and radiotherapy in children with Wilms tumor. Eur J Cancer 2009; 45: 99–106.

25.

Guo

Wei

Song

. Adult Wilms tumor with intracaval and intracardiac extension: report of a case and review of literature. J Cancer 2011; 2: 132–135.

26.

Zhang

. Long-term follow-up and therapy of adult Wilms’ tumor. Beijing Da Xue Xue Bao 2012; 44: 535–538.

27.

Aronson

Slaar

Heinen

. Long-term outcome of bilateral Wilms tumors (BWT). Pediatr Blood Cancer 2011; 156: 1110–1113.

28.

Van Dijk

Oldenburger

Cardous-Ubbink

. Evaluation of late adverse events in long-term Wilms’ tumor survivors. Int J Radiat Oncol Biol Phys 2010; 78: 370–378.

29.

Misch

Steffen

Schönberger

. Use of positron emission tomography for staging, preoperative response assessment and posttherapeutic evaluation in children with Wilms tumour. Eur J Nucl Med Mol Imaging 2008; 35: 1642–1650.