Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

Wilms Tumor: Imaging of Pediatric Renal Masses

Allison Young, HMS III Gillian Lieberman, MD

www.fraservalleymri.com/ gfx/doc4-5.jpg

Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

What is Wilms Tumor? ~defining features~

First classified as an embryonal sarcoma by Max Wilms in 1899 at the Institute of Pathology in Bonn, Germany. Also known as nephroblastoma, it is the most common solid renal tumor of childhood. Usually bulky, may arise in any portion of the kidney, and expands within the renal parenchyma to displace and distort the pelvicalyceal system. Distinguished by vascular invasion and displacement of surrounding structures.
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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

~ Epidemiology ~
Accounts for roughly 5% of childhood cancers and 87% of pediatric renal masses. Incidence = 1:10,000. Approximately 500 new cases annually. Peak incidence = 3-4 years of age (80% present before age 5). 5-10% present with bilateral Wilms. National Wilms Tumor Study (NWTS) - has 85% of all new cases diagnosed in North America enrolled in group protocols.
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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

Associated Syndromes ~ the minority of cases~

WAGR Syndrome Drash Syndrome male pseudo-hermaphroditism, progressive glomerulonephritis Overgrowth Syndromes Beckwith Wiedemann, hemihypertrophy. GU abnormalities hypospadias, cryptorchidism, horseshoe kidney.

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Abnl. WT 1 gene

Abnl. WT 2 gene

Patients with associated syndromes should be screened starting at 6 months of age, with initial CT and follow up US every 3 months up to 7 years of age.

Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

~ Pathogenesis of Wilms tumor ~

Wilms is an abnormal embryonal renal neoplasm, presumed to develop from abnormal histiogenesis. Precursor cells = renal blastemal tissue (nephrogenic rests) Normal nephrogenesis is complete at 36 weeks gestation. Kidneys of normal full-term newborns contain no foci of renal blastema. Wilms is thought to arise from metanephric precursor tissue that persists in the developing child.
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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006
Beginning at week 5 of development:

~Nephrogenesis ~
Ureteric buds penetrate metanephric tissue that is molded around the distal ends like a cap. Buds gives rise to collecting system (ureter, calcyes, renal pelvis). Epithelium of the ureteric bud from the MESONEPHROS interacts with mesenchyme of METANEPHRIC blastema.

Metanephric blastema

Metanephric blastemal tissue expresses WT1 (transcription factor) which enables metanephric tissue to respond to induction by ureteric buds. Nephrons are formed from metanphros through molecular signaling.

Langmans Medical Embryology, 9th Ed., T.W. Sadler, PhD. Lippincott, Williams & Wilkins, 2004.

Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

Gross Pathology
Solid multi-lobulated, gray/tan intrarenal mass with a pseudocapsule distorting the renal parenchyma and collecting system. Spreads by direct extension but does not encase the aorta.

Histology
*most important prognostic factor

Usually shows well-differentiated renal tissue with embryonic glomeruli and tubule formation surrounded by spindle cell stroma. Triphasic pattern = stromal, blastemal and tubular elements. 10% of Wilms tumors have unfavorable histology with anaplasia (atypical mitoses or hyperchromatic cells with large nuclei).

Tubular elements Stromal Elements

Blastemal elements

Lowe et al. Pediatric Renal Masses: Wilms Tumor and Beyond. Radiographics. 2000 Nov-Dec;20(6):1585-603.

Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

~ Renal Anatomy ~
Positions of Urinary Organs Left kidney and suprarenal gland in situ
Renal artery

Renal vein

Fibrous capsule Cortex Medulla Renal calyx Renal pelvis Grays Anatomy Online http://www.bartleby.com/107/253.html

Rohen, Johannes. Color Atlas of Anatomy, 5th Edition. 1998.

Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

Anatomy ~Axial View ~

Stomach Pancreas

Renal Vein Abdominal Aorta

http://radiology.med.sc.edu/%20Portalveinliver.htm

Kidney

Color Atlas of Anatomy, 5th Ed., Johannes Rohen. Lippincott, Williams & Wilkins 1998.

Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

Clinical Presentation of Wilms tumor

Common: Patient presents with an asymptomatic abdominal mass noted by patient, physician or parent. Uncommon: Patient can present with abdominal pain, anorexia, hematuria and hypertension due to renin production by tumor. Rare: Patient presents with dysuria and renal failure.
* Discovered after coincidental trauma in up to 10% of cases.

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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

Index Patient
KG is a 2 year-old girl who presented in January 2006 with left upper quadrant pain and a left flank mass detected by her parents. She underwent CT scan directly, which showed.
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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

MDCT Abdomen with Oral & Intravenous Contrast

a very large multi-lobulated, heterogenously enhancing mass replacing the pole of the left kidney. CLAW SIGN
The mass shows smooth margins. It measured 12 x 7 cm in its largest dimension and extended from approximately the iliac crest up to the diaphragm. The lesion itself appears to be comprised of either multiple confluent masses, or single large septated mass. It is exerting mass effect on the surrounding abdominal structures pushing the pancreatic tail and splenic vein, and the stomach superiorly and anteriorly. The left renal artery and vein are widely patent.
: 20 OP 320 30CC P 320 30CC ANDARD DOB: 6/9/2 1/19/2

Tumor mass

Normal enhancing renal parenchyma

Courtesy of Dr. Mara Barth Boston Childrens Hospital Boston

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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

Coronal and Sagittal Reconstructions

eed Pro 16 SYS#CT02_OC0 4 3 OP 320 30CC 30CC ARD H Acc Num: 10 002Y F 2 DOB: 6/ 1/1

o ro 16 SYS#CT02_OC0

Acc Num 002Y DOB

0 20 30CC

0 20 0 512X512 L MODE /15:05:16 C: 50 Z: 1

Compress Page: 77

12 512 E /15:05:16 Z: 1

Comp Page:

Tumor Mass heterogeneous, claw formation.

Courtesy of Dr. Mara Barth Boston Childrens Hospital Boston

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Harvard Mediical School, MS III Gillian Lieberamn, MD

Differential diagnosis of a Renal Mass

Malignant renal mass
Clear Cell Sarcoma Leukemia; Lymphoma Metastasis ( e.g. neuroblastoma) *Renal Cell CA* Rhabdoid tumor; rhabdomyosarcoma Wilms tumor
* Far more common in older age groups.*

March, 2006

*varies depending on clinical presentation + imaging features*

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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

KGs differential
Renal Mass Wilms Tumor Clinical and imaging features Large solid mass, often with vascular invasion. Most common solid renal mass of childhood. Congenital Mesoblastic Nephroma Most common solid renal mass in newborns and infants. Tends to be a large infiltrative mass with ill-defined margins and no capsule. Multilocular Cystic Nephroma. Multicystic mass with little solid tissue. Septa are the only solid components distinguished from Wilms by absence of expansile solid masses. Clear Cell Sarcoma Non-specific presentation. Manifests as abdominal mass. Distinguished by histology. Commonly shows skeletal mets. Rhabdoid Tumor Rare, highly aggressive. Imaging features can closely resemble Wilms. Usually diagnosed in infancy. Associated with brain malignancies.
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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

Diagnostic Imaging of suspected Wilms Tumor: low performance modalities ~Plain film, IVU~
*Common imaging challenge = stating the renal origin of the mass.* No longer commonly used: IVU shows distortion of Plain film minimal contribution; the pyelocaliceal system not may show typical changes of ribs sufficient for diagnosis and caused by compression by a slowly staging and now rarely growing tumor. (Modality of choice performed. to evaluate for presence of lung mets.)

Courtesy of Dr. Mike Geary, Boston Childrens Hospital

Kioumehr et al .Wilms Tumor in the Adult Patient. American Journal of Roentgenology 1989: 152 (2); 299.

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Harvard Mediical School, MS III Gillian Lieberamn, MD

Diagnostic Imaging of Suspected Wilms Tumor: high performance modalities US, CT, MR
US Demonstrates intrarenal mass with heterogenous echogenicity. bursts the normal kidney with a spur of normal parenchyma surrounding the tumor.
Color Doppler Study may help to better define and depict tumor extent and necrotic area, as well as vascular invasion.

March, 2006

CT Demonstrates heterogeneous mass with slightly lower attenuation than normal kidney. Allows exam of contralateral kidney.
IV contrast mandatory. Shows nodal, hepatic mets, and tumor extension into renal vein or IVC.

US (dorsolateral): Exophytic Wilms tumor on lower pole of kidney

Axial US: Shows thrombus in IVC.

MRI Heterogeneously hypointense on T1, hypo/iso. intense on T2. Most sensitive modality for determination of caval patentcy. [requires sedation not routinely done]

Contrast enhanced CT & MR: Abnormal tissue appears heterogeneously less enhancing.

Riccabona, Michael. Imaging of renal tumours in infancy and childhood. European Radiology 2003, 13:L116-L129.

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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

Back to KG
KG underwent left nephroureterectomy and adrenalectomy with complete resection of tumor. Pathology showed multifocal Wilms tumor with diffuse anaplasia, intact renal capsule, and focal invasion of renal sinus and renal sinus vessels. Multiple nephrogenic rests were present. Resected lymph nodes were negative for tumor involvement. There was no evidence of right kidney involvement or abdominal lymph node disease in preoperative scans. Chest CT was negative for metastases.
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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

Staging
Staging of Wilms Tumor: by imaging, surgery, and pathology Stage I Description Limited to the kidney and completely resectable with renal capsule intact; renal sinus may be inflitrated but not beyond hilum. Tumor infiltrates beyond kidney but completely resected. Residual tumor confined to abdomen and without hematogenous spread. Hematogenous metastases to lung (most common), bone, liver or brain. Bilateral renal involvement; each side staged separately.

II III IV V

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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

KG was found to have Stage II anaplastic Wilms Tumor

*Most recent trial showed that stage II disease did not have a worse prognosis with diffuse anaplasia than without.

Gross Pathology shows multilobular encapsulated tumor, originating from the kidney.
Courtesy of Dr. Mara Barth, Boston Childrens Hospital

Multifocal disease shows hyperchromatic cells with atypical mitoses and large nuclei. Each focus is at a slightly different stage of disease.
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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

Prognosis
5 year survival rates, based on recent studies:
Favorable histology survival approaches 90% Most important negative prognostic factors are unfavorable histologic subtypes. Recent NWTS data suggests 3-year survival rates for bilateral Wilms tumors = 82%

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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

KG multi-modal treatment
*Based on data from National Wilms Tumor Study Trials
Surgery: Radical nephrectomy via transabdominal incision is procedure of choice with biopsy of regional lymphatics and careful examination of opposite kidney for staging and prognosis. Major emphasis placed on avoiding spillage of tumor as this increases abdominal recurrence. Chemotherapy: Adjuvant therapy planned based on staging. Current studies are focusing on minimizing toxicity of therapy. Radiation: Complicated by potential for growth disturbance and organ toxicities. Only used for patients with III or IV unless unfavorable histology seen. Follow-up imaging: Ultrasound Based on the anaplastic features of her Stage II tumor, KG is currently undergoing chemotherapy and radiation.
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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

Companion Case ~ Patient # 2 ~

JC is a 7 year old boy, s/p resection for stage III Wilms tumor who presents for restaging due to recurrence of palpable abdominal mass.

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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

JCs preoperative CT Scan: dated April, 2005

CT abdomen with contrast: shows heterogeneously enhancing solid mass arising from the left kidney with adjacent soft tissue probably lymphadenopathy, and thrombus in the left renal vein. Venous extension of Wilms tumor follows the rule of 10s: 10% extend into renal vein; 10% of that group extend into IVC; 10% of the latter further extend into the right atrium.
Soft tissue: likely LAD
Courtesy of Dr. Melissa Gerlach, Boston Childrens Hospital

Thrombus in left renal vein. 24

Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

Restaging October 2005: status post Wilms resection ~Abdomen, Pelvis CT with contrast~
The left kidney is absent. There is a lobulated soft tissue mass in the left renal fossa and lower retroperitoneum associated with multiple vascular clips. It is bilobed with a large mass at the level of the SMA and another at the level of the IMA. The lower component demonstrates cystic degeneration in its inferior and lateral aspects.
Superior component
Courtesy of Dr. Melissa Gerlach, Boston Childrens Hospital

Inferior component with cystic degeneration. 25

Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

Restaging ~Chest CT with contrast~

Multiple poorly enhancing masses seen throughout the lungs. Largest in the anterior aspect of the apical posterior segment of the left upper lobe, measures approximately 3 .0 x 1.8 cm. Left upper mediastinal adenopathy.
Given the lung findings suggestive of hematogenous spread, JC likely has Stage IV disease.
Courtesy of Dr. Melissa Gerlach, Boston Childrens Hospital

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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

Potential diagnostic confusion ~ Patient #3 ~

KO is a 5-year-old girl from Puerto Rico, who presented to her physician last November with a reactive airway disease exacerbation. On chest X-ray, an incidental calcified right upper quadrant mass was discovered.

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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

Biopsy was performed and preliminary pathology was consistent with ganglioneuroma. Due to size of the massKO was referred to Boston for repeat metastatic workup and resection of the mass.

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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

~Abdominal CT with contrast~

From OSH
calcification

Show large right-sided adrenal mass with coarse central calcifications. Similar sized mass was seen in the left adrenal. Complete encasement of the IVC and partial encasement of the left renal vein and SMA were noted.

Crossing the midline

Courtesy of Dr. Melissa Gerlach Boston Childrens Hospital

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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

Final diagnosis s/p resection: Neuroblastoma

Pathologically distinct from Wilms tumor but frequently presents in the abdomen as a mass arising from adrenal glands or paraspinal ganglion. 2nd most common abdominal malignancy in children occurring as frequently as Wilms. Radiographically indistinguishable from Wilms tumors. Features that aid in diagnosis:
Neuroblastomas usually cross the midline whereas Wilms is confined to one side. Neuroblastomas may cause an outward and downward displacement of the kidney (drooping lily) whereas Wilms tumors are intrarenal masses, rarely causing a change in axis of the kidney. Neuroblastomas are more likely to present with mets, and tend to calcify at higher frequency. Tumor markers include VMA and other catecholamines.
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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

Wilms Tumor vs. Neuroblastoma

~Axial CT~

Contrast-enhanced axial scan at the level of the renal hilum: Large, well-defined tumor seen on the right attenuates similarly to the renal parenchyma which displaces the right kidney (double arrow) medially.
http://www.szote.u-szeged.hu/radio/a13.htm

Contrast-enhanced axial scan at the level of the upper pole of the kidneys: Large, irregularly-calcified tumor seen in the retroperitoneum, displacing left kidney dorsally (double arrow). 31

Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

Review take home points

Wilms is an embryonal renal neoplasm accounting for greatest percentage of pediatric renal masses (peak age 3-4). Can be difficult to distinguish radiographically from other renal masses & neuroblastoma. Diagnosis of a renal mass is made by confronting elements of clinical presentation with imaging definitive diagnosis often awaits path. Steps in diagnosis: radiologist localizes mass, analyses tumor features, searches for regional/distant spread. High performance imaging modalities commonly used:
US CT MR

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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

Review imaging of Wilms

US 1st imaging test for Wilms tumor excellent for depicting the mass, identifying adjacent organ invasion and tumor thrombus extension in renal vein and IVC. CT (contrast & non-contrast) Preferred modality for further staging and cross-sectional imaging enables eval. of lung mets and view of both kidneys. Controversy surrounding use of lung CT vs. plain film for mets. at initial diagnosis. MR Similar imaging benefit to CT. Most sensitive modality for determination of caval patentcy, but requires sedation.

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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

Acknowledgements
Many thanks to

Melissa Gerlach, MD Mara Barth, MD Mike Geary, MD Edward Lee, MD Gillian Lieberman, MD Pamela Lepkowski Larry Barbaras our Webmaster
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Harvard Mediical School, MS III Gillian Lieberamn, MD

March, 2006

References
Kirks, Donald R, Editor. Practical Pediatric Imaging: Diagnositc Radiology of Infants and Children, 3rd Edition. Lippincott Williams & Wilkins 1998; 1111- 1126. Kioumehr, Farhad et. al. Wilms Tumor (Nehproblastoma) in the Adult Patient: Clinical and Radiologic Manifestations. American Journal of Roentgenology 1989; 152(2):299. Lowe, Lisa H. et. al. Pediatric Renal Masses: Wilms Tumor and Beyond. RadioGraphics 2000; 20: 1585-1603. Reeder, Maurice. Gamuts In Radiology (Reeder & Felsons) Comprehensive List of Roentgen Differential Diagnoses, 4th Ed. 2003. Riccabona, M. Imaging of renal tumours in infancy and childhood. European Radiology 2003; 13:L116-L129. Rohan, Johannes. Color Atlas of Anatomy: A Photographic Study of the Human Body, 5th Edition. Lippincott Williams & Wilkins 1998. Sadler, T.W. Langmans Medical Embryology, 9th Edition. Lippincott Williams & Wilkins 2004. Tanagho, Emil and Jack McAnich. Smiths General Urology, 16th Edition. Lange 2004; 358362.

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