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~
¾
First classified as an embryonal sarcoma by Max Wilms in
1899 at the Institute of Pathology in Bonn, Germany.
¾
Also known as nephroblastoma, it is the most common solid
renal tumor of childhood.
¾
Usually bulky, may arise in any portion of the kidney, and
expands within the renal parenchyma to displace and distort
the pelvicalyceal system.
¾
Distinguished by vascular invasion and displacement of
surrounding structures.
2
Harvard Mediical School, MS III
Gillian Lieberamn, MD
March, 2006
~ Epidemiology ~
¾
¾
¾
¾
¾
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.
3
Harvard Mediical School, MS III
Gillian Lieberamn, MD
March, 2006
Associated Syndromes
~ the minority of cases~
¾
¾
¾
¾
}
WAGR Syndrome
Drash Syndrome – male pseudo-hermaphroditism,
progressive glomerulonephritis
Overgrowth Syndromes – Beckwith Wiedemann,
hemihypertrophy.
GU abnormalities – hypospadias, cryptorchidism,
horseshoe kidney.
}
Abnl. WT 1
gene
Abnl. WT 2
gene
ª 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.
4
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.
ÖPrecursor 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.
5
Harvard Mediical School, MS III
Gillian Lieberamn, MD
March, 2006
~Nephrogenesis ~
ƒ 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).
Beginning at week 5 of development:
Metanephric
blastema
ƒ Epithelium of the ureteric bud from the
MESONEPHROS interacts with
mesenchyme of METANEPHRIC blastema.
v
ƒ 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.
Langman’s Medical Embryology, 9th Ed., T.W. Sadler, PhD. Lippincott, Williams & Wilkins, 2004.
6
Harvard Mediical School, MS III
Gillian Lieberamn, MD
March, 2006
Gross Pathology
ƒ 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.
of Wilms tumors have unfavorable
histology with anaplasia (atypical mitoses or
hyperchromatic cells with large nuclei).
Tubular elements
Stromal Elements
„10%
Blastemal elements
Lowe et al. Pediatric Renal Masses: Wilms Tumor and
Beyond. Radiographics. 2000 Nov-Dec;20(6):1585-603.
7
Harvard Mediical School, MS III
Gillian Lieberamn, MD
March, 2006
~ Renal Anatomy ~
Left kidney and
suprarenal gland in situ
Positions of Urinary Organs
Renal artery
Renal vein
Fibrous
capsule
Cortex
Medulla
Renal calyx
Renal pelvis
Rohen, Johannes. Color Atlas of Anatomy, 5th Edition. 1998.
Gray’s Anatomy Online
http://www.bartleby.com/107/253.html
8
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.
9
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.
10
Harvard Mediical School, MS III
Gillian Lieberamn, MD
March, 2006
Index Patient
„ KG
is a 2 ½ 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….
11
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
ƒThe 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.
ƒThe lesion itself appears to be comprised
of either multiple confluent masses, or
single large septated mass.
ƒ It is exerting mass effect on the
surrounding abdominal structures pushing
the pancreatic tail and splenic vein, and
the stomach superiorly and anteriorly.
ƒThe 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 Children’s Hospital Boston
12
Harvard Mediical School, MS III
Gillian Lieberamn, MD
March, 2006
Coronal and Sagittal Reconstructions
eed Pro 16 SYS#CT02_OC0
4
3
H
Acc Num: 10
002Y F 2
DOB: 6/
1/1
OP 320 30CC
30CC
ARD
o 16 SYS#CT02_OC0
ro
H
Acc Num
002Y
DOB
0 30CC
20
0
20
0
512X512
L MODE /15:05:16
C: 50 Z: 1
F
Compress
Page: 77
12
512
E /15:05:16
Z: 1
F
Comp
Page:
Tumor Mass –
heterogeneous, “claw”
formation.
Courtesy of Dr. Mara Barth – Boston Children’s Hospital Boston
13
Harvard Mediical School, MS III
Gillian Lieberamn, MD
Differential diagnosis
of a Renal Mass
March, 2006
*varies depending on clinical presentation + imaging features*
„
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.*
14
Harvard Mediical School, MS III
Gillian Lieberamn, MD
March, 2006
KG’s differential
Renal Mass
„
Wilm’s 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.
15
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 Children’s Hospital
Kioumehr et al .Wilms Tumor in the Adult Patient. American Journal of
Roentgenology 1989: 152 (2); 299.
16
Harvard Mediical School, MS III
Gillian Lieberamn, MD
March, 2006
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.
„
„
CT – Demonstrates heterogeneous
mass with slightly lower attenuation
than normal kidney. Allows exam of
contralateral kidney.
„
„
Color Doppler Study – may help to better
define and depict tumor extent and necrotic
area, as well as vascular invasion.
US (dorsolateral):
Exophytic Wilms tumor
on lower pole of kidney
Axial US: Shows
thrombus in IVC.
IV contrast – mandatory. Shows nodal,
hepatic mets, and tumor extension into
renal vein or 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.
17
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.
18
Harvard Mediical School, MS III
Gillian Lieberamn, MD
March, 2006
Staging
„
Staging of Wilms Tumor: by imaging, surgery, and pathology
„
„
Stage
I
„
II
„
III
„
IV
„
V
Description
ª Limited to the kidney and
completely resectable with renal
capsule intact; renal sinus may be
inflitrated but not beyond hilum.
ª Tumor infiltrates beyond kidney
but completely resected.
ª Residual tumor confined to
abdomen and without hematogenous
spread.
ª Hematogenous metastases to lung (most
common), bone, liver or brain.
ª Bilateral renal involvement; each
side staged separately.
19
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 Children’s Hospital
Multifocal disease shows
hyperchromatic cells with atypical
mitoses and large nuclei. Each focus is
at a slightly different stage of disease.
20
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%
„
21
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.
22
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.
23
Harvard Mediical School, MS III
Gillian Lieberamn, MD
March, 2006
JC’s 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 10’s”: 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 Children’s 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~
ƒ The left kidney is absent.
ƒ 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 Children’s 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.
„
ªGiven the lung findings
suggestive of hematogenous spread,
JC likely has Stage IV disease.
Courtesy of Dr. Melissa Gerlach, Boston Children’s Hospital
26
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.
27
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 mass…KO was
referred to Boston for repeat metastatic
workup and resection of the mass.
„
28
Harvard Mediical School, MS III
Gillian Lieberamn, MD
March, 2006
~Abdominal CT with contrast~
From OSH
calcification
ƒ Show large right-sided adrenal
mass with coarse central
calcifications. Similar sized mass
was seen in the left adrenal.
ƒ 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 Children’s Hospital
29
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.
30
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
32
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.
33
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
™
34
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 & Felson’s) 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. Langman’s Medical Embryology, 9th Edition. Lippincott Williams & Wilkins
2004.
Tanagho, Emil and Jack McAnich. Smith’s General Urology, 16th Edition. Lange 2004; 358362.
35