Emir Sandhu, HMS III
Gillian Lieberman, MD
Nov-Dec 2011
Renal Angiomyolipoma
A Comparison of Sporadic and Genetic Cases
Emir S. Sandhu
Harvard Medical School, Year
III
Gillian Lieberman, MD
Emir Sandhu, HMS III
Gillian Lieberman, MD
Mini-Seminar Outline
1. Renal Angiomyolipoma (AML): Facts
2. Angiomyolipoma: Associated Syndromes
3. Clinical presentation of AMLs
4. Epidemiology
5. Overview of Renal Anatomy
6. Meet Our Patient: Clinical Presentation
7. Our Patient: Diagnostic Workup
8. AMLs: Role of Angiography
9. Our Patient: Therapeutic Management of AMLs
10. Companion Patient: Tuberous Sclerosis
11. Tuberous Sclerosis: Facts and Role of Imaging
2
Emir Sandhu, HMS III
Gillian Lieberman, MD
Renal Angiomyolipoma: Facts
• Benign renal tumor
• 3 major histologic components, consisting of
mature fat cells, smooth muscle, blood vessels.
• Characteristic features including adipose
tissue shown below:
Image: http://path.upmc.edu/cases/case165.html
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Emir Sandhu, HMS III
Gillian Lieberman, MD
Associated Syndromes:
Tuberous Sclerosis
• Neurocutaneous syndrome
• 10% of angiomyolipomas are associated with
Tuberous Sclerosis
• Rare multi-system genetic disease that causes nonmalignant tumor formation, typically manifesting in
brain, skin, kidney, heart, eyes, lungs.
• Associated symptoms include seizures,
developmental delay, lung and kidney disease.
More to come on Tuberous Sclerosis.
4
Emir Sandhu, HMS III
Gillian Lieberman, MD
Associated Syndromes:
Sporadic Lymphangioleiomyomatosis
• Smooth muscle
infiltration into alveoli.
• Female predominance.
• Often occurs
concurrently with TS.
• Rarely can occur
sporadically. 60% of
sporadic cases also
develop AMLs.
• AMLs histopathologically identical
to those seen in TS.
Images: (Left) High-resolution axial CT revealing
cystic parenchymal changes of LAM. (Right)
Renal CT showing multiple lesions (-15 to -100
HU) characteristic of fat.
Images: Bissler and Kingswood, (2004).
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Emir Sandhu, HMS III
Gillian Lieberman, MD
Angiomyolipoma: Clinical Presentation
• Most common symptoms are the following:
– Flank pain
– Hematuria: may lead to hypotension (parenchymal,
subcapsular, and/or perirenal hemorrhage)
• Underlying Pathology:
– Arteries within AMLs lack an internal elastic
membrane.
– AMLs have disorganized adventitial smooth muscle.
– Progresses to bleeding and aneurysms.
6
Emir Sandhu, HMS III
Gillian Lieberman, MD
AML: Internal Elastic Membrane
Shown above is an artery in AML (left) compared with a normal
artery (right). The AML artery characteristically lacks an internal
elastic membrane, surrounded by a collar of myomatous cells.
Image: Meilstrup et al, 1995
7
Emir Sandhu, HMS III
Gillian Lieberman, MD
Angiomyolipoma: Epidemiology
Based on a study performed by Fujii et al in 1995:
• Renal ultrasonography performed on 17,900 healthy adult
patients in Japan.
• Patients had no signs of urinary tract malignancies.
• Hyperechoic renal masses suggestive of angiomyolipoma
found in 41 (0.23%).
• Upon further diagnostic confirmation, renal
angiomyolipoma identified in 24 patients (0.13%)
• Stratification by gender reveals approximately 0.1% in
males and 0.22% in females
• Separate study of 8501 autopsies demonstrated similar
incidence.
8
Emir Sandhu, HMS III
Gillian Lieberman, MD
Mini-Seminar Outline
1.
2.
3.
4.
Renal Angiomyolipoma: Facts
Angiomyolipoma: Associated Syndromes
Clinical presentation of AMLs
Epidemiology
5. Overview of Renal Anatomy
6. Meet Our Patient: Clinical Presentation
7. Our Patient: Diagnostic Workup
8. AMLs: Role of Angiography
9. Our Patient: Therapeutic Management of AMLs
10. Companion Patient: Tuberous Sclerosis
11. Tuberous Sclerosis: Facts and Role of Imaging
9
Emir Sandhu, HMS III
Gillian Lieberman, MD
Renal Anatomy: An Overview
Images: Renal Anatomy at http://biomed.brown.edu. Accessed 12/11/11.
10
Emir Sandhu, HMS III
Gillian Lieberman, MD
Meet Our Patient: Clinical Presentation
• 38 year-old female who recently emigrated from
China, initially presents to nephrology clinic.
• When in China, patient had an MRI suggesting she
had a benign tumor on her right kidney.
• She was referred following renal ultrasound ordered
by her primary care physician, which revealed a
cortical-based echogenic mass in the right kidney,
measuring approximately 3.9 x 3.5 cm, that was
causing moderate hydronephrosis.
• On later visit, Urology felt the mass had been stable
for the past year, and wanted to repeat MRI in 6
months.
11
Emir Sandhu, HMS III
Gillian Lieberman, MD
Our Patient: Past Diagnostic Workup
• 10/2008 MRI: 4.8 x 4.2 cm
• 10/2010 MRI: 6.8 x 4.4 cm
• 1/2011 Presented to the BIDMC ED with
dull right flank pain. No hematuria,
dysuria, or urinary frequency.
• 5/2011: Seen by Urology, no plan for
procedure. Follow up in 6 months.
• 10/2011: MRI: 8.9 x 5.7 cm
• 11/2011: Decides on intervention.
12
Emir Sandhu, HMS III
Gillian Lieberman, MD
Our Patient: Echogenic Mass on US
Shown on sagittal ultrasound of the right kidney is a corticalbased, echogenic mass measuring 3.9 x 3.5 cm. There is
moderate hydronephrosis with no evidence of stones.
Image: BIDMC PACS
13
Emir Sandhu, HMS III
Gillian Lieberman, MD
Our Patient: Right Kidney Doppler
Shown is a sagittal ultrasound of the right kidney. Note the
poor Doppler flow evident within the renal mass.
Image: BIDMC PACS
14
Emir Sandhu, HMS III
Gillian Lieberman, MD
Companion Patient: AML on CT
• Presence of fat in
kidney highly
suggestive of AML.
• Fat is -20 to -80
Hounsfield Units
(prior to contrast)
• Contrast may be
given to reveal
aneurysms
Image above: Small AML shown in upper
pole of right kidney (arrow), measuring -46
HU on axial CT scan.
Image: Meilstrup et al. (1995)
15
Emir Sandhu, HMS III
Gillian Lieberman, MD
Our Patient: AML on Axial Vibe MRI
On axial MRI: Large 8.9 x 5.7 cm mass centered in lower pole of
the R kidney, extending into the R hilum inferiorly. Diffuse lowgrade enhancement seen, consistent with AML. There is also a 4mm lesion in the lower pole of the R kidney, also an AML.
Image: BIDMC PACS
16
Emir Sandhu, HMS III
Gillian Lieberman, MD
Our Patient: T1 Axial In-Phase MRI
Shown on the left is our patient’s T1 axial, in phase MRI.
Note the effect of fat suppression compared with the axial
vibe image shown on the right.
Image: BIDMC PACS
17
Emir Sandhu, HMS III
Gillian Lieberman, MD
Our Patient: T1 Out-of-Phase MRI
On axial out-of-phase MRI, the India Ink Artifact is shown, which
represents signal drop-out in voxels that contain both fat and non-fat
components. It is seen surrounding interfaces, as if someone had
outlined the interfaces with ink. A renal AML is also shown.
Image: BIDMC PACS
18
Emir Sandhu, HMS III
Gillian Lieberman, MD
Mini-Seminar Outline
1.
2.
3.
4.
5.
6.
7.
Renal Angiomyolipoma: Facts
Angiomyolipoma: Associated Syndromes
Clinical presentation of AMLs
Epidemiology
Overview of Renal Anatomy
Meet Our Patient: Clinical Presentation
Our Patient: Diagnostic Workup
8. AMLs: Role of Angiography
9. Our Patient: Therapeutic Management of AMLs
10. Companion Patient: Tuberous Sclerosis
11. Tuberous Sclerosis: Facts and Role of Imaging
19
Emir Sandhu, HMS III
Gillian Lieberman, MD
AML: Role of Renal Angiography
• Not often used to diagnosis
AML
• Often used for management
of bleeding
• AMLs have circumferential
peripheral vessels with
whorled appearance during
nephrographic phase
• Multiple aneurysms are also
characteristic.
Image above: Angiography of R kidney
• In study by Becker, et al:
aneurysms found on 16 of 34 revealing AML of the upper pole with
aneurysms.
AML cases
Image: Meilstrup et al. (1995)
20
Emir Sandhu, HMS III
Gillian Lieberman, MD
AML: Treatment Recommendations
Steiner Study: 35 patients with AML evaluated.
Recommendations:
• Lesions <4cm should be followed with yearly CT/US.
• Asymptomatic patient with lesion >4cm should have
semi-annual US.
• Symptomatic patient with lesion >4cm should
undergo renal-sparing surgery or arterial
embolization.
• Prophylactic intervention for patient with Tuberous
Sclerosis and lesion >4cm, irrespective of symptoms.
• Two established treatment options include renalsparing surgery or embolization.
From: Steiner MS, et al. (1993). 21
Emir Sandhu, HMS III
Gillian Lieberman, MD
Our Patient: AML Embolization
Based on these treatment recommendations, our patient
underwent embolization of her AML.
- Particle embolization was performed to reduce flow rate through
AML, closely monitored under fluoroscopic visualization.
-Post-emblotherapy R renal arteriogram demonstrated an avascular
tumor with no detectable venous or arterial flow from an inferior polar
branch of the R renal artery.
Images: BIDMC PACS 22
Emir Sandhu, HMS III
Gillian Lieberman, MD
Companion Patient #2: Tuberous Sclerosis
Image: T1-weighted coronal
MRI.
Shown to the left in our
companion patient are two
lesions with increasing
signal intensity (arrows)
similar to subcutaneous fat
(asterisk).
These are compatible with
large angiomyolipoma.
Image: Bissler and Kingswood, (2004).
23
Emir Sandhu, HMS III
Gillian Lieberman, MD
Mini-Seminar Outline
1.
2.
3.
4.
5.
6.
7.
8.
9.
Renal Angiomyolipoma: Facts
Angiomyolipoma: Associated Syndromes
Clinical presentation of AMLs
Epidemiology
Overview of Renal Anatomy
Meet Our Patient: Clinical Presentation
Our Patient: Diagnostic Workup
AMLs: Role of Angiography
Our Patient: Therapeutic Management of AMLs
10.Companion Patient: Tuberous
Sclerosis
11. Tuberous Sclerosis: Facts and Role of Imaging
24
Emir Sandhu, HMS III
Gillian Lieberman, MD
Tuberous Sclerosis: Facts
Bilateral renal involvement typical.
1/3 of cases are familial, remaining sporadic.
Transmitted in an autosomal dominant trait.
Characteristic formation of tubers in the skin,
brain, kidneys, and other organs.
• Incidence is estimated to be approximately 1 in
6,000 live births.
• Two genes identified, TSC1 and TSC2, located
on chromosomes 9 and 16 respectively.
•
•
•
•
From: Kumar V, et al. Robbins & Cotran Pathologic Basis of Disease.(2009).
25
Emir Sandhu, HMS III
Gillian Lieberman, MD
Tuberous Sclerosis: Diagnostic Criteria
Definitive diagnosis:
2 major features OR 1 major + 2 minor features required.
Major Features
Minor features
Facial anglofibromas/forehead plaque
Multiple pits in dental enamel
Non-traumatic ungual fibroma
Hamartomatous rectal polyps
Hypomelanotic macules
Bone cysts
Shagreen patch (connective tissue nevus)
Cerebral white matter radial migration lines
Multiple retinal nodular hamartomas
Gingival fibromas
Cortical tuber
Nonrenal hamartomas
Subependymal nodule
Retinal achromic patch
Subependymal giant cell astrocytoma
“Confetti” skin lesions
Cardiac rhabdomyoma
Multiple renal cysts
Lymphangiomyomatosis
Renal angiomyolipoma
From: Roach ES, et al. (1999).
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Emir Sandhu, HMS III
Gillian Lieberman, MD
Tuberous Sclerosis: Renal Manifestation
• Most common TS manifestation is the formation
of angiomyolipomas.
• Benign cysts and (less often) lymphangiomas can
also occur in patients with TS.
• Both cysts and angiomyolipomas tend to present
bilaterally.
• Many patients, however, have no symptoms
referable to the kidney.
From: Casper KA, et al. (2002).
27
Emir Sandhu, HMS III
Gillian Lieberman, MD
Tuberous Sclerosis: Role of Imaging
• Renal US should be performed at time of diagnosis to define
extent of angiomyolipomas and/or presence of polycystic
disease.
• US recommended every 1-3 years to monitor growth of
lesions and possible signs of malignancy.
– Ex: of concern would be a non-cystic mass lacking low
density (-10 to -100 HU) to suggest benign AML.
• If malignant transformation suspected or large
angiomyolipoma(s) present:
– CT or MR recommended to evaluate abnormality.
– Avoid gadolinium based imaging in those with GFR < 30
mL/min given risk of nephrogenic systemic fibrosis.
From: Roach ES, et al. (1999).
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Emir Sandhu, HMS III
Gillian Lieberman, MD
Tuberous Sclerosis: Renal Complications
• Angiomyolipomas can become quite large, leading to
abdominal or flank pain, bleeding into lesion
(typically when > 4 cm diameter)
• Renin-dependent hypertension, due to focal areas of
ischemia around lesions. Chronic renal failure also
can occur.
• RCC also is a known complication. Occurs in 1-2% of
patients, substantially lower than VHL syndrome.
– Histology is usually consistent with clear cell carcinoma.
From: Steiner MS, et al. (1993).
Rakowski SK, et al. (2006). 29
Emir Sandhu, HMS III
Gillian Lieberman, MD
Summary of Learning Objectives
In this mini-seminar, we have covered the following
topics:
–
Renal Angiomyolipoma:
• Clinical presentation
• Associated genetic syndromes
• Diagnostic evaluation
• Relevant imaging findings
• Therapeutic management
–
Tuberous Sclerosis:
• Clinical presentation
• Renal manifestations and complications
• Role of imaging and diagnostic criteria
30
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
Bissler JJ, Kingswood, JC. Renal angiomyolipomata. Kidney Int. 2004 Sep;66(3):92434.
Becker JA, et al. Angiomyolipoma (hamartoma) of the kidney: An angiographic review.
Acta Radiol Diagn. 1973 Sep;14(5):561-568.
Brown University. Brown L, et al. The Past, The Present and The Future of Dialysis:
Renal Anatomy. Accessed December 11, 2011.
http://biomed.brown.edu/Courses/BI108/BI108_2001_Groups/WAK/renalphys/renalana
tomy.html.
Casper KA, et al. Tuberous sclerosis complex: renal imaging findings. Radiology. 2002
Nov;225(2):451-6.
Kumar V, et al. Robbins & Cotran Pathologic Basis of Disease. 8th ed. Philadelphia,
PA: Saunders Elsevier; 2009.
Lemaitre L, et al. Imaging of angiomyolipomas. Semin Ultrasound CT MR. 1997
Apr;18(2):100-14.
Meilstrup JW, et al. Other renal tumors. Semin Roentgenol. 1995 Apr;30(2):168-84.
O’Callaghan FJ, et al. An epidemiological study of renal pathology in tuberous
sclerosis complex. BJU Int. 2004;94(6):853.
Rakowski SK, et al. Renal manifestations of tuberous sclerosis complex: Incidence,
prognosis and predictive factors. Kidney Int. 2006;70(10):1777.
Roach ES, et al. Tuberous Sclerosis Consensus Conference: recommendations for
diagnostic evaluation. National Tuberous Sclerosis Association. J Child Neurol. 1999
Jun;14(6):401-7.
Steiner MS et al: The natural history of renal angiomyolipoma. J Urol. 1993;150:1782.
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Acknowledgements
I would like to extend a warm thank you to the
following people for their help with my
presentation:
Dr. Gillian Lieberman
Dr. Samir Shah
Claire Odom
My fellow medical students
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