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Review on Angiomyolipoma (AML)www@AML
Dr KP WongUrology, PYNEH
Joint Surgical Grand Round
What is angiomyolipoma?
2nd commonest benign neoplasm in kidney
vessel
fat
smooth muscle
Imaging
How common? 1969: 8501 Autopsies without tuberous sclerosis
complex (TSC) 2 males (0.02%) 25 females (0.29%)
1995: Population based USG screening (Japanese Study) 13 out of 12970 males (0.1%) 11 out of 4971 females (0.22%)
pain
mass
haematuria
shock
haemorrhage
Lenk’s triad
1. Oesterling et al. The management of renal angiomyolipoma.J Urol, 135:121, 1986
Presentation
~59% symptomic on presentation
Presentation.
2. NELSON et al. Contemporary diagnosis and management of renal angiomyolipoma.J Uro 168:1315,
2002.
W - who is at risk ?
More common in Female ~86%
W - Who at risk @ AML
2. NELSON et al. Contemporary diagnosis and management of renal angiomyolipoma.J Uro 168:1315,
2002.
Tuberous Sclerosis Complex
Cortical tubers
Ash-leaf spots
W - Who at risk @ AML
2. NELSON et al. Contemporary diagnosis and management of renal angiomyolipoma.J Uro 168:1315,
2002.
~20% associated with Tuberous Sclerosis
W- who is at risk ?
Am I different from sporadic AML ?
In Which Way I was in difference?
Nature history - TSC
Young, Large, Multiple, more acute bleeding
2. NELSON et al. Contemporary diagnosis and management of renal angiomyolipoma.J Uro 168:1315,
2002.
Growth Characteristic - TSC Steiner et al.
35 patient: Follow up: 4 year
3. Steiner, et al. The natural history of renal angiomyolipoma. J Urol,150: 1782, 1993
67%
50%
21%28%
0%
20%
40%
60%
80%
100%
No. tumors thatgrow (%)
requir surgicalintervention
TSC
sporadic
W - When to intervent?
Symptomic vs Asymptomic
Intervention
Asymptomic AML no RCT available Limit prospective data, retrospective data:
symptomic or haemorrhage => likely larger tumorsLarger tumor => become symptomic with time
Large?
Tumor size → symptom Oesterling et al.
retrospective review (1948~ 1985) 253 patient: 8% from autopsy, 20% were TSC stratified into < 4cm (30%), > 4cm (70%)
1. Oesterling et al. The management of renal angiomyolipoma.J Urol, 135:121, 1986
Tumor size → treatment
43% 95%
1. Oesterling et al. The management of renal angiomyolipoma.J Urol, 135:121, 1986
Tumor size → symptoms Nelson et al.
Large tumors (>4cm) more likely symptomic
2. NELSON et al. Contemporary diagnosis and management of renal angiomyolipoma.J Uro 168:1315,
2002.
↑Need to intervene with larger tumor (>4cm)
Tumor size → treatment
2. NELSON et al. Contemporary diagnosis and management of renal angiomyolipoma.J Uro 168:1315,
2002.
Tumor size → Growth Steiner et al.
35 patient: Follow up: 4 year
3. Steiner, et al. The natural history of renal angiomyolipoma. J Urol,150: 1782, 1993
27%
46%
0%
10%
20%
30%
40%
50%
No. tumors that grow (%)
< 4cm
> 4cm
W - How to intervene?
Nephrectomy total
Nephron sparing approach Partial nephrectomy Enucleation of AML Cryotherapy (open or lap.) Trans-arterial embolization
Angiographic embolization
Emergency Avoid total nephrectomy Nephron sparing
Elective Reduce size
Efficacy Re-embolization ~14% Surgical intervention ~16%
Pre-embolization
Post-embolization
2. NELSON et al. Contemporary diagnosis and management of renal angiomyolipoma.J Uro 168:1315,
2002.
Take Home Message W – Who at risk
female Tuberous sclerosis complex
W - When to intervene Size:
W - How to intervene Nephron sparing approach would be choice of
management in AML
Q & A
More information
Presentation Histology Association
TSC LAM Malignant variant
Imaging
Intervention Consideration Surgical intervention Lap cryotherapy Embolization
Hormonal potentiation Molecular biology and
recent advance
Presentation
Presentation Classical triad
Flank pain, tender palpable mass, gross haematuria
Incidental finding Microscopic haematuria Others:
Renal failure, UTI, anemia
Presentation
Palpable mass – 20% Retroperitoneal hemorrhage – 15% Hypovolemic shock – 30% Renal insufficiency
Haemorrhagic aetiology
Wunderlich’s syndrome Spontaneous retroperitoneal haemorrhage
Trauma During pregnancy
haemorrhage
risk or haemorrhage: 25%~50% female 18%, male: 8%
6.KESSLER et al. Management of renal angiomyolipoma: Analysis of 15 cases. Eur Urol 33:572–5, 1998
7.WEBB et al. A population study of renal disease in patients with tuberous sclerosis. Br J Urol 74:151–4,1994
Growth Characteristic - Size Steiner et al.
35 patient: Follow up: 4 year
3. Steiner, et al. The natural history of renal angiomyolipoma. J Urol,150: 1782, 1993
Growth Characteristic - Size
< 4cm > 4cm
No. tumors that grow (%) 27% 46%
Require surgical intervention (%)
7% 53.8%
Large AML (>4cm) enlarged more likely than small AML
Steiner et al. 35 patient: Follow up: 4 year
3. Steiner, et al. The natural history of renal angiomyolipoma. J Urol,150: 1782, 1993
Growth Characteristic - Size Steiner et al.
35 patient: Follow up: 4 year
3. Steiner, et al. The natural history of renal angiomyolipoma. J Urol,150: 1782, 1993
27%
7%
46%
53.80%
0%
10%
20%
30%
40%
50%
60%
No. tumors thatgrow (%)
Require surgicalintervention (%)
< 4cm
> 4cm
Histology
Classification
Hamartoma? Fat and smooth muscle not normal found in kidney
Choristoma? Neoplastic?
Clonal expansion LN invasion
Extra-renal AML Adrenal gland, Liver, ovary, fallopian tube, spermatic cord,
colon
History
1900: Grawitz a large renal tumor comprised of fat, muscle and blood
vessels
1911: Fisher Histopathology: Contains fat cell, smooth muscle cell,
blood vessel in different proportions
1951: Morgan Name: angiomyolipoma
vascular
fat
smooth muscle
Pathological evaluation Fatty – normal Vascular – thicken
wall, lower elastin content, surround by cuff of smooth muscle cell
Smooth muscle – normal spindle cell or rounded epithelioid cells
histological stain
anti-smooth muscle stain: spindle and epithelioid cell
S-100 antibodies: fat cell
HMB-45 : perivascular epithelioid cell derived lesion
Histological examination
Percutaneous biopsy Tumor spread Complication Subsequent management
FNAC Correctly Dx: 5/8 Melanosome associated protein HMB-45: 7/8
Association of AML
Association
Association Tuberous Sclerosis complex Lymphangionleiomyomatosis (LAM)
40 % of TSC (young female)Rare for sporadic case - 60% associated with AML
Tuberous Sclerosis complex
Autosomonal dominant Mutation in TSC1 or
TSC 2 gene Incidence of AML in
TSC – 55~75%
Tuberous Sclerosis Complex
Tuberous Sclerosis Complex
Dermatological Ash-leaf spots Shagreen patch Adenoma sebaceum Ungal fibromas
Neurological Cerebral cortical tubers Epilepsy, infantile spasm Neruobehavorial disorder
Renal AML epithelial cyst, polycystic
kidney, RCC
Pulmonary Lymphangio-leiomyomatosis
Cardiac Rhabdomyomas
Growth Characteristic - TSC Steiner et al.
35 patient: Follow up: 4 year
3. Steiner, et al. The natural history of renal angiomyolipoma. J Urol,150: 1782, 1993
Growth Characteristic - TSC
TSC sporadic
No. tumors that grow (%)
67% 21%
requir surgical intervention
50% 28%
Steiner et al. 35 patient: Follow up: 4 year
3. Steiner, et al. The natural history of renal angiomyolipoma. J Urol,150: 1782, 1993
Growth Characteristic - TSC Ewalt et al.
60 children with TSC: 4 year FU50% had renal AML at initial stage During Fu, 40.7 % of children without AML at initial stage had
AML
De Luca et al. 51 patient with sporadic AML: 5 year Fu
92% without growth
AML with TSC enlarged more likely than sporadic AML
4. Ewalt, et al. Renal lesion growth in children with tuberous sclerosis complex. J Urol, 160: 141, 1998
5. De Luca et al. Management of renal angiomyolipoma: a report of 53 cases. BJU Int, 83: 215
Am I different from sporadic AML ?
In Which Way I was in difference?
When will disease be present?
Lymphangioleiomyomatosis (LAM)
Lymphangioleiomyomatosis (LAM)
Male Biopsy document LAM: 3 with TSC, 1 without TSC
Tuberous sclerosis complex 40% of TSC: had LAM 1% of TSC: symptoms
Sporadic Sporadic: rare < 1000 case 60% of LAM: had AML
Lymphangioleiomyomatosis (LAM)
Pathology Smooth muscle infiltration Cystic destruction of lung
Symptoms: Progressive SOBOE Recurrent pneumothorax Abdominal & thoracic
lymphadenopathy Abdominal tumor, e.g. AML,
lymphangiomyoma
Lymphangioleiomyomatosis (LAM)
Treatment – antagonism of estrogen action Progesterone im Oral progrestin GnRH agonist
Reversible Airflow limitation Bronchodilator
Lung transplantation
epithelioid subtype
histological classification
classical vascular, smooth muscle and adipose
epithelioid variant of angiomyolipoma large component of epithelioid cell
epithelioid subtype
more aggressive
recur after resection fatal
diagnostic imaging
Imaging - US
Mark hyperechoic signal and acoustic shadowing 8~47% RCC also
hyperechoic Some proportion of
AML not highly hyperechoic
Imaging - CT AML:
Fat contain renal lesion (< -15 HU)
Some lesion contain minimal fat
Malignant tumor (RCC): Tissue necrosis with lipid
formation, intratumoral bone metaplasia => areas of calcification (rare in AML)
Imaging – MRI AML
High signal intensity on T1 image
Low intensity on T2 image
RCC Low signal intensity
on T1 image High intensity on T2 Contrast MRI
Imaging – MRI
T1 imageT2 image
Consideration on intervention
Selective of intervention Multiple factor
symptom Lesion size Tuberous sclerosis Pregnancy plan Occupation, activity Renal reserve Co-morbidity Reliability and compliance
TSC and associated feature
Symptomic
Choice of treatment
Observation & Fu
Stenier et al
Sporadic < 4cm
Yearly imaging
> 4cm Asymptomic or mild:
semiannual USGrowth: surgerySevere symptoms:
surgery
TSC < 4cm
Semiannual USGrowth: Surgery
> 4cm Surgery
Surgical management
Intervention
Pre-embolization post-embolization
Surgical management
Indication Significant haemorrhage Haematuria Symptoms not responsive to conservative Tx Local tissure or vascular invasion Suspicion of malignancy after imaging
Total nephrectomy
Indication: Whole kidney replaced by AML Solitary AML near hilum or risk for partial than
complete nephrectomy Suspicion of malignancy Reperitoneal haemorrhage, unsuccessful or
unavailable embolization
laparoscopic cryoablation
Gregory et al.Laparoscopic Cryoablation of Renal Angiomyolipoma. J Uro. 176, 1512-1516, 2006
7 patient Average size – 4.2cm 3 minor complication in 2 patient Operative time – 170 miniutes, Blood loss of
116 cc Average decreased in CrCl 8.6 ml/min
Gregory et al.Laparoscopic Cryoablation of Renal Angiomyolipoma THE JOURNAL OF UROLOGY
Vol. 176, 1512-1516, October 2006
Angiographic embolization
Indication: Acute hemorrhage Symptomic tumor with limit renal reserve or
poor operative candidate Prophylatic treatment for asymptomic tumor
Materials: Gelatin sponge, alcohol, iodized oil, polyvinyl
alcohol particles, metal coils
Angiographic embolization
Pre-embolization post-embolization
Angiographic embolization
Pre-embolization post-embolization
Angiographic embolization
Pre-embolization post-embolization
Angiographic embolization Post embolization syndrome: 85% Complication: 10% of case
Abscess formation 5% Pleural effusion 3%
2. NELSON et al. Contemporary diagnosis and management of renal angiomyolipoma.J Uro 168:1315,
2002.
Kothary et alRenal Angiomyolipoma: Long-term Results after Arterial Embolization J Vasc Interv
Radiol 2005; 16:45–50
Retrospective review, mean Fu 51.5 months 19 patient (TSC: 10/19) 30 renal AML (TSC:21/30)
Recurrence 31.6% of patient (6/19) 30% of AML (9/30) – all from TSC group (9/21)
Time from embolization to recurrence Mean: 81.3 months (range: 36~132 months)
Angiographic embolization Efficacy
Difficult to assess in absence of controlled studies
Re-embolization ~14% Surgical intervention ~16%
2. NELSON et al. Contemporary diagnosis and management of renal angiomyolipoma.J Uro 168:1315,
2002.
Angiographic embolization
Pros Option in emergency
setting Nephron sparing
Cons no tumor diagnosis Difficult in Follow up Possibility of
revascularization
Pre-embolization
post-embolization
Angiographic embolization
Adipose tissue Not sign affected
Angiomyogenic component Responsed
Size Decrease is variable
Enhancement Decreased or absent
Pre-embolization
Post-embolization
Durability of embolization ?
Efficacy Durability Re-embolization rate
Conservative Treatment
Avoid contact activities which flank/abdominal impact is likely
Repeat yearly or half yearly CT or US
Horomal potentiation
Hormonal potentiation
Progestrone and estrogen receptor in smooth muscle cell nuclei of some AML
Cases of rapid growth during pregnancy
Hormonal therapy: Early stage => not well defined
Molecular biology recent advance
Molecular biology Tuberous sclerosis complex
TSC1 on chromosome 9q34 TSC2 on chromosome 16p13 => produce Tuberin
Tumor suppressor Gene AML tissue with TSC2 mutation: lack tuberin expression Heterozyogosity at ½ of TSC loci: consistent finding at TSC
associated AML
Other genes Loss of TSC2 heterozygosity in only 10% of sporadic AML
Animal modal in AML
Akt singaling pathway in tuberous sclerosis Rat with hepatic tumor (HMB45 positive)
Rapamycin: Quenches S6K phosphorylation Shrinkage of inappropriate cell growth Shrinkage of renal tumor in mice