Review on Angiomyolipoma

Review on Angiomyolipoma

Review on Angiomyolipoma (AML) [email protected] Dr KP Wong Urology, 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%) Presentation

Lenks triad pain shock mass haematuria haemorrhage 1. Oesterling et al. The management of renal angiomyolipoma.J Urol, 135:121, 1986 Presentation

. ~59% symptomic on presentation 2. NELSON et al. Contemporary diagnosis and management of renal angiomyolipoma.J Uro 168:1315, 2002. W - who is at risk ? W - Who at risk @ AML More common in Female

~86% 2. NELSON et al. Contemporary diagnosis and management of renal angiomyolipoma.J Uro 168:1315, 2002. Tuberous Sclerosis Complex Ash-leaf spots Cortical tubers W - Who at risk @ AML

~20% associated with Tuberous Sclerosis 2. NELSON et al. Contemporary diagnosis and management of renal angiomyolipoma.J Uro 168:1315, 2002. Am I different from sporadic AML ? W- who is at risk ? 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 100% 80% 67% 60% 40% 50%

21% TSC 28% 20% 0% No. tumors that grow (%) requir surgical intervention

3. Steiner, et al. The natural history of renal angiomyolipoma. J Urol,150: 1782, 1993 sporadic W - When to intervent? Symptomic vs Asymptomic Intervention Asymptomic AML

no RCT available Limit prospective data, retrospective data: symptomic or haemorrhage => likely larger tumors Larger 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%

1. Oesterling et al. 95% 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. Tumor size treatment Need to intervene with larger tumor (>4cm) 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 46% 50% 40% 30%

27% <4cm >4cm 20% 10% 0% No. tumors that grow (%) 3. Steiner, et al. The natural history of renal angiomyolipoma. J Urol,150: 1782, 1993

W - How to intervene? Nephrectomy total Nephron sparing approach Partial nephrectomy Enucleation of AML Cryotherapy (open or lap.)

Trans-arterial embolization Angiographic embolization Pre-embolization Emergency Avoid total nephrectomy Nephron sparing

Elective Reduce size Post-embolization Efficacy Re-embolization ~14% Surgical intervention ~16%

2. NELSON et al. Contemporary diagnosis and management of renal angiomyolipoma.J Uro 168:1315, Take Home Message W Who at risk W - When to intervene

female Tuberous sclerosis complex Size: W - How to intervene Nephron sparing approach would be choice of

management in AML end Q&A More information Presentation Histology Association

Consideration Surgical intervention Lap cryotherapy Embolization TSC LAM Malignant variant

Imaging Intervention 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

Wunderlichs 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 33:5725, 1998 7.WEBB et al. A population study of renal disease in patients with tuberous sclerosis. Br J Urol 74:1514,1994 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 Steiner et al.

35 patient: Follow up: 4 year No. tumors that grow (%) Require surgical intervention (%) < 4cm 27% > 4cm 46%

7% 53.8% Large AML (>4cm) enlarged more likely than small AML 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 60% 53.80% 46% 50% 40% 30% <4cm

27% >4cm 20% 7% 10% 0% No. tumors that grow (%)

Require surgical intervention (%) 3. Steiner, et al. The natural history of renal angiomyolipoma. J Urol,150: 1782, 1993 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

AML epithelial cyst, polycystic kidney, RCC Neruobehavorial disorder Pulmonary

Lymphangio-leiomyomatosis Neurological Cerebral cortical tubers Epilepsy, infantile spasm Renal 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 Steiner

et al. 35 patient: Follow up: 4 year TSC sporadic No. tumors that grow (%)

67% 21% requir surgical intervention 50% 28% 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 FU 50% 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) AML Imaging MRI

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 T2 image T1 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 Symptomic TSC and associated feature

Choice of treatment Observation & Fu Stenier et al Sporadic < 4cm Yearly imaging > 4cm

Asymptomic or mild: semiannual US Growth: surgery Severe symptoms: surgery TSC < 4cm Semiannual US

Growth: 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 al Renal Angiomyolipoma: Long-term Results after Arterial Embolization J Vasc Interv Radiol 2005; 16:4550

Retrospective review, mean Fu 51.5 months Recurrence

19 patient (TSC: 10/19) 30 renal AML (TSC:21/30) 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 Pre-embolization Cons no tumor diagnosis Difficult in Follow up Possibility of

revascularization post-embolization Angiographic embolization Adipose tissue Not sign affected

Angiomyogenic component Responsed Pre-embolization Size Decrease is variable

Enhancement Decreased or absent 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 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

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