Review on Angiomyolipoma (AML) www@AML

1. Review on Angiomyolipoma (AML)www@AML Dr KP Wong Urology, PYNEH Joint Surgical Grand Round

2. 2nd commonest benign neoplasm in kidney What is angiomyolipoma? vessel fat smooth muscle

3. Imaging

4. 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%)

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

6. Presentation. ~59% symptomic on presentation 2. NELSON et al.Contemporary diagnosis and management of renal angiomyolipoma.J Uro 168:1315, 2002.

7. W - who is at risk ?

8. 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.

9. Tuberous Sclerosis Complex Ash-leaf spots Cortical tubers

10. 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.

11. Am I different from sporadic AML ? W- who is at risk ? In Which Way I was in difference?

12. 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.

13. 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

14. W - When to intervent? Symptomic vs Asymptomic

15. Intervention • Asymptomic AML • no RCT available • Limit prospective data, retrospective data: • symptomic or haemorrhage => likely larger tumors • Larger tumor => become symptomic with time Large?

16. 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

17. Tumor size → treatment 43% 95% 1. Oesterling et al.The management of renal angiomyolipoma.J Urol, 135:121, 1986

18. 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.

19. 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.

20. 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

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

22. Emergency Avoid total nephrectomy Nephron sparing Elective Reduce size Efficacy Re-embolization ~14% Surgical intervention ~16% Angiographic embolization Pre-embolization Post-embolization 2. NELSON et al.Contemporary diagnosis and management of renal angiomyolipoma.J Uro 168:1315, 2002.

23. 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

24. end

25. Q & A

27. Presentation Histology Association TSC LAM Malignant variant Imaging Intervention Consideration Surgical intervention Lap cryotherapy Embolization Hormonal potentiation Molecular biology and recent advance More information

28. Presentation

29. Presentation • Classical triad • Flank pain, tender palpable mass, gross haematuria • Incidental finding • Microscopic haematuria • Others: • Renal failure, UTI, anemia

30. Presentation Palpable mass – 20% Retroperitoneal hemorrhage – 15% Hypovolemic shock – 30% Renal insufficiency

31. Haemorrhagic aetiology • Wunderlich’s syndrome • Spontaneous retroperitoneal haemorrhage • Trauma • During pregnancy

32. 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

33. 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

34. Growth Characteristic - Size • Steiner et al. • 35 patient: Follow up: 4 year Large AML (>4cm) enlarged more likely than small AML 3. Steiner, et al. The natural history of renal angiomyolipoma. J Urol,150: 1782, 1993

35. 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

36. Histology

37. 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

38. 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

39. vascular fat smooth muscle

40. Fatty – normal Vascular – thicken wall, lower elastin content, surround by cuff of smooth muscle cell Smooth muscle – normal spindle cell or rounded epithelioid cells Pathological evaluation

41. anti-smooth muscle stain: spindle and epithelioid cell S-100 antibodies: fat cell HMB-45 : perivascular epithelioid cell derived lesion histological stain

42. Histological examination • Percutaneous biopsy • Tumor spread • Complication • Subsequent management • FNAC • Correctly Dx: 5/8 • Melanosome associated protein HMB-45: 7/8

43. Association of AML

44. Association • Association • Tuberous Sclerosis complex • Lymphangionleiomyomatosis (LAM) • 40 % of TSC (young female) • Rare for sporadic case - 60% associated with AML

45. Autosomonal dominant Mutation in TSC1 or TSC 2 gene Incidence of AML in TSC – 55~75% Tuberous Sclerosis complex

46. Tuberous Sclerosis Complex

47. 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 Tuberous Sclerosis Complex

48. 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

49. 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

50. 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