Aggiornamento monografico
Gli emangiomi infantili
HAEMANGIOMAS IN INFANCY
GIANNI VERCELLIO, LETIZIA CIPOLAT, VITTORIA BARALDINI, FRANCESCA CIGOGNETTI, ELENA BIANCHINI*, MICHELE COLETTI
Unitŕ Operativa di Chirurgia Vascolare - Centro Angiomi e Malformazioni Vascolari,
*Servizio di Radiodiagnostica, Ospedale dei Bambini ”Vittore Buzzi”, Milano
Gennaio 2005 - pagg. 21 -29
Abstract
Over the last 20 years our knowledge of the peculiar characteristics of vascular malformations
and hemangiomas, both from a biological and histological point of view, has significantly improved.
The paper summarizes the most recent advances, drawing from the last meeting of
the International Society for Study of Vascular Anomalies (ISSVA), and presents the Authors’
own experience on the topic of infantile hemangiomas. For the majority of infantile hemangiomas,
given their natural tendency towards spontaneous involution, no treatment is required.
However, the recent identification of more aggressive forms makes it necessary an early
diagnosis to identify the most appropriate “timing” and type of treatment.
Classificazione MeSH
Bibliografia
1. Mulliken JB, Glowacky J. Hemangiomas
and vascular malformations in infants and children:
A classification based on endothelial
characteristics. Plast Reconstr Surg 1982;
69:412-20.
2. Muller BU, Mulliken JB. The Infant With a Vascular Tumor. Seminars in Perinatology 1999;4:332-340.
3. Amir J, Metzker A, Krikler R, et al. Stawberry hemangioma in preterm infants. Pediatr Dermatol 1986;3:331-32.
4. Drolet BA, Haggstrom AN, Baselga L, Chamlin S, Eichenfield L, Esterly NB, Frieden IJ, Garzon M, Lucky A, Metry D, Nopper A. Risk Factors for Haemangioma of infancy- A Cohort Prospective Study. Atti del 16th ISSVA Congress, 2004.
5. Enjolras O, Mulliken JB. Vascular Tumors and Vascular Malformations (New Issues). Advance in Dermat 1998;vol 13.
6. Burton BK, Schultz CJ, Angle B, et al. An increased incidence of haemangiomas in infants born following chorionic villus sampling (CVS). Prenat Diagn 1995;15:209-14.
7. Garzon MC, Drolet BA, Haggstrom A, Frieden IJ. Incidence and Clinical Association of Multiple Haemangioma of Infancy. Atti del 16th ISSVA Congress, 2004.
8. Redondo P, Fernandez M. Protocol for the treatment of haemangiomas and/or vascular malformations. An Sist Sanit Navar 2004; 1:133-40.
9. Enjolrs O. Classification, Diagnosis and Current Treatment of Vascular Anomalies. Atti del 16th ISSVA Congress, 2004.
10. Majno G, Joris I. Apoptosis, oncosis and necrosis: An overview of cell death. Am J Pathol 1995;146:3-15.
11. Iwata J, Sonobe H, Furihata M, et al. High frequency of apoptosis in infantile capillary haemangioma. J Pathol 1996;179:403-8.
12. Folkman J. Clinical application of research on angiogenesis. N Engl J Med 1995;333: 1757-63.
13. Dikov D, Stefanova P, Sarafian V. Mast Cells (MCS) Variation in Infantile Hemangioma. Atti del 14th ISSVA Workshop, 2000.
14. Marler JJ, Fang J, Requena-Kasserjian Y, Fishman S, Folkman J, Moses M. Increased Incidence of Matrix Metalloproteinases in the Urine of Children with Vascular Anomalies. Atti del 14th ISSVA Workshop, 2000.
15. Pepper MS. Role of the Matrix metalloproteinase and Plasminogen Activator-Plasmin System in Angiogenesis. Arterioscler Thromb Vasc Biol 2001;21:1104-17.
16. Pasyk KA. Classification and clinical and histopathological features of haemangioma and other vascular malformations. In: Ryan TJ, Cherry GW (eds). Vascular Birthmarks. Oxford University Press, 1987:1-54.
17. Glowacki J, Mulliken JB. Mast cells in hemangiomas and vascular malformations. Pediatrics 1982;70:48-51.
18. Boon L, Enjolras O, Mulliken JB. Congenital hemangioma: Evidence for accelerated involution. J Pediatr 1996;128:329-35.
19. Mulliken JB, Enjolras O. Congenital hemangiomas and infantile hemangioma: missing links. J Am Acad Dermatol 2004;6:875-82.
20. Berenguer B, Mulliken JB, Enjolras O, Boon LM, Wassef M, Josset P, Burrows PE, Perez-Atayde AR, Kozakewich HP. Rapidly involuting congenital hemangioma: clinical and histopathologic features. Pediatr Dev Pathol 2003;6:495-510.
21. Enjolras O, Mulliken JB, Boon LM, Wassef M, Kozakewich HP, Burrows PE. Noninvoluting congenital hemangioma: a rare cutaneous vascular anomaly. Plast Reconstr Surg 2001; 7:1647-54.
22. North PE, Waner M, James CA, Mizeracki A, Frieden IJ, Mhim MCJ. Congenital nonprogressive hemangioma: a distinct clinicopathologic entity unlike infantile hemangioma. Arch Dermatol 2001;12:1607-20.
23. Leung AK, Rafaat M. Benign neonatal hemangiomatosis. Pediatr Dermatol 2003;2:161-3.
24. Sidwell RU, Daubeney PE, Porter W, Roberts NM. Neonatal hemangiomatosis and atrial septal defect: a rare cause of right heart failure in infancy. Pediatr Dermatol 2004;1:66-9.
25. Balaci E, Sumner TE, Auringer ST, Cox TD. Diffuse neonatal hemangiomatosis with extensive involvement of the brain and cervical spinal cord. Pediatr Radiol 1999;6:441-3.
26. Stillman AE, Hansen RC, Hallilan V, Strobel C. Diffuse neonatal hemangiomatosis with severe gastrointestinal involvement. Favorable response to steroid therapy. Clin Pediatr 1983;8:589-91.
27. Lucas JW, Holden KR, Purohit DM, Cure JK. Neonatal hemangiomatosis associated with brachial plexus palsy. J Child Neurol 1995;5:411-3.
28. Boon LM, Burrows PE, Paltiel HJ, et al. Hepatic vascular anomalies in infancy: A twenty-seven-year experience. J Pediatr 1996; 129:346-354.
29. Cohen RC, Myers VA. Diagnosis and management of massive hepatic hemangiomas in childhood. J Pediatr Surg 1986;21:6-9.
30. Berman B, Lim HW. Concurrent cutaneous and hepatic hemangiomata in infancy. Report case and review of the literature. J Dermatol Surg Oncol 1978;4:869-73.
31. DeAos I, James CA, North PE. Hepatic “Haemangioma”: Not a Singular Entity. Atti del 16th ISSVA Congress, 2004.
32. Paltiel HJ, Burrows PE, Kozakewich HPW, Fishman SJ, Mulliken JB. Solitary Infantile Liver Haemangioma: A Distinct Clinicopathologic Entity. Atti del 16th ISSVA Congress, 2004.
33. Kassarjian A, Zurakowski D, Dubois J, Paltiel HJ, Fishman SJ, Burrows PE. Infantile hepatic hemangiomas: clinical and imaging findings and their correlation with therapy. AJR 1994;3:785-95.
34. Stanley P, Geer GD, Miller JH, Gilsanz V, Landing BH, Boechat IM. Infantile hepatic hemangiomas: clinical features, radiologic investigation, and treatment of 20 patients. Cancer 1989;64:936-49.
35. Burrows PE, Rosenberg HC, Chuang HS. Diffuse hepatic hemangiomas: percutaneous transcatheter embolization with detachable silicone baloon. Radiology 1985;156:85-8.
36. Frieden IJ, Reese V, Cohen D. PHACE syndrome: The association of posterior fossa brain malformations, hemangiomas, arterial anomalies, coartaction of the aorta and cardiac defects, and eye abnormalities. Arch Dermatol 1996;132:307-11.
37. Reese V, Frieden IJ, Paller AS, et al. Association of facial hemangiomas with Dandy- Walker and other posterior fossa malformations. J Pediatr 1993;122:379-84.
38. Hirsch JF, Pierre-Kahn A, Reiner D, et al. The Dandy-Walker malformation. A review of 40 cases. J Neurosurg 1984;61:515-22.
39. Brouillard P, Boon LM, Mulliken JB, Enjolras O, Ghassibe M, Warman ML, Tan OT, Olsen BR, Vikkula M. Mutations in a novel factor, glomulin, are responsible for glouvenous malformations (“glomangiomas”). Am J Hum Genet 2002;4:866-74.
40. Mounayer C, Wassef M, Enjolras O, Boukobza M, Mulliken JB. Facial “glomangiomas”: large facial venous malformations with glomus cells. J Am Acad Dermatol 2001; 2:239-45.
41. Stephen J Patrice, Karen Wiss, JB Mulliken. Pyogenic Granuloma (Lobular Capillary Hemangioma): A Clinicopathologic Study of 178 Cases. Pediatr Dermatol 1991;4:267-76.
42. Warner J, Wilson Jones E. Pyogenic granuloma recurring with multiple satellites: A report of 111 cases. Br J Dermatol 1968; 80:218-27.
43. Taira JW, Hill TL, Everett MA. Lobular capillary hemangioma (pyogenic granuloma) with satellitosis. J Am Acad Dermatol 1992; 27:297-300.
44. Enjolras O, Wassef M, Mazoyer E, et al. Infants with Kasabach-Merritt syndrome do not have “true” hemangioma. J Pediatr 1997;130: 631-40.
45. Zuckerberg LR, Nickoloff BJ, Weiss SW. Kaposiform hemangioendothelioma of infancy and childhood. An agressive neoplasm associated with Kasabach-Merritt syndrome and lymphangiomatosis. Am J Surg Pathol 1993;17:321-28.
46. Wilson-Jones E, Orkin M. Tufted angioma (angioblastoma): A benign progressive angioma not to be confused with kaposi’s sarcoma or low-grade angiosarcoma. J Am Acad Dermatol 1989;20:214-25.
47. Padilla RS, Orkin M, Rosai J. Acquired “tufted” angioma (progressive capillary hemangioma): a distinctive clinicopathologic entity related to lobular capillary hemangioma. Am J Dermatopathol 1987;9:292-300.
48. Esterly NB. Kasabach-Merritt syndrome in infants. J Am Acad Dermatol 1983;8:504-13.
49. Orchard PJ, Smith CM, Wodds WG, et al. Treatment of haemangioendothelioma with alpha-interferon. Lancet 1989;2:565-67.
50. White CW, Wolf SJ, Korones DK, et al. Treatment of childhood angiomatous diseases with recombinant interferon alfa-2a. J Pediatr 1991;118:59-66.
51. Perez-Payarols J, Pardo-Masferrer J, Gomez- Bellvert C. Treatment of life-threatening hemangiomas with vincristine. N Engl J Med 1995;333:69.
52. Dubois J, Garel L. Imaging and therapeutic approach of hemangiomas and vascular malformations in the pediatric age group. Pediatr Radiol 1999;29:879-93.
53. Dubois J, Patriquin HB, Garel L, et al. Soft tissue hemangiomas in infants and children: diagnosis using Doppler sonography. AJR 1998;171:247-52.
54. Burrows PE, Mulliken JB, Fellows KE, et al. Childhood hemangiomas and vascular malformations: angiographic differentiation. AJR 1983;141:483-88.
55. White CW, Sondheimer HM, Crouch EC, et al. Treatment of pulmonary hemangiomatosis with recombinant interferon alfa-2a. N Engl J Med 1989;320:1197-200.
56. Folkman J. Successful treatement of an angiogenic disease. N Engl J Med 1989;320: 1211-12.
57. Ricketts RR, Hatley RM, Corden BJ, et al. Interferon alpha-2a for the treatment of complex hemangiomas of infancy and childhood. Ann Surg 1994;219:605-14.
58. Ezekowitz RAB, Mulliken JB, Folkman J. Interferon alfa-2a for life-threatening hemangiomas of infancy. N Engl J Med 1992;326: 1456-63.
59. MacArthur CJ, Senders CW, Katz J. The use of interferon alpha-2a for life-threatening hemangiomas. Arch otolaryngol Head Neck Surg 1995;121:690-693.
60. Enjolras O, Breviere GM, Roger G, Tovi M, Pellegrino B, Varotti E, Soupre V, Picard A, Leverger G. Vincristine treatment for function- and life-threatening infantile hemangioma. Arch Pediatr 2004;2:99-107.
61. Garden JM, Bakus AD, Paller AS. Treatment of cutaneous haemangiomas by the flashlamp- pumped pulsed dye-laser: Prospective analysis. J Pediat 1992;120:555-60.
62. Poetke M, Philipp C, Berlien HP. Flashlamp- pumped pulsed dye laser for haemangiomas in infancy. Arch Dermatol 2000;136: 628-32.
63. Berlien HP, Waldschmidt J, Muller G. Laser treatment of cutaneous and deep vessel anomalies. In: Waidelich W (ed). Laser optoelectronics in medicine. Berlin, Heidelberg, New York: Springer, pp. 526-8.
2. Muller BU, Mulliken JB. The Infant With a Vascular Tumor. Seminars in Perinatology 1999;4:332-340.
3. Amir J, Metzker A, Krikler R, et al. Stawberry hemangioma in preterm infants. Pediatr Dermatol 1986;3:331-32.
4. Drolet BA, Haggstrom AN, Baselga L, Chamlin S, Eichenfield L, Esterly NB, Frieden IJ, Garzon M, Lucky A, Metry D, Nopper A. Risk Factors for Haemangioma of infancy- A Cohort Prospective Study. Atti del 16th ISSVA Congress, 2004.
5. Enjolras O, Mulliken JB. Vascular Tumors and Vascular Malformations (New Issues). Advance in Dermat 1998;vol 13.
6. Burton BK, Schultz CJ, Angle B, et al. An increased incidence of haemangiomas in infants born following chorionic villus sampling (CVS). Prenat Diagn 1995;15:209-14.
7. Garzon MC, Drolet BA, Haggstrom A, Frieden IJ. Incidence and Clinical Association of Multiple Haemangioma of Infancy. Atti del 16th ISSVA Congress, 2004.
8. Redondo P, Fernandez M. Protocol for the treatment of haemangiomas and/or vascular malformations. An Sist Sanit Navar 2004; 1:133-40.
9. Enjolrs O. Classification, Diagnosis and Current Treatment of Vascular Anomalies. Atti del 16th ISSVA Congress, 2004.
10. Majno G, Joris I. Apoptosis, oncosis and necrosis: An overview of cell death. Am J Pathol 1995;146:3-15.
11. Iwata J, Sonobe H, Furihata M, et al. High frequency of apoptosis in infantile capillary haemangioma. J Pathol 1996;179:403-8.
12. Folkman J. Clinical application of research on angiogenesis. N Engl J Med 1995;333: 1757-63.
13. Dikov D, Stefanova P, Sarafian V. Mast Cells (MCS) Variation in Infantile Hemangioma. Atti del 14th ISSVA Workshop, 2000.
14. Marler JJ, Fang J, Requena-Kasserjian Y, Fishman S, Folkman J, Moses M. Increased Incidence of Matrix Metalloproteinases in the Urine of Children with Vascular Anomalies. Atti del 14th ISSVA Workshop, 2000.
15. Pepper MS. Role of the Matrix metalloproteinase and Plasminogen Activator-Plasmin System in Angiogenesis. Arterioscler Thromb Vasc Biol 2001;21:1104-17.
16. Pasyk KA. Classification and clinical and histopathological features of haemangioma and other vascular malformations. In: Ryan TJ, Cherry GW (eds). Vascular Birthmarks. Oxford University Press, 1987:1-54.
17. Glowacki J, Mulliken JB. Mast cells in hemangiomas and vascular malformations. Pediatrics 1982;70:48-51.
18. Boon L, Enjolras O, Mulliken JB. Congenital hemangioma: Evidence for accelerated involution. J Pediatr 1996;128:329-35.
19. Mulliken JB, Enjolras O. Congenital hemangiomas and infantile hemangioma: missing links. J Am Acad Dermatol 2004;6:875-82.
20. Berenguer B, Mulliken JB, Enjolras O, Boon LM, Wassef M, Josset P, Burrows PE, Perez-Atayde AR, Kozakewich HP. Rapidly involuting congenital hemangioma: clinical and histopathologic features. Pediatr Dev Pathol 2003;6:495-510.
21. Enjolras O, Mulliken JB, Boon LM, Wassef M, Kozakewich HP, Burrows PE. Noninvoluting congenital hemangioma: a rare cutaneous vascular anomaly. Plast Reconstr Surg 2001; 7:1647-54.
22. North PE, Waner M, James CA, Mizeracki A, Frieden IJ, Mhim MCJ. Congenital nonprogressive hemangioma: a distinct clinicopathologic entity unlike infantile hemangioma. Arch Dermatol 2001;12:1607-20.
23. Leung AK, Rafaat M. Benign neonatal hemangiomatosis. Pediatr Dermatol 2003;2:161-3.
24. Sidwell RU, Daubeney PE, Porter W, Roberts NM. Neonatal hemangiomatosis and atrial septal defect: a rare cause of right heart failure in infancy. Pediatr Dermatol 2004;1:66-9.
25. Balaci E, Sumner TE, Auringer ST, Cox TD. Diffuse neonatal hemangiomatosis with extensive involvement of the brain and cervical spinal cord. Pediatr Radiol 1999;6:441-3.
26. Stillman AE, Hansen RC, Hallilan V, Strobel C. Diffuse neonatal hemangiomatosis with severe gastrointestinal involvement. Favorable response to steroid therapy. Clin Pediatr 1983;8:589-91.
27. Lucas JW, Holden KR, Purohit DM, Cure JK. Neonatal hemangiomatosis associated with brachial plexus palsy. J Child Neurol 1995;5:411-3.
28. Boon LM, Burrows PE, Paltiel HJ, et al. Hepatic vascular anomalies in infancy: A twenty-seven-year experience. J Pediatr 1996; 129:346-354.
29. Cohen RC, Myers VA. Diagnosis and management of massive hepatic hemangiomas in childhood. J Pediatr Surg 1986;21:6-9.
30. Berman B, Lim HW. Concurrent cutaneous and hepatic hemangiomata in infancy. Report case and review of the literature. J Dermatol Surg Oncol 1978;4:869-73.
31. DeAos I, James CA, North PE. Hepatic “Haemangioma”: Not a Singular Entity. Atti del 16th ISSVA Congress, 2004.
32. Paltiel HJ, Burrows PE, Kozakewich HPW, Fishman SJ, Mulliken JB. Solitary Infantile Liver Haemangioma: A Distinct Clinicopathologic Entity. Atti del 16th ISSVA Congress, 2004.
33. Kassarjian A, Zurakowski D, Dubois J, Paltiel HJ, Fishman SJ, Burrows PE. Infantile hepatic hemangiomas: clinical and imaging findings and their correlation with therapy. AJR 1994;3:785-95.
34. Stanley P, Geer GD, Miller JH, Gilsanz V, Landing BH, Boechat IM. Infantile hepatic hemangiomas: clinical features, radiologic investigation, and treatment of 20 patients. Cancer 1989;64:936-49.
35. Burrows PE, Rosenberg HC, Chuang HS. Diffuse hepatic hemangiomas: percutaneous transcatheter embolization with detachable silicone baloon. Radiology 1985;156:85-8.
36. Frieden IJ, Reese V, Cohen D. PHACE syndrome: The association of posterior fossa brain malformations, hemangiomas, arterial anomalies, coartaction of the aorta and cardiac defects, and eye abnormalities. Arch Dermatol 1996;132:307-11.
37. Reese V, Frieden IJ, Paller AS, et al. Association of facial hemangiomas with Dandy- Walker and other posterior fossa malformations. J Pediatr 1993;122:379-84.
38. Hirsch JF, Pierre-Kahn A, Reiner D, et al. The Dandy-Walker malformation. A review of 40 cases. J Neurosurg 1984;61:515-22.
39. Brouillard P, Boon LM, Mulliken JB, Enjolras O, Ghassibe M, Warman ML, Tan OT, Olsen BR, Vikkula M. Mutations in a novel factor, glomulin, are responsible for glouvenous malformations (“glomangiomas”). Am J Hum Genet 2002;4:866-74.
40. Mounayer C, Wassef M, Enjolras O, Boukobza M, Mulliken JB. Facial “glomangiomas”: large facial venous malformations with glomus cells. J Am Acad Dermatol 2001; 2:239-45.
41. Stephen J Patrice, Karen Wiss, JB Mulliken. Pyogenic Granuloma (Lobular Capillary Hemangioma): A Clinicopathologic Study of 178 Cases. Pediatr Dermatol 1991;4:267-76.
42. Warner J, Wilson Jones E. Pyogenic granuloma recurring with multiple satellites: A report of 111 cases. Br J Dermatol 1968; 80:218-27.
43. Taira JW, Hill TL, Everett MA. Lobular capillary hemangioma (pyogenic granuloma) with satellitosis. J Am Acad Dermatol 1992; 27:297-300.
44. Enjolras O, Wassef M, Mazoyer E, et al. Infants with Kasabach-Merritt syndrome do not have “true” hemangioma. J Pediatr 1997;130: 631-40.
45. Zuckerberg LR, Nickoloff BJ, Weiss SW. Kaposiform hemangioendothelioma of infancy and childhood. An agressive neoplasm associated with Kasabach-Merritt syndrome and lymphangiomatosis. Am J Surg Pathol 1993;17:321-28.
46. Wilson-Jones E, Orkin M. Tufted angioma (angioblastoma): A benign progressive angioma not to be confused with kaposi’s sarcoma or low-grade angiosarcoma. J Am Acad Dermatol 1989;20:214-25.
47. Padilla RS, Orkin M, Rosai J. Acquired “tufted” angioma (progressive capillary hemangioma): a distinctive clinicopathologic entity related to lobular capillary hemangioma. Am J Dermatopathol 1987;9:292-300.
48. Esterly NB. Kasabach-Merritt syndrome in infants. J Am Acad Dermatol 1983;8:504-13.
49. Orchard PJ, Smith CM, Wodds WG, et al. Treatment of haemangioendothelioma with alpha-interferon. Lancet 1989;2:565-67.
50. White CW, Wolf SJ, Korones DK, et al. Treatment of childhood angiomatous diseases with recombinant interferon alfa-2a. J Pediatr 1991;118:59-66.
51. Perez-Payarols J, Pardo-Masferrer J, Gomez- Bellvert C. Treatment of life-threatening hemangiomas with vincristine. N Engl J Med 1995;333:69.
52. Dubois J, Garel L. Imaging and therapeutic approach of hemangiomas and vascular malformations in the pediatric age group. Pediatr Radiol 1999;29:879-93.
53. Dubois J, Patriquin HB, Garel L, et al. Soft tissue hemangiomas in infants and children: diagnosis using Doppler sonography. AJR 1998;171:247-52.
54. Burrows PE, Mulliken JB, Fellows KE, et al. Childhood hemangiomas and vascular malformations: angiographic differentiation. AJR 1983;141:483-88.
55. White CW, Sondheimer HM, Crouch EC, et al. Treatment of pulmonary hemangiomatosis with recombinant interferon alfa-2a. N Engl J Med 1989;320:1197-200.
56. Folkman J. Successful treatement of an angiogenic disease. N Engl J Med 1989;320: 1211-12.
57. Ricketts RR, Hatley RM, Corden BJ, et al. Interferon alpha-2a for the treatment of complex hemangiomas of infancy and childhood. Ann Surg 1994;219:605-14.
58. Ezekowitz RAB, Mulliken JB, Folkman J. Interferon alfa-2a for life-threatening hemangiomas of infancy. N Engl J Med 1992;326: 1456-63.
59. MacArthur CJ, Senders CW, Katz J. The use of interferon alpha-2a for life-threatening hemangiomas. Arch otolaryngol Head Neck Surg 1995;121:690-693.
60. Enjolras O, Breviere GM, Roger G, Tovi M, Pellegrino B, Varotti E, Soupre V, Picard A, Leverger G. Vincristine treatment for function- and life-threatening infantile hemangioma. Arch Pediatr 2004;2:99-107.
61. Garden JM, Bakus AD, Paller AS. Treatment of cutaneous haemangiomas by the flashlamp- pumped pulsed dye-laser: Prospective analysis. J Pediat 1992;120:555-60.
62. Poetke M, Philipp C, Berlien HP. Flashlamp- pumped pulsed dye laser for haemangiomas in infancy. Arch Dermatol 2000;136: 628-32.
63. Berlien HP, Waldschmidt J, Muller G. Laser treatment of cutaneous and deep vessel anomalies. In: Waidelich W (ed). Laser optoelectronics in medicine. Berlin, Heidelberg, New York: Springer, pp. 526-8.