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Misdiagnosed as infantile hemangioma: Early presentation of small vessel-rich AVM
International Journal of Pediatric Otorhinolaryngology Extra 8 (2013) 71–74
Contents lists available at SciVerse ScienceDirect
International Journal of Pediatric Otorhinolaryngology Extra journal homepage: www.elsevier.com/locate/ijporl
Case report
Misdiagnosed as infantile hemangioma: Early presentation of small vessel-rich AVM§ Luke A. Jakubowski a, Robert H. Chun a,*, Beth A. Drolet b, John N. Jensen c, Paula E. North d a
Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, United States Department of Dermatology, Medical College of Wisconsin, United States c Department of Plastic Surgery, Medical College of Wisconsin, United States d Department of Pathology, Medical College of Wisconsin, United States b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 15 January 2013 Received in revised form 11 April 2013 Accepted 12 April 2013
Arteriovenous malformations (AVMs) are typically present at birth but may not become clinically significant till later in life. The rarity of AVMs leads to misdiagnosis, as they can be confused in young patients with infantile hemangioma (IH). Small vessel-rich AVM can be radiologically consistent with an IH, while the clinical presentation is that of a slowly growing vascular anomaly. These cases highlight the clinical dilemma that while a vascular anomaly may appear by imaging studies to be the common and generally innocuous IH, an atypical growth pattern should raise clinical suspicion for an AVM. ß 2013 Elsevier Ireland Ltd. All rights reserved.
Keywords: Infantile hemangioma Hemangioma Arteriovenous malformations AVM Small vessel AVM
1. Introduction Arteriovenous malformations (AVMs) are rare vascular malformations which are typically present at birth but may not become clinically significant till later in life. Of all vascular malformations, AVMs are the most aggressive, leading to significant deformity and functional impairment [1]. The rarity of AVMs leads to a fair amount of confusion and delayed diagnosis in young children, as they are often confused with a common vascular birthmark, infantile hemangioma (IH). The natural history of AVMs is one of progression with soft tissue destruction, deformity, bleeding, and pain. AVMs are frequently identified at birth as a blush or swelling of the skin. Their presentation can vary, and delayed diagnosis is not uncommon, although progressive recruitment of collateral flow into the low-resistance nidus may cause significant progressive expansion. Unlike IH, AVMs typically grow relatively synchronously with the child’s development. Rapid enlargement can occur secondary to hormonal influences (puberty) or local trauma [1].
§ Presented in poster form at the American Academy of Otolaryngology, September 2011, San Francisco. * Corresponding author at: Department of Otolaryngology, Children’s Hospital Clinics Building, Suite 350, 9000 West Wisconsin Avenue, Milwaukee, WI 53226, United States. Tel.: +1 414 266 8383; fax: +1 414 266 2693. E-mail address: [email protected] (R.H. Chun).
1871-4048/$ – see front matter ß 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.pedex.2013.04.002
The morbidity associated with AVMs is secondary to the progressive expansion and thickening of vessels leading to ischemic compression and destruction of adjacent tissues, resulting in cosmetic and functional deformities. In contrast to AVMs, IHs are the most common tumor of infancy. IHs are present in approximately 2–3% of neonates and by one year are present in 10% of children [2]. Typically they first appear at about 2 weeks of age as a blanched, blushed, or telangiectatic area [3]. However they may be present at birth in approximately 30% of cases. The natural history of IHs typically follows three predictable stages: a rapidly proliferating stage (generally lasting 8–12 months), followed by a prolonged involuting stage (1–12 years), and finally by a variably prominent end-stage fibrofatty residuum [3]. Complications related to IHs occur in less than 10% of cases [4,5]. Approximately 9% of cases require surgical resection secondary to complications [6]. 1.1. Case one A 16 month old female presented to clinic with left neck mass. The mass first appeared at 6 months as a small bump and progressively and grew in size, but was otherwise asymptomatic. MRI and CT angiogram were performed and showed a heterogeneous enhancing 29 mm 39 mm 29 mm mass along the course of the inferior left spinal accessory lymph node chain (Fig. 1). Small discrete flow voids were seen
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L.A. Jakubowski et al. / International Journal of Pediatric Otorhinolaryngology Extra 8 (2013) 71–74
Fig. 1. MRA (A) and CTA (B) demonstrate a well marginated left supraclavicular mass. No large feeding arteries or drain veins supply the mass. A few small vessels from the left subclavian artery and left vertebral artery supply the inferior margin of the mass. Small arteries from the left vertebral artery supply the inferior and superior margin of the mass, respectively. MRI (C) demonstrates a heterogeneous enhancing mass along the course of the inferior left spinal accessory lymph node chain.
throughout the mass and the impression was that this was a likely IH. This was an atypical presentation for an IH and a diagnosis of an AVM was considered. Imaging revealed large feeding vessels from the left subclavian artery. As the risk of hemorrhage was significant, preoperative embolization was performed. A complete excision was not performed due to unknown pathology and increased morbidity. The histology and immunonegativity for glucose transporter protein isoform 1 (GLUT 1) confirmed that the vascular mass was not IH but rather was a small vessel-rich arteriovenous malformation. A decision was made to let the child grow to 20 months of age in order to allow for the vessels to accommodate larger catheters, providing more extensive preoperative embolization. The subsequent surgical resection had less than 50 cm3 of blood loss. 18 month post op MRI shows no residual AVM. 1.2. Case two A 20-month-old girl presented to clinic with a nasal tip vascular anomaly. The mass has no appreciable growth until 1 year of age (Fig. 2). In addition to cosmesis, she occasionally experienced epistaxis, controlled with localized pressure. MRI demonstrated a lobulated soft tissue mass which measures 15.5 mm 13.3 mm 11.7 mm in the nasal tip. MRA and MRV
were consistent with IH with no identifiable dominant arterial feeder or nidus. As this would be an atypical clinical presentation for an IH, an incisional biopsy was performed. Pathology with immunonegativity for GLUT-1 confirmed that the vascular mass was not IH but was a small vessel-rich AVM (Fig. 3). The decision was made to proceed to the operative theater for excision of the small vessel-rich AVM of the nasal tip via an open rhinoplasty approach. At 30 months of age, she was taken back to the OR for a hernia repair. At which time an exam under anesthesia was performed revealing no signs of residual vascular anomaly. At 38 months she developed recurrent epistaxis. MRI shows an 11 mm anterior nasal tip mass, consistent with a recurrence of the small vessel-rich AVM. Surgical resection is currently planned. 2. Discussion The clinical importance of differentiating IH and AVM relates to their differing patterns of disease progression and clinical management needs. While observation and medical therapy has been shown to be beneficial for IH, medical therapy has a minimal role in treatment of AVMs and delay in treatment will only lead to further growth of the AVM and progression of complications. Diagnosis of IHs is typically a clinical one. The role for imaging IHs is often to support the clinical diagnosis. Ultrasound (US) with Doppler is typically the first line [7]. CT and MR imaging
L.A. Jakubowski et al. / International Journal of Pediatric Otorhinolaryngology Extra 8 (2013) 71–74
73
Fig. 2. Slowly growing nasal mass with growth beyond the normal age for the proliferative phase of an infantile hemangioma.
Fig. 3. (A) Nasal mass, 100 original magnification, hematoxylin & eosin: an increased vasculature consisting of tightly packed vessels of with variably thickened walls rimmed by smooth muscle and pericytes and lined by mitotically quiescent endothelial cells. The surrounding stroma is fibrotic and focally myxoid. Moderately enlarged arterial feeders (not shown) permeate the lesion and (B) the lesional endothelial cells are globally negative for the infantile hemangioma-associated marker GLUT 1, 200 original magnification (intra-luminal erythrocytes are GLUT 1 positive, serving as an internal positive control).
appearances of IH depend on their evolutionary phase. During the proliferating phase of IHs, CT and MR demonstrates a wellcircumscribed, densely lobulated, uniformly enhancing lesion with dilated feeding and draining vessels in the center or at the periphery [8]. Similarly to IH, AVMs exhibit high vascular density with high Doppler shift on US. MRI of AVMs demonstrates a tangle of prominent vessels and a ‘‘field defect,’’ involving large areas and crossing contiguous tissue planes [8]. Unlike the more typical AVM in which large arterial and venous channels are dominant, some AVM’s are small-vessel rich and these often appear as relatively well-circumscribed ‘‘tumor-like’’ vascular masses by MRI [8]. When imaging findings conflict with clinical presentation, biopsy to provide a histological diagnosis should be considered. Histopathological evaluation with the assistance of immunohistochemistry can easily differentiate IH from other vascular tumors and malformations. During the proliferating phase, IH are well-defined, nonencapsulated masses of endothelial cells and pericytes that form small round lumina. During the involuting phase capillaries are progressively replaced by loose fibroadipose tissue. Persistent larger feeding and draining vessels may mimic vascular malformations. Several large studies have shown that the endothelial cells of IH are strongly and uniformly positive for GLUT 1, whereas the endothelial cells of all other vascular proliferations and malformations are negative for this marker [3,8,9]. GLUT 1 expression remains high in IH endothelial cells throughout proliferation and involution. In contrast, AVMs demonstrate a variably composed collection of arterial and venous channels. A significant proportion of AVMs are rich in closely packed small vessels, typically interspersed between much draining veins and tortuous feeding arteries. Veins within AVMs typically demonstrate irregular mural thickening and reactive change due to
abnormally elevated venous pressure caused AV shunting. Endothelial cells of AVMs, as with other all other benign vascular tumors and malformations except IH, are negative by immunohistochemistry for GLUT 1 [9,10]. 3. Conclusion We present two cases of clinically diagnosed IH who presented with continued growth after 12 months, which led to the suspicion of a misdiagnosed small vessel-rich AVM or other entity. In both cases imaging supported the diagnosis of IH. With conflicting clinical behavior and radiologic diagnosis, surgical biopsy was obtained. In these cases, the biopsies revealed immunonegativity to GLUT-1 in addition to histology consistent with small vesselrich AVM. Guided by this strong clinicopathological diagnosis, an aggressive treatment plan guided by a multidisciplinary vascular anomalies team was implemented, including preoperative embolization and surgical resection. These cases highlight that while a vascular anomaly may appear to be a common vascular tumor such as an IH that would be expected to spontaneously regress, an atypical growth pattern such as in our patients should prompt further evaluation. When diagnosis remains elusive after imaging, tissue biopsy and immunohistostaining can clarify the diagnosis and guide therapy. In our cases, was key in establishing a diagnosis leading to prompt surgical intervention. Early diagnosis and treatment of AVMs is important, as the natural history of AVMs is one of progressive expansion and associated morbidity. The likelihood of cure may be improved with treatment of AVMs at an earlier stage of development, as demonstrated by Richter in a recent case series of tongue AVMs
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L.A. Jakubowski et al. / International Journal of Pediatric Otorhinolaryngology Extra 8 (2013) 71–74
[9]. Treatment of AVMs often involves early intervention with a multidisciplinary team of medical specialists representing medicine, surgery, interventional radiology and pathology. Although AVM’s are relatively rare compared to IHs, physicians treating vascular anomalies must maintain a high level of clinical suspicion for this entity. Conflicts of interest The authors have nothing to declare. Funding No financial support of funding. References [1] K.B. Puttgen, M. Pearl, A. Tekes, S.E. Mitchell, Update on pediatric extracranial vascular anomalies of the head and neck, Child’s Nervous System 26 (10) (2010) 1417–1433. , http://dx.doi.org/10.1007/s00381-010-1202-2.
[2] K.N. Smolinski, A.C. Yan, Hemangiomas of infancy: clinical and biological characteristics, Clinical Pediatrics 44 (9) (2005) 747–766. [3] P.E. North, M. Waner, L. Buckmiller, C.A. James, M.C. Mihm Jr., Vascular tumors of infancy and childhood: beyond capillary hemangioma, Cardiovascular Pathology 15 (6) (2006) 303–317. , http://dx.doi.org/10.1016/j.carpath.2006.03.001. [4] L.C. Chang, A.N. Haggstrom, B.A. Drolet, et al., Growth characteristics of infantile hemangiomas: implications for management, Pediatrics 122 (2) (2008) 360–367. , http://dx.doi.org/10.1542/peds.2007-2767. [5] K.E. Holland, B.A. Drolet, Infantile hemangioma, Pediatric Clinics of North America 57 (5) (2010) 1069–1083. , http://dx.doi.org/10.1016/j.pcl.2010.07.008. [6] O.O. Daramola, R.H. Chun, J.J. Nash, et al., Surgical treatment of infantile hemangioma in a multidisciplinary vascular anomalies clinic, International Journal of Pediatric Otorhinolaryngology 75 (10) (2011) 1271–1274. , http://dx.doi.org/ 10.1016/j.ijporl.2011.07.007. [7] O.M. Navarro, Soft tissue masses in children, Radiologic Clinics of North America 49 (6) (2011) 1235–1259. , http://dx.doi.org/10.1016/j.rcl.2011.07.008, vi–vii. [8] P.E. Burrows, T. Laor, H. Paltiel, R.L. Robertson, Diagnostic imaging in the evaluation of vascular birthmarks, Dermatologic Clinics 16 (3) (1998) 455–488. [9] P.E. North, M. Waner, A. Mizeracki, M.C. Mihm Jr., GLUT1: a newly discovered immunohistochemical marker for juvenile hemangiomas, Human Pathology 31 (1) (2000) 11–22. [10] P.E. North, M. Waner, A. Mizeracki, et al., A unique microvascular phenotype shared by juvenile hemangiomas and human placenta, Archives of Dermatology 137 (5) (2001) 559–570.
Contents lists available at SciVerse ScienceDirect
International Journal of Pediatric Otorhinolaryngology Extra journal homepage: www.elsevier.com/locate/ijporl
Case report
Misdiagnosed as infantile hemangioma: Early presentation of small vessel-rich AVM§ Luke A. Jakubowski a, Robert H. Chun a,*, Beth A. Drolet b, John N. Jensen c, Paula E. North d a
Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, United States Department of Dermatology, Medical College of Wisconsin, United States c Department of Plastic Surgery, Medical College of Wisconsin, United States d Department of Pathology, Medical College of Wisconsin, United States b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 15 January 2013 Received in revised form 11 April 2013 Accepted 12 April 2013
Arteriovenous malformations (AVMs) are typically present at birth but may not become clinically significant till later in life. The rarity of AVMs leads to misdiagnosis, as they can be confused in young patients with infantile hemangioma (IH). Small vessel-rich AVM can be radiologically consistent with an IH, while the clinical presentation is that of a slowly growing vascular anomaly. These cases highlight the clinical dilemma that while a vascular anomaly may appear by imaging studies to be the common and generally innocuous IH, an atypical growth pattern should raise clinical suspicion for an AVM. ß 2013 Elsevier Ireland Ltd. All rights reserved.
Keywords: Infantile hemangioma Hemangioma Arteriovenous malformations AVM Small vessel AVM
1. Introduction Arteriovenous malformations (AVMs) are rare vascular malformations which are typically present at birth but may not become clinically significant till later in life. Of all vascular malformations, AVMs are the most aggressive, leading to significant deformity and functional impairment [1]. The rarity of AVMs leads to a fair amount of confusion and delayed diagnosis in young children, as they are often confused with a common vascular birthmark, infantile hemangioma (IH). The natural history of AVMs is one of progression with soft tissue destruction, deformity, bleeding, and pain. AVMs are frequently identified at birth as a blush or swelling of the skin. Their presentation can vary, and delayed diagnosis is not uncommon, although progressive recruitment of collateral flow into the low-resistance nidus may cause significant progressive expansion. Unlike IH, AVMs typically grow relatively synchronously with the child’s development. Rapid enlargement can occur secondary to hormonal influences (puberty) or local trauma [1].
§ Presented in poster form at the American Academy of Otolaryngology, September 2011, San Francisco. * Corresponding author at: Department of Otolaryngology, Children’s Hospital Clinics Building, Suite 350, 9000 West Wisconsin Avenue, Milwaukee, WI 53226, United States. Tel.: +1 414 266 8383; fax: +1 414 266 2693. E-mail address: [email protected] (R.H. Chun).
1871-4048/$ – see front matter ß 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.pedex.2013.04.002
The morbidity associated with AVMs is secondary to the progressive expansion and thickening of vessels leading to ischemic compression and destruction of adjacent tissues, resulting in cosmetic and functional deformities. In contrast to AVMs, IHs are the most common tumor of infancy. IHs are present in approximately 2–3% of neonates and by one year are present in 10% of children [2]. Typically they first appear at about 2 weeks of age as a blanched, blushed, or telangiectatic area [3]. However they may be present at birth in approximately 30% of cases. The natural history of IHs typically follows three predictable stages: a rapidly proliferating stage (generally lasting 8–12 months), followed by a prolonged involuting stage (1–12 years), and finally by a variably prominent end-stage fibrofatty residuum [3]. Complications related to IHs occur in less than 10% of cases [4,5]. Approximately 9% of cases require surgical resection secondary to complications [6]. 1.1. Case one A 16 month old female presented to clinic with left neck mass. The mass first appeared at 6 months as a small bump and progressively and grew in size, but was otherwise asymptomatic. MRI and CT angiogram were performed and showed a heterogeneous enhancing 29 mm 39 mm 29 mm mass along the course of the inferior left spinal accessory lymph node chain (Fig. 1). Small discrete flow voids were seen
72
L.A. Jakubowski et al. / International Journal of Pediatric Otorhinolaryngology Extra 8 (2013) 71–74
Fig. 1. MRA (A) and CTA (B) demonstrate a well marginated left supraclavicular mass. No large feeding arteries or drain veins supply the mass. A few small vessels from the left subclavian artery and left vertebral artery supply the inferior margin of the mass. Small arteries from the left vertebral artery supply the inferior and superior margin of the mass, respectively. MRI (C) demonstrates a heterogeneous enhancing mass along the course of the inferior left spinal accessory lymph node chain.
throughout the mass and the impression was that this was a likely IH. This was an atypical presentation for an IH and a diagnosis of an AVM was considered. Imaging revealed large feeding vessels from the left subclavian artery. As the risk of hemorrhage was significant, preoperative embolization was performed. A complete excision was not performed due to unknown pathology and increased morbidity. The histology and immunonegativity for glucose transporter protein isoform 1 (GLUT 1) confirmed that the vascular mass was not IH but rather was a small vessel-rich arteriovenous malformation. A decision was made to let the child grow to 20 months of age in order to allow for the vessels to accommodate larger catheters, providing more extensive preoperative embolization. The subsequent surgical resection had less than 50 cm3 of blood loss. 18 month post op MRI shows no residual AVM. 1.2. Case two A 20-month-old girl presented to clinic with a nasal tip vascular anomaly. The mass has no appreciable growth until 1 year of age (Fig. 2). In addition to cosmesis, she occasionally experienced epistaxis, controlled with localized pressure. MRI demonstrated a lobulated soft tissue mass which measures 15.5 mm 13.3 mm 11.7 mm in the nasal tip. MRA and MRV
were consistent with IH with no identifiable dominant arterial feeder or nidus. As this would be an atypical clinical presentation for an IH, an incisional biopsy was performed. Pathology with immunonegativity for GLUT-1 confirmed that the vascular mass was not IH but was a small vessel-rich AVM (Fig. 3). The decision was made to proceed to the operative theater for excision of the small vessel-rich AVM of the nasal tip via an open rhinoplasty approach. At 30 months of age, she was taken back to the OR for a hernia repair. At which time an exam under anesthesia was performed revealing no signs of residual vascular anomaly. At 38 months she developed recurrent epistaxis. MRI shows an 11 mm anterior nasal tip mass, consistent with a recurrence of the small vessel-rich AVM. Surgical resection is currently planned. 2. Discussion The clinical importance of differentiating IH and AVM relates to their differing patterns of disease progression and clinical management needs. While observation and medical therapy has been shown to be beneficial for IH, medical therapy has a minimal role in treatment of AVMs and delay in treatment will only lead to further growth of the AVM and progression of complications. Diagnosis of IHs is typically a clinical one. The role for imaging IHs is often to support the clinical diagnosis. Ultrasound (US) with Doppler is typically the first line [7]. CT and MR imaging
L.A. Jakubowski et al. / International Journal of Pediatric Otorhinolaryngology Extra 8 (2013) 71–74
73
Fig. 2. Slowly growing nasal mass with growth beyond the normal age for the proliferative phase of an infantile hemangioma.
Fig. 3. (A) Nasal mass, 100 original magnification, hematoxylin & eosin: an increased vasculature consisting of tightly packed vessels of with variably thickened walls rimmed by smooth muscle and pericytes and lined by mitotically quiescent endothelial cells. The surrounding stroma is fibrotic and focally myxoid. Moderately enlarged arterial feeders (not shown) permeate the lesion and (B) the lesional endothelial cells are globally negative for the infantile hemangioma-associated marker GLUT 1, 200 original magnification (intra-luminal erythrocytes are GLUT 1 positive, serving as an internal positive control).
appearances of IH depend on their evolutionary phase. During the proliferating phase of IHs, CT and MR demonstrates a wellcircumscribed, densely lobulated, uniformly enhancing lesion with dilated feeding and draining vessels in the center or at the periphery [8]. Similarly to IH, AVMs exhibit high vascular density with high Doppler shift on US. MRI of AVMs demonstrates a tangle of prominent vessels and a ‘‘field defect,’’ involving large areas and crossing contiguous tissue planes [8]. Unlike the more typical AVM in which large arterial and venous channels are dominant, some AVM’s are small-vessel rich and these often appear as relatively well-circumscribed ‘‘tumor-like’’ vascular masses by MRI [8]. When imaging findings conflict with clinical presentation, biopsy to provide a histological diagnosis should be considered. Histopathological evaluation with the assistance of immunohistochemistry can easily differentiate IH from other vascular tumors and malformations. During the proliferating phase, IH are well-defined, nonencapsulated masses of endothelial cells and pericytes that form small round lumina. During the involuting phase capillaries are progressively replaced by loose fibroadipose tissue. Persistent larger feeding and draining vessels may mimic vascular malformations. Several large studies have shown that the endothelial cells of IH are strongly and uniformly positive for GLUT 1, whereas the endothelial cells of all other vascular proliferations and malformations are negative for this marker [3,8,9]. GLUT 1 expression remains high in IH endothelial cells throughout proliferation and involution. In contrast, AVMs demonstrate a variably composed collection of arterial and venous channels. A significant proportion of AVMs are rich in closely packed small vessels, typically interspersed between much draining veins and tortuous feeding arteries. Veins within AVMs typically demonstrate irregular mural thickening and reactive change due to
abnormally elevated venous pressure caused AV shunting. Endothelial cells of AVMs, as with other all other benign vascular tumors and malformations except IH, are negative by immunohistochemistry for GLUT 1 [9,10]. 3. Conclusion We present two cases of clinically diagnosed IH who presented with continued growth after 12 months, which led to the suspicion of a misdiagnosed small vessel-rich AVM or other entity. In both cases imaging supported the diagnosis of IH. With conflicting clinical behavior and radiologic diagnosis, surgical biopsy was obtained. In these cases, the biopsies revealed immunonegativity to GLUT-1 in addition to histology consistent with small vesselrich AVM. Guided by this strong clinicopathological diagnosis, an aggressive treatment plan guided by a multidisciplinary vascular anomalies team was implemented, including preoperative embolization and surgical resection. These cases highlight that while a vascular anomaly may appear to be a common vascular tumor such as an IH that would be expected to spontaneously regress, an atypical growth pattern such as in our patients should prompt further evaluation. When diagnosis remains elusive after imaging, tissue biopsy and immunohistostaining can clarify the diagnosis and guide therapy. In our cases, was key in establishing a diagnosis leading to prompt surgical intervention. Early diagnosis and treatment of AVMs is important, as the natural history of AVMs is one of progressive expansion and associated morbidity. The likelihood of cure may be improved with treatment of AVMs at an earlier stage of development, as demonstrated by Richter in a recent case series of tongue AVMs
74
L.A. Jakubowski et al. / International Journal of Pediatric Otorhinolaryngology Extra 8 (2013) 71–74
[9]. Treatment of AVMs often involves early intervention with a multidisciplinary team of medical specialists representing medicine, surgery, interventional radiology and pathology. Although AVM’s are relatively rare compared to IHs, physicians treating vascular anomalies must maintain a high level of clinical suspicion for this entity. Conflicts of interest The authors have nothing to declare. Funding No financial support of funding. References [1] K.B. Puttgen, M. Pearl, A. Tekes, S.E. Mitchell, Update on pediatric extracranial vascular anomalies of the head and neck, Child’s Nervous System 26 (10) (2010) 1417–1433. , http://dx.doi.org/10.1007/s00381-010-1202-2.
[2] K.N. Smolinski, A.C. Yan, Hemangiomas of infancy: clinical and biological characteristics, Clinical Pediatrics 44 (9) (2005) 747–766. [3] P.E. North, M. Waner, L. Buckmiller, C.A. James, M.C. Mihm Jr., Vascular tumors of infancy and childhood: beyond capillary hemangioma, Cardiovascular Pathology 15 (6) (2006) 303–317. , http://dx.doi.org/10.1016/j.carpath.2006.03.001. [4] L.C. Chang, A.N. Haggstrom, B.A. Drolet, et al., Growth characteristics of infantile hemangiomas: implications for management, Pediatrics 122 (2) (2008) 360–367. , http://dx.doi.org/10.1542/peds.2007-2767. [5] K.E. Holland, B.A. Drolet, Infantile hemangioma, Pediatric Clinics of North America 57 (5) (2010) 1069–1083. , http://dx.doi.org/10.1016/j.pcl.2010.07.008. [6] O.O. Daramola, R.H. Chun, J.J. Nash, et al., Surgical treatment of infantile hemangioma in a multidisciplinary vascular anomalies clinic, International Journal of Pediatric Otorhinolaryngology 75 (10) (2011) 1271–1274. , http://dx.doi.org/ 10.1016/j.ijporl.2011.07.007. [7] O.M. Navarro, Soft tissue masses in children, Radiologic Clinics of North America 49 (6) (2011) 1235–1259. , http://dx.doi.org/10.1016/j.rcl.2011.07.008, vi–vii. [8] P.E. Burrows, T. Laor, H. Paltiel, R.L. Robertson, Diagnostic imaging in the evaluation of vascular birthmarks, Dermatologic Clinics 16 (3) (1998) 455–488. [9] P.E. North, M. Waner, A. Mizeracki, M.C. Mihm Jr., GLUT1: a newly discovered immunohistochemical marker for juvenile hemangiomas, Human Pathology 31 (1) (2000) 11–22. [10] P.E. North, M. Waner, A. Mizeracki, et al., A unique microvascular phenotype shared by juvenile hemangiomas and human placenta, Archives of Dermatology 137 (5) (2001) 559–570.