DOI: 10.1148/radiol.2413031669
(Radiology 2006;241:939-942.)
© RSNA, 2006
Case 103: PHACE Syndrome1
Daniel G. Church, MD and
Lisa H. Lowe, MD
1 From the Department of Radiology, St Luke's Hospital of Kansas City, 4401 Wornall Rd, Kansas City, MO 64111. Received October 14, 2003; revision requested January 8, 2004; final revision received June 21; final version accepted July 2.
Address correspondence to D.G.C. (e-mail: Danielgenechurch{at}yahoo.com).
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HISTORY
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A 10-month-old girl had an enlarging, warm, reddish left periorbital cutaneous and subcutaneous mass since infancy. Her medical history was otherwise unremarkable. Magnetic resonance (MR) imaging of the brain was performed.
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IMAGING FINDINGS
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Gadopentetate dimeglumine–enhanced (Magnevist; Berlex, Montville, NJ) T1-weighted fat-suppressed coronal MR imaging of the orbits revealed an enhancing left orbital and periorbital mass with retrobulbar extension that grew around the orbital structures (Fig 1). The left superior ophthalmic vein was mildly enlarged, likely in relation to the increased blood flow from the hemangioma. Transverse T2-weighted MR imaging (Fig 2a) and MR angiography (Fig 2b) revealed a markedly tortuous petrous and cavernous right internal carotid artery and cerebellar hypoplasia (Fig 3). There was resultant ex vacuo dilatation of the fourth ventricle and cisterna magna.
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Figure 1a: (a, b) Contiguous coronal T1-weighted gadopentetate dimeglumine–enhanced fat-suppressed spin-echo (repetition time msec/echo time msec, 634/15) MR images of the orbits show an enhancing left orbital and periorbital hemangioma (arrows) with retrobulbar extension that grew around the orbital structures. Note the enlarged left superior ophthalmic vein (arrowhead).
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Figure 1b: (a, b) Contiguous coronal T1-weighted gadopentetate dimeglumine–enhanced fat-suppressed spin-echo (repetition time msec/echo time msec, 634/15) MR images of the orbits show an enhancing left orbital and periorbital hemangioma (arrows) with retrobulbar extension that grew around the orbital structures. Note the enlarged left superior ophthalmic vein (arrowhead).
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Figure 2a: (a) Transverse fast spin-echo T2-weighted (4330/113) MR image and (b) right posterior oblique three-dimensional time-of-flight gradient-recalled-echo (36/5) MR angiogram of the circle of Willis show a markedly tortuous petrous and cavernous right internal carotid artery (arrow). Questionable tortuosity of the left internal carotid artery is projectional because of overlapping vessels in b.
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Figure 2b: (a) Transverse fast spin-echo T2-weighted (4330/113) MR image and (b) right posterior oblique three-dimensional time-of-flight gradient-recalled-echo (36/5) MR angiogram of the circle of Willis show a markedly tortuous petrous and cavernous right internal carotid artery (arrow). Questionable tortuosity of the left internal carotid artery is projectional because of overlapping vessels in b.
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Figure 3: Transverse fast spin-echo T2-weighted (4410/101) MR image of the posterior fossa shows cerebellar hypoplasia is greater in the left hemisphere (arrow) than in the right hemisphere, with associated ex vacuo dilatation of the fourth ventricle and cisterna magna.
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DISCUSSION
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In this case, the constellation of imaging findings (a T2-weighted bright lesion with brisk enhancement and internal flow voids that grew between structures) and the patient's clinical history were consistent with a diagnosis of hemangioma. Rather than invade the orbital structures, the markedly enhancing mass grew between them.
Hemangiomas are the most common benign tumors in infants, occurring in up to 10% of children younger than 1 year (1). Hemangiomas occur most commonly in white children, girls, and premature infants, and the average age at presentation is 9.8 months (age range, 0–3 years) (2,3). In the biological classification system of vascular anomalies proposed by Mulliken and Glowacki (4), hemangiomas are tumors that consist of proliferative endothelial cells as opposed to vascular malformations (such as arteriovenous fistulas), arteriovenous malformations, capillary and venous malformations, or lymphatic malformations (2). They have a predictable clinical course that includes rapid growth in the 1st year of life (proliferative phase) followed by regression from 1 to 7 years of age (involuting phase) (5).
The MR imaging appearance of hemangiomas is dependent on the evolutionary phase (6). Proliferative lesions are well-defined, lobulated, intensely enhancing soft-tissue masses that are isointense to muscle on T1-weighted images, are hyperintense to muscle on T2-weighted images, and contain internal flow voids. Gradual replacement by fat occurs during the involuting phase (6).
Since hemangiomas will resolve spontaneously if given adequate time, treatment is not usually required unless patients are suspected of having complicating features (airway compromise, skin necrosis, or superinfection) that are commonly associated with large facial lesions.
PHACE syndrome is commonly described in the dermatology literature. This acronym denotes the features most commonly associated with this neurocutaneous syndrome, which are as follows: posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities (1). Sternal clefting, which is a less common anomaly, may also occur; in this case, the acronym PHACES has been used to describe the condition (7).
Metry et al (3) reviewed 14 cases of hemangioma and PHACE syndrome and an additional 116 cases in the literature and found the V1 segment of the fifth cranial nerve was the most commonly affected dermatome. Associated structural brain anomalies included Dandy-Walker malformation (most common) and hypoplasia or agenesis of the corpus callosum and cerebellum (Fig 3). Described arterial anomalies include cerebral aneurysm, intracranial internal carotid artery and central branch stenoses, anomalous branches of the internal carotid artery, persistence of primitive embryonic channels (eg, persistent trigeminal artery), and hypoplasia or absence of main channels (carotid and vertebral). Anomalous branches of the internal carotid artery were found more frequently than were intracranial aneurysms (3). Cardiac and aortic anomalies included ventricular septal defects, patent ductus arteriosus, and aortic coarctation. Coarctation of the aorta was the most common cardiac and aortic anomaly (3). Optical findings included increased retinal vascularity, bilateral retinal hyperemia, and Horner syndrome (3). The trigeminal dermatome pattern of hemangioma involvement may be mistaken for a capillary malformation (port-wine stain), thus leading to the clinical misdiagnosis of Sturge-Weber syndrome (3). A distinguishing feature of Sturge-Weber syndrome is the primary central nervous system abnormality of leptomeningeal vascular malformation, which is commonly referred to as leptomeningeal angiomatosis (1).
The differential diagnosis of hemangioma on MR images includes lymphatic malformation, venous malformation, and rhabdomyosarcoma. Lymphatic malformation can be distinguished by finding cystic spaces with rim enhancement (2). Venous malformation has many of the same imaging characteristics as hemangioma (isointense to muscle on T1-weighted images, hyperintense to muscle on T2-weighted images, and diffuse or inhomogeneous enhancement), and it can be difficult to differentiate one from the other (2). However, differentiation is made easier by the fact that venous malformation and hemangioma have a different time course and age of presentation. Venous anomalies are present at birth, but they are not always evident (5). Venous malformations grow in proportion to the child, expand slowly, and often enlarge during puberty (5).
Rhabdomyosarcoma typically has an aggressive appearance, with destructive invasion of the orbital structures. The differential diagnosis for tortuous ectatic internal carotid artery includes arteriovenous malformation with or without aneurysms. Arteriovenous malformation should have a nidus of abnormal feeding arteries and draining veins. The differential diagnosis for cerebellar hypoplasia includes Dandy-Walker malformation, arachnoid cyst, mega cisterna magna, and prior ischemic injury. The Dandy-Walker malformation consists of partial or complete absence of the vermis; dilatation of the fourth ventricle, which communicates posteriorly with a retrocerebellar cyst; enlargement of the posterior fossa; hydrocephalus; and torcular-lambdoid inversion. A retrocerebellar arachnoid cyst causes a mass effect on the cerebellum, which was not seen in our patient. Prior ischemic injury could result in hemispheric atrophy, but there was no corresponding history of injury in this patient. The constellation of findings and clinical history in this case are consistent with a diagnosis of PHACE syndrome. Metry et al (3) emphasized that PHACE syndrome represents a spectrum of anomalies, with 70% of children having only one extracutaneous manifestation. The infant in this case had cerebellar hypoplasia, a cerebral artery anomaly, and orbital and periorbital hemangioma.
Burrows et al (8) recognized progressive arterial occlusion and cerebral infarction in five of eight patients with cervicofacial hemangioma and intracranial vascular anomalies. Neurologic symptoms included seizures, hemiparesis, and motor delay (8). The cause of arterial occlusion is not known, but its presence could affect future preventative treatment. In a similar series, Luo et al (9) observed neurologic deficits in four of eight patients with PHACE syndrome and argued that patients with aneurysms should be observed closely and evaluated with three-dimensional computed tomograpic angiography (9). Because some patients may develop progressive arterial occlusive disease, cerebral infarction, and aneurysm with subsequent rupture, radiologists must be aware of PHACE syndrome and carefully search for additional brain anomalies in patients referred for CT and MR imaging of facial hemangiomas. The radiologist may be the first physician to suggest a diagnosis of PHACE syndrome to family physicians and pediatricians who may be less acquainted with this syndrome.
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FOOTNOTES
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| Part one of this case appeared 4 months previously and may contain larger images.
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References
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- Frieden IJ, Reese V, Cohen D. PHACE syndrome: the association of posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities. Arch Dermatol 1996;132:307–311.[Abstract/Free Full Text]
- Burrows PE, Laor T, Paltiel H, Robertson RL. Diagnostic imaging in the evaluation of vascular birthmarks. Dermatol Clin 1998;16(3):455–488.
- Metry DW, Dowd CF, Barkovich AJ, Frieden IJ. The many faces of PHACE syndrome. J Pediatr 2001;139:117–123.[CrossRef][Medline]
- Mulliken JB, Glowacki J. Hamangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics. Plast Reconstr Surg 1982;69:412–420.[Medline]
- Mulliken JB, Fishman SJ, Burrows PE. Vascular anomalies. Curr Probl Surg 2000;37:517–584.[CrossRef][Medline]
- Robertson RL, Robson CD, Barnes PD, Burrows PE. Head and neck vascular anomalies of childhood. Neuroimaging Clin N Am 1999;9:115–132.[Medline]
- Slavotinek AM, Dubovsky E, Dietz HC, Lacbawan F. Report of a child with aortic aneurysm, orofacial clefting, hemangioma, upper sternal defect, and marfanoid features: possible PHACE syndrome. Am J Med Genet 2002;110:283–288.[CrossRef][Medline]
- Burrows PE, Robertson RL, Mulliken JB, et al. Cerebral vasculopathy and neurologic sequelae in infants with cervicofacial hemangioma: report of eight patients. Radiology 1998;207:601–607.[Abstract/Free Full Text]
- Luo CB, Lasjaunias P, Teng MM, Chang FC, Lirng JF, Chang CY. Cervico-cerebrovascular anomalies in children with PHACE syndrome. J Formos Med Assoc 2003;102:379–386.[Medline]
Congratulations to the 150 individuals and four resident groups that submitted the most likely diagnosis (PHACE syndrome) for Diagnosis Please, Case 103. The names and locations of the individuals and resident groups, as submitted, are as follows:
Individual responses
- Hisashi Abe, MD, Osaka, Japan
- Gholamali Afshang, MD, Tinley Park, Ill
- Dr Erhan Akpinar, Ankara, Turkey
- Canan Altay, MD, Balcova, Izmir, Turkey
- Albert J. Alter, Madison, Wis
- Arangasamy Anbarasu, MD, Coventry, United Kingdom
- Rajeev Anugu, MD, Bryn Mawr, Pa
- Asim Kumar Bag, MBBS, Kolkata, West Bengal, India
- Aaron Scott Bailey, MD, San Antonio, Tex
- Ken Baliga, Rockford, Ill
- Gregory J. Balmforth, MD, Tucson, Ariz
- Fabrice Basseau, Tarbes, France
- Michael Lewis Black, MD, Irvine, Calif
- Susan I. Blaser, MD, Toronto, Ontario, Canada
- Eric L. Bressler, MD, Minnetonka, Minn
- Daniel F. Broderick, MD, Jacksonville, Fla
- Douglas C. Brown, MD, Virginia Beach, Va
- Dr Marcelo F. Cabrini, Buenos Aires, Argentina
- Carlos Capiel, Jr, MD, Mar del Plata, Buenos Aires, Argentina
- Luisa F. Cervantes, Miami, Fla
- Kam Wai Chan, Hong Kong, Hong Kong
- Anísio F. Chaves, Maceio, Brazil
- Govind Chavhan, MD, Toronto, Ontario, Canada
- Natesan Chidambaranathan, MD, Chennai, India
- Haris Chrysikopoulos, MD, Kerkyra, Greece
- Ming-Tsung Chuang, MD, Kaohsiung, Taiwan
- Neal R. Conti, MD, Seattle, Wash
- Yves-Sebastien Cordoliani, MD, Paris, France
- Marco Antonio Cura, MD, San Antonio, Tex
- Marc G. de Baets, MD, Lugano, Switzerland
- Peter C. De Baets, MD, Damme, Belgium
- J. F. K. de Villiers, Gisborne, New Zealand
- Jon James De Witte, Bishop, Ga
- Mustafa Kemal Demir, MD, Ataköy, Istanbul, Turkey
- Thaworn Dendumrongsup, MD, Hat Yai, Songkla, Thailand
- Luiz Carlos Donoso Scoppetta, MD, São Paulo, Brazil
- Seyed Emamian, MD, PhD, Rockville, Md
- Juliet H. Fallah, MD, Chicago, Ill
- Shella Farooki, MD, Dublin, Ohio
- Gabriel C. Fernéndez, Vigo, Spain
- Francis Flaherty, MD, Ridgefield, Conn
- Thiago Junqueira Franco, São Paulo, Brazil
- Akira Fujikawa, Tokyo, Japan
- Rajneesh Galwa, Jaipur, India
- Ram Prakash Galwa, Chandigarh, India
- Karthik Ganesan, Mumbai, India
- Douglas Joseph Gardner, MD, Windsor, Ontario, Canada
- William Gawman, MD, Waterloo, Ontario, Canada
- Gilles Genin, MD, Annecy, France
- Mark G. Goldshein, MD, Andover, Mass
- Francisco Jose Gonzalez, MD, Cantabria, Spain
- Dan G. Gridley, MD, Phoenix, Ariz
- Flavius Guglielmo, MD, Basking Ridge, NJ
- Ferris M. Hall, MD, Boston, Mass
- Clare M. Hartigan, MBBCh, Dublin, Ireland
- Andreas Harzheim, MD, Cologne, Germany
- Rufus Womack Head, MD, North Bridgton, Me
- Yuusuke Hirokawa, MD, Kyoto, Japan
- Helen T. Ho, MD, Chicago, Ill
- Ronald J. Homer, MD, Weston, Conn
- Alberto Iaia, MD, Wilmington, Del
- Rajapandian Ilangovan, MD, FRCR, London, United Kingdom
- Kiriakos Kalampoukas, MD, Athens, Greece
- Shinichi Kan, MD, Sagamihara-shi, Kanagawa, Japan
- Katsuhiko Kato, MD, PhD, Nagoya, Japan
- Nurettin Katranci, MD, Antalya, Turkey
- Steven A. Klein, MD, Shrewsbury, Mass
- Mehmet Kocak, MD, Milwaukee, Wis
- Stefanos Lachanis, MD, Athens, Greece
- Alexis Lacout, MD, Paris, France
- Mario Laguna, West Allis, Wis
- Dr Martin Lecompte, Ottawa, Ontario, Canada
- John T. Lim, MD, Newport Coast, Calif
- David A. Lisle, Brisbane, Australia
- Patricia Lowry, MD, Richmond, Va
- Umapathi Mahesh, Sr, MBBS, DMRD, Kerala, India
- Naganathan B. S. Mani, MD, Nassau, Bahamas
- Franklin Marden, MD, Fairfax, Va
- Paulo Mariz Filho, MD, Salvador, Buenos Aires, Brazil
- Michael B. Martin, MD, Austin, Tex
- Waldir Heringer Maymone, MD, Rio de Janeiro, Brazil
- Frank McKowne, MD, Vancouver, Wash
- Rogério Melo, Belo Horizonte, Brazil
- Nikolaos Michailidis, MD, Thessaloniki, Greece
- Mehran Midia, MD, Springfield, Ill
- Manabu Minami, MD, Tsukuba, Ibaraki, Japan
- Jose Mondello, MD, Buenos Aires, Argentina
- Franklin G. Moser, MD, Los Angeles, Calif
- Utaroh Motosugi, MD, Yamanashi, Japan
- Bruno M. Moura de Sousa, Rio de Janeiro, Brazil
- Sugoto Mukherjee, MBBS, Charlottesville, Va
- Tammam Naim Nehme, MD, East Wenatchee, Wash
- Honorio Chiminazzo Neto, Campinas, São Paulo, Brazil
- Hiroshi Nobusawa, MD, Tokyo, Japan
- Laura Oleaga, MD, Bilbao, Spain
- Sanford M. Ornstein, MD, Phoenix, Ariz
- Dr Klaus Orth, Aachen, Germany
- Carlos Ovejero Vela, MD, Barcelona, Spain
- Rajeev Padmanabhan, MBBS, Newcastle upon Tyne, United Kingdom
- Neeraj J. Panchal, MD, San Diego, Calif
- Harish Panicker, MD, Hermitage, Pa
- Narendrakumar P. Patel, MD, Newburgh, NY
- Prakash N. Patel, MD, New City, NY
- Ernesto Oscar Pearson II, MD, Besan
on, France
- Cecilio R. Poyatos, MD, Benimamet, Valencia, Spain
- Henry F. W. Pribram, MD, Laguna Beach, Calif
- Prashant Raghavan, MD, Charlottesville, Va
- Daniel C. Rappaport, MD, FRCPC, Toronto, Ontario, Canada
- Enrique Remartinez Escobar, MD, Melilla, Spain
- Matthew C. Rheinboldt, MD, Nashville, Tenn
- Elisabeth Rivera Codias, Barcelona, Spain
- Mathieu Henri Rodallec, MD, Paris, France
- Marcio Bustamante Sa Rodrigues, MD, Rio de Janeiro, Brazil
- Tsutomu Sakamoto, MD, Tokyo, Japan
- Hatice Tuba Sanal, MD, Ankara, Turkey
- Shilpa S. Sankhe, Bombay, Maharashtra, India
- Steven Schepers, MD, Herent, Belgium
- Janet Scheraga, Syracuse, NY
- Anthony J. Scuderi, Johnstown, Pa
- Matt Shapiro, MD, Charlottesville, Va
- Hideki Shima, MD, Tokyo, Japan
- Taro Shimono, MD, Sakai, Osaka, Japan
- Ken Simmons, Sydney, Australia
- Annemie Snoeckx, MD, Edegem, Belgium
- James D. Sprinkle, Jr, MD, Spotsylvania, Va
- Scott David Steenburg, MD, Mount Pleasant, SC
- Kouichi Sugiyama, Numazu, Japan
- Vinod Sukumaran II, MD, Trivandrum, India
- Venkateswar Rao Surabhi, MBBS, Herndon, Va
- Norio Takahashi, MD, Fukui, Japan
- Eliko Tanaka, MD, Yokohama, Japan
- Sidhartha Tavri, Mumbai, India
- Douglas L. Teich, MD, Brookline, Mass
- Eugene Tong, MD, Austin, Tex
- William C. Torreggiani, MB, Dublin, Ireland
- Dr Özgür Tosun, Bilkent, Ankara, Turkey
- Hiroyuki Ueda, MD, Kyoto, Japan
- Shigeaki Umeoka, MD, Wakayama, Japan
- Eleni Vafeiadou, Thessaloniki, Greece
- Piet Vanhoenacker, MD, Moorsel, Belgium
- Joan C. Vilanova, MD, Girona, Spain
- Christopher P. Vittore, MD, Rockford, Ill
- Jesús Ig. Vivancos, MD, Tenerife, Spain
- Ivan Vollmer, MD, Barcelona, Spain
- Dr Silvio Vollmer, Cipolleti, Rio Negro, Argentina
- Nikolaos Vougiouklis, Kalamaria, Greece
- Edward Williams, Isle of Man, United Kingdom
- Kenneth Dean Williams, MD, San Antonio, Tex
- Joe Yut, Olathe, Kan
- Yu Zhang, San Francisco, Calif
Resident group response
- Trakya University School of Medicine Radiology Residents, Edirne, Turkey
- Kyoto City Hospital Radiology Residents, Kyoto, Japan
- Maine Medical Center Radiology Residents, Portland, Me
- University of Pennsylvania Radiology Residents, Philadelphia, Pa
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TOP
HISTORY
IMAGING FINDINGS
