AJR 2003; 181:1041-1048
© American Roentgen Ray Society
Imaging Characteristics of Blue Rubber Bleb Nevus Syndrome
Ara Kassarjian1,2,
Steven J. Fishman3,
Victor L. Fox4 and
Patricia E. Burrows1
1 Department of Radiology, Children's Hospital, 300 Longwood Ave., Boston, MA
02115.
2 Present address: Department of Radiology, Division of Musculoskeletal
Radiology, Massachusetts General Hospital, 15 Parkman St., WACC 515, Boston,
MA 02114.
3 Department of Surgery, Children's Hospital, Boston, MA 02115.
4 Division of Gastroenterology and Nutrition, Children's Hospital, Boston, MA
02115.
Received October 15, 2002;
accepted after revision February 14, 2003.
Address correspondence to A. Kassarjian.
Presented at the annual meeting of the American Roentgen Ray Society,
Washington, DC, May 2000.
Introduction
Blue rubber bleb nevus syndrome is a rare condition that consists of
multiple venous malformations involving several organ systems, particularly
the skin and the gastrointestinal tract. Although the condition was first
described by Gascoyen [1] in
1860, Bean [2] is credited with
naming the syndrome in 1958. Additional cases of blue rubber bleb nevus
syndrome have been sporadically reported during the intervening decades.
However, some cases have shown an autosomal dominant inheritance pattern. The
venous malformations may cause symptoms related to gastrointestinal bleeding
or the effect of the malformations on the surrounding structures. The skin
lesions are usually present at birth, but other lesions, particularly those
that affect the gastrointestinal tract, may become clinically apparent later
[3–5].
We present the imaging findings from eight patients with blue rubber bleb
nevus syndrome who have been evaluated at our institution over the past 8
years and review the patterns of imaging findings in cases previously reported
in the medical literature.
Cutaneous and Musculoskeletal Manifestations
The cutaneous venous malformations of blue rubber bleb nevus syndrome are
usually diagnosed shortly after birth and grow in both number and size as the
child ages. The size and depth of the venous malformations vary widely; some
lesions may extend into underlying muscles, joints, or both
[6].
Typically, venous malformations of the skin are small (1–3 cm) blue
"nipples" or "buttons" that are covered by skin and
feel hard or rubbery (Fig. 1).
The lesions may be painful and are most commonly found on the limbs, trunk,
soles of the feet, and perineum, although any region of the body may be
involved. Also, some patients may have irregular papules or macules that
blanch when compressed as blood is expelled from the venous malformations
[3]. Histologically, the
lesions are characterized by dysplastic venous channels with flat endothelia
and irregularly attenuated walls with deficient smooth-muscle cells
[7].
View larger version (98K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 1. —Photograph of 4-year-old boy with blue rubber bleb nevus
syndrome. On plantar surface of right foot, subcutaneous venous malformations
(arrows) characteristic of blue rubber bleb nevus syndrome are
observed.
|
|
Visual inspection of the skin easily reveals the number, location, and size
of the lesions. Cross-sectional imaging may be needed to assess large
cutaneous or deep lesions and their relationship to underlying structures.
Both sonography and MRI have proven to be valuable tools in confirming the
nature of individual cutaneous venous malformations. Doppler interrogation can
confirm the low-flow nature of the lesions. MRI is the best method to depict
the extent of deep lesions including the degree of involvement of underlying
bones and joints (Fig. 2A,
2B,
2C,
2D).
View larger version (120K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 2A. —2-year-old boy with subcutaneous and intramuscular venous
malformations. Color Doppler sonogram of abdominal wall shows well-defined
hypoechoic mass in anterior wall. Lesion shows flow within large cystic region
(arrow) that represents venous malformation.
|
|
View larger version (137K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 2B. —2-year-old boy with subcutaneous and intramuscular venous
malformations. Axial T2-weighted image of pelvis shows multiple
well-circumscribed strongly hyperintense masses (arrows) in
subcutaneous tissues, muscles, and retroperitoneum. This type of T2 signal is
characteristic of vascular anomalies such as venous malformations.
|
|
View larger version (140K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 2C. —2-year-old boy with subcutaneous and intramuscular venous
malformations. Anteroposterior digital subtraction image of abdomen after
percutaneous injection of contrast material into venous malformation of
abdominal wall shows contrast material pooling in lesion.
|
|
View larger version (79K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 2D. —2-year-old boy with subcutaneous and intramuscular venous
malformations. Axial T2-weighted image of pelvis obtained with fat saturation
shows bilateral parailiac lesions (arrows). Additional lesions can be
seen adjacent to right iliac vessels and along right anterior abdominal wall
(arrowheads). Symmetric iliac location is characteristic for blue
rubber bleb nevus syndrome.
|
|
The venous malformations in blue rubber bleb nevus syndrome may directly or
indirectly cause skeletal abnormalities. The intramuscular lesions can affect
the shape of an adjacent bone by exerting direct pressure, thereby causing a
bowing deformity. In addition, intraarticular and periarticular venous
malformations can significantly affect joint biomechanics and result in
remodeling of the joint or damage to cartilage because of repeated episodes of
hemarthrosis. Radiographic findings in patients with multiple venous
malformations include limb over-growth or undergrowth, abnormal bowing,
coarsened trabeculae, and focal lytic defects or cortical remodeling of bones
[6].
On MRI, the venous malformations show well-defined, often septate lesions
that are isointense relative to the muscle on T1-weighted images and strongly
hyperintense on T2-weighted images
[8]. After IV administration of
contrast material, the lesions show avid homogeneous enhancement (Figs.
3A,
3B,
4A,
4B,
5,
6A,
6B,
6C,
6D). Because they are low-flow
lesions, no abnormal vascular flow voids are present, and flow-sensitive
sequences show no enlarged regional arteries or veins. Thrombi and phleboliths
are common and may appear as small focal signal voids.
View larger version (81K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 3A. —4-year-old boy with intramuscular venous malformations. Axial
T2-weighted image of thighs reveals well-circumscribed, strongly hyperintense
intramuscular venous malformation (arrow) on left thigh.
|
|
View larger version (100K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 4A. —4-year-old boy with intramuscular venous malformations.
Coronal T1-weighted contrast-enhanced image of lower legs shows multiple
well-delineated densely enhancing masses (arrow) in left
gastrocnemius muscle.
|
|
View larger version (102K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 4B. —4-year-old boy with intramuscular venous malformations.
Anteroposterior digital fluoroscopic spot image obtained during percutaneous
injection of contrast material into venous malformation in calf shows small
draining vein.
|
|
View larger version (123K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 6A. —14-year-old girl with mass in forearm and lower
gastrointestinal bleeding. Axial T2-weighted image of forearm shows multiple
strongly hyperintense masses (arrow) displacing muscles
anteriorly.
|
|
View larger version (83K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 6B. —14-year-old girl with mass in forearm and lower
gastrointestinal bleeding. Technetium-99m (99mTc)–labeled RBC
scan shows abnormal pooling of radionuclide in abdomen attributable to
multiple small-bowel venous malformations (arrows).
|
|
View larger version (157K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 6D. —14-year-old girl with mass in forearm and lower
gastrointestinal bleeding. Selective superior mesenteric artery angiogram
obtained during venous phase shows pooling of contrast material in small
bowel, particularly in distal ileum (arrow).
|
|
Findings on intralesional injection of contrast material correlate well
with the MRI findings. The lesions appear as clusters of interconnecting
vascular spaces with minimal or no communication with draining veins, which
contributes to the excellent response of these lesions to sclerosant
injections. On the other hand, scalp lesions may communicate with the dural
sinuses and thus represent a form of sinus pericranii. At our institution,
percutaneous injections are only performed immediately before
sclerotherapy.
Gastrointestinal Manifestations
The gastrointestinal system is involved in all patients with blue rubber
bleb nevus syndrome. The most common site of involvement in our eight
patients, as in the patients in most series, was the small bowel, although in
our study, we found lesions anywhere along the gastrointestinal tract, from
the mouth to the anus. Typically, the gastrointestinal lesions eventually
bleed, requiring administration of iron supplements and often repeated
transfusions throughout a patient's life. Evaluation of gastrointestinal
lesions includes upper and lower gastrointestinal tract endoscopy, barium
studies, nuclear imaging, CT, and MRI.
Barium studies may show polypoid filling defects that indicate the presence
of a polyposis syndrome (Fig.
7A,
7B). The vascular nature of
the lesions cannot be differentiated from other types of polyps solely on the
findings of barium studies. Thus, the differential diagnosis based on barium
studies includes polyposis syndromes such as Peutz-Jeghers, juvenile
polyposis, and Cronkhite-Canada, among others. The polypoid nature of the
lesions makes them a potential lead point for intussusception
[9]. Venous malformations have
even been reported to cause volvulus, infarction, and rectal prolapse
[3,
4].
View larger version (122K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 7A. —2-year-old boy with gastrointestinal bleeding and abdominal
pain. Radiograph obtained with patient supine shows multiple dilated loops of
bowel, indicating bowel obstruction. Suggestion of soft-tissue mass is seen in
right lower quadrant.
|
|
View larger version (107K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 7B. —2-year-old boy with gastrointestinal bleeding and abdominal
pain. Lateral image from barium enema shows abnormal kink in hepatic flexure
with at least one rounded filling defect (black arrow). Residual
contrast material from recent upper gastrointestinal series (white
arrows) is visible.
|
|
Labeled RBC nuclear scans may be used to localize the site of bleeding in
patients who present with gastrointestinal hemorrhage and negative results on
endoscopy. In patients with no active bleeding, the labeled RBC scans may show
pooling of the radionuclide within the venous malformations and thus prompt
further evaluation of the gastrointestinal tract (Fig.
6A,
6B,
6C,
6D). Lesions in other sites
(e.g., the musculoskeletal system) are also shown on labeled RBC scans, making
such scanning a useful total-body screening procedure.
Although CT rarely can show the small- or large-bowel lesions, CT is
commonly used to evaluate patients who have abdominal symptoms related to the
previously discussed complications of the venous malformations, particularly
intussusception. In addition, CT may show phleboliths within some of the
lesions and lesions within solid organs (Fig.
8A,
8B).
View larger version (98K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 8A. —6-year-old boy with abdominal pain. Contrast-enhanced CT scan
of abdomen shows high-grade small-bowel obstruction with multiple dilated
loops of small bowel with air–fluid levels. Tiny foci (arrow)
of calcification can be seen in wall of small-bowel loops, indicating presence
of phleboliths.
|
|
MRI is excellent for revealing lesions in the liver, spleen, and pancreas.
As with intramuscular lesions, solid organ venous malformations are well
defined and isointense on T1-weighted images and are strongly hyperintense on
T2-weighted images. These lesions enhance relatively homogeneously after IV
contrast administration (Figs.
9A,
9B,
9C and
10A,
10B). Such enhancement is
unlike the typical peripheral nodular enhancement with subsequent centripetal
enhancement commonly seen in hemangiomas. Selective visceral angiography is
not generally indicated for these patients, although some lesions may be
identified by the presence of contrast material pooling during the venous
phase.
View larger version (109K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 9B. —4-year-old boy with abdominal pain and gastrointestinal
bleeding. Axial T2-weighted image obtained with fat saturation shows multiple
venous malformations (arrows) in liver. Well-defined strongly
hyperintense nature of lesions is characteristic of vascular lesions.
|
|
View larger version (162K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 9C. —4-year-old boy with abdominal pain and gastrointestinal
bleeding. Intraoperative photograph shows one of subserosal small-bowel venous
malformations (arrow). Multiple similar venous malformations were
found throughout small and large bowels.
|
|
View larger version (107K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 10B. —10-year-old boy with vague abdominal and back pain. Axial
T2-weighted image of abdomen again shows strongly hyperintense masses in
retroperitoneum causing anterior displacement of branches of superior
mesenteric artery (arrow).
|
|
Although upper gastrointestinal and colonic lesions can be directly
visualized on endoscopy, only a limited area of the small bowel can be
completely imaged by peroral push enteroscopy. A new technology, wireless
capsule endoscopy, should be capable of providing complete direct small-bowel
examination in future patients
[10]. At our institution,
patients with significant bowel involvement have undergone laparotomy with
direct visualization and total enteroscopy to localize small-bowel lesions and
to limit the extent of bowel resection (Fig.
11A,
11B). In our series, we found
that noninvasive imaging often led to underestimation of the number of
gastrointestinal lesions.
View larger version (124K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 11B. —35-year-old woman with gastrointestinal bleeding. Endoscopic
sonogram shows submucosal lesion (single solid arrow) in stomach that
extends to but does not penetrate muscularis propria (open arrow).
Probe is indicated by double solid arrows.
|
|
Other Sites of Involvement
Although the skin and the gastrointestinal tract are the two most common
sites of involvement in blue rubber bleb nevus syndrome, any part of the body
may be affected. Among the patients in our study, other sites of involvement
(one patient each) were the vulva, submandibular region, parotid region,
thymus, masticator space, and the cranium (sinus pericranii) (Fig.
12A,
12B). Involvement of the
orbits, thyroid, heart, pericardium, lungs, peritoneal cavity, adrenal glands,
and kidneys has been reported
[3,
4]. Complications such as
hemothorax and hemopericardium have also been described
[3,
4].
View larger version (129K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 12A. —2-year-old boy with venous malformation in masticator space.
Axial contrast-enhanced T1-weighted image of posterior fossa and midface shows
densely enhancing mass in right masticator space (infratemporal fossa),
resulting in anterior bowing of posterior wall of maxillary sinus
(arrow).
|
|
View larger version (136K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 12B. —2-year-old boy with venous malformation in masticator space.
Lateral digital fluoroscopic spot image obtained during percutaneous injection
of scalp lesion shows opacification of sagittal sinus (arrow),
finding that is characteristic of sinus pericranii lesion.
|
|
Although rare, an association between blue rubber bleb nevus syndrome and
other diseases such as medulloblastoma, chronic lymphocytic leukemia,
hypernephroma, and squamous cell carcinoma has been suggested by some
investigators [3,
8]. No such association was
present in the eight patients evaluated at our institution.
Treatment Options
The cutaneous lesions in blue rubber bleb nevus syndrome usually do not
require treatment except for cosmetic purposes. In such cases, treatment
usually consists of neodynium:yttrium–aluminum–garnet laser
therapy. However, repeated treatments are often necessary because the lesions
recur. Larger soft-tissue lesions, particularly those that are symptomatic,
can be treated with direct percutaneous sclerotherapy with substances such as
ethanol or sodium tetradecyl (Figs.
13 and
14).
View larger version (98K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 13. —14-year-old girl with intramuscular, cutaneous, and
gastrointestinal venous malformations. Lateral digital subtraction image
obtained during percutaneous sclerotherapy of intramuscular lesion in forearm
shows pooling of contrast material in lesion.
|
|
View larger version (116K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 14. —9-year-old boy with submandibular venous malformation.
Digital subtraction image obtained during percutaneous injection shows
contrast material pooling in large submandibular venous malformation. Lesion
was subsequently treated with percutaneous sclerotherapy. Submandibular
location and lack of venous outflow are characteristic of lesions seen in blue
rubber bleb nevus syndrome.
|
|
Gastrointestinal lesions in the esophagus, stomach, proximal duodenum, and
colon may be treated with endoscopic band ligation or sclerotherapy.
Perforation is a serious risk with these techniques because the transmural
extension of lesions grossly appears to be mucosal. Small-bowel lesions
require surgical resection or ligation.
To date, published reports of medical therapy using steroids or interferon
alfa-2a have shown no definite benefit
[3]. This result is not
unexpected because lesions in blue rubber bleb nevus syndrome are venous
malformations, not vascular neoplasms (e.g., hemangiomas) and thus would not
be expected to respond to angiogenesis inhibitors. Although there are isolated
reports of medical therapy using corticosteroids, interferon, and
somatostatin, we know of no convincing evidence of durable response has been
presented.
Conclusion
The venous malformations of blue rubber bleb nevus syndrome may involve any
organ system, with cutaneous, musculoskeletal, and gastrointestinal lesions
being the most common. Multiple imaging modalities are often needed to show
all the lesions. MRI accurately shows the musculoskeletal lesions, which have
a fairly consistent appearance. Labeled RBC nuclear scanning is the best
noninvasive method for revealing small-bowel involvement. Imaging is also used
to evaluate complications, particularly those stemming from gastrointestinal
lesions, and to plan appropriate therapy. The presence of multiple discrete
cutaneous, musculoskeletal, hepatic, or gastrointestinal vascular lesions
should suggest the diagnosis of blue rubber bleb nevus syndrome.
Acknowledgments
We thank Jarry Tkacz and Adam Zoga for their help with the images and
manuscript.
References
- Gascoyen M. Case of naevus involving the parotid gland causing
death from suffocation: naevi of the viscera. Trans Pathol Soc
Lond 1860;11:267
- Bean WB. Blue rubber bleb naevi of the skin and gastrointestinal
tract. In: Thomas CC, ed. Vascular spiders and related lesions of
the skin. Spring-field, IL: Thomas, 1958:178
–185
- Boente MD, Cordisco MR, Frontini MD, Asial RA. Blue rubber bleb
nevus (Bean syndrome): evolution of four cases and clinical response to
pharmacological agents. Pediatr Dermatol1999; 16:222
–227[Medline]
- Moodley M, Ramdial P. Blue rubber bleb nevus syndrome: case report
and review of the literature. Pediatrics1993; 92:160
–162[Abstract/Free Full Text]
- Wong YC, Li YW, Chang MH. Gastrointestinal bleeding and paraparesis
in blue rubber bleb nevus syndrome. Pediatr Radiol1994; 24:600
–601[Medline]
- McCarthy JC, Goldberg MJ, Zimbler S. Orthopaedic dysfunction in the
blue rubber bleb nevus syndrome. J Bone Joint Surg Am1982; 64:280
–283[Free Full Text]
- Robinowitz LE, Esterly NB. Blue rubber bleb nevus syndrome. In:
Schachner LA, Hansen RC, eds. Pediatric dermatology,
2nd ed. New York: Churchill Livingstone, 1995:969
–970
- Jorizzo JR, Amparo EG. MR imaging of blue rubber bleb nevus
syndrome. J Comput Assist Tomogr1986; 1:686
–688
- Browne AF, Katz S, Miser J, Boles ET. Blue rubber bleb nevi as a
cause of intussusception. J Pediatr Surg1983; 18:7
–9[Medline]
- Lewis BS, Swain P. Capsule endoscopy in the evaluation of patients
with suspected small intestinal bleeding: results of a pilot study.
Gastrointest Endosc2002; 56:349
–353[Medline]
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. I. Alomari
Vascular Anomalies: Nosologic and Diagnostic Dilemma
Am. J. Roentgenol.,
October 1, 2008;
191(4):
W192 - W192.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. M. Elsayes, C. O. Menias, J. R. Dillman, J. F. Platt, J. M. Willatt, and J. P. Heiken
Vascular Malformation and Hemangiomatosis Syndromes: Spectrum of Imaging Manifestations
Am. J. Roentgenol.,
May 1, 2008;
190(5):
1291 - 1299.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. D. Lee, P. J. Pickhardt, D. V. Gopal, and A. J. Taylor
Venous Malformations Mimicking Multiple Mucosal Polyps on Screening CT Colonography.
Am. J. Roentgenol.,
April 1, 2006;
186(4):
1113 - 1115.
[Full Text]
[PDF]
|
|
|
Top
Introduction
Cutaneous and Musculoskeletal...
