Keywords
vascular malformation - capillary malformation - venous malformation - lymphatic malformation
- arteriovenous malformation
Vascular anomalies, a group encompassing a wide variety of lesions related to the
disorder of vascular development, remain both diagnostic and treatment challenges
to treating physicians. The terminology used to describe and classify vascular anomalies
is the key for proper diagnosis and treatment. The classification system established
by the International Society for the Study of Vascular Anomalies (ISSVA) is now a
widely accepted system used to categorize vascular anomalies into two types: (1) vasoproliferative
or vascular neoplasms such as hemangioma, and (2) vascular malformations.[1]
The distinction between the two is based on histopathological assessment of increased
cell turnover. Vascular tumors, formerly classified as hemangiomas, are true neoplasms
with pathologic cell proliferation. These tumors typically exhibit rapid postnatal
growth and slow regression into late childhood.[2] Vascular malformations, on the other hand, are comprised of abnormally formed channels
within a vascular apparatus that are lined by endothelial cells and do not undergo
abnormal cellular turnover. They too are congenital in nature, but often go unnoticed
at birth, never regress, and grow proportionally with the individual.[3]
In this article, we will focus solely on vascular malformations, reviewing the basic
nomenclature, etiology, and diagnostic criteria for each subcategory and discussing
treatment options available today. An in-depth review of vascular malformations associated
with known syndromes as well as vascular tumors will be provided in separate articles.
It is important to be able to make accurate diagnosis, understand the basic physiology,
and use appropriate diagnostic and treatment modalities to optimize outcome.
Vascular Malformations
Vascular malformations are grouped together based upon their common embryological
origin of having a single endothelial cell lining.[3] Vascular malformations are thought to result from developmental errors during embryogenesis,
such as abnormal signaling processes that control apoptosis, maturation, and growth
of vascular cells. These errors lead to the persistence of vascular plexus cells with
a certain degree of differentiation.[4] There are four major categories of vascular malformations based on their flow characteristics:
slow-flow (capillary malformation, venous malformation, lymphatic malformation) and
fast-flow (arteriovenous malformation). These lesions often have components of multiple
malformations, such as a mixed lymphatico-venous malformation, further adding to the
confusion with respect to proper nomenclature ([Fig. 1]).
Fig. 1 Mixed lymphatico-venous malformation (LVM) involving lower extremity. (A) Ulceration is an indication for intervention. (B) Axial, contrast-enhanced magnetic resonance image shows both irregular but extensive,
contrast-enhancing lesion indicative of a venous malformation of the lateral thigh
as well as (C) cystic, nonenhancing densities along gluteus muscle and pararectal area indicative
of a lymphatic malformation.
As with any medical or surgical anomaly, accurate diagnosis is paramount to successful
treatment. With vascular malformations, a thorough history and physical exam will
allow the astute physician to make a sound diagnosis for a majority of the clinical
cases presented. Additionally, proper imaging modalities such as ultrasound (US) with
gray scale, color Doppler and spectral Doppler tracings, or magnetic resonance imaging
(MRI) can aid when the diagnosis is in question, as there may be overlap in clinical
appearance in these anomalies.[5] These imaging modalities can assist in confirming particular attributes of the lesion,
defining anatomic locations/boundaries, and planning potential surgical intervention.
In general, the management of vascular malformation is expectant in nature with both
noninvasive and invasive treatment of symptomatic lesions. Lesions located in the
head and neck region, however, require special attention as they can cause obstruction
of critical structures such as the visual axis or the airway ([Fig. 2]).
Fig. 2 Very large lymphatic malformation involving the right head and neck region and compressing
the airway.
Capillary Malformation
Capillary malformations (CMs) affect the capillaries in the papillary dermis and commonly
appear as a macular, pink or purple stain that is present at birth and persists throughout
life.[6] Capillary malformations, found in 0.5% of the population, were initially referred
to as “port-wine stain,” which is inaccurate, but has persisted due to its widespread
use throughout the literature. The majority of CMs appear in the face and tend to
be in the trigeminal nerve distribution, especially ophthalmic (V1) and maxillary
(V2) divisions.[7] Capillary malformations in the V1 or midline distribution should alert physicians
of possible central nervous system (CNS) involvement and warrant imaging studies as
this is highly associated with leptomeningeal involvement and subsequent seizure disorders
(i.e,, Sturge-Weber syndrome).
As the patient progresses into adulthood, the stains tend to darken and thicken into
a “cobblestone” appearance and can distort facial features, including the underlying
bony structures. There is currently no imaging modality needed to assist in diagnosis,
but MRI is strongly recommended to rule out CNS involvement. Positive findings include
gyral enhancement, enlargement and enhancement of ipsilateral choroid plexus, progressive
cortical atrophy and calcification.[8] Cerebral angiography can detect parenchymal contrast stasis and abnormal cortical
veins associated with CNS involvement.
The majority of treatment modalities are ablative in nature, such as the pulsed-dye
laser (580–595 nm).[9] Significant improvement in the color of the stain can be seen when laser treatment
is begun in infancy and when applied to CMs of the lateral face. Noticeable lightening
is typically seen in greater than 75% of patients. Better results are achieved when
therapy is initiated early, thus it is recommended that treatment commence before
6 months of age. Surgery is reserved for lesions that are refractory to ablative treatment
or are causing significant disfigurement ([Fig. 3]).[10]
Fig. 3 A 19-year-old man with a capillary malformation in V1 and V2 distribution, status
post-serial laser treatments, lip debulking, and excision of redundant tissue through
alar and upper lip incision.
Venous Malformations
Venous malformations (VMs), like other vascular malformations, are present at birth.
They are the most common type of vascular malformation, affecting 1% to 4% of individuals,
and clinically appear as a bluish, soft, compressible lesions typically found on the
face, limbs, or trunk ([Fig. 4]). Venous malformations are composed of masses of veins and venulae of different
dimensions lined by a single endothelial layer.[6] Venous malformations are dependent lesions, meaning that they expand and contract
based on patient positioning. They tend to grow proportionally with the child and
often increase in size with puberty, hormonal changes, or infection.[11] They show a predisposition to thrombosis, forming phleboliths, which are pathognomonic
of VM and are diagnostic on imaging studies. Phleboliths are intralesional calcifications
formed as a result of venous stasis and inflammation.[12]
Fig. 4 Various manifestations of localized venous malformations. Venous malformations are
bluish, soft, compressible lesions typically found on the (A,B) face, (C) limbs, or trunk.
Although US and color Doppler are first-line modalities for diagnosis, showing low
flow lesions with phleboliths, MRI is most useful for defining the extent of the disease.[13] Angiography is also a useful modality for defining extent of disease, especially
when identifying deep or small VMs, such as intracranial sinus pericranii or gastrointestinal
VM, as traditional MRI and magnetic resonance angiography (MRA) is not as sensitive
in identifying these lesions.[14] Beyond imaging, it is sometimes prudent to obtain a coagulation profile if the patient
has a large VM given the risk for localized intravascular coagulopathy.[15]
Treatment options for VM depend on both the extent of the lesion and the location.
Typically, functional or aesthetic limitations will drive the initiation of therapy.
Interventional radiology can deliver primary treatment such as staged sclerotherapy
and embolization, or play a supportive role with pre- or intraoperative embolization.
Sclerotherapy with absolute ethanol is effective for treatment of large, extensive
VMs, but should be used with caution as it can damage nerves, cause skin necrosis,
and induce systemic toxicity.[16]
[17] Other common sclerosants used include 3% sodium tetradecyl sulfate (STS) and bleomycin.
Surgery is rarely first-line therapy, but may be considered in select situations,
such as (1) to ligate efferent veins to improve the results with sclerotherapy, (2)
to remove residual VM after sclerotherapy, (3) to remove lesion resistant to sclerotherapy,
or (4) localized lesion amenable to complete excision ([Fig. 5]).[18] It is important to recognize that resection can be arduous and technically demanding;
thus, it should not be undertaken without a thorough discussion of all operative risks.
Fig. 5 Venous malformation involving a volar forearm. (A,B) Magnetic resonance imaging (coronal and axial views) shows a contrast-enhancing
lesion. (C) Clinically, the mass was bluish, soft, and compressible. (D) Pathologic examination confirmed this mass to be a venous malformation.
Lymphatic Malformation
Lymphatic malformations (LMs) are vascular channels, pouches, or vesicles filled with
lymphatic fluid with a single endothelial cell lining, 75% of which occur in the cervicofacial
region ([Fig. 6]). They were referred to as “lymphangioma” in the past, which is a misnomer because
LMs lack cellular hyperplasia. Lymphatic malformations are categorized by the size
of the lymphatic chamber: macrocystic (> 2 cm), microcystic (< 2 cm), or mixed. Lymphatic
malformations never regress yet expand and contract based on the amount of lymphatic
fluid present and the presence of bleeding or inflammation.[6] These lesions are often evident at birth and appear as small, crimson dome-shaped
nodules as a result of intralesional bleeding. Many macrocystic LMs can enlarge significantly
leading to distortion of anatomy, especially of the soft tissues and bones of the
face. Along with tissue distortion, frequent bouts of bleeding and cellulitis will
dictate the need for intervention.
Fig. 6 A 4-year-old boy with lymphatic malformations (LMs) involving the chin, tongue, and
sublingual spaces. (A) Ultrasound shows avascular, cystic soft tissue masses consistent with an LM. (B) Axial and (C) sagittal views of contrast-enhanced magnetic resonance imaging show a nonenhancing
bilobed chin mass as well as a multispacial lesion involving the tongue and sublingual
spaces.
Most cases of LM are clinically obvious and require no imaging for diagnosis. When
a diagnosis is not so clear, imaging modalities such as US and color flow Doppler
are particularly useful in establishing a diagnosis.[5] Ultrasound is performed to identify the characteristic cystic appearance of these
lesions. Magnetic resonance imaging is helpful not only in diagnosis, but also for
evaluating the extent of the disease. Classic appearance on MRI is mild enhancement
of the septae and walls, which creates a characteristic enhancement pattern of rings
and arcs. Magnetic resonance imaging is also useful in distinguishing microcystic
versus macrocystic lesions as therapeutic modalities differ between the two.[14]
Treatment options for LM begin with expectant management of symptomatic lesions, such
as pain control and compression for intralesional bleeding and antibiotics for infection,
which can often be life threatening. Sclerosants are first-line therapy with options
such as absolute ethanol, doxycycline, STS, or picibanil (OK-432).[19] These agents cause irreversible damage to the endothelium, inducing local inflammation
and ultimately fibrosis. The only potentially curative modality is surgical resection.
The goals of resection focus on gross debulking of defined anatomic field, limiting
blood loss, and minimizing damage to surrounding structures ([Fig. 7]). It is important to remember that complete resection is typically not possible
as remaining channels will regenerate and extensive radical resection is typically
performed at the expense of surrounding normal structures.[20]
[21]
Fig. 7 A 4-year-old boy with lymphatic malformation involving the (A,B) chin, (C,D) status postradical resection.
Arteriovenous Malformation
Arteriovenous Malformation
Arteriovenous malformations (AVM) represent a class of vascular malformations that
develop from an identifiable source vessel called the “nidus,” which conducts an abnormal
connection of arterial and venous systems.[22] This type of shunt is usually present at birth, but does not become apparent until
the first or second decade of life. Arteriovenous malformations may be slightly compressible
and pulsatile with a palpable thrill. This type of lesion is most commonly found intracranially
and can expand in response to certain stimuli such as trauma or puberty. Clinically,
AVMs can appear in soft tissues or bone and are typically not accompanied by pain,
but rather frequent episodes of bleeding.[23] These lesions have a reliable natural history comprised of four distinct stages:
quiescent, growing, symptomatic, and decompensating.[24]
Imaging plays an important role in the diagnosis of an AVM, but more so in operative
planning. As with other vascular malformations, US and MRI can identify high flow
patterns as well as determine the extent of the lesion. Lesions are often multispacial
and hypervascular on color Doppler US. Magnetic resonance imaging is especially useful
in defining the extent of AVMs, and typically shows numerous flow voids and hyperintense
signal without an obvious mass.[8] Unlike other vascular malformations, computerized tomography (CT) can be valuable,
especially for bony AVMs. Angiography can also be utilized for defining the feeding
and draining vessels prior to sclerotherapy or surgical intervention.[5]
Treatment of an AVM is based on the concept of obliteration of the nidus as this is
thought to be responsible for the growth of the lesion through recruitment of new
vessels from neighboring regions. Sclerotherapy and embolization remain first-line
options to allow for safer intraoperative resection with less blood loss.[25] Ligation of feeding vessels should never be done as this leads to rapid recruitment
of collaterals and heightens vascularity. When considering resection of an AVM, it
is paramount to realize that these lesions are rarely curable, but rather one should
focus on disease control. Indications for intervention include ischemic pain, recurrent
ulcerations/bleeding, or perturbed cardiac function.[26] Resection of these lesions can create large defects that may require flap coverage
or formal reconstruction and should only be performed if the benefits greatly outweigh
the risks ([Fig. 8]).
Fig. 8 A 12-year-old boy with biopsy-proven right periorbital arteriovenous malformation
(AVM) causing (A) vertical dystopia and proptosis. (B) Angiogram was obtained confirming AVM, but was not amenable to embolization due
to involvement of the ophthalmic artery. (C) Given the bony involvement, CT scan was useful for operative planning. (D) A radical resection was performed with subsequent orbital roof and forehead reconstruction
with alloplast. (E,F) Vertical dystopia and proptosis was improved postoperatively.
Conclusion
Vascular malformations are a source of great concern and anxiety not only for patients
and their families, but also for the treating physicians. Proper identification as
well as multidisciplinary approach is paramount for proper treatment. Understanding
the clinical aspects, tools available for diagnosis, and options for interventions
of each subtype of lesion will enable appropriate care to be provided and results
to be maximized.
