Vascular tumours, malformations and related disorders Flashcards
1
Q
What is PHACE syndrome?
A
A clinical syndrome with the following features:
**P **- posterior fossa malformation = Dandy Walker and cerebellar hypoplasia
**H **- Haemangioma - large segmental
**A **- Arterial anomolies (internal carotid and cerebral arteries)
C - Cardiac anomolies (coarctation of the aorta, ventral and atrial septal defects)
**E **- eye abnormalities (optic atrophy, cataracts, strabismus, exopthalmus)
**S **- Sternal cleft or supraumbillical raphe
2
Q
What is an IH-MAG?
A
A subtype of Infantile haemangioma.
Often fully formed at birth, with minimal further growth
AND minimal tendency to grow above the surface of the skin
Key Features:
○ Reticulated erythema
○ Telangectasia
○ Venules
○ Matte / dull erythema
○ Light and dark area
○ Peripheral bright red papules
○ Dusky erythema
○ Rarely ulcerated
Background of pallor
3
Q
What are the histological features of IH-MAG?
A
○ Moderately dilated small vessles within the superficial dermis
○ Flat endothelial cells ○ Thin wall vessels ○ Positive for GLUT 1 and CD34 ○ NO epidermal atrophy or fibrous tissye
4
Q
Extracutanoeus IH - when to suspect?
A
Multipel (>5) cutaneous IH = risk for liver involvement.
Beard distribution haemangiomas = ass with Laryngeal heamangiomatosis
Midline spine IH = ass with occult spinal dysraphism.
LUMBAR syndrome
PHACES syndromem
5
Q
What are the complications of haemangioma’s?
A
Ulceration - 10% of IHs
**Disfigurement **
Interferance with function
- ocular
- oral
- auricular
- limbs
**Secondary infection **
**Pain **
**Hypothyroidism **
**High output cardiac failure **
6
Q
What is the mechanism of hypothyroidism for infantile haemangiomas?
A
Increased levels of type 3 iodothyronine deiodinase, an enzyme that deactivates thyroid hormone, have been identified in tissue from proliferating hemangiomas.
The consumptive nature of the hypothyroidism often makes it difficult to correct, but it resolves as the tumour regresses
7
Q
What is LUMBAR syndrome?
A
Ass with Large haemangiomas on the lower body, especially extensive seg- mental IHs-MAG
L = Lower body/lumbosacral haemangioma and lipomas or other cutaneous anomalies (e.g. “skin tags”);
U = Urogenital anomalies and ulceration
M = Myelopathy (spinal dysraphism)
B = Bony deformities
A = Anorectal and arterial anomalies
R = Renal anomalies
8
Q
Natural Hx of infantile haemangiomas
A
Usually absent at birth / or subtle precursor lesion evident
**Rapid proliferation **
○ Early proliferation:
§ The majority of haemangiomas reach 80% of their final size by the end of the early proliferative phase, which occurs at a mean age of 3 months, and growth is usually most rapid from 5 to 8 weeks of age
○ Late proliferation
§ The small minority of hemangiomas that grow after 9 months of age tend to have a deep component and/or segmental morphology, and IHs in the parotid gland area are particularly prone to this behavior
Plateau
Involution
○ may begin as early as the first year of life and continues for several years.
○ colour change from bright red to grey– purple
○ flattening of the surface are often the earliest signs of involution in superficial lesions
Classic studies:
§ 30% of lesions involute fully by 3 years of age, 50% by 5 years, 70% by 7 years, and >90% by 9 years
○ Recent studies have concluded that the median age of completed involution is 36 months, with >90% of children showing no further improvement after 4 years of age
○ Some hemangiomas involute completely, while others leave atrophic, fibrofatty, or telangiectatic residua
9
Q
RFs for IHs?
A
Prematurity - RF for multifocal
Low birth weight (independent from prematurity)
Mothers who had CVS or older mothers
Factors associated with placental insufficiency (e.g. preeclampsia, placenta previa)
Multiple gestation pregnancies - RF for mulitfocal IH
10
Q
Subtypes of IH?
A
Superficial
Deep
Mixed
IH-MAG
11
Q
Treatment options for IH
A
1/ Active surveillance
2/ Topical Timolol
3/ Oral Beta-blokcker
- atenolol 1mg/kg/dose BD
- propranolol
4/ PDL 595nm vascular laser (ulceration)
5/ Surgical excision
12
Q
Management of an ulcerated IH?
A
Local wound care
○ Saline solution compresses may be used to gently debride thick crusts,
○ Topical antibiotics such as mupirocin and bacitracin ointment
○ Occlusive dressings
§ Hydrocolloid dressings (e.g. Duoderm®, Duoderm Extra Thin®) and foam dressings (e.g. Mepilex®) are good for intertriginous zones
**Treatment of infection **
○ Swab for culture
○ relatively uncommon
**Specific therapies **
○ Beta Blockers (as above)
○ Pulsed dye laser
§ Some uncontrolled studies demonstrated healing of ulcerations and resolution of pain after two to three treatments1
○ Excisional surgery may be considered for small or pedunculated ulcerated lesions.
○ Application of becaplermin (recombinant platelet-derived growth factor) 0.01% gel has been reported in small series to promote healing of chronically ulcerated IHs
Pain Control
- topical lignocaine gel
13
Q
What is a congential haemangioma?
A
fully developed haemangioma in the immediate Newborn period.
14
Q
What are the subtypes of congenital haemangioma?
A
RICH - rapidly involuting
PICH - partially involuting
NICH - non-involuting
15
Q
What is the mutation that causes congential haemangiomas?
A
GNAQ or GNA11
16
Q
Are congential haemangiomas GLUT + or -?
A
GLUT negative
17
Q
What are the clinical features of a congenital haemangioma?
A
○ a raised violaceous mass with prominent radiating veins,
○ a hemispheric nodule
○ coarse telangiectasias
○ surrounded by a pale rim, or a firm, pink to violaceous plaque
○ often located on the lower extremity
18
Q
What are the histological features of a congential haemangioma?
A
○ striking lobularity with densely fibrotic stroma,
○ stromal hemosiderin deposits,
○ focal thrombosis and sclerosis of capillary lobules,
○ fewer mast cells, and the
○ coexistence of proliferating vasculature with multiple thin-walled vessels.
○ lack immunoreactivity to GLUT1 and Lewis Y antigen
19
Q
How are vascular malformations classified?
A
Capillary malformation
Venous malformation
Arterial malformation
Lymphatic malformation
Ateriovenous malformaiton
20
Q
What is Kasabach Meritt phenomenon?
A
Occurs in the context of a tufted angioma of kaposiform haemangioma
Abnormal endothelium of these tumours causes a **consumptive coagulopathy **
Can also cause high output cardiac failure, internal haemorrhage and 10 - 30% mortality risk
Sudden growth with induration, oedema and advancing purpuric edge
21
Q
What is a naevus Flammeus?
A
A port wine stain
(a type of capillary malformation)
22
Q
What mutation/s causes port wine stains?
A
GNAQ (classic)
PIK3CA (geographic)
23
Q
What syndromes are ass. with port wine stains?
A
Sturg Webber Syndrome
Klippel Trenaunay Syndrome
Parkes Webber Syndrome
Proteus Syndrome
PTEN harmatoma syndromes
Cobb syndrome
Beckweith weidermann syndrome
CM- AVM
24
Q
What causes sturg webber syndrome?
A
Somatic activating mutation in GNAQ
25
Who is at risk of Strug Webber syndrome?
Patients with a capillary malformation affecting the forehead
More extensive CM = higher risk
26
What are the features of Sturg Webber Syndrome?
Ipsilateral leptomeningeal Capillary malformation
Neurologic complications (seizures, developmental delay, interlectual disability, focal neurological deficits)
Opthalmic issues (glaucoma) - occurs in 60%
27
Which conditions are in the PIK3CA related overgrowth spectrum?
Klippel - Trenaunay Syndrome
Macrocephaly capillary malformation syndrome
CLOVES syndrome
Proteus Syndrome
Beckwith Wiedermann syndrome
28
What is Klippel Trenaunay syndrome?
A syndrome caused by PIK3CA mutation - (mTOR pathway)
Characterised by:
- Capillary malformation
- Venous malformation
- Lymphatic malformation
- Soft tissue and/ or bone HYPERTROPHY of onel limb (95% are lower extremities)
29
What are some of the complications of Klippel Trenaunay syndrome?
DVT
Thrombophelebitis
Pulmonary Embolism
GI bleeding
Vascular Blebs
Pain
High output cardiac failure
30
What is macrocephaly capillary malformation syndrome?
A **PIK3CA **syndrome characterised by:
- **Macrocephaly** and frontal bossing
- **Capillary malformation** - widespread, prominently invovling the midface ( **philrum** and **glabella**)
- **Progressive neurological dysfunction** - seizures, developmental delay, hypotonia (polymicrogyria, cerebral assymetry, ventricular megaly, cortical heniation, cortical dysplasia)
- **Syndactyly** -
- increased risk of **Wilms tumour**
31
What is CLOVES syndrome?
A PIK3CA syndrome chacterised by:
- **CLO** - congential lipomatous overgrowth
- **V** - vascular malformation (inc. geographic capillary malformation)
- **E**pidermal naevi
- **S**coliosis or spinal anomolies
Associations:
- Wilms tumour (3 monthly USS until age 8)
- thromboembolic events (PE, CVA)
32
Infantile haemangiomas are GLUT 1 postive
True
33
List 5 benign vascular tumours
Infantile Haemangioma
Congenital Haemangioma
Tufted angioma
Spindle cell haemangioma
Pyogenic granuloma
34
Congenital haemangiomas are more common in girls
False - M = F
35
What is a kaposiform haemangioendothelioma?
Rare, locally aggressive tumour
Histologically similar to kaposi's sarcoma
Present at birth, or early childhood.
Slightly raised, subcut mass with purpuric, bruised appearance and occasionally overlying telangectasias.
Often on the extremities, of unifocal
36
What is Kasabach Merritt Phenomenon?
50 - 70% of patients with Kaposiform haemangioendothelioma develop the Kasabach Merritt phenomenon.
Characterised by:
- rapid enlargement of the vascular malformation
- severe **thrmobocytopaenia **
-** hypofibrinogenaemia**
- microangiopathic **haemolytic anaemia **
- consumptive **coagulopathy **
Also ass with tufted angiomas.
37
What Ix would you do for a kaposiform haemoendothelioma?
FBC
Coagulation profile - inc fibrinogen
+/- Biopsy
+/- MRI
38
What does a kaposiform haemoendothelioma show on Bx?
Irregular sheets of spindle shaped endothelial cells
Slit like vascular channels
Positive stains:
- D2 -40
- LYVE1
- PROX 1, 8
- Negative for GLUT -1
39
Patients with Kasabach Merritt syndorme and thrombocytopaenia need to be given platelets to prevent bleeding
False - often makes things wrose
40
Treatment of Kaposiform haemangioendothelioma with kasabach merritt syndroem?
First Line - Oral Sirolimus
Second line - Vincristine and Sysemic steroids
Third line - surgical excision, embolisation
41
What is a tufted angioma?
**A vascular tumour** - characterised by dermal capillary tufts on histology.
Characterised by:
- red, pink, violaceous or blue papule or plaque or nodule
- overlying hypertrichosis or hyperhidrosis is common
- can be painful
- Will thicken and become indurated overtime
only 10% of tufted angiomas develop kasabach merrit syndrome
42
What is a pyogenic granuloma?
A common, benign, vascular tumour
Children > Adults
43
Treatment of a pyogenic granuloma?
Surgical excision
Curette and Cautery
PDL
CO2 laser
44
Treatment of a tufted angioma?
Observation
Surgical exicsion
Oral sirolimus if develops kasabach Merritt phenomenon
45
Key features?
Round to spindled epithelial cells
Many tightly compressed small vascular channels
Entrapped erythrocytes / fragments of red cells
Cannon balls in the dermis
Immunostains to confirm:
- CD 31
- CD 61 (platelets)
Dx: kaposiform haemangioendothelioma
DDx: tufted angioma
46
Describe?
Papule
w Epidermal collarete
Loss of epidermis above
Appearance similar to granulation tissue.
Small vasular channels
Ulcerated
+/- Neutrophils
47
What is proteus syndrome?
Syndrome caused by a mutation in the AKT1 gene
Clinical features:
- **asymmetrical, progressive, disproportionate, severly deforming overgrowth **of body parts with bony hypertrophy,
- disregulated adipose tissue
- vascular malformations (CM, VM, LM)
- increased tumour risk
- Epidermal naevi
**Cerebriform connective tissue thickening** on the palms and soles
48
What are vascular malformations?
Congenital errors in vascular development that persist and grow in proportion to the patient.
49
How do vascular malformations differ from infantile hemangiomas?
Vascular malformations are present at birth and remain stable, while hemangiomas proliferate then involute.
50
What are the ISSVA categories of vascular malformations?
Capillary, venous, lymphatic, arteriovenous, and combined malformations.
51
What examples fall under capillary malformations?
Port wine stains, nevus simplex, and telangiectasias.
52
Which mutation is most commonly associated with port wine stains?
A somatic activating mutation in GNAQ (occasionally GNA11).
53
How do port wine stains typically appear?
Well-demarcated red to purple patches that may thicken or develop nodularity over time.
54
What is the typical appearance of venous malformations (VMs)?
Soft, compressible, blue lesions that enlarge with dependency.
55
What genes are commonly mutated in VMs?
Often TEK (TIE2) mutations and sometimes PIK3CA mutations.
56
How do glomuvenous malformations differ from common VMs?
They are painful, partially compressible lesions resulting from GLMN mutations.
57
What are the two main types of lymphatic malformations?
Macrocystic (cystic hygroma) and microcystic (lymphangioma circumscriptum).
58
Which mutation is most frequently seen in lymphatic malformations?
Activating mutations in PIK3CA.
59
What defines an arteriovenous malformation?
A high-flow lesion with direct artery-to-vein shunting that may lead to high-output cardiac failure.
60
What are the Schobinger stages of AVMs?
Stage 1: quiescent; Stage 2: expansion; Stage 3: destruction; Stage 4: cardiac decompensation.
61
Which mutation is most commonly involved in AVMs?
Frequently MAP2K1; less commonly KRAS, NRAS, or BRAF mutations.
62
What conditions are part of the PIK3CA-Related Overgrowth Spectrum (PROS)?
Klippel–Trenaunay syndrome, CLOVES, Megalencephaly–CM, and CLAPO syndrome.
63
What is the first-line treatment for port wine stains?
Pulsed dye laser (PDL) therapy.
64
How are venous malformations managed?
With sclerotherapy, surgical excision, compression garments, and sometimes anticoagulation (e.g., low-dose aspirin).
65
How are macrocystic lymphatic malformations typically treated?
Percutaneous sclerotherapy; microcystic forms may need surgery or laser.
66
Why is genetic testing useful in vascular malformations?
It confirms the diagnosis and guides targeted therapy decisions.
67
What are the hallmark features of Sturge–Weber syndrome?
Facial port wine stain with leptomeningeal and ocular vascular anomalies due to GNAQ mutation.
68
What characterizes HHT?
Autosomal dominant telangiectasias and AVMs with ENG or ACVRL1 mutations, leading to recurrent epistaxis and visceral bleeding.
69
What is important to consider in the differential diagnosis of vascular malformations?
Distinguishing them from vascular tumors like infantile hemangiomas and nonvascular lesions (e.g., cysts, lipomas).
70
What are arteriovenous malformations?
Fast‐flow vascular malformations with direct arteriovenous shunting that form a nidus; rare and among the most dangerous vascular anomalies.
71
What is the purpose of Schobinger staging in AVMs?
To classify AVMs by clinical severity and guide management.
72
What characterizes Stage 1 AVMs?
Quiescent/dormant lesions: macular or slightly infiltrated, red, warm, mimicking capillary malformations.
73
What does Stage 2 AVM present as?
Expanding masses with throbbing, palpable thrills, and dilated draining veins.
74
What features define Stage 3 AVMs?
Destruction: necrosis, hemorrhage, ulceration, and sometimes lytic bone lesions (with stage 2 findings).
75
What is seen in Stage 4 AVMs?
Cardiac decompensation, combined with features of stages 2 and/or 3.
76
Which genetic mutations are most commonly associated with AVMs?
Somatic activating mutations in MAP2K1; less commonly in KRAS, NRAS, or BRAF.
77
How can early-stage AVMs be distinguished from capillary malformations?
They exhibit heterogeneous color intensity, peripheral pallor, sharply demarcated “archipelago‐like” borders, warmth, soft tissue swelling, and prominent veins.
78
Where are AVMs most frequently located and what factors worsen them?
Approximately 70% are cephalic; puberty, pregnancy, and trauma can worsen their presentation.
79
What complications can occur with Stage 3 cephalic AVMs?
They can be disfiguring, function- or life-threatening—potentially requiring amputation—and multifocal AVMs may lead to cardiac overload and distal ischemia.
80
What does Stewart–Bluefarb syndrome represent?
Acroangiodermatitis (pseudo-Kaposi sarcoma) associated with an AVM of the lower extremity.
81
What are the key features of Cobb syndrome?
A rare condition with segmental cutaneous, intraspinal (intramedullary/meningeal), and vertebral AVMs; often presents as red–brown birthmarks and leads to neurologic deficits in young adulthood.
82
How does Bonnet–Dechaume–Blanc syndrome present?
A segmental AVM extending from the craniofacial region to the orbit/brain; may cause seizures, hemiparesis/hemiplegia, and visual disturbances—with brain AVMs commonly involving the chiasm, choroid plexus, or thalamus.
83
What distinguishes Parkes Weber syndrome?
A fast-flow syndrome with limb overgrowth due to AV fistulae, along with red capillary malformations, excess fat, and lymphatic anomalies; often associated with RASA1/EPHB4 mutations and a poor prognosis after puberty.
84
What characterizes capillary malformation–arteriovenous malformation (CM-AVM) syndrome?
An autosomal dominant disorder (due to RASA1 or less commonly EPHB4 mutations) with multiple small, scattered pink to red–brown macules (often with blanched borders and hypotrichosis) that may represent incipient AVMs; can include CNS involvement.
85
What are the vascular features of PTEN hamartoma tumor syndrome?
Multifocal, intramuscular fast-flow AVMs (renamed PTEN hamartomas of soft tissue) with associated ectopic fat dilation, plus mucocutaneous lesions; part of a syndrome with macrocephaly and a predisposition to certain malignancies.
86
Which imaging modalities are used in AVMs and why?
Ultrasonography (for flow dynamics and extent) and MRI (for lesion delineation and tissue involvement).
87
What clinical clues help differentiate an early-stage AVM from a capillary malformation?
Heterogeneous color saturation, peripheral pallor, sharply demarcated “archipelago‐like” borders, warmth, and associated soft tissue swelling with prominent veins.
88
What complications may occur with multifocal AVMs in an extremity?
Cardiac overload and distal ischemia.
89
Why can arterial/venous ligatures or proximal embolization be problematic in AVMs?
They may precipitate complications by encouraging recruitment of adjacent vessels and worsening the lesion.
90
What neurologic symptoms are associated with Cobb syndrome?
Symptoms range from back pain and radiculalgia to bladder/rectal dysfunction and paraparesis/paraplegia.
91
What characterizes Bonnet–Dechaume–Blanc syndrome?
A segmental AVM extending from the craniofacial region to the orbit/brain; brain involvement can lead to seizures, hemiparesis/hemiplegia, and even cerebral hemorrhage.
92
How is Parkes Weber syndrome distinguished from other malformations?
It is a fast-flow syndrome with limb overgrowth due to arteriovenous fistulae and is associated with lytic bone lesions and potential cardiac failure, often linked to RASA1 or EPHB4 mutations with an additional “second hit.”
93
What are the typical cutaneous findings in CM-AVM syndrome?
Multiple small pink to red–brown macules, often with narrow blanched borders and sometimes warmer than adjacent skin; Doppler may reveal decreased peripheral resistance.
94
What CNS complications may be seen in CM-AVM syndrome?
Intracranial or intraspinal AVMs that can present with headaches, seizures, and sensorimotor deficits.
95
What vascular and cutaneous features are seen in PTEN hamartoma tumor syndrome?
Multifocal intramuscular fast-flow AVMs with ectopic fat deposition (renamed PTEN hamartomas of soft tissue), macrocephaly, and mucocutaneous lesions (eg, tricholemmomas, neuromas), along with an increased cancer risk.
96
What are the key histologic features of capillary malformations (CMs)?
CMs consist of ectatic (dilated) capillaries in both the papillary and reticular dermis, lined by a flat, continuous endothelium.
97
How do capillary malformations change histologically over time?
They may gradually thicken due to a progressive increase in capillary diameter, dermal and subcutaneous involvement, fibrosis, and occasionally the presence of venous channels in the subcutis.
98
Describe the histologic appearance of venous malformations (VMs).
VMs are characterized by large, convoluted, interconnected venous channels that dissect normal connective tissue and muscle.
99
What specific histologic features are often seen in venous malformations?
They commonly show organized thrombi, phleboliths (round calcifications), and intravascular papillary endothelial hyperplasia. The vessels have a continuous flat endothelium with a thin basement membrane, and their walls display discontinuous media due to focal absence of smooth muscle cells.
100
What are phleboliths, and in which vascular anomaly are they typically found?
Phleboliths are round calcifications resulting from organized thrombi, typically observed in venous malformations.
101
What are the histologic features of microcystic lymphatic malformations?
They show enlarged, distorted, irregular lymphatic channels with very thin endothelium and variable numbers of smooth muscle cells. Larger vessels may have valves, and the channels are usually separated by fibrous septa; hyperkeratotic epidermis may cover clusters of dermal lymphatic vesicles.
102
What distinguishes macrocystic lymphatic malformations histologically?
They consist of large lymphatic cisterns, often interconnected with thinner channels. The cysts usually contain watery fluid with lymphocytes and macrophages, and hemorrhage may be present.
103
Which immunohistochemical markers are used to identify lymphatic endothelium?
Podoplanin, LYVE‐1, and Prox1.
104
What are the key histological features of arteriovenous malformations (AVMs)?
AVMs have irregularly thickened vessel walls, are randomly distributed in the dermis and deeper tissues, and show direct communications between vessels with different elastic properties (arteries and veins).
105
What additional histologic feature is often seen in AVMs?
An obvious capillary component with a lobular architecture in the overlying papillary dermis.
106
What does direct communication between vessels in AVMs indicate?
It indicates abnormal arteriovenous shunting, bypassing the usual capillary network.
107
How does the distribution of smooth muscle cells differ in venous versus lymphatic malformations?
In venous malformations, the vessel walls show discontinuous media with focal absence of smooth muscle cells, whereas microcystic lymphatic malformations show a variable number of smooth muscle cells within their walls.
108
Which feature best distinguishes capillary malformations from venous malformations histologically?
A. Capillary malformations display ectatic capillaries with a continuous endothelial lining, whereas venous malformations show large venous channels with discontinuous smooth muscle layers.
B. Capillary malformations contain phleboliths; venous malformations do not.
C. Capillary malformations have organized thrombi; venous malformations lack thrombi.
D. Capillary malformations demonstrate direct arteriovenous communications; venous malformations do not.
A: Capillary malformations feature ectatic capillaries with a continuous endothelial lining, while venous malformations show large, irregular venous channels with discontinuous smooth muscle.
109
Phleboliths, commonly seen in venous malformations, represent:
A. Clusters of lymphatic vesicles
B. Calcified thrombi within venous channels
C. Foci of intravascular papillary endothelial hyperplasia
D. Areas of focal hemorrhage in AVMs
B: Phleboliths are calcified thrombi typically found within venous malformations.
110
An additional finding often observed in the overlying papillary dermis of an AVM is:
A. Lobular capillary proliferation
B. Dense lymphocytic infiltrate
C. Hyperkeratosis with excessive melanin deposition
D. Granulomatous inflammation
A: A lobular capillary component is often present in the overlying papillary dermis of AVMs.
111
Arteriovenous malformations (AVMs) are histologically defined by:
A. Being composed solely of dilated capillaries
B. Irregularly thickened vessel walls with direct communications (shunting) between arteries and veins
C. Consisting primarily of lymphatic vessels with valves
D. Organized arrays of venous channels with intact muscular layers
AVMs have irregularly thickened vessel walls with direct communications between arteries and veins.
112
Macrocystic lymphatic malformations are best described as:
A. Numerous small vesicles in the dermis
B. Large lymphatic cisterns often interconnected with thinner channels, containing watery fluid, lymphocytes, and macrophages
C. Dense vascular proliferation in the papillary dermis
D. A random arrangement of arteries and veins
B: They are composed of large lymphatic cisterns, often with interconnecting thinner channels, containing watery fluid with lymphocytes and macrophages (and sometimes hemorrhage).
113
Which dermatologic lesions can mimic capillary malformations (CMs)?
Erythematous lesions seen in lupus erythematosus, plaque-type angiofibromas, telangiectasia macularis eruptiva perstans, and other telangiectatic conditions.
114
What condition may be mistaken for a venous malformation due to its deep blue color?
Dermal melanocytosis, which can be misdiagnosed as a venous malformation (VM).
115
Which masses beneath normal skin in infants and children can be erroneously diagnosed as macrocystic lymphatic malformations?
Lipoblastoma, teratoma, bronchogenic cyst, branchial cleft cyst, thyroglossal duct cyst, myofibroma, rhabdomyosarcoma, and fibrosarcoma.
116
What acquired condition can imitate a lymphatic malformation?
Acquired cutaneous lymphangiectasia, which can develop in a variety of settings.
117
What factors determine the treatment choice for lymphatic malformations?
The type (macrocystic vs. microcystic) and extent of the LM.
118
What is the preferred treatment for macrocystic lymphatic malformations?
Percutaneous sclerotherapy using agents such as OK-432 (picibanil), Ethibloc®, sodium tetradecyl sulfate, ethanol, doxycycline, or bleomycin.
119
How does sclerotherapy treat macrocystic LMs?
It induces an inflammatory reaction that leads to fibrosis and shrinkage of the cysts, often requiring repeated treatments.
120
What is the next step if sclerotherapy for a macrocystic LM fails?
Surgical excision may be employed if sclerotherapy yields incomplete results.
121
What is the treatment of choice for microcystic lymphatic malformations?
Surgical excision (direct closure, or with skin grafts/tissue expanders), though incomplete excision is common due to functional concerns or underestimating extent.
122
Which therapies are often combined with surgery for microcystic LMs?
Laser therapy (CO₂, Nd:YAG, diode), radiofrequency ablation, cryoablation, and sclerosants; topical sirolimus can help reduce vesicle volume, leakage, and bleeding.
123
What management consideration is important for microcystic LMs of the tongue and floor of the mouth?
They are particularly difficult to treat, so meticulous dental hygiene and specialized care are essential.
124
What is the typical treatment for transient inflammatory swelling of LMs?
NSAIDs, corticosteroids, and/or antibiotics.
125
What additional supportive measures may benefit patients with complex lymphatic anomalies?
Replacement of albumin and immunoglobulins, and a low-fat diet with long-chain fatty acids substituted by medium-chain fatty acids for cases with intestinal lymphangiectasia.
126
Which systemic agents are used in treating LMs, GLA, or Gorham–Stout disease?
Oral sirolimus has been used successfully; additionally, PI3K inhibition with alpelisib is a promising strategy. Sildenafil may help large LMs (with variable outcomes), and zoledronate can benefit osteolysis in Gorham–Stout disease.
127
What is the treatment strategy for cephalic venous malformations?
Multiple sclerotherapy procedures over years combined with surgical excision to maintain facial symmetry, preserve muscular function, and restore smile dynamics.
128
How are limb venous malformations typically managed?
They may be treated with sclerotherapy and resection if feasible; however, many are too extensive, so elastic compression garments are used to reduce swelling and pain.
129
Which agents are used to manage chronic coagulopathy in venous malformations?
Low-molecular-weight heparin (especially before surgery and during painful thrombotic events) and low-dose aspirin (3–5 mg/kg/day, up to 81 mg/day) for mild cases.
130
How do oral sirolimus and alpelisib benefit patients with venous malformations?
They improve the associated coagulopathy and reduce lesion size and pain; sirolimus is particularly effective in combined lesions with a lymphatic component.
131
What are the primary goals when treating venous malformations?
To minimize disfigurement by maintaining facial symmetry, preserve function (especially muscular and smile dynamics), and alleviate pain and swelling.
132
What is the treatment of choice for PWBs and telangiectasias?
Pulsed dye laser (PDL) therapy.
133
When should PDL treatment ideally begin for facial PWBs, and why?
Early in life, to reduce psychosocial impact and prevent lesional thickening.
134
What are the common side effects of PDL treatment, and how do skin phototypes influence them?
Temporary purpura with low risk of hypo-/hyperpigmentation and scarring; darker skin (e.g., phototype V) may experience more pigmentary changes but can still respond well.
135
What modifications are recommended for PDL in infants?
Use a longer wavelength, increased pulse duration, higher fluence (11–12 J/cm²), dynamic cooling spray, and topical anesthetic to reduce the need for general anesthesia.
136
What long-term trend has been observed in facial PWBs treated with classic PDL?
About one-third of lesions redarken over a median 10-year follow-up, though earlier treatment tends to lower relapse rates.
137
What potential complications can develop if PDL treatment is delayed in PWBs?
Facial and gingival PWBs may develop hyperplastic changes requiring additional dermatologic (e.g., dermabrasion), orthodontic, and surgical interventions (e.g., to correct open-bite deformities and macrocheilia).
138
Which alternative laser therapies may be useful for PWBs resistant to PDL?
Alexandrite or Nd:YAG lasers may be effective alternatives.
139
How might topical sirolimus enhance PDL treatment in PWBs?
When combined with PDL, topical sirolimus may provide additional benefits by reducing lesion size and improving clearance.
140
What is the cornerstone of seizure management in Sturge–Weber syndrome?
Anticonvulsants are the mainstay, with surgical intervention in select severe cases.
141
What additional treatments are important for SWS management besides anticonvulsants?
Low-dose aspirin (3–5 mg/kg), oral sirolimus for uncontrolled seizures and cognitive improvement, appropriate glaucoma management, and psychological counseling.
142
What is the recommended treatment for stage 2–3 AVMs of the head and neck?
Complete excision after careful preoperative embolization (using arterial and/or direct puncture techniques) to minimize intraoperative bleeding, often with reconstruction via skin grafting, tissue expansion, and free tissue transfer.
143
Why is subtotal excision of an AVM problematic?
It frequently leads to progression by recruiting adjacent vessels and prompting angiogenesis, ultimately worsening the lesion.
144
How are stage 1 and early stage 2 AVMs typically managed?
They are often managed conservatively if surgery might produce suboptimal cosmetic results—but early resection can prevent further progression.
145
Can embolization alone cure superficial AVMs?
No; although embolization (often with pure ethanol) can be life-saving in bleeding AVMs, it generally cannot cure superficial AVMs and carries significant risks like renal/pulmonary toxicity and cardiac arrest.
146
What are the challenges in treating distal hand or foot AVMs with embolotherapy?
They are rarely controlled long-term by embolotherapy, and ischemic complications (extreme pain, necrosis, bleeding) may eventually necessitate amputation.
147
Which alternative treatment showed a sustained improvement for a diffuse AVM in a young patient?
A metalloproteinase inhibitor (Marimastat®) with antiangiogenic effects was used successfully over 12 years, including reconstruction of affected bones.
148
How was trametinib employed in AVM management?
Trametinib, a MEK inhibitor, proved beneficial in a child with a large, progressive truncal MAP2K1-related AVM and in a young woman with cardiac compromise from CM-AVM syndrome.
149
What is the main goal of preoperative embolization in AVM surgery?
To reduce the risk of excessive intraoperative bleeding and facilitate complete excision.
150
Why is complete resection generally preferred for advanced head and neck AVMs?
Because incomplete (subtotal) excision leads to lesion recurrence and progression, while complete resection prevents the recruitment of new vessels.
151
Under what circumstances might conservative management be chosen for AVMs?
For early-stage AVMs when anticipated postsurgical cosmetic results might be worse than the lesion, though careful balance is required to prevent progression.
152
How should combined vascular malformations in a limb be managed?
They require an individualized management plan—integrating both vascular and orthopedic evaluations—tailored to the lesion’s type, extent, and the patient’s growth status.
153
What is the role of longitudinal orthopedic evaluation in patients with limb overgrowth disorders?
It is essential for lower extremity lesions in growing children to monitor and manage leg-length discrepancies and other skeletal issues.
154
How does epiphysiodesis impact leg-length discrepancy in Klippel–Trenaunay syndrome (KTS) compared to Parkes Weber syndrome?
In KTS, carefully timed epiphysiodesis before growth cessation can correct leg-length discrepancies; in Parkes Weber syndrome, it may worsen the underlying vascular disease.
155
What conservative measures are indispensable for managing limb combined malformations?
Use of elastic support garments and a compensatory shoe-lift helps reduce swelling and improve limb function when surgeries are not feasible.
156
What is alpelisib and what outcomes has it demonstrated in PROS patients?
Alpelisib is a PI3K inhibitor, FDA-approved for patients ≥2 years with severe PROS manifestations. In a retrospective study of 32 patients, 24 weeks of treatment yielded improvement in vascular malformations (79%), overgrowth (74%), with 38% achieving a ≥20% reduction in lesion volume.
157
Which targeted therapy has shown benefit in treating Proteus syndrome and what are its effects?
Miransertib, an oral AKT inhibitor, has led to stabilization of overgrowth and improvement in pain in patients with Proteus syndrome.
158
What is Hereditary Hemorrhagic Telangiectasia (HHT) and what are its hallmark features?
HHT (Osler–Weber–Rendu disease) is an autosomal dominant disorder characterized by visceral arteriovenous malformations (AVMs) and mucocutaneous telangiectasias that tend to bleed.
159
Which genes are commonly mutated in classic HHT?
HHT is most often caused by heterozygous mutations in ENG (endoglin; HHT1) or ACVRL1 (ALK1; HHT2), which encode TGF-β receptor components.
160
What are the typical clinical manifestations of HHT?
The first sign is usually epistaxis during childhood/adolescence (mean age ~12), with mucocutaneous telangiectasias often appearing after puberty.
161
Why is screening for visceral AVMs important in suspected HHT?
Many visceral AVMs (especially in the lungs, brain, and liver) can be asymptomatic yet predispose to life‐threatening complications such as hypoxemia, intracranial hemorrhage, paradoxical emboli, and high‐output heart failure.
162
What differences exist between HHT1 and HHT2 in terms of AVM risk?
HHT1 (ENG mutations) has a higher risk of pulmonary and cerebral AVMs, whereas HHT2 (ACVRL1 mutations) is more associated with liver AVMs. Rare cases may involve GDF2 or SMAD4 mutations.
163
What is Ataxia–Telangiectasia and which gene is affected?
It is an autosomal recessive disorder due to mutations in the ATM gene, presenting with early ataxia and later telangiectasias.
164
What are the key clinical features of ataxia–telangiectasia?
Early onset ataxia (typically in toddlers), telangiectasias appearing at 4–6 years (mainly on conjunctivae, face, and ears), immunoglobulin deficiencies (IgA, IgG), recurrent sinopulmonary infections, and elevated α-fetoprotein levels. There is also an increased risk of lymphoma and leukemia.
165
What risks are increased in ATM heterozygotes?
Carriers have an elevated risk of breast cancer and other hematologic malignancies.
166
How are angiokeratomas characterized histologically and clinically?
They are ectasias of dermal vessels with an acanthotic, hyperkeratotic epidermis; these dark red-to-purple papular lesions vary in size/depth and are provisionally unclassified by ISSVA.
167
What are the two most common clinical types of angiokeratomas?
Solitary papular angiokeratomas (often on the lower extremity and can mimic melanoma) and angiokeratomas of the scrotum and vulva.
168
What is angiokeratoma circumscriptum and what may its deeper component indicate?
It presents as clusters or a linear plaque of ectatic vessels, often present at birth on an extremity; a deeper dermal component with thick-walled vessels may indicate a verrucous venulocapillary malformation, associated with MAP3K3 mutations.
169
What characterizes angiokeratoma corporis diffusum and with which disorders is it associated?
It features widespread lesions (often in a bathing trunk distribution) and is associated with hereditary lysosomal storage disorders such as Fabry disease (α-galactosidase A deficiency) and α-fucosidase deficiency. It can also occur on geographic capillary malformations in Klippel–Trenaunay syndrome.
170
What is Familial VMCM and what causes it?
It is an autosomal dominant condition characterized by multiple venous malformations affecting the skin, oral mucosa, and muscles, sometimes with visceral and cardiac involvement. It is caused by heterozygous germline mutations in the TEK gene, which lead to hyperphosphorylation and constitutive activation of the TIE-2 receptor.
171
What are the key clinical features and genetic findings in BRBNS?
BRBNS is a sporadic disorder characterized by progressive appearance of dark blue papules, nodules, and skin-colored “rubber blebs” in a widespread distribution with larger subcutaneous lesions. Gastrointestinal lesions cause bleeding and iron deficiency anemia. It is associated with double (cis) somatic activating TEK mutations.
172
What defines Maffucci syndrome and which gene is implicated?
Maffucci syndrome is a sporadic condition presenting with venous malformations as blue or skin-colored nodules and enchondromas resembling Ollier disease. It most often affects the extremities and may have neuro-ophthalmologic complications in cephalic lesions. It is associated with heterozygous somatic mutations in IDH1 (and rarely IDH2) found in both spindle cell hemangiomas and enchondromas.
173
How do glomuvenous malformations differ from classic venous malformations?
GVMs (formerly glomangiomas) are characterized by rows of glomus cells surrounding distorted venous channels. They are often painful, partially compressible, and display a hyperkeratotic, cobblestone-like surface. They typically do not involve viscera or joints and are associated with a heterozygous germline mutation in the GLMN gene plus a somatic “second hit.”
174
What is HCCVM and with which gene mutation is it most frequently associated?
Hyperkeratotic cutaneous capillary–venous malformation (HCCVM) is a distinctive skin lesion seen in a subset of familial cerebral cavernous malformation patients. It presents as irregular, dark crimson or reddish-purple plaques, most often congenital and on the extremities. Approximately 90% of affected familial CCM cases with cutaneous involvement have KRIT1 mutations.
175
How can cutaneous lesions in these syndromes be differentiated?
VMCM: Multiple VMs on skin/mucosa, often with a family history mediated by TEK mutations.
BRBNS: Dark blue “rubber blebs” and papules, with GI bleeding; caused by double TEK mutations.
Maffucci: VMs plus enchondromas; spindle cell hemangiomas with IDH1 mutations.
GVM: Painful, hyperkeratotic, partially compressible lesions on extremities with GLMN mutation.
HCCVM: Hyperkeratotic, dark plaques on extremities seen with KRIT1 mutations in familial CCM.
176
What is the molecular mechanism underlying familial cutaneous and mucosal venous malformation (VMCM)?
A heterozygous germline mutation in the TEK gene causes hyperphosphorylation and constitutive activation of the TIE‑2 receptor, leading to abnormal venous formation.
177
Which additional organ systems may be involved in familial VMCM?
Besides skin and mucosa, visceral venous malformations can occur in the intestines, lungs, CNS, and occasionally cardiac malformations.
178
What key complication is associated with Blue Rubber Bleb Nevus Syndrome (BRBNS)?
Gastrointestinal bleeding leading to iron deficiency anemia is a significant complication in BRBNS.
179
Which bony lesions are characteristic of Maffucci syndrome and what risk do they pose?
Enchondromas occur alongside venous malformations and can lead to skeletal deformities and orthopedic complications.
180
How do glomuvenous malformations (GVMs) clinically differ from classic VMs?
GVMs are typically painful, partially compressible, and exhibit a hyperkeratotic, cobblestone-like appearance; they rarely involve viscera or joints.
181
What is the common inheritance pattern for familial VMCM, GVM, and familial cerebral cavernous malformations (associated with HCCVM)?
All are autosomal dominant disorders.
182
With which gene mutation is hyperkeratotic cutaneous capillary–venous malformation (HCCVM) most frequently associated?
HCCVM is most commonly linked to KRIT1 mutations in familial cerebral cavernous malformation cases.
183
What immunohistochemical marker has been documented in HCCVM lesions?
GLUT1 positivity has been described in HCCVM.
184
What is Klippel–Trenaunay syndrome?
KTS is defined by a triad of a port‐wine birthmark (PWB), anomalous veins (venous malformation), and progressive overgrowth of the affected extremity.
185
What three features constitute the classical triad of KTS?
A PWB, anomalous (combined capillary–venous) malformation, and limb overgrowth.
186
How is the KTS eponym sometimes erroneously used?
It is sometimes used for any capillary malformation associated with limb hypertrophy, not just the classic triad.
187
What type of vascular malformation is typically seen in KTS?
KTS usually features a combined capillary–venous malformation (CVM or CLVM) that may be localized or extensive.
188
Which gene mutations have been identified in KTS-related malformations?
Somatic mutations in PIK3CA and, in some cases, PIK3R1 mutations have been linked to the vascular anomalies in KTS.
189
What is a 'geographic CM' in the context of KTS?
A well-demarcated, dark red-to-purple birthmark with irregular borders—often on the lateral thigh and sometimes associated with a lymphatic component.
190
What does the presence of superimposed purple papules and a persistent lateral marginal vein indicate in KTS?
It predicts more severe and progressive overgrowth, with a higher likelihood of complications such as cellulitis.
191
If a child has a capillary birthmark with overgrowth but no venous malformation, what alternative diagnosis should be considered?
They may be classified as having diffuse capillary malformation with overgrowth (DCMO) or simply a PWB with associated overgrowth.
192
What is commonly associated with foot and hand malformations in KTS?
They are usually linked to deep venous system anomalies.
193
What orthopedic issue is frequently seen in lower extremity KTS?
Progressive leg length discrepancy requiring ongoing orthopedic care.
194
Name two additional complications that can occur in severely affected KTS patients.
Lymphedema leading to massive limb overgrowth and vascular anomalies affecting the anogenital, GI, or retroperitoneal regions that may bleed.
195
What laboratory findings may be associated with the venous malformation network in KTS?
Chronic intravascular coagulopathy with high D-dimer levels and variably low fibrinogen, increasing the risk for deep vein thrombosis and pulmonary embolism.
196
Which imaging modalities are commonly used to evaluate KTS?
Duplex ultrasonography, multidetector CT (MDCT), and 3D magnetic resonance venography (MRV) are used to assess extent, bone involvement, and deep venous patency.
197
What is CLOVES syndrome?
A 'Proteus-like' syndrome characterized by asymmetric, progressive, infiltrative congenital lipomatous overgrowth (typically truncal), vascular anomalies, epidermal nevi, scoliosis/skeletal abnormalities, and spinal/paraspinal AV lesions.
198
Which mutation is primarily responsible for CLOVES syndrome?
Somatic activating mutations in the PIK3CA gene.
199
With which other syndromes does CLOVES share overlapping features?
It overlaps with other forms of the PIK3CA-related overgrowth spectrum (PROS), including KTS and Megalencephaly–capillary malformation.
200
What vascular anomalies are typical in CLOVES syndrome?
Lymphatic malformations within the lipomatous truncal mass, and geographic capillary or capillary–lymphatic malformations overlying the mass.
201
What increases the risk of pulmonary embolism in CLOVES syndrome?
The presence of aberrant superficial veins and phlebectasia of central veins, particularly during surgical interventions.
202
What are the primary features of Megalencephaly–capillary malformation syndrome?
Asymmetric overgrowth, progressive (hemi)megalencephaly, and a widespread reticulated capillary malformation, often with a midline abdominal demarcation.
203
Name three additional features seen in Megalencephaly–CM.
Persistent midfacial nevus simplex, frontal bossing, and developmental delay (with syndactyly, polydactyly, joint laxity, and hyperelastic skin).
204
What typical neuroimaging findings are observed in Megalencephaly–CM?
Ventriculomegaly, acquired cerebellar tonsillar ectopia (with or without herniation), polymicrogyria, and cerebral asymmetry.
205
Which mutation causes Megalencephaly–CM?
Postzygotic mutations in the PIK3CA gene.
206
What are the defining features of CLAPO syndrome?
A capillary malformation of the lower lip, a lymphatic malformation of the tongue and neck, combined with asymmetry and partial facial and extremity overgrowth.
207
How is the capillary malformation of the lower lip described in CLAPO syndrome?
It is always midline, symmetrical, and often extends to the adjacent skin.
208
Which gene mutation is responsible for CLAPO syndrome?
Somatic mutations in the PIK3CA gene.
209
What is Proteus syndrome?
A mosaic disorder characterized by progressive overgrowth and a mosaic distribution of anomalies, including vascular malformations, skeletal overgrowth, and distinct cutaneous features.
210
Which mutation causes Proteus syndrome?
Somatic activating mutations in the AKT1 gene.
211
Name three key clinical features evident in Proteus syndrome.
Asymmetric, disproportionate bone overgrowth (e.g., megaspondylodysplasia, macrodactyly), cerebriform connective tissue nevi of palms/soles, and lipomatous overgrowth.
212
What are two severe complications seen in Proteus syndrome?
Deep vein thrombosis (with risk of premature death) and the development of specific neoplasms (e.g., ovarian cystadenoma, parotid adenoma).
213
What characterizes Cutis marmorata telangiectatica congenita (CMTC) and what are its associated findings?
CMTC is marked by a dark purple to red–purple, broad reticulated vascular pattern with telangiectasias and prominent veins; it persists on warming, may show atrophic depressions (risking ulceration/scarring), and is associated with limb hypoplasia, skeletal anomalies, and may be confused with syndromes such as Adams–Oliver syndrome or mimic effects of neonatal lupus.
214
Which of the following best describes the two major types of venous malformations (VMs)?
B. Common/familial VMs and glomuvenous malformations (GVMs)
215
Common and familial VMs (excluding GVMs) account for approximately what percentage of all VMs?
C. 95%
216
What clinical features best characterize common and familial VMs?
B. Blue hue, softness, compressibility, and dependency filling
217
Which gene mutation is found in approximately 50% of sporadic common VMs?
B. TEK
218
Which gene mutation accounts for roughly 25% of sporadic common VMs?
C. PIK3CA
219
Which imaging modality is best suited to evaluate venous malformations?
B. T2-weighted MRI
220
Cephalic venous malformations (VMs) may involve which additional structures besides the skin?
B. Lips, oral mucosa, muscles, and orbit
221
Cephalic VMs typically expand when the head is in which position?
B. Dependent (lowered)
222
Approximately what percentage of patients with extensive cephalic VMs have developmental venous anomalies?
D. 25%
## Footnote
The passage states approximately 25% have developmental venous anomalies, whereas <1% is seen in the general population.
223
Trunk and limb VMs are best described as forming what type of masses?
B. Spongy masses of saggy, ectatic venous channels
224
What is the primary cause of pain in muscle involvement in limb VMs?
B. Thromboses inside the low‐flow channels
225
The chronic localized intravascular coagulopathy seen in large VMs is reflected by which laboratory finding?
B. Elevated D-dimer and low fibrinogen
226
Compared to Klippel–Trenaunay syndrome (KTS), limb involvement by a simple venous malformation is more likely to present with:
B. Undergrowth
227
Sinusoidal hemangioma is best described as:
B. A distinctive type of venous malformation presenting as deep, bluish nodules in adults
228
Fibro‑adipose vascular anomaly (FAVA) typically presents as:
B. A painful intramuscular mass often in the calf associated with contracture
229
Which treatment option is used for FAVA?
B. Image‑guided percutaneous cryoablation or excision
230
Verrucous venulocapillary malformation (also known as verrucous hemangioma) is associated with which gene mutation?
B. MAP3K3
231
Verrucous venulocapillary malformations often clinically overlap with:
B. Angiokeratoma circumscriptum
232
Familial cutaneous and mucosal venous malformation (VMCM) is inherited in an autosomal:
B. Dominant manner
233
Which gene is mutated in familial VMCM?
B. TEK
234
Besides skin and mucosa, familial VMCM may also affect which of the following?
B. Visceral organs (intestines, lungs, CNS) and cardiac structures
235
Blue rubber bleb nevus syndrome (BRBNS) is best characterized as:
B. A sporadic disorder
236
BRBNS is caused by what type of mutation in the TEK gene?
B. Double (cis) somatic activating mutations
237
What is a hallmark clinical feature of BRBNS?
B. Progressive, dark blue papules, nodules, and “rubber blebs” with compressibility
238
Maffucci syndrome is characterized by venous malformations and which additional lesion?
B. Enchondromas
239
Which gene is most commonly mutated in Maffucci syndrome?
C. IDH1
240
Glomuvenous malformations (GVMs) are inherited in an autosomal:
B. Dominant manner
241
Which gene mutation is responsible for glomuvenous malformations (GVMs)?
C. GLMN
242
Compared to classic VMs, GVMs tend to be:
B. Painful, partially compressible with a hyperkeratotic, cobblestone-like appearance
243
Hyperkeratotic cutaneous capillary–venous malformations (HCCVMs) are most commonly associated with mutations in which gene?
C. KRIT1
244
HCCVM lesions are typically found on which part of the body?
B. The extremities (arms and legs)
245
HCCVM is a cutaneous manifestation seen in association with which condition?
C. Familial cerebral cavernous malformations
246
What neurologic symptoms may develop in patients with HCCVM associated with cerebral cavernous malformations?
B. Headaches, seizures, and cerebral hemorrhage
247
Which gene mutation in venous malformations is most likely to affect the surface of the skin?
B. TEK
248
Somatic activating mutations in PIK3CA are found in approximately what percentage of sporadic common VMs?
B. 25%
249
Phleboliths, or round calcifications, are most commonly associated with which type of venous malformation?
B. Common and familial VMs
250
Which syndrome is characterized by a large congenital VM exhibiting a darker purple–blue fern‐shaped pattern on the surface?
C. Blue rubber bleb nevus syndrome (BRBNS)
251
Patients with cephalic VMs involving the parapharyngeal and laryngeal regions are monitored for which complication?
C. Sleep apnea leading to sudden death
252
At what age does joint involvement due to deep infiltration of venous malformations in the limbs typically become symptomatic?
B. Before 10 years
253
How does the growth pattern of a limb with a simple venous malformation typically compare to that seen in Klippel–Trenaunay syndrome (KTS)?
B. Limb undergrowth is more common in simple VMs
