KEY NOTES CHAPTER 2: SKIN AND SOFT TISSUE LESIONS: Vascular anomalies.

Question 0

What are the different vascular tumours?

Answer 0

Benign
• Infantile haemangioma
• Congenital haemangioma
• Tufted angioma
• Spindle-cell haemangioma
• Epithelioid haemangioma
• Pyogenic granuloma.

Locally aggressive or borderline
• Kaposiform haemangioendothelioma
• Retiform haemangioendothelioma
• Papillary intralymphatic angioendothelioma
• Composite haemangioendothelioma
• Kaposi sarcoma.

Malignant
• Angiosarcoma
• Epithelioid haemangioendothelioma.

Question 1

How do you classify vascular anomalies?

Answer 1

The 2014 International Society for the Study of Vascular Anomalies (ISSVA) classification (based on original work by Mulliken and Glowacki).

1. VASCULAR TUMOURS
2. VASCULAR MALFORMATIONS

Question 2

How are vascular malformations classified?

Answer 2

Simple
• Capillary malformations
• Lymphatic malformations
• Venous malformations
• Arteriovenous malformations∗
• Arteriovenous fistula.∗

Combined
• Capillary venous malformation
• Capillary lymphatic malformation
• Lymphatic venous malformation
• Capillary lymphatic venous malformation
• Capillary arteriovenous malformation∗
• Capillary lymphatic arteriovenous malformation∗
• Others.

• high flow

Question 3

How can vascular malformations also be classified?

Answer 3

Of major named vessels
• Anomalies of:
∘ Origin
∘ Course
∘ Number
∘ Length
∘ Diameter (aplasia, hypoplasia, stenosis, ectasia/aneurysm)
∘ Valves
∘ Communication (arteriovenous fistula)
∘ Persistence (of embryonal vessel).

Associated with other anomalies
• Klippel-Trénaunay syndrome
• Parkes-Weber syndrome
• Sturge-Weber syndrome
• Others.

Question 4

How is classification useful?

Answer 4

∘ Diagnosis
∘ Planning
∘ Management
∘ Predicting future behaviour of lesions.

Question 5

What do you know about infantile haemangiomas?

Answer 5

• Most common tumour of infancy.
• Incidence: 10% in white infants; 23% in premature babies with low birthweight (<1kg).
• Male:female ratio 1:3.
• Approximately 80% focal, 20% multifocal.
• 60% in the head and neck.

Question 6

How can you classify infantile haemangiomas?

Answer 6

By pattern or type.

1. Pattern
• Focal
• Multifocal
• Segmental
• Indeterminate.

2. Type
• Superficial
• Deep
• Mixed (superficial and deep)
• Reticular/abortive/minimal growth
• Others.

Question 7

What are the possible causes of infantile haemangiomas?

Answer 7

∘ PLACENTAL EMBOLISATION, evidenced by expression of GLUT1 and other placental antigens.

∘ MUTATION IN AN ENDOTHELIAL CELL leading to clonal expansion.

∘ GERMLINE MUTATION, evidenced by hereditary transmission.

Question 8

What is the pathogenesis of infantile haemangiomas?

Answer 8

• ‘Herald patch’ may be noticed at birth, most appear at 2wks; later for deep-seated tumours (2-4mths).

PROLIFERATING STAGE (duration 6-8 months).
• Raised, bosselated, deep red, blue hue if deep-seated.
• Rapidly dividing endothelial cells form tightly packed sinusoidal channels.
• Increased vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) upregulates angiogenesis.

INVOLUTING STAGE (duration 5-10 years).
• Red fades, pale patches develop within lesion.
• Regression, decreased endothelial cell activity, luminal enlargement.
• Fibrous tissue, mast cells, fibroblasts, macrophages.
• Increased tissue inhibitor of metalloproteinase (TIMP)-1 suppresses angiogenesis.

INVOLUTED PHASE
• 50% involuted by 5 years of age, 60% by 6, 100% by 10 - 12.
• Sparse capillaries and veins with multilaminated basement membranes.
• Residual loose fibrofatty tissue, stretched, crêpe-like skin (50% cases, skin is near normal).

Question 9

What syndrome can infantile haemangiomas be associated with?

Answer 9

∘ PHACES association
- Posterior cranial fossa cystic malformations
- Haemangioma on the face, often large and plaque-like
- Arterial anomalies
- Cardiac defects
- Eye anomalies
- Sternal cleft/supraumbilical raphe.
∘ Lumbosacral haemangioma associated with occult spinal dysraphism.
∘ Diffuse perineal haemangioma associated with urogenital/anorectal anomalies.

Question 10

What complications may be encountered with infantile haemangiomas?

Answer 10

1 Intrinsic to the haemangioma.
2 Due to obstruction of a body orifice.

Intrinsic complications
• Ulceration (10%) 
- painful; can lead to scarring
- areas repeatedly traumatised susceptible e.g. perineum.
• Infection 
• Bleeding 

Obstructive complications
• Deprivational amblyopia: from visual obstruction.
• Anisometropia: eyes have unequal refractive power from direct pressure on globe, causing deformation or strabismus.
• Airway obstruction (cervicofacial haemangioma): Subglottic lesions: insidious onset biphasic stridor at 6-8 weeks of age.
• External acoustic meatus obstruction: conductive deafness.

Question 11

What are the indications for starting treatment?

Answer 11

∘ Obstruction of a vital structure
∘ Ulceration or bleeding due to local trauma
∘ Significant distortion and aesthetic considerations.

Question 12

What are the treatments available for infantile haemangiomas?

Answer 12

Usually non-operative:

1. Observation
2. Local treatments
3. Pharmacological agents.

Question 13

How are most infantile haemangiomas managed?

Answer 13

• Most haemangiomas are managed with observation alone.
• Spontaneous involution occurs in 85-90%.
• More limited involution may occur at the nasal tip (Cyrano nose) and parotid region.

Question 14

How do you manage an ulcerated haemangioma?

Answer 14

Bleeding and pain may be distressing to baby and parents.
• Bleeding: gentle direct pressure.
• Analgesics: paracetamol, oral morphine, intranasal diamorphine.
• Topical lignocaine gel
• Hydrocolloid dressing, e.g. DuoDERM to reduce pain.
• Topical antibiotics, e.g. mupirocin or metronidazole ointment.

Question 15

Tell me about pharmacological agents for the treatment of infantile haemangiomas.

Answer 15

Propranolol
Systemic corticosteroids
Intralesional corticosteroids
Vincristine
Interferon α-2a
(Imiquimod)

Question 16

What is the first-line pharmacological treatment?

Answer 16

Propranolol (β-blocker)
• Chance discovery in 2008 in two children with cardiopulmonary conditions.
• 12 month course usually to avoid rebound growth.
• Side effects 
∘ Hypoglycaemia
∘ Bronchospasm
∘ Hypotension
∘ Hypothermia.

• Full history, examination, ECG and echocardiogram prior to commencing
treatment.
• Heart rate, blood pressure and blood glucose should be monitored during initiation of treatment.

• Absolute contraindications: 
∘ sick sinus syndrome, 
∘ 2nd or 3rd-degree heart block.
• Relative contraindications:
∘ Impaired cardiac function
∘ Sinus bradycardia
∘ Hypotension
∘ First-degree heart block
∘ Chronic renal insufficiency
∘ PHACES syndrome, where cerebral perfusion can be compromised.
• Topical β-blockers, e.g. 0.5% timolol, can be considered for superficial lesions when systemic propranolol is contraindicated

Question 17

What are the other pharmacological treatments?

Answer 17

Systemic corticosteroids
• Alternative or adjunct to β-blockers.
• Up to 12 months.
• Close monitoring (rebound growth on withdrawl).

• Side effects:
∘ Cushingoid appearance
∘ Irritability
∘ Gastrointestinal upset
∘ Fungal infections
∘ Growth retardation
∘ Hypertension
∘ Adrenal suppression
∘ Immunosuppression - live vaccines should be avoided.

Intralesional corticosteroids
• Best on localised superficial haemangioma.
• Triamcinolone monthly.

Vincristine
• Adjunctive treatment of resistant, life-threatening haemangiomas.
• Inhibits cellular proliferation.
• Joint care with oncologist.

Interferon α-2a
• Used for life-threatening haemangiomas resistant to propranolol and steroids.
• Not usually given concomitantly with steroids.
• Side effects: flu-like illness and spastic diplegia.

Imiquimod
• Not an accepted treatment, but reportedly accelerates involution.

Question 18

What interventional treatments may be offered?

Answer 18

Surgery
• Not usually required in proliferative phase (excision / debulking only indicated to preserve critical function after failure of all other treatment).
• May be offered at involuted phase for cosmesis.

Laser
• Vascular lasers do not penetrate deeply enough to ablate haemangiomas.
• Can be used for acute ulceration, or residual telangiectasia or baggy skin after involution.

Question 19

What are congenital haemangiomas?

Answer 19

• Rare vascular tumours; completely formed at birth.
• Do not rapidly proliferate.

• Two main types:
1 Rapidly involuting congenital haemangioma (RICH)
2 Non-involuting congenital haemangioma (NICH).

• Both are GLUT1 negative.
• Large lesions can cause high-output cardiac failure.
∘ Presents on antenatal ultrasound as hydrops fetalis.

• RICH undergoes accelerated regression after a few weeks; usually complete by 14 months.
• NICH does not involute; continues to grow in proportion to child.

Question 20

What is pyogenic granuloma?

Answer 20

• Acquired lesions composed of proliferative vascular tissue.
• Common on face and hands.
• May arise following seemingly trivial trauma.
• Rapid growth, may bleed, can be confused with cutaneous malignancy.
• Easily treated by curettage or excision.

Question 21

What is Kasabach-Merritt phenomenon?

Answer 21

• Associated with:

• Kaposiform haemangioendothelioma
• Tufted angioma.
• Described by two paediatricians in 1940.
• Rare, life-threatening condition - mortality rate up to 30%.
• Peak incidence is in early infancy.
• Managed in PICU setting.

• Characterised by:
∘ Enlarging invasive vascular tumour.
∘ Platelet trapping within lesion, leading to profound thrombocytopenia.
∘ Secondary consumptive coagulopathy and hypofibrinogenaemia.
• Risk of spontaneous internal haemorrhage into any body cavity.

Question 22

What are vascular malformations? How do they differ from vascular tumours?

Answer 22

• Occur due to intrinsic abnormality of development (not tumour).
• Present at birth; generally grow in proportion to body.
∘ Can increase in size after weight gain, trauma or hormonal surges of puberty/pregnancy.
• Causative genes have been identified in some cases.

Question 23

How can vascular malformations be investigated?

Answer 23

• Gadolinium-enhanced MRI: assesses flow characteristics and extent of involvement.
• CT: intraosseous lesions.
• Conventional angiography: treatment rather than diagnosis.

Question 24

What are the different types of capillary malformations?

Answer 24

1. Cutaneous and/or mucosal CMs (port wine stains)
2. Naevus simplex
3. Telangiectasia

Question 25

How do cutaneous and/or mucosal CMs present, and what may certain CMs be associated with?

Answer 25

• Birth: red macules
• Youth: flat and pale
• With age: raised, nodular and dark.
• Treatment: vascular laser, e.g. pulsed dye laser or KTP.
• Better results if treatment initiated in infancy or childhood.
• Most CMs are harmless and confined to the skin.

Sturge-Weber syndrome

• associated with CMs in ophthalmic division of trigeminal nerve (V).
• Ipsilateral leptomeningeal and ocular vascular anomalies.

Glaucoma
- CMs of ophthalmic / maxillary division of V.

Encephalocele or spinal dysraphism
- midline cephalic or spinal CMs.

Question 26

What are naevus simplex and telangiectasia? How are they treated?

Answer 26

Naevus simplex, aka
∘ Angel kiss
∘ Salmon patch
∘ Stork mark.
• Typically: nape of neck or glabella in 40% of neonates.
• Flat, pale pink and fade slowly; do not usually require treatment.

Telangiectasia
• May be inherited (hereditary haemorrhagic telangiectasia) or acquired.
• Commonly occur on face, neck, thorax and arms.
• Easily treated with a vascular laser.

Question 27

How do common VMs present?

Answer 27

Common VMs
• Present at birth; may not be noticed until older, may enlarge during puberty.
• Usually solitary faint blue patch or soft blue compressible mass (cutaneous or visceral).
• Easily compressible, swell when dependant, empties when elevated.
• Phleboliths; recurrent episodes of thrombosis.
• Risk of DIC with very large lesions: platelets and PT/APTT may be normal, but fibrinogen is low with increased levels of fibrin degradation products (unlike Kasabach-Merritt phenomenon).

Question 28

What are the indications for treatment for VM?

Answer 28

Treatment: for function or cosmesis:

1. Limb compression garments: minimises painful thrombosis.
2. Sclerosant:
   ∘ Small cutaneous VMs:
   - 1% sodium tetradecyl sulphate

∘ Large deep VMs:

• Experienced specialists, GA, fluoroscopic monitoring.
• 3% sodium tetradecyl sulphate for high risk areas.
• OK 432 = lyophilised incubation mixture of grp A Strep pyogenes
• Ethanol (may cause nerve damage)

Complications:
∘ Local: blistering, necrosis, nerve deficit.
∘ Systemic: cardiac arrest, renal toxicity.

3. Surgical debulking: after completion of sclerotherapy (if required).

Question 29

What conditions are associated with VMs:

Answer 29

• Blue rubber bleb naevus (BRBN) syndrome

- Multiple cutaneous and mucosal venous malformations (aka VMCM)

Question 30

Please elaborate on

• Blue rubber bleb naevus (BRBN) syndrome
• Multiple cutaneous and mucosal venous malformations

Answer 30

1. Blue rubber bleb naevus (BRBN) syndrome
   • Characterised by multiple VMs of skin and viscera.
   • Rare, but significant intestinal haemorrhage, which can be fatal.
2. Multiple cutaneous and mucosal venous malformations (aka VMCM)
   • Characterised by small, multifocal bluish cutaneous and/or mucosal VMs.
   • Autosomal dominant (1% of all VMs)
   • Small lesions asymptomatic; larger lesions can invade muscle, causing pain.

Question 31

How are lymphatic malformations classified?

Answer 31

Common (cystic) LMs are classified as:
∘ Microcystic
∘ Macrocystic
∘ Mixed cystic.

Question 32

How do lymphatic malformations present?

Answer 32

• Most are evident at birth or detected within the first 2 years.
• Soft tissue and bony hypertrophy can occur.
• Expand and contract depending on movement of lymphatic fluid.
• Sudden enlargement can be caused by intralesional bleeding or infection.

Question 33

What is the treatment for lymphatic malformations, and what are the complications?

Answer 33

1. Compression garments
2. Analgesia, antibiotics, rest: during acute exacerbations of intralesional bleeding, infection and sudden enlargement.
3. Aspiration and sclerotherapy e.g. tetracycline, bleomycin (risk of pulmonary fibrosis - need pre and post PFTs), absolute ethanol, sodium tetradecyl sulphate, doxycycline, OK-432.
4. Surgery
   • Localised disease may be curative.
   • Diffuse disease requires complex, staged surgery, (blood loss measured in ‘no. of blood volumes replaced’).

• Complications of surgery:
∘ Infection
∘ Haematoma
∘ Prolonged drainage
∘ Incomplete excision and recurrence.

Question 34

How do AVMs present?

Answer 34

• Usually present at birth but only become apparent in infancy or childhood.
• Commoner intracranially than extracranially.
• Epicentre/nidus: compact tangle of dysplastic, thin-walled vessels, connecting feeding arteries to ectatic draining veins via numerous micro- and macroarteriovenous fistulas.

• Trauma or puberty triggers expansion, manifest by:
∘ Darkening of overlying skin (red or violaceous)
∘ Palpable mass
∘ Local warmth, bruit and thrill.

• Sequelae of expansion:
∘ Ischaemic skin changes
∘ Ulceration
∘ Bleeding
∘ Significant pain
∘ Increased cardiac output (very large lesions).

Question 35

How are AVMs classified?

Answer 35

Classification
• Sporadic
• In hereditary haemorrhagic telangiectasia
• In CM-AVM
• Others.

Question 36

How are AVMs staged and who described it?

Answer 36

Schobinger
Stage I: Quiescence - pink-blush stain with warmth.
Stage II: Expansion - mass associated with bruit and thrill.
Stage III: Destruction - mass associated with ulceration, bleeding and pain.
Stage IV: Decompensation - stage III plus heart failure.

Question 37

How are AVMs treated?

Answer 37

• Notoriously difficult to treat.
• Treatment is targeted at the nidus.
• Intervention is usually indicated for Schobinger III and IV lesions.
• MRI or MR angiography: to delineate extent of disease.
• Conventional angiography: only when therapeutic embolisation is planned.

• DO NOT ligate or embolise proximal feeding arteries; it limits endovascular access to nidus and recruits more collaterals.
• Superselective angiography and embolisation of nidus is done 24-72 hours prior to
planned surgical resection.
• Wide excision aims to remove all involved tissues, including overlying skin if abnormal.
• Curative resection is not usually achievable.

Question 38

What is Klippel-Trénaunay syndrome (KTS)?

Answer 38

• Combined capillary-lymphaticovenous malformation associated with soft tissue and skeletal hypertrophy in one or more limbs (rarely, it is associated with limb undergrowth).
1. Port-wine stain(s) with sharp borders.
2. Varicose veins.
3. Hypertrophy of bony and soft tissues, may lead to local gigantism or shrinking.
4. Improperly developed lymph system.
• Most common in the anterolateral thigh, buttock and trunk.
• Venous anatomy often aberrant and complex.
• Specialist assessment is required prior to any treatment.

Question 39

What are the non-surgical and surgical treatments for SWS?

Answer 39

Non-surgical

• Compression garments
• Sclerotherapy

Surgical

• Debulking / excision operations
• Epiphysiodesis (limb length and correction of bone deformity)

Question 40

What is Parkes-Weber syndrome?

Answer 40

• Combined capillary lymphatic arterial venous malformation; presents at birth.
• Lower limb is usually affected.
• Angiography shows multiple microscopic arteriovenous fistulae throughout the affected limb.