Vascular tumours, malformations and related disorders Flashcards
What is PHACE syndrome?
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
What is an IH-MAG?
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
What are the histological features of IH-MAG?
○ 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
Extracutanoeus IH - when to suspect?
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
What are the complications of haemangioma’s?
Ulceration - 10% of IHs
**Disfigurement **
Interferance with function
- ocular
- oral
- auricular
- limbs
**Secondary infection **
**Pain **
**Hypothyroidism **
**High output cardiac failure **
What is the mechanism of hypothyroidism for infantile haemangiomas?
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
What is LUMBAR syndrome?
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
Natural Hx of infantile haemangiomas
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
RFs for IHs?
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
Subtypes of IH?
Superficial
Deep
Mixed
IH-MAG
Treatment options for IH
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
Management of an ulcerated IH?
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
What is a congential haemangioma?
fully developed haemangioma in the immediate Newborn period.
What are the subtypes of congenital haemangioma?
RICH - rapidly involuting
PICH - partially involuting
NICH - non-involuting
What is the mutation that causes congential haemangiomas?
GNAQ or GNA11
Are congential haemangiomas GLUT + or -?
GLUT negative
What are the clinical features of a congenital haemangioma?
○ 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
What are the histological features of a congential haemangioma?
○ 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
How are vascular malformations classified?
Capillary malformation
Venous malformation
Arterial malformation
Lymphatic malformation
Ateriovenous malformaiton
What is Kasabach Meritt phenomenon?
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
What is a naevus Flammeus?
A port wine stain
(a type of capillary malformation)
What mutation/s causes port wine stains?
GNAQ (classic)
PIK3CA (geographic)
What syndromes are ass. with port wine stains?
Sturg Webber Syndrome
Klippel Trenaunay Syndrome
Parkes Webber Syndrome
Proteus Syndrome
PTEN harmatoma syndromes
Cobb syndrome
Beckweith weidermann syndrome
CM- AVM
What causes sturg webber syndrome?
Somatic activating mutation in GNAQ
Who is at risk of Strug Webber syndrome?
Patients with a capillary malformation affecting the forehead
More extensive CM = higher risk
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%
Which conditions are in the PIK3CA related overgrowth spectrum?
Klippel - Trenaunay Syndrome
Macrocephaly capillary malformation syndrome
CLOVES syndrome
Proteus Syndrome
Beckwith Wiedermann syndrome
Diffuse capillary malformation with overgrowth
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)
What are some of the complications of Klippel Trenaunay syndrome?
DVT
Thrombophelebitis
Pulmonary Embolism
GI bleeding
Vascular Blebs
Pain
High output cardiac failure
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
What is CLOVES syndrome?
A PIK3CA syndrome chacterised by:
- CLO - congential lipomatous overgrowth
- V - vascular malformation (inc. geographic capillary malformation)
- Epidermal naevi
- Scoliosis or spinal anomolies
Associations:
- Wilms tumour (3 monthly USS until age 8)
- thromboembolic events (PE, CVA)
Infantile haemangiomas are GLUT 1 postive
True
List 5 benign vascular tumours
Infantile Haemangioma
Congenital Haemangioma
Tufted angioma
Spindle cell haemangioma
Pyogenic granuloma
Congenital haemangiomas are more common in girls
False - M = F
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
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.
What Ix would you do for a kaposiform haemoendothelioma?
FBC
Coagulation profile - inc fibrinogen
+/- Biopsy
+/- MRI
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
Patients with Kasabach Merritt syndorme and thrombocytopaenia need to be given platelets to prevent bleeding
False - often makes things wrose
Treatment of Kaposiform haemangioendothelioma with kasabach merritt syndroem?
First Line - Oral Sirolimus
Second line - Vincristine and Sysemic steroids
Third line - surgical excision, embolisation
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
What is a pyogenic granuloma?
A common, benign, vascular tumour
Children > Adults
Treatment of a pyogenic granuloma?
Surgical excision
Curette and Cautery
PDL
CO2 laser
Treatment of a tufted angioma?
Observation
Surgical exicsion
Oral sirolimus if develops kasabach Merritt phenomenon
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
Describe?
Papule
w Epidermal collarete
Loss of epidermis above
Appearance similar to granulation tissue.
Small vasular channels
Ulcerated
+/- Neutrophils
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
