Naevi & Dev defects Dan Flashcards
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Cutaneous anomalies due to chimerisim in humans are always pigmentary
True
Chimerisim = the presence of 2 or more genetically distinct cell populations in an individual derived from 2 different zygotes
Can occur by the fusion of dizygotic twin embryos or by the fertilization of a single ovum by 2 sperm
There are two different normal clones of cells rather than one normal and one abnormal as in mosaicism
What is epidermal naevus syndrome?
Occurs in 10% of kids with an epidermal naevus
Remember:NCI(eye)S SHALER
Naevus – non-epidermolytic verrucous, organoid, SCAP or comedo – can extend to mucosa, eyes and nails
CNS -seizures, paresis, developmental delay/retardation
Eyes – extension of naevus, colobomas, lipodermoids, corneal opacity
Skeletal – limb defects, scoliosis
Skin – naevi, melanocytic naevi, haemangiomas, CALMs, spitz naevi, lipomas, cyclindromas
Heart
Aortic coarctation
Liver
Endocrine – precocious puberty SIADH, Vit D resistant rickets
Renal and GU
What are the features of lumbosacral infantile hameangioma? What is management?
(L)LUMBAAR – Lumbosacral haemangioma, often ulcerated Lipoma or other skin lesions Urogenital anomalies Myelopathy (dysraphism) Bony deformities Anorectal malformations Arterial anomalies Renal anomalies investigate even if neurologically normal – USS under 4 months of age, MRI if older
What is PHACES syndrome?
Who gets it?
How do you procede?
Association of a large segmental facial infantile haemangioma (>5cm) with one or more significant malformations - 70% only have IH + one feature
90% are female;
PHACES
Posterior fossa defects (Dandy-Walker most common)
Haemangiomas
Arterial anomalies (esp carotid artery)
Cardiac defects (coarctation of aorta, septal defects)
Eye abnormalities (con cataracts, coloboma, optic atrophy)
Sternal clefts or pits, supraumbilical raphe (=ventral developmental defects)
Upper face lesions linked with brain, cerebrovascular and eye abnormalities
Lower face lesions linked with ventral developmental defects
Scan head if concerns; USS if less than 4 months, MRI with angiography if over (preferable)
What is Kasabach-Merritt phenomenon?
What tumours are associated?
Rapidly enlarging vascular tumour in an infant w/ syndrome of; Thrombocytopenia Microangiopathic haemolytic anaemia Consumptive coagulopathy Tumour often trunk, neck, limb girdle Mostly Kaposiform Haemangioendothelioma (KHE) Can be Tufted angioma, rarely haemangiopericytoma Can also be an internal vascular tumour Self limiting - resolves over 1-6 years Rx if life threatening complications Pred Vincristine IFN alpha surgery if small transfusions if active bleeding
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Infantile haemangioma affects 20% or more of infants by end of first year
False 10% or more Most common paediatric tumour Other names; Capillary/cavernous haemangioma, Strawberry naevus
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Infantile haemangioma is twice as common in girls
False
4 x more common in girls
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Infantile haemangioma is more common in prem babies
True
esp if low birthweight
(30% of less than 1kg, 15% of
How to remember Parkes-Weber and Sturge-Weber syndromes?
PALSC
Parkes Arterial Limb Sturge Capillary
What is Adams-Oliver syndrome?
A capillary malformation syndrome
CAST (as in the cast of Oliver! – the musical)
Cutis marmorata telangiectatica congenita
Aplasia cutis (congenita)
Skull defects
Transverse limb abnormalities (syndactyly, polydactyly, brachydactyly)
What is Phakomatosis Pigmentovascularis?
Rare sporadic syndrome due to twin spotting
capillary malformation + pigmented naevi of various types
e.g. epidermal naevus, Mongolian blue spots, naevus aneamicus, naevus spillus
May have eye and CNS issues if overlying skin affected
‘syndromic form’ – above + one of; Sturge-Weber syndrome, Klipper-Trenaunay syndrome or naevus of Ota
NB dont confuse w phakomatosis pigmentokeratotica = v rare epidermal naevus syndrome
What is Beckwith-Wiedemann syndrome?
Exomphalos Macroglossia Gigantism syndrome
AR, WT2 gene mutation
If its Black + White I’d-LIKE a TORCH
Overproduction of Insulin-like Growth factor 2
NSD1 or KIP2 gene mutation, sporadic or AD
Tumours - hepatoblastoma, Wilms tumour, Neuroblastoma, Rhabdomyosarcoma
Overgrowth - Exomphalos, Macroglossia, Gigantism
Renal malformations
Centrofacial Capillary Malformation
Helical pits + Hypoglycaemia
What is Mafucci’s syndrome?
Presents in infancy
Cutaneous venous malformations + enchondromas
Deformed hands and feet
High risk of malignancy - enchondromas can transform into chondrosarcomas.
Also angiosarcomas, lymphangiosarcomas, fibrosarcomas, osteosarcomas
Also CALMs
F/u long term
What is Blue rubber bleb syndrome?
Sporadic or AD
Usually presents in adulthood
Multiple venous malformations of skin, gut, spinal cord and viscera - skin lesions are painful
No glomus cells
Which syndromes may be associated with non-epidermolytic verrucous epidermal naevus?
Epidermal naevus syndromes Proteus syndrome McCune-Albright Klippel-Trenauny Phakomatosis pigmentokeratotica
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Some cases of comedo naevus are due to mosaic form of Apert’s syndrome
True
FGFR2 mutation confirmed in at least one example
Skeletal malformations fit with a mosaic form of Apert’s syndrome (broad distal thumb, syndactyly, mid facial hypoplasia etc)
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A linear mosaic form of Gorlin’s syndrome has been described
False
postulated but not described
Linear basal cell naevus is described
Cases w/ palmar pits or skeletal malformations are esp suggestive of Gorlin’s but PTCH gene mutation not identified
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PTCH gene putations have been found in SCAP
True
also P16 mutations
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an ILVEN is always present from birth
False
rarely seen at birth
75% present in first 5 years esp first 6 months
later onset reported
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ILVEN are always itchy
True
can be severe
NB lichen striatus is asymptomatic
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ILVEN may resolve completely
False
persist - 75% stable while 25% enlarge after presentation
NB lichen striatus often resolves spontaneously
What is a basal cell naevus?
A BCC clinically resembling a melanocytic naevus
What is ptychotropism?
predilection for body folds
e.g. CHILD naevus, many demratoses
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Linear mosaic porokeratosis can be inherited from a parent with DSAP
True
by Happle 2 mosaicism;
mosaic mutation of the normal allele in an AD condition means that the linear area has homozygous gene for the disease so is markedly affected while the background heterozygous skin is relatively spared, but, may flare to active disease at a later date
What is Phakomatosis pigmentokeratotica?
Very rare epidermal naevus syndrome
Sebaceous or verrucous epidermal naevus with speckled lentiginous naevus and extracutaneous defects
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Becker’s naevus is twice as common in males
False
5x more common in males
but Becker naevus syndrome more commonin females
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collagenomas are collagen naevi
True
show accumulation of collagen which often appears altered and a sparsity of other dermal matrix components
Shagreen patch of TSC is most well known example
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The skin chnages in PXE are regarded as an elastic naevus
True
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striated muscle hamartoma is more common than smooth muschle hamartoma
False
smooth muscle much more common; 1:3000 birhs
May demonstrate pseudo-Darier sign
striated muscle hamartoma may be part of v rare Dalleman’s syndrome
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Vascular Tumours often appear after birth; Malformations usually present at birth
True
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Vascular malformations often proliferate after birth; Vasc tumours don’t proliferate
False
other way around
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Vascular Tumours may resolve spontaneously; Malformations don’t resolve
True
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Vascular Tumours are rarely multiple; There are several malformations with multiple lesions
True
But the vasc tumours w/ multiple lesions include;
- Neonatal haemangiomatosis - benign/diffuse
- Eruptive pseudoangiomatosis
- Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT)
- Glomuvenous malformations
Verrucous haemangioma can consist of several close lesions
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All vascular malformations with proliferating endothelial cells express WT1 (Wilms tumour antigen)
False
This is vascular tumours
malformations dont proliferate and rarely express WT1
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GLUT1 is only positive in infantile haemangiomas and not other vascular tumours
False
usually this is true and can be useful for diagnostic purposes but GLUT1 may be positive in verrucous haemangioma
What is the natural Hx of infantile haemangioma?
Lesion may be present at birth as small precursor
within days to weeks starts to grow rapidly
Proliferates for average 5 months
Deeper lesions proliferate until 12 months of age
Period of stability - varies - then begins to involute
Involution may begin in first year or later – parts can be involuting while others are still proliferating
Involution completed by;
- 5 years in 50%
- 7 years in 70%
- 9 years in 90%
But can continue for up to 10 years
Lesions which start to involute late tend to regress incompletely
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90% of infantile haemangiomas are superficial
False
at least 1 quarter mixed; up to 1 quarter deep
50-60% superficial – bright red while proliferating
25-35% mixed
10-25% deep – More blue colour
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>50% of infantile haemangiomas occur on head and neck
True
How can IH be differentiated from other tumours or vascular malformations?
Biopsy and staining for GLUT1 is probably best way to tell quickly
watching for the natural Hx of the lesion also helps
serial USS can pick up subtle changes in appearance/flow
NB CT and MRI cannot distinguish IH from other lesions
When should you look for visceral haemangiomas?
If 5 or more cutaneous haemangiomas should USS liver (+/- other sites) to look for visceral haemangiomas
get scans done ASAP
skin only = (Benign) Neonatal haemangiomatosis
Visceral = Diffuse (disseminated/multifocal/miliary) neonatal haemangiomatosis (strictly only if 2 sites other than skin)
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steroids are first line for diffuse neonatal hameangiomatosis
False
propanolol now being used first line
steroids second line
IFNα 3rd line
What are diagnostic criteria for Diffuse neonatal haemangiomatosis?
Need al 3 of;
- Onset in neonatal period
- Involvement of 3 or more organs (skin, liver, GIT, lungs, brain most frequent)
- No malignant transformation
What are complications of Diffuse neonatal haemangiomatosis?
what is prognosis?
Complications; - CCF about 40% (due to hepatic dx) - Haemorrhage about 10% - Multiorgan failure about 10% Scan abdo, chest, CNS, echo, FOBTs Mortality is about 75% if untreated or about 25% if treated
What are the complications of infantile hameangiomas?
Ulceration Scarring (residuum) – disfigurement Heart failure esp if hepatic Outer Ear/canal obstruction Airway obstruction Visual impairment
What are the mechanisms of action of beta blocker sin infantile haemangioma?
Increasing contractility of haemangioma pericytes
May reduce catecholamine-induced angiogenesis
May induce apoptosis of haemangioma-derived endothelial cells
Inhibition of Renin-angiotensin system may play a role but unclear
NB
No effect on normal pericytes
Do not seem to influence vasculogenesis (precursor cells turning into blood vessels)
Whats the dose of propanolol for IH?
Whats the dose of atenolol for IH?
Propanolol 2mg/kg/day in 3 divided doses
- titrate to this over 2 weeks
Atenolol 1mg/kg/day in a single daily dose
- titrate to this over 1 week
What can be used for IH if beta blockers fail?
Prednisolone;
2-5mg/kg/day OD in morning for 1-3 months then taper slowly – study showed dose over 3mg/kg more effective but more risk of AEs
Vincristine - severe AEs
IFNα - risk permanent diplegia
ILCS - ?radiology guidance
laser (PDL or Nd:YAG) - little evidence but safer than second line systemic agents above
Cryo - no good evidence
compression banadaging - risk of heart failure
embolization - liver mainly
XRT - if v severe/life threatening
surgery
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there is no overlap between the congenital haemangiomas RICH and NICH
False
Can be hard to distinguish RICH and NICH
Some lesions appear to begin to involute then persist
i.e. a so-called RICH stops involuting and turns into a NICH
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congenital haemangiomas are WT1 positive and GLUT1 positive
False
WT1 positive and GLUT1 negaive
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RICH usually involutes over many years like IH
False
Rapidly involutes during first year (up to 14 months) of life
Leaves dermal or subcuaneous atrophy
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Glomuvenous malformation is a painful tumour
False
Glums tumour is painful
Glomuvenous malformation is not
What are the types of angiokeratomas?
My Ford Car Solely Plays CDs Angiokeratoma of Mibelli Angiokeratoma of Fordyce (scrotal angiokeratoma) Angiokeratoma Circumscriptum Solitary Papular angiokeratoma Angiokeratoma Corporis Diffusum
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peripheral pallor is characteristic of IH
False
characteristic of congenital haemangiomas
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Eruptive pseudoangiomatosis looks a lot like neonatal haemangiomatosis but the lesions occur later and resolve quickly
True
both can look like many cherry angiomas
Eruptive pseudoangiomatosis occurs from infancy up to about age 6
Often preceded by systemic symptoms of fever, URTI etc
May be triggered by; echovirus, EBV, CMV, insect bites
lesions resolve in 1-2 weeks
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Benign vascular tumours are soft; aggressive tumours may be coarse
True
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Benign vascular tumours are poorly demarcated; aggressive tumours are well demarcated
False
other way around
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Benign vascular tumours do not infiltrate surrounding tissue; aggressive tumours may infiltrate
True
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Benign vascular tumours are not associated w/ low plts/DIC; aggressive tumours may be
True
NB – rare cases of RICH can also be
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The term ‘hobnail haemangioendotheliomas’ cna be used to describe both Papillary intralymphatic angioendothelioma (PILA) and Retiform haemangioendothelioma (RHE)
True
Both have prominent hobnail cells lining vascular structures
PILA may be juvenile for of RHE
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Kaposis sarcoma is cuased by KS-associated strains of HHV8 whoch infect vascular endothelial cells causing ‘lymphatic reprogramming’
True
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Angiosarcoma occurs on the legs of adults but on the head and neck of kids
False
Mainly seen on head and neck of adults esp if sun damaged; M>F
Multifocal in adults
In kids is small, focal, often on leg and F>M
Histo similar in adults and kids but >90% of kids ones are epithelioid variant
What is Klippel-Trenaunay syndrome?
Capillary malformation on a limb + limb soft tissue swelling (with or without boney hypertrophy)
Due to Slow flow complex combined capillary venous malformation (CVM) or Capillary Venous-lymphatic malformation (CVLM)
Cf- Parkes-Weber (AVM-high flow)
May have; lymphangioma circumscriptum, angiokeratomas, pseudo-kaposi’s sarcoma, Venous varicosities common
Mx
Differentiate from; Parkes-Weber, CMTC, Proteus
Duplex and Doppler USS
MRI
Regularly monitor leg length discrepancy
preventing DVT/PE; treat venous insuffiency – compression stockings
Refer; vascular surgeon; paeds ortho
Multiple infantile haemangiomas occur in 10-25% of cases
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