phacomatosis

1. NEUROCUTANEOUS SYNDROMES
(NF-1, NF-2, Sturge–weber syndrome)

2. Neurocutaneous syndromes(Phakomatoses)
• These are group of heterogeneous disorders
involving the structures derived from the
embryonic neuroectoderm- the central
nervous system, eyes and skin.
• The syndromes are characterized by
distinctive CNS, cutaneous , ocular and
oncological manifestations .
• usually present in childhood, with new
manifestations occurring over lifetime

3. Common syndromes :
• Neurofibromatosis type I.
• Neurofibromatosis type 2.
• Sturge – weber syndrome.
• Von hippel – lindau disease.
• Tuberous sclerosis.

4. • Neurofibromatoses (NFs) are a subgroup of
phakomatoses and are classified into three
types:
1)NF1 or peripheral neurofibromatosis,
2)NF2 or central neurofibromatosis
3)Schwannomatosis

5. Neurofibromatosis type 1
• It is the most common neurocutaneous
syndrome.
• von Recklinghausen disease
• It is an autosomal dominant condition
• Characterized by neoplastic and nonneoplastic
involvement of skin, eye, bone, endocrine and
central nervous system.

6. Genetics :
Chr 17q11.2 – Tumour suppressor gene (NF1
gene , Neurofibromin protein)
(Germ line mutation)
Loss of tumour supressor function
Abnormal , uncontrolled proliferation of these
cells (neurons , glial cells , schwann cells)
Hyperplasia , hamartomas , neoplasms (Bening
and malignant)

7. Clinical features
• Café au lait macules
• Lisch nodules
• Neurofibromas
• Axillary / inguinal freckling

8. Café au lait macules:
• Oval or round,
• hyperpigmented spots
• Smooth borders
• May be seen at birth.
• "coast of California" pattern
McCune–Albright syndrome
"coast of Maine" pattern.

9. Freckling :
• Freckles are brown macules of 1–3 mm size.
• Location: axillary, inguinal, sub mammary and
neck regions.
• Appear by 4-5 yrs of age even before
cutaneous neurofibromas.

10. Lisch nodules :
• These are melanocytic hamartomas of iris .
• Appears as small, dome-shaped hyper
pigmented macules.
• Do not cause functional impairment of vision.

11. Neurofibromas
 These are one of the hallmarks of NF1.
 Bening peripheral nerve sheath tumors.
Based on location they are :
• Cutaneous
• Subcutaneous

12. Cutaneous neurofibromas:
Appears at puberty.
Size : mm-cm
Skin colored to brown.
Polypoidal / pedunculated soft lesions.
Classical button hole sign.

13. Subcutaneous NF:
• Firm and nodular lesions
From dorsal root ganglion – Dumb bell shaped
tumours.
• In neck – beaded neckalce pattern(mimicking
lymphadenitis.)

15. Based on morphology NFs are :
• Localized
• Diffuse
• Plexiform.
• MPNSTs.

16. Localized NFs:
• Most common type of neurofibroma in NF1
pateints.
• They can be sporadic (involve superficial
cutaneous nerves) , NF1 associated(tend to
involve deep nerves , multiple , large).

17. On CT :
• well-defined, soft-tissue mass, hypodense to
muscle and showing little or no enhancement
with contrast.

18. On MRI :
• T1W : Low to intermediate signal intensity .
• T2W images : homogeneous high signal
intensity.

19. Specific signs for neurogenic tumors
• Target sign
• Reverse target sign
• Split fat sign
• Fascicular sign
• Nerve entering or exiting the lesion.
• Muscle atrophy in nerve distribution.

20. T2W – Hypointense center – fibrocollagenous core.
Hyperintense periphery – myxoid tissue

21. Split fat sign:
Fat around periphery of lesion more pronounced
at the proximal and distal ends.
Not specific for neurogenic tumors.
But confirms intramuscular location.
Absent in MPNSTs.

23. • Neurofibromas and schwannomas : fusiform,
circumscribed soft-tissue masses.
• Neurofibroma appears centred on
and indistinctive from nerve.
schwannoma - eccentrically to the nerve.
• Neurofibromas- homogeneous lesions .
Schwannomas - heterogeneous
appearance with cystic,
necrotic and calcific areas.

24. Diffuse neurofibroma –
Most common among children and young adults, typically involving the skin
and subcutaneous tissues of the head and neck , may extend to the
underlying fascia and muscles.
These are poorly defined , that spreads along connective tissue septa and
surrounds rather than destroys adjacent normal structures
Four morphological patterns on imaging:
• Plaque-like lesions
• Infiltrative lesions
• Mass-like lesions
• Mixed pattern.
Diffuse neurofibroma has a very low probability of malignant
transformation (Surgical excision is not mandatory)

25. Plaque like NF:
• Patch of abnormal tissue without intervening
normal tissue.
• show prominent internal vascularity

26. Infiltrative Diffuse NF:
Ill defined lesions with interspersed normal
tissue.

27. Mass-like lesions:
Well defined margins

28. Plexiform neurofibroma
• It is unique and pathognomic to NF1.
• PN present in childhood before cutaneous NFs.
• Significant risk of malignant transformation - 5%–10%.
• Involves multiple branches of large nerves, growing along their
length and causing
-expansion of the nerves
-extend beyond epineurium into surrounding tissues
-Marked disfigurement
-compression of vital structures
-progressive neurological deficit
-pain.

29. Plexiform neurofibroma :
• Classical bag of worms
• Scrotum without testicle
• Hyperpigmented and
hypertrichosis of overlying
skin.

30. On CT:
• Large, hypodense, infiltrative lesions
• No significant contrast enhancement and
cause erosion of adjacent bones.
On MRI
• Multinodular coalescent lesions
• T1W images - hypointense
• T2W images - heterogeneously hyperintense
with multiple target signs
• variable contrast enhancement.

33. • Rapid growth and atypical pain in a PN are
alarming signs for malignant transformation.
• Elephantiasis neuromatosa - PN occurring in
an extremity causing gigantic enlargement
with substantial disfigurement

34. Malignant peripheral nerve sheath tumour
• Preexisting plexiform neurofibroma
• Tend to involve larger nerve trunks such as
sacral plexus, brachial plexus and sciatic nerve.
Signs of malignant transformation-
• Sudden increase in size
• worsening pain
• Neurological symptoms

35. • MPNSTs – Sporadic (>60 yrs) ,
NF1associated(15-40yrs)
• These are high grade sarcomas with poor
prognosis.
• Complete surgical excision followed by
chemoradiotherapy is the treatment of choice

36. MPNSTs –
• Fusiform masses with heterogeneous
appearance (haemorrhagic and necrotic
components).
• Size > 5 cm.
• Irregular margins due to infiltration of adjacent
tissues.
• Perilesional edema
• Heterogeneous enhancement (peripheral
nodular enhancement ).
• 10-15% are FDG PET +.

39. Skeletal manifestations
• These are one among most frequent
manifestation of NF1 with incidence of 25-
40%.
 Dysplasia of tibia and other long bones.
 Vertebral and spinal manifestations.
 Sphenoid wing dysplasia.
 Multiple NOF’s.
 Other skeletal manifestations.

40. • Dysplasia of tibia and other long bones

41. Vertebral deformities
• Scoliosis - most common skeletal
manifestation of NF1
• Commonly involves the thoracic region.
• These are generally classified into non-
dystrophic and dystrophic types based on the
absence or presence of skeletal dysplasia on
plain radiographic evaluation.

42. Dysplastic features
• vertebral scalloping ( depth of scalloping is more
than 3 mm in thoracic and 4 mm in lumbar
vertebrae ),
• Rib pencilling (width of the involved rib < narrowest
portion of second rib),
• wedging of the vertebra,
• Paraspinal or intraspinal soft-tissue masses,
• Intervertebral foramina enlargement,
• Dysplastic pedicles and interpedicular distance
widening.

43. • This dysplastic features occurs due to - congenital
osteopathy of vertebrae .Dural ectasia and spinal
neurofibromas may contribute to its progression.
• Non dystrophic scoliosis – more common , ~
adolescent idiopathic scoliosis.
• Dystrophic scoliosis – short segment (4-6 vertebral
levels) , sharply angulated , associated with kyphosis.
• Dystrophic curves should be further evaluated with
whole spine MRI to assess intraspinal mass lesions,
especially when surgery is planned.
• Dystrophic scoliosis has a progressive course
demanding aggressive surgical treatment

44. • Dural ectasia is another spinal manifestation
of NF1 resulting from expansion of the thecal
sac and spinal nerve root sleeve, causing
posterior vertebral scalloping and lateral
thoracic meningocele formation.
• Dural ectasia may cause vertebral
instability with subluxations and
dislocations.

46. Spinal canal lesions
• IDEM NF’s are common lesions ,
foraminal/extraforaminal neurofibromas. They
can cause scalloping of vertebrae and
widening of neural foramina.
• IM lesions - astrocytomas .

47. Sphenoid wing dysplasia
• Sphenoid wing dysplasia is seen in approximately 11% of
NF1 patients
• It is almost always unilateral causing orbital asymmetry.
• It is characterized by hypoplasia of greater wing of sphenoid
bone with enlargement of the middle cranial fossa.
• Herniation of dura, CSF spaces or anterior temporal lobe
into posterior aspect of orbit and anterior temporal
arachnoid cysts are often seen.
• Bare orbit sign is a classical radiographic finding of NF1.
• It describes the absence of innominate line on the frontal
radiograph of the skull, which is formed by the greater wing
of sphenoid bone.

49. CNS manifestations
Neoplastic lesions:
• Optic pathway glioma (OPG)
• Nonoptic gliomas

50. Optic pathway glioma (OPG)
• OPG is the most common CNS neoplasm in paediatric patients.
• The presence of bilateral optic nerve gliomas (ONG) is considered
pathognomonic for NF1.N
The main radiologic criteria to diagnose ONG are
• Thickened optic nerve(>3.9 mm )
• With or without prominence of perioptic CSF spaces.
• They show interrupted ‘dotted i’ appearance on axial images
• Beanshaped kinky appearance in coronal images .
• The optic canal may be widened with bony remodelling and
scalloping.
• The lesions may extend along optic pathway to the optic chiasm, the
optic tracts and optic radiations.

52. Nonoptic gliomas :
• They are commonly seen in cerebellum,
brainstem, tectal plate and basal ganglia
regions.
• The vast majority are low-grade gliomas
mainly pilocytic astrocytomas;

53. Benign nonneoplastic lesions
Foci of altered signal intensity(FASI’s or UBO’s) :
• Hamartomatous lesions of white matter, involve basal
ganglia, thalami, dentate nuclei, cerebellar peduncles,
optic radiations and brainstem in children and adolescents.
• Represent regions of myelin vacuolization.
• They are hyperintense on T2 sequences and typically iso-
to mildly hyperintense on T1 images.
• They do not show mass effect or enhancement unlike low-
grade gliomas which show mass effect and sometimes
enhancement.

55. Cardiac and vascular manifestations
• NF1 vasculopathy is one of the leading causes of death
in NF1 patients.
• Renal artery stenosis with renovascular hypertension is
the most frequent presentation, usually in the second
decade of life.
• Aneurysms and stenoses of aortic, renal, mesenteric
and intracranial vasculature - younger patients.
• Degenerative atherosclerotic aneurysm of the aorta -
older patients.
• Abnormalities of cerebral vasculature –”moyamoya”
pattern.

56. Thoracic manifestations
• Neurofibromas at different locations
• Interstitial lung disease, late onset complication
- cysts or bullae
- upper lobe
- diffuse ground-glass opacities with mosaic pattern
and bibasilar reticular opacities.
• Neurofibromas involving trachea and oesophagus
have also been reported.

58. Abdominal manifestations
• Broad spectrum of benign and malignant
neoplasms.
• Most frequent – neurofibroma , plexiform
type .
• Location - Paraspinal and presacral region ,
mesentery, gastrointestinal tract, liver and
biliary tract, urinary bladder.
• In GIT - GISTs are most common , multifocal ,
small bowel.

62. Breast manifestations
• Multiple subcutaneous neurofibromas in
periareolarregion.
• On mammo- multiple, circumscribed and may
be surrounded by a rim of air owing to their
superficial nature.
• On USG- similar to fibroadenomas in the
subcutaneous plane.
• NF1 is also associated with an increased risk of
breast cancer development.

63. Orbital manifestations
• Orbital–periorbital plexiform neurofibroma
(OPPN) - Plexiform neurofibroma involving the
orbit, eyelid, periorbital and facial structures
and usually arise from the trigeminal nerve.
• It is associated with sphenoid wing dysplasia
on the same side.
• OPPN is seen as poorly defined infiltrative
lesion of the orbit and may extend to involve
face and cranium.

67. Neurofibromatosis 2
• Less common than NF1.
• Characterized by multiple cranial nerve
schwannomas, meningiomas and spinal
tumours.
• It is considered synonymous with bilateral
acoustic schwannomas.

69. GENETICS:
• Autosomal dominant inheritance.
• Chr.22
• NF2 gene
• Merlin protien(regulates growth of schwann
cells and arachnoid cap cells)

70. Clinical manifestations:
• Hearing loss, tinnitus, headache followed by
diplopia, vertigo, dizziness, imbalance and
facial weakness.
• Other presentations are neuropathies,
scoliosis, paraplegia or neck pain, extremity
weakness and cataract.

71. Cutaneous manifestations:
• CALMs – Few , no freckles.
• Cutaneous schwannomas – slightly raised ,
plaque like , pigmented lesions.

72. Central nervous system:
• Cranial nerve schwannomas- 8th
nerve ,MC.
• Meningiomas
• Meningioangiomatosis.
• Glial hamartomas.

73. Schwannomas:
The characteristic imaging features include
• well-defined, encapsulated lesions
• with or without cystic degeneration and
haemorrhage.
• well-circumscribed margins.
• Smooth expansion of osseous foramina, osseous
remodelling .
• Deformation of adjacent brain parenchymal tissue.
• Various degrees of solid nodular enhancement
with internal cystic degeneration.

74. • T1W : Isointense to muscle.
• T2W : Heterogenously hyperintense.
• T1+C : Heterogenous moderate to intense
enhancement (cystic / necrotic areas)

75. Meningiomas.
• Meningiomas are second most common type
of lesions in neurofibromatosis 2.
• Meningiomas can be seen in the cranial and
spinal regions.
• Meningioma in first decade of life is highly
suspicious of NF2.

76. Spinal tumours:
• IM - Ependymomas are the most common.
These tumours cause focal cord enlargement
and may be associated with proximal syrinx.
• IDEM - Schwannomas of exiting nerve roots,
spinal meningiomas.
• MISME, which constitute multiple inherited
schwannomas, meningiomas and
ependymomas.

80. Ophthalmic manifestations:
• Optic nerve sheath meningioma.
• Juvenile posterior subcapsular cataract.
• Retinal hamartomas.

81. Optic nerve sheath meningioma:
• Sporadic (adults), NF2 associated(children).
• Arise from arachnoid cap cells of optic sheath.
• Visual loss – due to compression on optic nerve.
• Axial MRI – Tramtrack sign , Coronal MRI –
Doughnut sign.
• Calcifications +.
• Hyperostosis of adjacent bones may be seen.

83. SCHWANNOMATOSIS
• Multiple schwannomas without vestibular or
cutaneous schwannomas.
• Mutation in LZTR1 and SMARCB1 gene on
Chr.22.
• Pain is most common symptom.
• >3rd
– 6th
decade .

84. Sturge–Weber syndrome
• Sturge–Weber syndrome (SWS) is also known
as encephalo-trigeminal angiomatosis.
• Vascular and cutaneous features predominate
without neoplasms.

85. Genetics:
• Sporadic mutation of GNAQ gene located on
Chr.9q21.
• Lack of maturation of primordial thin walled
vessels Abnormal capillary and venous
channels seen over leptomeninges ,
face , eye as Angiomas longstanding –
venous ischemia.

86. Clinical presentation:
• Seizures in infancy
• Glaucoma.
• Hemiparesis
• Hormonal deficiencies,other vascular
malformations are also known in SWS.

87. Neuroimaging in Sturge–Weber syndrome
On CT scan- dystrophic cortical and subcortical
calcifications - tram track gyriform calcification.
-U/L – 80%.
-MC location – parietooccipital region.

88. • Focal cerebral atrophy .
• Thickened skull vault.
• Ipsilateral choroid plexus enlargment.
• Ipsilateral PNS and mastoid air cells dilated.

89. MRI:
• Ipsilateral cerebral atrophy.
• Enlargement of subarchnoid spaces.
• Calcifications – T2 – Hypo, GRE – blooming.
• T1+C – intense leptomeningeal enhancement.
• MRS – Reduced NAA.

91. OPTHALMIC MANIFESTATIONS:
• Choroid angiomas – Crescentric thickening of
posterior wall of globe.
• T1 : Hyper , T2 : Iso , T1+C : Intense
enhancement.
• Glaucoma.
• Visual disturbance.
• Buphthalmos.

92. Cutaneous manifestations:
• Port wine stain – capillary vascular malformation
in face along the divisions of trigeminal nerve
(ophthalmic division is most commonly involved
– fore head and upper eye lid).
• Focal soft tissue mass in skin and subcutaneous
plane.
CT : Iso – hypo to muscle.
T1W : Iso – hypo
T2W : Hyper
Post contrast – intense enhancement.

94. DD’s:
• Acquired meningeal processes – Meningitis ,
tumour spread , hemorrhage.
• Meningioangiomatosis – It is rare
meningovascular hamartomatous plaque like
mass .No PWS.
• Klippel–trenaunay–webersynd : pial angiomas
present associated soft tissue and bone
hypertrophy.
• PHACES syndrome(posterior fossa malformations ,
infantile hemangiomas , arterial anamolies ,
coarctation of aorta , cardiac , eye and sternal
anamolies ).

96. THANK YOU

97. • Tommorow case presentations by Dr . Reshma
(HRCT temporal bone anatomy) and Dr . Avani
(Pylonephritis)