Presentation2, radiological imaging of phakomatosis.

Health&Medicine

1. Dr/ ABD ALLAH NAZEER. MD. Radiological imaging of Phakomatosis.

2. Phakomatosis is a term derived from the Greek root phako, which refers to the lens; phakomatosis thus means a tumour-like condition of the eye(lens).

3. Neurofibromatosis. Autosomal dominant. -NF1- Mutation of the NF1 gene on chromosome 17. -NF2- Mutation of the NF2gene on chromosome 22. NF1 presents in children and NF2 seen at a later age.  

4. Diagnostic Criteria of NF1 Two of the following must be present to diagnose as NF1: . 6 or more cafe-au- lait macules. . 2 or more neurofibromas of any type or plexiform neurofibroma. . Freckling in the axillary or inguinal regions. . Optic glioma. . 2 or more Lisch nodules. . Distinctive bony lesion(i.e. sphenoid dysplasia, thinning of the long bone cortex with or without pseudoarthrosis). . A first degree relative diagnosed with NF1.

5. Cutaneous neurofibromatosis of neurofibromatosis.

6. Neurofibromatosis type 1. - Scalp/skull, meninges and orbit. -Cuteneous scalp, plexiform neurofibroma . .Solitary/multifocal scalp nodules. . Plexiform neurofibroma infiltrate and may extend to the cavernous sinus. -Sphenoid wing dysplasia. . Hypoplasia Enlarged orbital fissure . . Enlarged middle cranial fossa. .Temporal lobe may protrude into the orbit. -Dural ectasia. . Tortuous optic nerve sheath. . Patulous Meckel Caves. . Enlarged IACs.

7. Axial contrast-enhanced computed tomography scan (a) showing plexiform neurofibroma involving the subcutaneous aspect in right occipital region (arrow) with meningoencephalocele (arrowhead). (b) Magnetic resonance (MR) axial T2-weighted-image confirming the above findings (arrow) and (c) axial T2 MR image showing well-defined benign hamartomatous lesions in right basal ganglia and optic tracts (arrows).

8. ( a) Magnetic resonance (MR) coronal T2-weighted-image showing plexiform neurofibroma with target-appearance (black arrow) involving the left brachial plexus invading the humerus (white arrow) (b) MR coronal contrast-enhanced T1-weighted-image showing peripheral enhancement of nerve fascicles

9. Axial contrast-enhanced computed tomography scan (a) showing plexiform neurofibroma with calcifications (arrow) in left parapharyngeal and carotid space (b, c) axial magnetic resonance T1- and T2- weighted images showing heterogeneous signal intensity lesion (arrows) with flow voids within the lesion.

10. Neurofibromatosis type 1. Dysplasia of the left sphenoid wing with plexiform neurofibromatosis shown on a 3D CT image of the face and skull (A) and on T2W axial (B), coronal (C), gadolinium-enhanced T1W (D) MR images. Partial agenesis of the left greater sphenoid wing (arrowheads, A) and secondary expansion of the left orbit can be seen on CT. T2W images show multiple nodular and diffuse hyperintense lesions in the left orbit and extracranial region (arrows, B, C). Some nodular lesions show the target appearance (arrowheads, B, C). The lesions also show heterogeneous enhancement (D).

11. (A and B) Coronal short TI inversion recovery (STIR) images of (A) cervical and (B) lumbosacral spine of patient I:1 of family 2. At 30 years of age, multiple lesions are present bilaterally, most marked in the mid and lower cervical levels (A; arrowed) and in the sacrum, particularly of the S1 nerve root (B; arrowed). A mild thoracic kyphoscoliosis is also seen (A), and degenerative change of the L5/S1 intervertebral disc (B). (C) Coronal maximum intensity projection (MIP) 2 cm thick STIR image from the whole body MRI scan of patient II:1 of family 5. At 43 years of age, spinal nerve sheath tumours can be seen bilaterally at nearly every vertebral level: cervical and lumbar lesions are demonstrated. Alongside the extensive nerve root tumours, multiple subcutaneous lesions can be seen in the scalp (arrow) and extremities. (D) Coronal curved plane reformat MIP STIR image from the whole body MRI scan of patient III:

12. Spinal and Paraspinal Plexiform Neurofibromas in Patients with Neurofibromatosis Type 1

13. Hamartomas.

14. Neurofibromatosis type 1. Coexisting tumoral and hamartomatous lesions and zones of myelin vacuolization (ZMVs) in a 4-year-old boy. Axial T2W (A), T1W (B), and gadolinium-enhanced T1W (C) MR images. Several small ZMVs in the globi pallidi and the thalami are seen as slight hyperintense foci on a T2W image (arrows, A). The foci in the globi pallidi show slight T1 shortening (arrows, B). An astrocytoma appears in the left occipital deep white matter as a well-defined markedly T1- and T2-prolonged lesion with gadolinium enhancement (arrowheads, A-C).

15. Contrast-enhanced T1-weighted axial MRI of the orbits of the patient in which demonstrates a large optic pathway glioma with posterior extension into the optic tracts and radiations. 

16. Neurofibromatosis type 1. Optic pathway glioma in a 3-year-old girl is evident on gadolinium-enhanced T1W sagittal (A, B) and coronal (C, D) MR images. Enlargement of the left optic nerve is seen in the intraorbital portion (arrows, A, B), prechiasmatic portion (arrowheads, A, B), and the optic chiasm (arrows, C, D). The tumor shows diffuse enhancement, and the optic nerve is markedly tortuous.

17. Optic pathway glioma.

18. NF1 and an optic nerve glioma which has extended to involve the chiasm. (A) Pre- and (B) post-contrast T1-weighted coronal images reveal a large suprasellar mass with an enhancing component (arrow) seen separately from the normally enhancing pituitary gland. C: Axial scans through the suprasellar cistern show the tumor is high signal on T2-weighted scans. D: Enlargement of the chiasm, optic nerve, and hypothalamus is visible on the post-contrast T1-weighted sagittal image.

19. Brain stem glioma in neurofibromatosis type 1

20. Neurofibromatosis type 1. Brain stem glioma or unidentified bright objects in a 4-year-old boy as shown on axial (A) and sagittal (B) T2W MR images. Enlargement and ill-defined heterogeneous hyperintensity are seen in the pons, right middle cerebellar peduncle, and cerebellar white matter (arrows, A, B). It cannot be determined if this is a glioma or a zone of myelin vacuolation.

21. Pilocytic astrocytoma.

22. Callosal thickening of neurofibromatosis type 1. A midsagittal T1W MR image shows diffuse thickening of the corpus callosum (arrows).

23. Aqueduct stenosis in a patient with neurofibromatosis type 1. Midsagittal T2W (A) and gadolinium-enhanced T1W (B) images. The distal potion of the aqueduct shows stenosis (arrows) without any surrounding tumoral lesion. The proximal potion of the aqueduct is dilated.

24. Vascular dysplasia of neurofibromatosis type 1. MR angiography demonstrates stenosis of the distal portion of the left internal carotid and proximal portion of the left middle cerebral arteries (arrows).

25. Neurofibromatosis type 2 (NF2)  is a rare autosomal dominant neurocutaneous disorder ( phakomatosis ) manifesting as a development of multiple CNS tumours. Unlike  neurofibromatosis type 1 (NF1) , it is not associated with neurofibromas.  Instead, patients with this disease have: intracranial  schwannoma(s) : mostly  vestibular schwannoma(s)  sometimes patients may have  spinal schwannomas intracranial and spinal  meningioma(s) intraspinal-intramedullary  ependymoma(s) MISME: multiple inherited schwannomas, meningiomas, ependymoma.

26. Bilateral acoustic schwannomas on a background of neurofibromatosis type 2

27. T1 spin echo sequences (axial—A and coronal—B), both with fat saturation and contrast administration showing the typical imaging phenotype of a patient with neurofibromatosis Type 2 . There are bilateral vestibular schwannomas that have a component within the internal auditory meatus (dashed arrow) as well as within the cerebello-pontine angle (CPA, solid arrows). These components are in continuity and thought to represent one tumour mass. Further discrete disease is seen in the right vestibule (dotted arrow). The coronal sequence again shows the bilateral CPA angle components of the tumours compressing the brainstem (white arrows).

28. MISME syndrome (NF2).

29. Neurofibromatosis type 2: Images of a 12-year-old boy with deafness and weakness in his arms and legs, whose father has bilateral deafness. A: Axial T2-weighted and (B) post-contrast axial T2-weighted images reveal bilateral vestibular schwannomas, which are also known as acoustic neuromas (arrows). This is the classic finding of NF2. B, C: Bilateral schwannomas are seen in Meckel’s cave (arrowheads) and a (D) lower left cranial nerve schwannoma extends into the pars nervosa of the jugular foramen (arrow). E: A part cystic and part solid enhancing ependymoma are seen within the cervical cord and medulla and within the distal cord and conus.

30. Neurofibromatosis type 2

31. A : Spinal MRI shows a relative-demarcated, heterogeneously enhanced mass lesion accompanied by perifocal edema in C5-7 level (arrow). B : A left-sided T11 spinous process heterogeneously enhanced mass in soft tissue (thick arrow), and intervertebral disk hernia in L2-5 level (thin arrows). C, E, F, and G : Post-gadolinium T1 weighted sagittal imaging revealed widespread punctum enhancing lesion in her scalp and in T11-L5 level. D : Follow-up MRI revealed stable postsurgical changes in the C4-7 level with no evidence of tumor recurrence one year later. H, I, and J : Head MRI suggests no evidences of optic pathway glioma and neurofibromatosis 2.

32. Musculoskeletal manifestations of neurofibromatosis type 1 (NF1), are relatively common among these patients with skeletal abnormalities occurring in up to 50% of them. Radiographic features: Sphenoid wing dysplasia. Lambdoid suture defects. kyphoscoliosis vertebral scalloping : can be associated with dural ectasia or neurofibromas dural ectasia Hypoplastic posterior elements: thinning of the pedicles, transverse processes, and lamina Transverse process spindling Enlarged neural foramina Ribbon rib deformity ,  rib notching  and dysplasia  Tibial pseudoarthrosis  or less commonly ulnar pseudoarthrosis Limb hemihypertrophy

33. Neurofibromatosis type-1: Skull X-ray anteroposterior view (a) showing right sided bare orbit with absent greater wing of sphenoid (b) axial contrast-enhanced computed tomography scan image showing dysplasia of greater wing of sphenoid (black arrow) on right side with temporal lobe herniation, associated arachnoid cyst and plexiform neurofibroma of trigeminal nerve (white arrow).

34. Bare orbit sign.

35. Bone defect along the sagittal and lambdoid sutures in a 2-year-old girl with neurofibromatosis type 1. Anteroposterior skull radiograph shows multiple bone defects along the sagittal and lambdoid sutures (arrows). Mild dysplasia of the right sphenoid wing is also noted.

36. Neurofibromatosis type 1. Lumbar scoliosis, multiple paravertebral neurofibromas, and development of a malignant peripheral nerve sheath tumor are shown on a radiograph of the lumbar spine (A), T2W (B) and gadolinium-enhanced T1W (C) coronal MR images, and follow-up axial T2W MR image (D) and apparent diffusion coefficient map (E) 3 years later. Numerous plexiform neurofibromas showing target signs are noted in the bilateral paravertebral regions and pelvis (arrows, B, C). Some tumors extend to the spinal canal (arrowheads, B, C). The lumbar spine shows secondary scoliosis with bone erosion (arrows, A). A follow-up MRI examination after 3 years shows an enlarged tumor with heterogeneous T2 prolongation and low apparent diffusion coefficient (arrows, D, E). The tumor was resected and proved to be a malignant peripheral nerve sheath tumor.

37. Sturge-Weber syndrome, or encephalotrigeminal angiomatosis, is a phakomatosis characterised by facial port wine stains and pial angiomas.

38. Sturge Weber syndrome.

39. leptomeningeal angioma in Sturge-Weber syndrome.

40. Von Hippel-Lindau (VHL) disease is characterised by the development of numerous benign and malignant tumours in different organs (at least 40 types 1) due to mutations in the VHL tumour suppressor gene on chromosome 3. Epidemiology The disease is rare with an estimated prevalence of 1:35,000-50,000. Clinical presentation Clinical presentation is varied, depending on the site of disease manifestation (see below). Most commonly these are either within the abdominal cavity or central nervous system.

41. Distribution Patients may develop some or all of the various lesions which include: Abdominopelvic Renal lesions renal cell carcinoma(s) (RCCs): usually of the clear cell type 70% life time risk RCCs present at an earlier age in those with VHL Renal cysts can occur in up to 75% of cases often tend to be bilateral and multiple Renal angiomyolipoma(s) Pheochromocytoma(s) Numerous pancreatic lesions (may be the earliest manifestation) Pancreatic cysts pancreatic endocrine tumours: usually non-functional pancreatic serous cystadenoma pancreatic adenocarcinoma (rare) Liver cysts Papillary cystadenoma(s) of the epididymis Paraganglioma (rare).

42. CNS CNS hemangioblastoma(s): occur in ~70% Cerebellar (~75%) Spinal (~25%) Choroid plexus papilloma Head and neck retinal hemangioblastoma(s) most common presenting feature vision loss in 35-55% of patients endolymphatic sac tumours (ELST) bilateral ELSTs considered pathognomonic for VHL Mnemonic Features can be remembered by the mnemonic HIPPEL: Hemangioblastoma Increased risk of RCC Pheochromocytoma Pancreatic lesions (cysts, cystadenomas, cystadenocarcinomas) Eye dysfunction (retinal hemangioblastomas) Liver, renal and pancreatic cysts.

43. Cerebellar Hemangioblastomas in von Hippel- Lindau Disease.

44. Cerebellar Hemangioblastomas in von Hippel-Lindau Disease.

45. VHL disease shows hemangioblastomas (arrows) in (A) Brain and (B) Spine.

46. Spinal Hemangioblastoma.

47. Von Hippel-Lindau syndrome.

48. Multifocal Spinal Hemangioblastoma in von Hippel-Lindau Syndrome:

49. Von Hippel Lindau pancreatic cysts.

50. Pancreatic diffuse microcystic serous cystadenoma and pancreatic non functioning neuroendocrine tumor in the same patient. Asymptomatic 34-year-old woman, member of family affected to VHL disease.

51. Intestinal polyposis.

52. Endolymphatic Sac Tumor (ELST) ELST is a rare entity. These tumors originate from the endolymphatic sac. We will discuss them because their CT appearance is very typical. At CT a destructive process is seen on the dorsal surface of the petrosal part of the temporal bone with punctate calcifications. On MRI there is usually strong enhancement. The amount of destruction in this case would be atypical for a meningioma.

53. Endolymphatic Sac Tumor.

54. A classic presentation of endolymphatic sac tumor

55. Cowden syndrome, also known as multiple hamartoma syndrome, is characterised by multiple hamartomas throughout the body and increased risk of several cancers. Pathology The disease is characterised by: Dysplastic cerebellar gangliocytoma. Mucocutaneous lesions: present in >90% of cases trichilemmomas Mucocutaneous papillomata's papules gastrointestinal hamartomatous polyps (small and large bowel) glycogenic acanthosis thyroid abnormalities Thyroid adenomas Multinodular goiter Fibrocystic disease of the breast

56. Lhermitte-Duclos-Cowden syndrome

57. Lhermitte-Duclos disease.

58. 46-year-old female with history of neurofibromatosis Type 1 presented with left breast mass diagnosed as metaplastic breast carcinoma. Breast MRI with (a) T1-weighted, (b) short tau inversion recovery (STIR), and (c and d) subtraction post-contrast images demonstrate a large mass (long arrows) in the central left breast with low T1 (a), high T2 (b), and rim-like enhancement (c). Small enhancing nodules (neurofibromas) (short arrows) are also noted at the skin of the left breast, consistent with patient's known neurofibromatosis (d). d c

59. Thank You.