Tuberous Sclerosis A Radiological Perspective

Transcription

1 November 2001 Tuberous Sclerosis A Radiological Perspective Heather Brandling-Bennett, Harvard Medical School, Year III

2 Tuberous Sclerosis Also referred to as Bourneville s disease or tuberous sclerosis complex (TSC) Characterized by hamartomas in multiple organs Wide-range of clinical manifestations, predominantly affecting the skin, brain, kidney, heart, lung, eye and bone Autosomal dominant disorder, although spontaneous mutation in up to two-thirds of cases Associated with abnormalities of chromosomes 9 & 16 Prevalence of 1/10,000 to 1/100,000 Most common of dominantly inherited genetic disorders 2

3 Vogt s Classic Triad (1908) Adenoma sebaceum (facial angiofibromas) Seizures Mental Retardation Facial angiofibromas However, only 30% of patients with tuberous sclerosis have all three features of the triad. Guerrero et al. Circulation. 1994; 90(6):

4 Dermatological Manifestations Facial angiofibromas Forehead fibrous plaques Periungual fibromas Shagreen patch Connective tissue nevus usually on the dorsal surface Hypomelanocytic macules (Ash leaf spot) Use Wood (UV) light Zeller et al. Arch Derm. 1995; 131(12): Jalou et al. Arch Ped & Adol Med. 2001; 155(1):89. 4

5 Neurological Manifestations Subependymal glial nodules Cortical tubers Subependymal giant cell astrocytomas Seizures, mental retardation, autism, ADHD 5

6 Patient A 48 year-old male patient at the Beth Israel Deaconess Medical Center with tuberous sclerosis Suffers from seizures and severe mental retardation Has hamartomas in the kidney, eye and brain 6

7 Patient A s Head CT Calcified subependymal glial nodules BIDMC BIDMC 7

8 Patient B s Head MRI Superior for identifying cortical tubers Rarely, subependymal nodules transform into giant cell astrocytomas When in the region of the foramen of Munro, cause hydrocephaly Major cause of death in patients with tuberous sclerosis MRI of a 6 year-old showing a giant cell astrocytoma resulting in hydrocephaly and enlargement of left ventricle Nabbout et al. J of Neurology, Neurosurgery, & Psychiatry. 1994; 66(3):373. 8

9 Renal Manifestations Renal angiomyolipomas (AMLs) Renal cysts Rarely, renal cell carcinoma 9

10 Patient A s CT of the Abdomen Multiple renal angiomyolipomas BIDMC 10

11 Renal Angiomyolipomas on CT Another slice of patient A s abdominal CT BIDMC Renal angiomyolipomas are hamartomas consisting of fat, smooth muscle, and blood vessels Often multiple and bilateral Occur in up to 80% of patients with TS, incidence increases with age On CT, renal AMLs appear as well-marginated cortical masses of predominantly fat attenuation with scattered heterogeneous soft-tissue attenuation due to hemorrhage, fibrosis, or vascular and smooth muscle components 11

12 Interesting finding By the way, did you notice the interesting finding on patient A s abdominal CT? A beautiful example of INTUSSUSCEPTION in the distal duodenum There is no described association between tuberous sclerosis and intussusception in the literature. BIDMC 12

13 Patient C s Renal Angiomyolipomas on MRI T 1 weighted image On T 1 weighted images, AMLs appear as areas of high signal intensity. On fat suppression sequences, AMLs would appear as areas of signal loss. Evans and Curtis. British J of Radiology. 2000; 73:96. 13

14 Patient D s Renal Angiomyolipomas on Ultrasound On ultrasound, AMLs appear as heterogeneous masses which are predominantly hyperechoic with acoustic shadowing Difficult to distinguish AML from renal cell carcinoma on US Renal cysts would appear as echolucent lesions on US Normal renal US of a 4 yearold boy with TS Follow-up US 18 months later shows development of a new AML Ewalt et al. J of Urology. 1998; 160(1):

15 Gross pathology of renal angiomyolipomas Gross specimen showing the heterogeneous composition of AMLs Complication of AMLs: hemorrhage Wagner et al. Radiographics. 1997; 17(1):

16 Patient E s Angiomyolipomas on Angiography Intrarenal, perirenal, retroperitoneal and intraperitoneal hemorrhage have been reported as complications of angiomyolipomas. Transcatheter embolization of the AMLs is a potential treatment, sparing the patient from undergoing a nephrectomy or partial nephrectomy. Evans and Curtis. British J of Radiology. 2000; 73:96. 16

17 Patient F s Cardiac Manifestations Cardiac rhabdomyomas Hamartomas within myocardium Associated with arrhythmias, inflow and outflow obstruction, and heart failure On echocardiography, appear as smooth, ovoid, hyperechoic lesions 80% of individuals with cardiac rhabdomyomas have TS Most regress spontaneously during childhood Echocardiogram of a 14 year-old boy with TS shows intracardiac masses in the left ventricle Guerrero et al. Circulation. 1994; 90(6):

18 Patient G s Fetal Ultrasound: Cardiac Rhabdomyomas Echocardiogram of a fetus at about 22 weeks gestation shows hyperechoic masses within the myocardium of both ventricles and atria Abnormal fetal heart rhythm Diagnosis of tuberous sclerosis confirmed at autopsy, which showed multiple cardiac rhabdomyomas and multifocal cortical tubers in the brain Lethor and de Moor. Circulation. 2001; 103(10):55. 18

19 Lung Manifestations Lymphangioleiomyomatosis (LAM) Micronodular pneumocyte hyperplasia Hamartomatous proliferation of type 2 pneumocytes 19

20 Patient H s Lymphangioleiomyomatosis High-resolution chest CT shows numerous cysts Characterized by proliferation of smooth muscle cells of bronchi, alveoli, vessels, and lymphatics Interstitial infiltrates seen on plain film or CT progresses to honeycomb lung: multiple thinwalled cysts throughout lungs Found in about 1% of patients with tuberous sclerosis, almost exclusively female Complications: pneumothoraces, pneumomediastinum, chylous pleural effusions, pulmonary hypertension and cor pulmonale Evans and Curtis. British J of Radiology. 2000; 73:97. 20

21 Skeletal Manifestations Sclerosis Predilection for calvaria, spine, ribs, long bones, metacarpals, metatarsals and phalanges Sclerosis of two pedicles in the lumbar spine of a patient with TS Patient J Patient I Sclerosis in phalanges of index & middle finger and 2 nd metacarpal in a 5 yearold boy with TS Evans and Curtis. British J of Radiology. 2000; 73:

22 Skeletal Manifestations (cont.) Bone cysts Distal phalanges Osteomatous-like protuberances Tubular bone of hands and feet Patient K Jacobson. Skeletal Radiology. 1985; 13(1):11. 22

23 Other Non-Radiological Manifestations Retinal involvement: Mulberry retinal astrocytomas Plaque-like hamartomas Achromic patches Dental issues: Dental enamel pitting Gingival hamartomas Intestinal hamartomatous polyps 23

24 Summary Tuberous sclerosis is a disease that affects multiple organ systems Many different imaging modalities can be used to diagnose and follow patients with TS Cranial CT and MRI Abdominal ultrasound, CT and MRI; Angiography (treatment) Echocardiography High-resolution chest CT Skeletal radiographs 24

25 References BIDMC patient files. Castro M, Shepherd CW, Gomez MR, Lie JT, Ryu JH. Pulmonary Tuberous Sclerosis. Chest. 1995; 107(1): Evans, JC, Curtis J. The radiological appearances of tuberous sclerosis. The British Journal of Radiology. 2000; 73: Ewalt DH, Sheffield E, Sparagana SP, Delgado MR, Roach ES. Renal lesion growth in children with tuberous sclerosis. The Journal of Urology. 1998; 160(1): Guerrero H, Campos P, Harrison C. Cardiac rhabdomyomas in tuberous sclerosis. Circulation. 1994; 90(6): Hyman MH, Whittemore VH. National Institutes of Health consensus conference: Tuberous Sclerosis Complex. Archives of Neurology. 2000; 57(5): Jacobson, HG. Dense bone too much bone. Skeletal Radiology. 1985l 13(1):1-20. Jalou H, Hutcheon RG, Sanz, A. Radiological case of the month. Archives of Pediatrics & Adolescent Medicine. 2001; 155(1): Lethor JP, de Moor M. Multiple cardiac tumors in the fetus. Circulation. 2001; 103(10):55. Nabbout R, Santos M, Rolland Y, Delalande O, Dulac O, Chiron C. Early Diagnosis of subependymal giant cell astrocytoma in children with tuberous sclerosis. Journal of Neurology, Neurosurgery, & Psychiatry. 1999; 66(3): Patel NA, Bahri NU, Murjani DM, Shah TS. Ind J Radiol Imag. 1999; 9(2): Wagner, BJ, Wong-You-Cheong JJ, Davis JD. Adult Renal Hamartomas. Radiographics. 1997; 17(1) Zeller J, Friedmann D, Clerici T, Revuz J. The significance of a single periungual fibroma. Archives of Dermatology. 1995; 131(12):

26 Acknowledgements Chad Brecher, MD Larry Barbaras and Cara Lyn D amour Pamela Lepkowski 26