Imaging of tuberous sclerosis complex

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1 Imaging of tuberous sclerosis complex Poster No.: C-0388 Congress: ECR 2015 Type: Educational Exhibit Authors: M. V. Vu#kovi#, N. Menkovic, A. Petkovic, S. Ognjanovic, J. Markov, M. Ilic, D. Grujicic, P. D. S. Damjanovic, D Masulovic ; Belgrade/RS, Vrsac/RS Keywords: CNS, Lung, Abdomen, CT, CT-Angiography, MR, Computer Applications-Detection, diagnosis, Computer Applications-3D, Congenital, Developmental disease, Genetic defects DOI: /ecr2015/C-0388 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 29

2 Learning objectives The purpose of this study is to evaluate significance of imaging modalities in detection of clinical features of tuberous sclerosis complex (TSC) at the time of diagnosis and during surveillance. Background TSC is a multisystem autosomal-dominant disorder affecting children and adults, results from mutations in one of two tumor suppressor genes, TSC1 (encoding hamartin) or TSC2 (encoding tuberin). TSC causes non-malignant tumors to form in many different organs, primarily in brain, eyes, heart, kidney, skin and lungs. The 2012 International TSC Consensus Group provided guideline to definite diagnose based on genetic and clinical diagnostic features (Table 1). Table 1. Clinical Diagnostic Criteria for Tuberous Sclerosis Complex Major features Minor features 1. Hypomelanotic macules 1. "Confetti" skin lesions (>3, at least 5-mm diameter) 2. Dental enamel pits (>3) 2. Angiofibromas 3. Intraoral fibromas (>2) (>3 or fibrous cephalic plaque) 4. Retinal achromatic patch 3. Ungual fibromas (>2) 5. Multiple renal cysts 4. Shagreen patch 6. Nonrenal hamartomas 5. Multiple retinal hamartomas 6. Cortical dysplasias 7. Subependymal nodules (SEN) 8. Subependymal giant cell astrocytoma (SEGA) Page 2 of 29

3 9. Cardiac rhabdomyoma 10. Lymphangioleiomyomatosis 11. Angiomyolipomas (>2) Definite diagnosis: Two major features or one major feature with >2 minor features. Possible diagnosis: Either one major feature or >2 minor features. While skin lesion are visible by inspection, others major and minor features are diagnosed by imaging modalities (Magnetic Resonance Imaging - MRI, Multi Detector Computed Tomography - MDCT, ultrasound). Once diagnosed, the 2012 International TSC Consensus Conference provided recommendations of its surveillance and management. The common features that radiologist could come across during screening and surveillance are: A. Central nervous features Cortical dysplasia are mostly supratentorial, in the frontal lobes, commonly located at the gray-white junction. Occasionally, cortical tubers act as epileptogenic foci. SEN are located around the wall of the lateral and third ventricle, usually in close proximity to the foramen of Monro. They are more prone to calcification than cortical tubers, typically measure # 1 cm in size, but may grow over time and give rise to SEGAs. SEGA - WHO grade 1 tumors with slow growth, minimal parenchymal invasion, absence of adjacent brain edema and no predilection for CSF spread. Commonly they are located at the foramen of Monro, and their rapid growth can result in acute obstructive hydrocephalus. B. Pulmonary lesions LAM - diffuse interstitial proliferation of smooth muscle cells and appearance of cysts in pulmonary parenchyma, which are main cause of spontaneous pneumothorax. C. Angiomyolipomas (AML) Renal - if greater than 4 cm in diameter, the likelihood of aneurysm formation and potential life-threatening bleeding rises. Page 3 of 29

4 Findings and procedure details Retrospective study was performed from 2001 to 2014 year. We examined 7 patients with genetic proven TSC. Mean age at the time of diagnosis was 23 ± 22, with male to female ratio 1:6. There were two first and five follow up exams. Used imaging modalities were: 1. MRI of brain gadolinium contrast enhanced - T1, T2 and FLAIR 2. MDCT of head acquisition 25 seconds delay after intravenous administration of contrast material at flow rate 4 ml/s 3. MDCT of thorax acquisition 40 seconds delay after intravenous administration of contrast material at flow rate 3ml/s 4. MDCT of abdomen dual phase scanning, 25 and 60 seconds delay after intravenous administration of contrast material at flow rate 4 ml/s In software analysis we used 2D (MPR, MIP, MinIP) and 3D reconstructions (VR). We observed presence of major (from1 to 4) and minor (from 1 to 3) features. Usually diagnose had been set based on two major and one minor feature (Table 2.). Table 2. Presence of major and minor features Patients 7 Central nervous features Pulmonary AML features Cortical SEN dysplasia SEGA LAM Renal Hepatic Renal cysts 3 Page 4 of 29

The most constant major features were subependymal nodules, subependymal giant cell astrocytoma and angiomyolipomas. Multiple renal cysts and nonrenal hamartomas were most common minor features.

Central nervous lesions - cortical tubers, SEN and SEGA Patient No 1. - Female patient with diagnosed subependimal giant cell astrocytoma at age of 21.

5 The most constant major features were subependymal nodules, subependymal giant cell astrocytoma and angiomyolipomas. Multiple renal cysts and nonrenal hamartomas were most common minor features. Two complications that were recognized during surveillance period were hydrocephalus and spontaneous pneumothorax. Images of major features 1. Central nervous lesions - cortical tubers, SEN and SEGA Patient No 1. - Female patient with diagnosed subependimal giant cell astrocytoma at age of 21. Tumor is seen as large inhomogeneous enhancing lobulated lesion localized at frontal horn and body of right lateral ventricle with propagation to body of left lateral ventricle. There is progression in time span of eight years with development of obstructive hydrocephalus (enlargement of atrium and occipital horns, dominantly right). At age of 29 patient was operated on with definite diagnosis of SEGA WHO grade 1. Fig. 1: At age of 21, Gadolinium-enhanced, axial T1-weighted images through the brain Fig. 2: At age of 29, gadolinium-enhanced, axial T1-weighted images through the brain Page 5 of 29

Fig. 3: At age of 29, gadolinium-enhanced, coronal T1-weighted images through

4: At age of 29, gadolinium-enhanced, sagittal T1-weighted images through the

visualize calcifications of SEGA, small SEN along the lateral wall of left

6 Fig. 3: At age of 29, gadolinium-enhanced, coronal T1-weighted images through the brain Fig. 4: At age of 29, gadolinium-enhanced, sagittal T1-weighted images through the brain In the meantime, at age of 26, head CT was performed, where we can better visualize calcifications of SEGA, small SEN along the lateral wall of left lateral ventricle and cortical tubers in parietal and occipital lobes. Fig. 5: At age of 26, contrast enhanced MDCT of head, axial sections Page 6 of 29

Cortical tubers are better visualized at T2-weighted sequence as hyperintense lesions. At this case they were localized at parietal and occipital lobes and were epileptogenic silent. Fig.

7 Cortical tubers are better visualized at T2-weighted sequence as hyperintense lesions. At this case they were localized at parietal and occipital lobes and were epileptogenic silent. Fig. 6: At age of 29, axial T1-weighted images through the brain 2. Pulmonary lesions - Lymphangioleiomyomatosis Patient No year old female patient with progressive form of LAM, that led to restrictive ventilation disorder and partial respiratory failure complicated by pneumothoracies twice. Thin-walled cysts of variable size and contour are present in pulmonary parenchyma of both lungs diffusely. Dominant cyst is localized at superior segment of left lower lobe. Page 7 of 29

8 Fig. 7: MDCT of thorax, MPR, axial reformatted image Page 8 of 29

9 Fig. 8: MDCT of thorax, MPR, coronal reformatted image Page 9 of 29

10 Fig. 9: MDCT of thorax, MPR, axial refomatted image in MinIP Page 10 of 29

11 Fig. 10: MDCT of thorax, MPR, coronal refomatted image in MinIP Page 11 of 29

12 Fig. 11: MDCT of thorax, MPR, sagittal refomatted image in MinIP 3. Angiomyolipomas Page 12 of 29

Patient No. 3. - Female patient with multiple bilateral renal AMLs and their progression in size during 13 years period.

13 Patient No Female patient with multiple bilateral renal AMLs and their progression in size during 13 years period. They present as fatty rich heterogeneous, contrast enhanced lesions. Fig. 12: At age of 21, AML of right kidney - MDCT of abdomen, MPR, axial refomatted image Page 13 of 29

14 Fig. 13: 13 years after, at age of 34, significant progression in size. MDCT of abdomen, MPR, axial reformatted image Page 14 of 29

15 Fig. 14: At age of 21, AML of left kidney - MDCT of abdomen, MPR, axial refomatted image Page 15 of 29

16 Fig. 15: 13 years after, at age of 34, at similar section visiable significant progression in size. MDCT of abdomen, MPR, axial reformatted image. At age of 34 aneurysm of AML of left kidney was diagnosed which could lead to potential retroperitoneal bleeding. Page 16 of 29

17 Fig. 16: Aneurysm of AML of left kidney. MDCT of abdomen, MPR, axial reformatted image. Page 17 of 29

18 Fig. 17: Aneurysmatic vessels of AMLs. MDCT of abdomen, 3D-VR reformatted image. Page 18 of 29

Fig. 18: Aneurysm of AML of left kidney. MDCT of abdomen, 3D-VR reformatted image. Patient No. 4.

19 Fig. 18: Aneurysm of AML of left kidney. MDCT of abdomen, 3D-VR reformatted image. Patient No year old male patient with AML of right kidney without progression in size for a few years. Page 19 of 29

20 Fig. 19: AML of right kidney. MDCT of abdomen, MPR, axial reformatted image. Page 20 of 29

21 Fig. 20: AML of right kidney. MDCT of abdomen, MPR, sagittal reformatted image. Page 21 of 29

Patient No. 5. - Hepatic AMLs, are group of non-renal AMLs, that are considered to be major features.

22 Patient No Hepatic AMLs, are group of non-renal AMLs, that are considered to be major features. We present 14 year old girl with hepatic AMLs. Fig. 21: MDCT of abdomen, MPR, axial reformatted image in MinIP. Page 22 of 29

23 Fig. 22: MDCT of abdomen, MPR, axial reformatted image. Page 23 of 29

24 Fig. 23: MDCT of abdomen, MPR, sagittal reformatted image. Images of minor features 1. Multiple renal cysts Patient No year old girl with multiple bilateral simple renal cysts. Page 24 of 29

25 Fig. 24: MDCT of abdomen, MPR, axial reformatted image. Page 25 of 29

26 Page 26 of 29

27 Fig. 25: Multiple cysts of left kidney. MDCT of abdomen, MPR, sagittal reformatted image. Fig. 26: MDCT of abdomen, MPR, coronal reformatted image. Conclusion Imaging modalities are useful: Page 27 of 29

28 A. at the time of initial diagnosis to confirm presence of TSC and to determine the extent of disease B. during follow-up period to monitor progression of known problems or lesions or emergence of new one. The recommendations for surveillance of TSC are: 1. MRI of brain - every 1-3 years until the age of 25 years. Individuals without SEGA by the age of 25 years do not need continued surveillance imaging. Individuals with asymptomatic SEGA continue to be monitored because of the possibility of growth. 2. MDCT of thorax - in patients with no clinical symptoms and no evidence of lung cysts every 5-10 years, once cysts are detected every 2-3 years. 3. MDCT of abdomen - at the same time as brain surveillance imaging in order to diagnose changes in angiomyolipoma and polycystic disease as well as appearance of renal cell carcinoma or other tumors. Personal information References Crino P, Nathanson KL, Henske EP. The Tuberous sclerosis complex. The New England Journal of Medicine 2006; 355: Northrup H, Krueger D. Tuberous sclerosis complex diagnostic criteria update: Recommendations of the 2012 international tuberous sclerosis complex consensus conference. Pediatr Neurol 2013; 49(4): Krueger D, Northrup H. Tuberous sclerosis complex surveillance and management: Recommendations of the 2012 international tuberous sclerosis complex consensus conference. Pediatr Neurol 2013; 49(4): Radhakrishnan R, Verma S. Clinically relevant imaging in tuberous sclerosis. Journal of clinical imaging science 2011; 1(2): Cudzilo C, Szczesniak R, Brody A et al. Lymphangioleiomyomatosis screening in women with tuberous sclerosis. Chest 2013; 144(2): Page 28 of 29

29 6. 7. Lu J, Xiong XZ, Cheng NS. Hepatobiliary and pancreatic: Hepatic and renal angiomyolipomas associated with tuberous sclerosis complex. Journal of gastroenterology and hepatology 2014; 29: Page 29 of 29

Diagnosing TSC by Making Clinical Connections

Diagnosing TSC by Making Clinical Connections TSC = tuberous sclerosis complex. Diagnosing tuberous sclerosis complex: MORE CLUES Definite Diagnosis of Tuberous Sclerosis Complex (TSC) Possible Diagnosis