False positive PET in lymphoma Thomas Krause
Introduction and conclusion 2
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Introduction 4
FDG-PET in staging of lymphoma 34 studies with 2227 Patients CT FDG-PET Sensitivity 63 % 89 % (58%-100%) (63%-100%) Specificity 93 % 97 % (17%-97%) (69%-100%) Gambhir et al.; J Nucl Med. 2001: 42: 18S 5
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Causes of false-positive interpretation Technical artifacts Physiological uptake patterns Non-malignant pathological conditions Post therapy 7
18F-FDG - embolism Chondrosarcoma post therapy 8
18F-FDG - contamination B.M. m; 65y; Colon Ca., hemicolectomy 11/2010 9
18F-FDG para vascular injection G.R. m; 72y; squamous cell cancer 10
Causes of false-positive interpretation Technical artifacts Physiological uptake patterns Non-malignant pathological conditions Post therapy 11
Metabolism (Glucose) Plasma Glucose Cell Hexokinase GLUT Glucose Glucose-6-Phosphate Phosphatase CO2 H2 O Hexokinase 18 FDG GLUT 18FDG Phosphatase 18FDG-6-Phosphate 12
18F-FDG normal distribution I A.L. m; 46y; papillary thyroid cancer 13
18F-FDG normal distribution II A.L. m; 46y; papillary thyroid cancer 14
18F-FDG normal distribution III A.L. m; 46y; papillary thyroid cancer 15
18F-FDG normal distribution IV A.L. m; 46y; papillary thyroid cancer 16
18F-FDG normal distribution V C.G. m; 53 y; supraglottic squamous cell cancer 17
Negative influence on FDG uptake ingestion glucose injection diabetes mellitus increased chance of a false positive physical stress interpretation activation of brown fat chemotherapy 18
Diabetes mellitus M.J. 40J, m, Diabetes mellitus Sarkoidose 19
Metastasis in Seminoma? 18F-FDG Projektion - PET Coronal 3879/03: M.S., m, cryptorchidism; hemi-orchiectomy 20
Hodgkin Lymphom 4759/05, B.D. m, 10y, HD ED 05/03, LN resection, chemotherapy (2 cycles) 21
Hodgkin Lymphom 5829/05,, B.D. m, 10y, HD ED 05/03, LN resection, after chemotherapy 22
Hodgkin Lymphoma 2549879/11G.V. f, 61y, HD IIA ED 02/11; activated bone marrow after chemotherapy / G-CSF 23
Causes of false-positive interpretation Technical artifacts Physiological uptake patterns Non-malignant pathological conditions Post therapy 24
Non-malignant diseases Sarcoidosis Infection Warthin s tumour Langerhans cell histiocytosis Fracture Osteoarthitis Vasculitis 25
Benign diseases with high FDG uptake Sarcoidosis Hodgkin s disease 26
NSCLC 2624/06, K.D. f, 50y, NSCLC IIIB restaging after chemotherapy; Paget disease of the sacrum 27
CUP Ascariasis 317/09, K.E., f, 69y, CUP, metastases of the liver? 28
Recent rip fracture m, 11y, HD IV 29
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Maligne transformation Hexokinase Hexokinase 31
SUV 20 18 16 14 12 10 8 6 4 2 0 Nodular lymphocytic predominace Clasical Hodgkin lymohoma Nodular sclerosis Mixed cellularity Not specified 32
SUV 40 35 30 25 20 15 10 5 0 33
FDG uptake and histology T-cell lymphoma Mantle cell lymphoma 34
Development of PET and PET/CT 2001 6.3mm 2006 4.5mm 2010 2mm Transaxial resolution 35
Development of PET respectively PET/CT 2006 4.5mm 2010 2mm A.S. f; 25y, Ovarian cancer 36
What is a positive finding? Any distinquishable uptake?* Focal or diffuse uptake above background?** Uptake greater than blood pool? Liver?*** Hepatic or splenic lesions 1.5 cm or larger, if uptake is more than uptake in liver or spleen; or diffusely increased splenic uptake?** Any increased uptake in a mass smaller than 2 cm?** Clearly increased focal or multifocal bone involvement?** * Young H. et al: Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer. 1999;35:1773 **Juweid ME et al.: Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol. 2007;25:571 *** Wahl RL et al.: From RECIST to PERCIST: Evolving Considerations for PET Response Criteria in Solid Tumors. JNM 2009; 50: 122S 37
Causes of false-positive interpretation Technical artifacts Physiological uptake patterns Non-malignant pathological conditions Post therapy 38
FDG uptake after therapy What is the time course of uptake after therapy? How much uptake is normal? Are there typical differences depending on Histology? Therapy regimen? Tumor stage? 39
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M. Hodgkin 641/06, Z.P., m, 11y, HD IV before therapy and after 3 cycles COPDIC 10.05 02.06 41
Mantle cell lymphoma 1167/06, K.A., m 61J, Mantle cell lymphoma before therapy and after 4 cycles' R-CHOP 42
Hodgkin disease 21.03.2011 11.10.2010 28.05.2010 2638591, C.R., m, 42y, Hodgkin disease St. IIIA before, after 2 cycles and after completion of chemotherapy 43
Hodgkin disease 15.02.2011 11.03.2010 28.01.2010 2602571, W.F., m, 32y, Hodgkin disease St. III before, after 2 cycles and after completion of chemotherapy 44
4 Endoxan 3.5 Tumour mouse model 3 2.5 SUV 2 Viable Tumor Cells % 1.5 Mononuclear Infiltration % 1 0.5 0 Day 0 Day 1 Day 3 Day 8 Day 10 Day 15 45
Timing of Restaging 2-3 weeks after chemotherapy or chemoimmunotherapy 8-12 weeks after radiation or chemoradiotherapy 4-8 weeks after surgery 46
What is a positive finding after therapy? Any distinquishable uptake?* Focal or diffuse uptake above background?** SUV > 1.5 x mean liver SUV + 2 SDs of mean SUV SUV > XY SUV Decrease < 25% (after 2 cycles)* * Young H. et al: Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer. 1999;35:1773 **Juweid ME et al.: Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol. 2007;25:571 47
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Background Initial staging of a patient (74) with cervical cancer: PET-positive distant metastases 49
but considered negative in CT and MRI FDG PET-CT T1 fat sat with iv contrast CT 2mm slice thickness 50
Patient treated as planned: Follow-up PET-CT after chemotherapy and radiotherapy 51
PET guided Biopsy ARTORG CENTER BIOMEDICAL ENGINEERING RESEARCH 52
45-year-old woman with breast cancer > Suspicion of local recurrence CT: no morphological changes PET: Increased FDG uptake PET-guided biopsy of the hypermetabolic region Histology: Bone metastasis 53
Take home message Artifact must be detected by your nuclear medicine specialist. The physiological pattern of metabolism must be known. Correct patient preparation is mandatory. There is no false positive PET but wrong interpretation. Most inflammatory deceases show increased metabolism. Positive or negative interpretation depends on histology, therapy and anatomy. Patient s history is helpful to prevent misinterpretation. Histology? Inflammation? Therapy? Holistic image reading is essential. In a therapeutic setting a basic scan for comparison may be helpful. PET guided biopsy can help to avoid wrong interpretation. 54
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