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Common Causes of False Positive F18 FDG PET/CT …

29. , Special Number : pp. 29-35, September 2007. ISSN 1516-8913 Printed in Brazil BRAZILIAN ARCHIVES OF. BIOLOGY AND TECHNOLOGY. A N I N T E R N A T I O N A L J O U R N A L. Common Causes of False Positive F18 FDG PET/CT Scans in Oncology Kevin R. Carter* and Eduard Kotlyarov Michigan State University, POH Medical Center, 50 N. Perry, Pontiac 48342 - Michigan - USA. ABSTRACT. PET/CT is a Common imaging modality used in the evaluation of oncology patients. While being extremely sensitive to identifying sights of malignancy F18 FDG is very non-specific. We attempted to provide a brief review of some of the more Common processes that a nuclear radiology physician may encounter in daily clinical practice that could result in a False Positive diagnosis with F18 FDG PET/CT . A fundamental understanding of the limitations of this technology by the interpreting physician is necessary to avoid making inaccurate diagnosis and potentially limiting important treatments for our patients.

Common Causes of False Positive F18 FDG PET/CT Scans in Oncology Brazilian Archives of Biology and Technology 31 Figure 3 - This 6 year old child underwent PET/CT for evaluation of right supraclavicular lymphadenopathy. The MIP image (A and B) shows intense uptake of FDG in the

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Transcription of Common Causes of False Positive F18 FDG PET/CT …

1 29. , Special Number : pp. 29-35, September 2007. ISSN 1516-8913 Printed in Brazil BRAZILIAN ARCHIVES OF. BIOLOGY AND TECHNOLOGY. A N I N T E R N A T I O N A L J O U R N A L. Common Causes of False Positive F18 FDG PET/CT Scans in Oncology Kevin R. Carter* and Eduard Kotlyarov Michigan State University, POH Medical Center, 50 N. Perry, Pontiac 48342 - Michigan - USA. ABSTRACT. PET/CT is a Common imaging modality used in the evaluation of oncology patients. While being extremely sensitive to identifying sights of malignancy F18 FDG is very non-specific. We attempted to provide a brief review of some of the more Common processes that a nuclear radiology physician may encounter in daily clinical practice that could result in a False Positive diagnosis with F18 FDG PET/CT . A fundamental understanding of the limitations of this technology by the interpreting physician is necessary to avoid making inaccurate diagnosis and potentially limiting important treatments for our patients.

2 Key words: PET/CT , False Positives INTRODUCTION staging of multiple malignancies (Carter and Kotlyarov, 2005). It is approved in the United Radiologic imaging provides an important States for the characterization of solitary component to both the diagnosis and management pulmonary nodules, the diagnosis-staging- of oncology patients. Through the accurate restaging of colon carcinoma, lymphoma, noninvasive visualization of pathologic processes, melanoma, esophageal carcinoma, and head and there is a resulting decrease in the overall neck cancers. (See Fig. 1) It is also useful to morbidity and mortality. Traditionally, evaluate the efficacy of chemotherapy and/or Computerized Tomography (CT) has been utilized radiation therapy following treatment (MNCDM, to evaluate anatomical pathology. This 2007). (See Fig. 2). information was visually combined with the PET/CT offers a unique approach to the diagnosis functional information of Positron Emission and staging of malignancy by exploiting the Tomography (PET) with F18 fluorodioxyglucose biochemical differences between benign and (FDG).

3 Current technology allows for malignant cells Kostakoglu et al., 2003). FDG is simultaneous acquisition of this information which an analog of glucose and is used as a marker of allows precise localization and characterization of glucose metabolism. It is taken up in both tumor pathological processes. Utilization of PET/CT has cells and cells involved in other pathologic been shown to be beneficial in altering the conditions due to an overall increase in the number management of patients compared to imaging with of glucose transporter proteins and increased just CT or PET alone (Mavi et al., 2005). intracellular hexokinase and phosphofructokinase PET/CT is currently utilized in the diagnosis and levels, which promote glycolysis. FDG acts *. Author for correspondence Brazilian Archives of Biology and Technology 30 Carter, K. R. and Kotlyarov, E. similarly to D-glucose in transport through the cell This result in increased uptake of FDG within membrane and phosphorylation by hexokinase.

4 Metabolically active cells. Sites of physiologic Once FDG is phosphorylated, hexose-phosphate accumulation of FDG include organs which enzyme prevents FDG from being further normally utilize glucose for metabolism (brain, catabolized or transported back into extracellular muscles striated and smooth, salivary glands, space in substantial amounts, essentially trapping myocardium, gastrointestinal system, urinary the FDG (Kostakoglu et al., 2003). system, thyroid gland, and gonadal issues). B. C. A. Figure 1 - This 56 year old male presented with an abnormal pre-employment screening chest x- ray. The PET/CT was performed to determine if an abnormality present in the lung was malignant or benign. Whole body maximum intensity projection (MIP) image (A). shows a focal area of FDG uptake in the right lower lobe (arrow). Axial PET image at the level of the lesion (B) showed the approximate location of the area of increased activity (arrow), but the fused PET/CT image (C) confirmed that this lesion was actually within the lung.

5 This lesion underwent biopsy and proved to be well differentiated adenocarcinoma A B. Figure 2 - This 47 year old female initially presented for a lymphoma staging exam in March 2007 (A) Whole body MIP image, demonstrated marked uptake of FDG within the lymph nodes of the mediastinum and right supraclavicular region (arrow). Following chemotherapy, whole body MIP image obtained July 2007, (B) there has been a dramatic reduction in the uptake of FDG within the mediastinum and supraclavicular region, but there is increased uptake within the bone marrow that is related to increased hematopoietic activity as a response to chemotherapy Brazilian Archives of Biology and Technology Common Causes of False Positive F18 FDG PET/CT Scans in Oncology 31. B. A C. Figure 3 - This 6 year old child underwent PET/CT for evaluation of right supraclavicular lymphadenopathy. The MIP image (A and B) shows intense uptake of FDG in the bilateral supraclavicular regions that would be suspicious for disease, but when correlated with the fused image (C), this area of increased uptake is in the region of fat and is consistent with brown fat.

6 The CT portion of the exam helped exclude our original diagnosis of lymphoma that was obtained from interpreting only the PET. images DISCUSSION result in a False Positive diagnosis for malignancy on PET/CT . Several cases have been reported FDG is not only a cancer specific imaging agent, including abscesses (brain, abdominal, renal, tubo- False Positive results may be observed with benign ovarian), osteomyelitis, sinusitis, myositis, diseases. False Positive results are commonly thryoridits, matitis, esophagitis and gastritis (Alavi observed in areas of active inflammation or et al., 2002). Other described etiologies include infection (Gupta et al., 20000), with a reported pneumonia from multiple Causes (Bunyaviroch False Positive rate of 13% and False negative rate and Coleman, 2005). While there are numerous of 9% (Alavi et al., 2002). Inflammatory cells etiologic Causes for infection, tuberculosis and the (neutrophils and activated macrophages) at the fungal infections (Cryptococcosis, Histoplasmosis, sites of inflammation or infection will show Coccidioidomycosis, Blastomycosis, and increased FDG accumulation (Alavi et al.))

7 , 2002). Aspergillosis) are most commonly described as These False - Positive areas of metabolic activity source of False Positive results with PET/CT . have the potential for significant morbidity and examinations (Bunyaviroch and Coleman, 2005). mortality if not accurately recognized. Tuberculosis is one of the oldest diseases to affect Brown adipose tissue has been reported to be humans. It is caused by bacteria belonging to the observed in 2-4% of patients and is especially mycobacterium tuberculom complex (Raviglione Common to be observed in women and children and O'Brien, 2005). It usually affects the lungs, during cold weather months. This tissue is but in one third of cases, other organs are responsible for cold induced and diet induced involved. Extrapulmonary sites may also be thermogenesis. Mitochondria in brown adipose involved including: regional and distant lymph tissue exclusively express the thermogenic protein, nodes, pulmonary pleura, genitourinary system, and F18 FDG uptake in this hypermetabloic brown gastrointestinal system, skeletal system, fat can occur (Kostakoglu et al.

8 , 2003). FDG is pericardium, and the central nervous system normally taken up in brown adipose tissue in the (Raviglione and O'Brien, 2005). All of these neck, paraspinal location as well as in the areas of infection/inflammation will demonstrate pararenal space (See Fig. 3). intense uptake of FDG and unless correlated with Multiple nonspecific infectious/ inflammatory the patient's clinical history and pathologic biopsy processes can cause increased FDG uptake and will result in an incorrect diagnosis. (See Fig. 4). Brazilian Archives of Biology and Technology 32 Carter, K. R. and Kotlyarov, E. Figure 4 - Coronal, Sagital, and axial PET/CT images of the brain that shows a focal area of increased metabolism within the Right occipital lobe (arrow). This area correlated with the enhancing mass that was observed on an MRI (not shown) and was felt to represent a primary brain neoplasm (astrocytoma). Biopsy revealed that this lesion was actually a walled off abscess resulting from infection with M.

9 Tuberculosis Many noninfectious inflammatory granulomatous with increased FDG accumulation is also processes can also lead to localized and commonly observed on PET/CT (Shreve et al., disseminated inflammatory processes throughout 1999). Approximately 5-10% of patients with the body that may result in focal areas of increased sarcoidosis will manifest cardiac involvement with metabolism on PET/CT examinations resulting in reduced left ventricular function, valvular a False Positive diagnosis. While there may be abnormalities, pericardial effusions, and multiple etiologies, those most commonly ventricular aneurysms (Brudin et al., 1994). Other encountered includes: sarcoidosis, athrosclerosis, areas of involvement include the skin, ears, and and pneumoconiosis (Shreve et al., 1999). central nervous system (Shreve et al., 1999). Sarcoidosis is a chronic multisystem noncaseating Involvement of the kidneys and liver is also granulomatous disease. It is characterized by known, with almost 40-70% of patients having accumulation of T lymphocytes and mononuclear granulomatous involvement of the liver at biopsy phagocytes, noncaseating epithelioid granulomas, (Shreve et al.)

10 , 1999). Any of these sites of active and derangements of the normal tissue architecture involvement will show accumulation of FDG on in affected organs. The etiology is unknown, but is PET/CT and this accumulation as long as not though to be caused by an exaggerated cellular mistaken for malignancy may be useful for immune response. Several groups have reported assessing systemic involvement and the response FDG uptake by sarcoid granulomas (Shreve et al., to therapy (Alavi et al., 2002). In cases of 1999; Brudin et al., 1994; Lewis and Salama, suspected sarcoid based upon PET/CT findings 1994; Yasuda et al., 1996) due to the inflammatory and clinical history; correlation with bronchoscopy cell infiltrates composed of lymphocytes, and bronchoalveolar lavage, or biopsy of an macrophages, and epithelioid cells. Sarcoidosis accessible lymph node may is necessary to may show multiorgan involvement at PET/CT differentiate this entity from metastasis, military examination.


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