FDG PET/CT of Primary Bone Tumors

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1 Musculoskeletal Imaging Review Costelloe et al. FDG PET/CT of one Tumors Musculoskeletal Imaging Review Colleen M. Costelloe 1 Hubert H. Chuang 2 John E. Madewell 1 Costelloe CM, Chuang HH, Madewell JE Keywords: bone, FDG, malignancy, PET/CT, tumor DOI: /JR Received ugust 30, 2013; accepted after revision November 7, Division of Diagnostic Imaging, Department of Diagnostic Radiology, The University of Texas M. D. nderson Cancer Center, 1515 Holcombe lvd, Unit 1273, Houston, TX ddress correspondence to C. M. Costelloe (ccostelloe@mdanderson.org). 2 Department of Nuclear Medicine, The University of Texas M. D. nderson Cancer Center, Houston, TX. This article is available for credit. WE This is a web exclusive article. JR 2014; 202:W521 W X/14/2026 W521 merican Roentgen Ray Society FDG PET/CT of Primary one Tumors OJECTIVE. Numerous primary bone tumors are encountered on 18 F-FDG PET/CT, and many are FDG avid. The degree of FDG uptake in bone tumors does not necessarily reflect malignant potential. In conjunction with radiographs, evaluation of morphologic characteristics on the CT portion of PET/CT scans is important for characterization of the lesions. FDG PET/CT has been found to be useful for staging and has also been found to reflect prognosis in some primary bone malignancies. The purpose of this article is to familiarize the reader with topics regarding FDG PET/CT and both malignant and benign primary bone tumors. CONCLUSION. FDG uptake alone is not adequate for characterizing primary bone tumors, and morphologic evaluation is an important factor in the interpretation of PET/CT scans. fter diagnosis, FDG avidity and morphologic features can play an important role in staging and determining response to therapy. On completion of this article, readers should have an improved ability to evaluate the FDG uptake and CT morphologic features of malignant and benign primary bone tumors. Readers should also have a better understanding of the potential role of FDG PET/CT in the management of patients with osteosarcoma and Ewing sarcoma. P rimary bone tumors are often found on 18 F-FDG PET/CT, and many are FDG avid. lthough malignancies are significantly more avid than benign lesions overall, numerous exceptions exist. Therefore, interpreting the morphologic characteristics of the tumors is important. Radiographs are essential in the evaluation of primary bone tumors [1] but may not be immediately available. The morphologic characteristics of the lesions can be preliminarily evaluated on the CT portion of the examination, which is obtained simultaneously with the PET dataset, and then further assessed on radiographs. iopsy is recommended for tumors that appear morphologically aggressive, whereas nonaggressive lesions can be followed with radiographs, MRI, or CT. fter the diagnosis of certain primary bone malignancies, such as osteosarcoma and Ewing sarcoma, FDG PET/CT can also be used for indications such as whole-body staging and the evaluation of therapeutic response. FDG Uptake in Primary one Tumors spectrum of FDG uptake has been discovered in primary bone tumors, with more- aggressive lesions tending to be more FDG avid than nonaggressive lesions. Several studies have found malignancies to be significantly more avid than benign lesions overall [2 6]. The concept of the spectrum holds true particularly well when comparing tumors of the same histologic type, such as cartilage tumors. For example, it has been shown that FDG uptake of higher-grade chondrosarcomas is greater than that for lower-grade cartilage malignancies in general and that benign cartilage lesions typically have lower FDG uptake than do chondrosarcomas [2, 5, 7, 8]. This orderly spectrum is less likely to apply when comparing tumors of differing histologic groups. FDG avidity of several benign tumors can be as high as or higher than some of the malignancies. For example, giant cell tumors of bone have been repeatedly reported to be more avid than grouped chondrosarcomas [2, 3, 5] (Fig. 1). Schulte et al. [2] studied 202 lesions and found no significant difference between the FDG uptake of high-grade malignancies and benign aggressive lesions [2], and a different study found a trend toward higher uptake in the benign aggressive lesions than the malignancies [5]. enign aggressive lesions, such as gi- JR:202, June 2014 W521

2 Costelloe et al. ant cell tumors of bone and giant cell reparative granuloma, can be locally destructive but do not typically metastasize with the resultant death of the patient. dditional examples of tumors that may exhibit deceptively high FDG avidity include chondroblastomas, osteoblastomas, osteoid osteomas, Langerhans cell histiocytosis, chondromyxoid fibromas, brown tumors, fibrous dysplasias, fibroxanthomas (nonossifying fibromas), desmoplastic fibromas, and aneurysmal bone cysts [2 6, 9]. Nevertheless, individual tumor types can have widely varying FDG uptake. For example, a study that included 15 aneurysmal bone cysts and six nonossifying fibromas (fibroxanthomas) found approximately half of each lesion type to be avid enough to be confused with malignancies [2]. rown tumors have been found to lose their FDG avidity after treatment of hyperparathyroidism [10]. With the exception of some fibrous lesions, it has been observed that most highly avid benign bone tumors contain significant numbers of histiocytic or giant cells [3]. Some malignancies may exhibit a confusing paucity of FDG uptake. One study found that six low-grade chondrosarcomas had FDG avidity low enough to be confused with benign lesions [2]. Similar findings have been reported for low-grade osteosarcoma and Ewing sarcoma [6]. enign lesions with typically low FDG avidity included osteochondromas, enchondromas, hemangiomas, and intraosseous lipoma [2 5, 9]. Morphologic Features of Primary one Tumors on CT ecause of the lack of predictable FDG uptake in a sizeable minority of primary bone tumors, morphologic assessment remains necessary to evaluate their biologic potential and form a plausible differential diagnosis. Radiography is the preferred method of analysis [5], but important information is immediately available from the CT that is simultaneously acquired with the PET dataset. n aggressive biologic potential indicates that the tumors are capable of metastasizing and/ or producing excessive local destruction and/ or local recurrence. nonaggressive biologic potential indicates that the lesions are indolent or quiescent and not worrisome, unless they predispose to pathologic fracture or produce deleterious mass effect on adjacent structures. ggressive Features The margin of a primary bone tumor is one of the most sensitive indicators of biologic potential that can be evaluated on imaging studies [1, 11]. The edge of most aggressive tumors will appear unsharp or indistinct, reflective of active osteolysis. The lack of a sclerotic margin is worrisome and may indicate that the reparative mechanisms of the bone are unable to equal or exceed the rate of osteolysis caused by the tumor. Nevertheless, aggressive tumors may have partial sclerotic margins, and nonaggressive lesions may produce small areas of severe cortical thinning or absence. The lesser the degree of marginal sclerosis, the more likely the lesion is to be aggressive. ggressive lesions may be geographic (round or oval) but often show a wide zone of transition between the tumor and host bone. Highly aggressive lesions may present as a large field of osteolysis, rather than a discrete round or oval lesion. The osteolysis may resemble numerous holes of varying size (moth eaten; Fig. 2) or may be associated with fine fuzzy-appearing areas of bone destruction (permeated; Fig. 3). ggressive tumors often extend through the cortex directly into the adjacent soft tissues. Less-aggressive malignancies and benign lesions may expand the cortex (Fig. 4). These lesions grow slowly enough to allow the cortex to remodel around the periphery of the tumor. Nevertheless, even relatively indolent malignancies will often produce cortical breakthrough of the expanded cortex. Some forms of periosteal reaction are seen more typically with aggressive than with nonaggressive primary bone tumors. efore skeletal maturity, a major function of the periosteum is to enlarge the circumference of the bone. Throughout life, the periosteum also produces callous that aids in the stabilization of fractures when motion occurs at the fracture site [12]. When irritated by a primary bone tumor, the periosteum can produce new bone in various forms. ony spicules that form perpendicular to the cortex are found in a sunburst or hair-on-end periosteal reaction (Fig. 5). Layers that form parallel to the long axis of the bone describe an onionskin periosteal reaction (Fig. 6). Typically, the larger the number of spicules or layers, the more aggressive the underlying process, though aggressive malignancies may produce only mild or no periosteal reaction. Interruption of periosteal reaction by the tumor is also an aggressive feature. Periosteal reaction at the interface between the bone and tumor extending into adjacent soft tissues is termed a Codman triangle [11]. Indeterminate margins also exist and can be seen with malignant or benign geographic primary bone tumors. These margins are well defined with no sclerotic rims. They may result from tumors that destroy the bone incrementally faster than the rate at which it can repair itself, or they may be seen in tumors that either do not induce or suppress the reparative response (multiple myeloma). iopsy is recommended when encountering tumors with indeterminate margins, and to confirm the diagnosis of any potentially aggressive primary bone process. enign (Nonaggressive) Features Nonaggressive lesions are typically benign. Their margins often show a rim that is predominantly or completely sclerotic (Fig. 7). The spicules associated with periosteal reactions incited by benign lesions are often few, unilaminar, and thick. Solid cortical thickening is often indicative of a healed prior periosteal reaction. The cortical expansion of nonaggressive lesions is typically not interrupted by lysis, and the expanded cortex may be relatively thick (Fig. 8). The simple lack of aggressive features in a primary bone tumor can be reassuring. This discussion does not apply to metastases. lthough they are malignant by definition, sclerotic metastases may have sharply defined margins and lytic metastases may have sclerotic rims. Cartilage Lesions Enchondromas represent a common exception to the concept that the rim of a benign bone tumor should be predominantly sclerotic. On radiographs and CT, the intramedullary margin of enchondromas is often poorly discerned (Fig. 1), and cartilaginous matrix mineralization (arc-and-ring or stippled) and/or small areas of endosteal scalloping (cortical thinning) are the most readily visible features. The tumor can be distinguished from marrow on MRI, which typically depicts a finely lobulated margin. Some enchondromas show a predominantly sclerotic rim, which can be confused with bone infarct. painless lesion that is found incidentally and shows no aggressive features can be followed with radiographs. Low-grade chondrosarcomas may appear deceptively nonaggressive unless one is familiar with their appearance (Fig. 9). Particularly when they involve the diaphysis of the long bones of the appendicular skeleton, they are often large (> 5 cm) and thin, more than two thirds the thickness of the cortex over a length of more than two thirds of the lesion [13]. They often produce circumferential expansion of the bone and are typically associated with pain. W522 JR:202, June 2014

3 FDG PET/CT of one Tumors ll suspicious lesions that are not immediately biopsied must be followed regularly with imaging studies, such as radiography, CT, or MRI, until biologic potential is established. Therapeutic Response FDG PET/CT scans have been successfully shown to predict therapeutic response in primary bone malignancies, such as osteosarcoma and Ewing sarcoma. Changes in FDG avidity and morphologic features can be indicators of the efficacy of the regimen. Morphologic nalysis Morphologic changes on the CT portion of the PET/CT scan can be a valuable adjunct to the metabolic analysis. positive response is typically accompanied by partial or complete reconstitution of cortex that was previously interrupted by tumor lysis, maturation of periosteal reactions, and an increase in central mineralization (Fig. 10). Nevertheless, morphologic analysis is limited for assessing tumor response. For example, osteosarcomas may not diminish sufficiently in size to satisfy response criteria for therapeutic protocols, such as the Response Evaluation Criteria in Solid Tumors version 1.1, which require a minimum 30% decrease [14, 15]. Investigations of the impact of change in tumor size and volume on therapeutic response in Ewing and osteosarcoma have been mixed [16 20]. When a poor response is morphologically apparent, the aggressive features previously discussed can develop or progress. Metabolic nalysis ecause of the limitations of morphologic analysis, tumor metabolism has been investigated as a prognostic indicator. Osteosarcoma and Ewing sarcoma are the two most common primary nonhematologic bone malignancies for which standard chemotherapy regimens exist. Researchers who investigate these tumors have found that one or a combination of pretherapeutic FDG avidity [21 23], posttherapeutic FDG avidity [19, 22, 24 29], or change in FDG uptake between the two scans [19, 22, 24 32] correlate with outcome in osteosarcoma [19, 21 27, 29, 30, 32] and Ewing sarcoma [28, 31]. The two most robust reference standards for the outcome of patients with osteosarcoma or Ewing sarcoma are the histologic response of the resected tumor and short-term patient prognosis. Most of the studies investigating the role of FDG PET/CT in this context have used histologic response as their reference standard [19, 21, 24 29, 31]. Histologic response is determined by postchemotherapeutic tumor necrosis. lthough tumor necrosis is only a surrogate for actual prognosis, it is considered a strong indicator of patient outcome, and treatment decisions are commonly based on this result. Patients with tumors that undergo 90% or more tumor necrosis have been shown to experience a better prognosis than patients with more viable tumors [33]. Patients with suboptimal tumor necrosis will often undergo postoperative (adjuvant) chemotherapy in addition to the standard preoperative (neoadjuvant) chemotherapy. FDG avidity has been successfully correlated with tumor necrosis in osteosarcoma [22] and Ewing sarcoma [31]. One of the greatest potential advantages of FDG PET/CT in determining therapeutic response is through the early identification of poor responders. This can allow preoperative chemotherapy to be modified or extended while eliminating the delay associated with surgery and histopathologic analysis of the resected specimen. The relationship between FDG uptake and prognosis may be different in osteosarcoma than Ewing sarcoma. Denecke et al. [19] found significant relationships between FDG uptake and tumor necrosis in osteosarcoma but not in Ewing sarcoma. Gaston et al. [26] found a posttherapeutic maximum standardized uptake value of less than 2.5 to be predictive of tumor necrosis in osteosarcoma but not in Ewing sarcoma. They also discovered that a 50% decrease in metabolic tumor volume was predictive of tumor necrosis in osteosarcoma, whereas a 90% reduction in metabolic tumor volume was necessary for statistical significance in Ewing sarcoma. Clinical therapeutic indicators, such as progression-free survival and/or overall survival, have also been used as the reference standard for outcome in patients with osteosarcoma [22, 23, 27, 29] and Ewing sarcoma [28]. Progression-free survival is defined as the time from treatment until tumor recurrence, progression, or stability at the study endpoint. Overall survival is defined by whether the patient is alive or has died of their disease by the end of the observation period. Short-term prognosis is considered a robust reference standard, provided that an adequate number of years are allowed for follow-up. The median follow-up periods of studies that have used this reference standard was years [22, 23, 28, 29] with a preferred interval of 3 or more years. Pretherapeutic FDG uptake [22, 23], posttherapeutic FDG uptake [22, 29], and change in FDG uptake [22, 29] have been found to correlate with progression-free [22, 23, 29] and overall survival [22, 23] in osteosarcoma. Posttherapeutic avidity was found to correlate with progression-free survival in Ewing sarcoma [28]. Irrespective of the reference standard, FDG PET/CT has been found to be beneficial for the assessment of therapeutic response. Staging FDG PET/CT is a whole-body imaging modality that has been found to be successful in the staging of malignancies (Fig. 11). In a study that compared FDG PET, bone scan, and bone marrow biopsy or aspirate in 91 patients with Ewing sarcoma, Newman et al. [34] found that FDG PET detected bone metastases in all patients who had lesions detected by biopsy or bone marrow aspirate. PET found a metastasis in one patient with a negative bone scan. Overall, bone scan found more metastases in the skull, likely because of the close proximity of the highly metabolic gray matter on the PET scans [34]. PET-only scans have been found to be comparable to conventional imaging for detecting local and distant metastases from Ewing and osteosarcoma [35], but the PETonly scans were inferior to diagnostic CT for detecting lung nodules [36, 37]. London et al. [38] compared PET/CT with conventional imaging (CT, MRI, ultrasound, and bone scan) in a study that included 314 lesions on 86 scans in children with metastatic osteosarcoma and Ewing sarcoma. They showed that PET/CT had a higher sensitivity (98% vs 83%) and specificity (97% vs 78%) than did conventional imaging for detecting distant metastases, with the exception of pulmonary nodules. Regarding pulmonary nodules, PET/CT was found to have a higher specificity (96% vs 87%) but lower sensitivity (80% vs 93%) than did conventional imaging [38]. The acquisition of PET data requires several sets of images to cover the chest and upper abdomen, each lasting several minutes. ecause of the length of the acquisitions, full inspiratory PET is not feasible. The PET and CT portions of the examination are therefore typically obtained with quiet respiration to prevent misregistration artifact. The lack of full inspiration limits the quality of the CT, and it is recommended that the lungs be staged with diagnostic fullinspiratory CT to allow better evaluation of small pulmonary nodules. JR:202, June 2014 W523

4 Costelloe et al. Imaging Techniques and Emerging pplications of FDG PET/CT Dual-Time-Point Imaging Uptake time (i.e., the duration between radiopharmaceutical administration and imaging) is an important factor in the acquisition of PET scans. Published recommendations from a workshop sponsored by the National Cancer Institute [39] and from European sources [40] indicate that PET should be performed using a 60-minute uptake period and with a less than 10-minute variation between studies. ecause malignancies can progressively accumulate FDG for several hours and background activity is continually cleared, prolonged uptake periods often result in increased lesion conspicuity and higher measured tumor activity. lthough this phenomenon can cause difficulty in comparing the response of lesions on subsequent scans if uptake periods differ, it has also been studied as a potential diagnostic tool. Delayed imaging, using prolonged uptake periods, has been found to be efficacious in many circumstances, such as enhancing the ability of FDG PET/CT to reveal lesions such as breast carcinomas [41], primary malignancies in the head-and-neck region [42], solitary pulmonary nodules [43], and hepatic tumors [44]. Imaging that is performed with both standard and prolonged tracer uptake periods is termed dual-time-point imaging, and this technique had also been studied with primary bone tumors. Tian et al. [4] compared the maximum standardized uptake value (SUV max ) of primary bone tumors using standard (1-hour) and delayed (2-hour) FDG acquisition times in the context of differentiating malignant from benign bone lesions. lthough the FDG accumulation of malignancies tends to increase for several hours, the FDG uptake of benign lesions typically undergoes an early plateau, providing a potential means of differentiation. The sensitivity, specificity, and accuracy of PET using the standard image acquisition time were 96.0%, 44.0%, and 72.4%, respectively, and changed to 90.6%, 76.0%, and 83.7%, respectively, with the delayed imaging technique. Dual-time-point imaging has also been used to evaluate soft-tissue sarcomas [45]. Malignancies were found to take up FDG over 4 hours, whereas the activity in the benign lesions was observed to plateau at 30 minutes [45]. However, the use of dual-time-point imaging may not be practical because of prolonged scheduling time requirements; moreover, there is no consensus on the timing of delayed imaging (90- to 270-minute uptake time) or on the threshold value of FDG uptake for discriminating between malignant and benign lesions [46]. CT Technique The role of the CT that is obtained with each FDG PET/CT scan has been investigated in the diagnosis of primary bone tumors. In a study of 33 malignant and 17 benign lesions, Strobel et al. [47] found that combined PET/ CT (sensitivity, 91%; specificity, 77%; accuracy, 86%) was significantly more accurate than PET alone (sensitivity, 85%; specificity, 35%; accuracy, 68%; p = 0.039). They also found that morphologic analysis from the CT that accompanies the PET was helpful for correctly identifying benign tumors with high avidity, such as fibrous dysplasia, fibrous cortical defect, and aneurismal bone cyst, as well as malignancies with low FDG avidity, such as chondrosarcoma and leiomyosarcoma. They also found CT to be helpful in distinguishing osteomyelitis from bone tumors. The efficacy of bone windowing in FDG PET/CT of primary bone tumors has also been investigated. one windowing was compared with standard soft-tissue windowing in a study that included 64 malignant and 34 benign lesions [5]. CT in bone windows had higher specificity than did PET only (90% vs 75%; p = ) and trended toward higher sensitivity than did CT in soft-tissue windows (96% vs 90%; p = ). These findings support the time expenditure that is necessary for the use of bone windowing. PET/MRI FDG PET/MRI is an emerging imaging modality. The first PET-only scans provided limited anatomic information. To identify the location of tumor sites, early PET readers were compelled to rely primarily on their knowledge of anatomy and physiology, with the help of anatomic imaging studies that were usually performed noncontemporaneously. Later, CT scans acquired during the same session provided for attenuation correction and lesion localization, quickly leading to the widespread use of hybrid PET/CT scanners. The latest development in hybrid PET technology is PET/ MRI. Different manufacturers have produced scanners in different configurations. One approach is sequential. With this technique, the PET and MRI scanners are in close proximity but physically separated because the magnetic field necessary for MRI can adversely affect the electronics used in PET detectors, resulting in distorted images. With this technique, CT may still also be performed to provide attenuation correction of PET data, allow SUV calculation, and preserve the advantages of CT that are not available with MRI, such as excellent imaging of mineralized structures. rigid patient transport system is used between scanners to minimize motion and misregistration artifacts when the PET and MRI datasets are fused. True hybrid PET/MRI scanners have been developed that use solid-state photon detectors, avalanche photodiodes, or silicon photomultipliers to allow simultaneous PET and MRI without distortion from the magnetic field. Simultaneous PET and MRI significantly reduces total imaging time compared with sequential imaging. Hybrid PET/MRI may also reduce the misregistration artifacts from patient motion (including respiratory motion artifact) that are frequently present with traditional PET/CT. However, the calculation of attenuation correction based on MRI is more complicated than that with CT, and current algorithms can lead to an approximately 10 20% decrease in calculated SUV compared with measurements on the same patients using PET/CT [48]; this may cause difficulty in comparing the measurement of tumor activity between PET/MRI and PET/CT studies. lthough hybrid PET/CT has become the standard for PET, PET/MRI is in its early stages and without clear application at the time of this writing. It is expected that PET/ MRI could be more beneficial than PET/CT for situations where MRI has proven advantages over CT, such as in evaluating brain and soft-tissue lesions. For example, Kong et al. [49] investigated the point of maximum FDG uptake in osteosarcomas on PET/CT and PET/MRI. These investigators used hybrid PET/CT scanners for the PET portion of the examination and then imaged the patient in sequential fashion on an MRI scanner located 10 m from the PET/CT scanner. They performed a detailed histopathologic examination of the resected tumor and found that the posttherapeutic SUV max corresponded to the amount of tumor necrosis in the tissue at the point of greatest metabolic activity (presumably the most aggressive portion of the tumor), which was localized through the use of PET/ MRI. They also found a significant correlation between tumor necrosis in the location of the SUV max and overall tumor necrosis. Prior investigators attempting a similar analysis using PET/CT were unsuccessful [50]. The success of Kong et al. may indicate an advantage W524 JR:202, June 2014

5 FDG PET/CT of one Tumors provided by the superior anatomic resolution of MRI in comparison with CT. Combining PET with MRI also results in reduced radiation exposure, which is of increasing concern not only in pediatric but also in adult patients. lthough any potential synergistic benefit of PET/MRI has yet to be defined, experts think that the high sensitivity of PET and high softtissue contrast resolution of MRI will be found to be complementary [51]. Further technologic advances are expected to facilitate the usage of PET/MRI. FDG PET/CT has revolutionized cancer imaging by providing a whole-body method of evaluating patients with cancer that combines the sensitivity of metabolic imaging with the specificity of anatomic imaging. In addition to common malignancies such as lung cancer, breast cancer, and lymphoma, FDG PET/CT has been shown to be a useful method of evaluating bone tumors during initial staging and for monitoring therapeutic response. References 1. 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6 Costelloe et al. mors. J Nucl Med 2007; 48: Franzius C, Daldrup-Link HE, Sciuk J, et al. FDG-PET for detection of pulmonary metastases from malignant primary bone tumors: comparison with spiral CT. nn Oncol 2001; 12: London K, Stege C, Cross S, et al. 18 F-FDG PET/ CT compared to conventional imaging modalities in pediatric primary bone tumors. Pediatr Radiol 2012; 42: Shankar LK, Hoffman JM, acharach S, et al. Consensus recommendations for the use of 18 F- FDG PET as an indicator of therapeutic response in patients in National Cancer Institute Trials. J Nucl Med 2006; 47: oellaard R, Oyen WJ, Hoekstra CJ, et al. The Netherlands protocol for standardisation and quantification of FDG whole body PET studies in multi-centre trials. Eur J Nucl Med Mol Imaging 2008; 35: Mavi, Urhan M, Yu JQ, et al. Dual time point 18 F-FDG PET imaging detects breast cancer with high sensitivity and correlates well with histologic subtypes. J Nucl Med 2006; 47: Hustinx R, Smith RJ, enard F, et al. Dual time point fluorine-18 fluorodeoxyglucose positron emission tomography: a potential method to differentiate malignancy from inflammation and normal tissue in the head and neck. Eur J Nucl Med 1999; 26: Matthies, Hickeson M, Cuchiara, lavi. Dual time point 18 F-FDG PET for the evaluation of pulmonary nodules. J Nucl Med 2002; 43: Lin WY, Tsai SC, Hung GU. Value of delayed 18 F- FDG-PET imaging in the detection of hepatocellular carcinoma. Nucl Med Commun 2005; 26: Lodge M, Lucas JD, Marsden PK, Cronin F, O Doherty MJ, Smith M. PET study of 18 FDG uptake in soft tissue masses. Eur J Nucl Med 1999; 26: Schillaci O. Use of dual-point fluorodeoxyglucose imaging to enhance sensitivity and specificity. Semin Nucl Med 2012; 42: Strobel K, Exner UE, Stumpe KD, et al. The additional value of CT images interpretation in the differential diagnosis of benign vs. malignant primary bone lesions with 18 F-FDG-PET/CT. Eur J Nucl Med Mol Imaging 2008; 35: Wiesmüller M, Quick HH, Navalpakkam, et al. Comparison of lesion detection and quantitation of tracer uptake between PET from a simultaneously acquiring whole-body PET/MR hybrid scanner and PET from PET/CT. Eur J Nucl Med Mol Imaging 2013; 40: Kong C, yun H, Lim I, et al. 18 F-FDG PET SUVmax as an indicator of histopathologic response after neoadjuvant chemotherapy in extremity osteosarcoma. Eur J Nucl Med Mol Imaging 2013; 40: Costelloe CM, Raymond K, Fitzgerald NE, et al. Tumor necrosis in osteosarcoma: inclusion of the point of greatest metabolic activity from F-18 FDG PET/CT in the histopathologic analysis. Skeletal Radiol 2010; 39: Catana C, Guimaraes R, Rosen R. PET and MR imaging: the odd couple or a match made in heaven? J Nucl Med 2013; 54: Fig. 1 Comparison of benign and malignant tumors in three different patients., 39-year-old woman with enchondroma of humerus (maximum standardized uptake value [SUV max ], 2.3)., 39-year-old woman with chondrosarcoma of ninth rib (SUV max, 5.5). enign lesions are typically less avid than malignancies, particularly when lesions are of same histologic group, such as cartilage lesions. C, 33-year-old woman with giant cell tumor of bone in T6 (benign lesion, SUV max, 10.5). Predictable spectrum of FDG uptake does not always apply, particularly when comparing tumors of differing histologic group. C W526 JR:202, June 2014

7 FDG PET/CT of one Tumors Fig year-old boy with osteosarcoma of femur., Image shows moth-eaten pattern of osteolysis. Lucencies of various size (arrows) are seen throughout affected bone, indicating aggressive lesion., In setting of moth-eaten osteolysis, maximum standardized uptake value of 10.7 is supportive of lesion s aggressive character. Fig year-old man with lymphoma of bone in femur., Image shows permeative pattern of osteolysis. Lucencies (arrows) are so small that they are not individually discerned. Permeative pattern is most aggressive pattern of osteolysis., Maximum standardized uptake value is high (22), and extensive FDG uptake is present in soft tissues. lthough color field associated with FDG uptake often overestimates margins of tumors, it can give general indication of soft-tissue extension. MRI is recommended for further evaluation of extent of lesion on basis of its high soft-tissue contrast resolution. Fig year-old woman with giant cell reparative granuloma of right maxillary sinus., Image shows marked expansion of anterior, lateral, and posterior walls of sinus (arrowheads). one is markedly thin but intact. This behavior is most commonly shown by benign aggressive lesions that grow just slowly enough to allow bone remodeling and is suggestive of nature of tumor despite destruction of medial wall of sinus. Mucous retention cyst of left maxillary sinus is incidentally noted (asterisk)., Intense FDG uptake is not rare in benign aggressive bone tumors (maximum standardized uptake value, 17.7). JR:202, June 2014 W527

8 Costelloe et al. Fig year-old boy with osteosarcoma of femur, with hair-on-end or sunburst periosteal reaction., Exuberant periosteal reaction with spicules oriented perpendicular (arrow) or nearly perpendicular (arrowhead) to long axis of cortex indicates aggressive process., High maximum standardized uptake value of 10.3 reinforces morphologic findings. Fig year-old boy with Ewing sarcoma of femur with onionskin periosteal reaction., In this type of periosteal reaction, layers are parallel to long axis of bone and cortex (arrowhead)., Multiplicity of layers is consistent with aggressive process despite modest maximum standardized uptake value of 5.2. Fig year-old man with incidental fibrous dysplasia of femur., Image shows well-defined sclerotic margin (arrowheads) that is indicative of nonaggressive process., Fibrous dysplasia is benign lesion that can show deceptively high FDG uptake (maximum standardized uptake value, 4.3). W528 JR:202, June 2014

9 FDG PET/CT of one Tumors Fig year-old woman with nonaggressive fibrous dysplasia of intertrochanteric region of femur, producing mild cortical expansion and moderate cortical thickening., Unlike marked cortical expansion and thinning produced by benign aggressive lesion, as seen in Figure 4, cortical expansion of this nonaggressive tumor is less pronounced. Indolent growth pattern allowed formation of thick reparative periosteal new bone around lesion. When cortical remodeling is insufficient, benign lesions can predispose to pathologic fracture., Soft-tissue windowing makes ground-glass fibrous matrix (arrowheads) more conspicuous than does bone windowing used in panel. Typically, bone windows allow better visualization of fine details of mineralized structures. Exceptions tend to occur when mineralization is sparse. C, Different tumors of same histologic type do not always show consistent degree of FDG uptake. Maximum standardized uptake value of this lesion is 2.9. Note higher FDG uptake in equally nonaggressive fibrous dysplasia in Figure 7. Fig year-old woman with low-grade chondrosarcoma of femur., Radiographically, lesion is elongated, measuring approximately 15 cm, and occupies entire marrow cavity for majority of its length. Characteristic arc-and-ring cartilage matrix mineralization indicates cartilage tumor. Lesion shows thickened cortex with numerous areas of deep endosteal scalloping (arrows). Thick cortex indicates chronicity, which can be deceptive unless other factors are considered., Fat-saturated T2-weighted MRI shows finely lobulated margin composed of cartilage lobules. C, FDG PET/CT of lesion shows low maximum standardized uptake value of 1.3. Morphologic features of lesion and presence of pain are more helpful indicators of malignancy than degree of FDG uptake in this particular tumor. C C JR:202, June 2014 W529

10 Costelloe et al. Fig year-old boy with Ewing sarcoma. and, ggressive lesion (arrow, ) with moth-eaten osteolysis and pathologic fracture of left pubic body is seen, with high activity on pretherapeutic PET/CT () and maximum standardized uptake value (SUV max ) of C, fter chemotherapy, cortical margin has reconstituted and fracture has healed. Internal architecture of lesion simulates mineralized chondroid matrix (arrowheads). If study were read in isolation and without knowledge of clinical history, lesion could be mistaken for enchondroma. Clinical history is essential for proper interpretation. D, fter successful therapy, FDG uptake virtually resolves and SUV max falls to 2.1. C D Fig year-old man with esophageal carcinoma., Initial staging FDG PET/CT was performed. Coronal fused image is representative of entire study and shows solitary bone metastasis (arrow) in right sacrum. (Figure 1 continues on next page) W530 JR:202, June 2014

11 FDG PET/CT of one Tumors FOR YOUR INFORMTION D Fig. 11 (continued) 66-year-old man with esophageal carcinoma. and C, xial fused image () shows lesion, which is virtually imperceptible on CT alone (C). CT is commonly used for staging, and distant metastasis could have been overlooked without metabolic data. Incidental note is made of bone island directly lateral to metastasis (arrow, C). D, Metastasis is further validated on fat-saturated T1-weighted contrast-enhanced MRI. Rounded lesion (arrowheads) enhances less intensely than does surrounding bone marrow edema. Solitary metastases should be confirmed with biopsy. This article is available for CME and Self-ssessment (S-CME) credit that satisfies Part II requirements for maintenance of certification (MOC). To access the examination for this article, follow the prompts. C JR:202, June 2014 W531