common pitfalls in oncologic fdg pet/ct imaging · radiology studies. patient preparation,...

J Am Osteopath Coll Radiol 2018; Vol. 7, Issue 1

Over the last decade, F-18 fluorode-oxyglucose (FDG) PET/CT has

continued to have an ever-increasing role in staging malignancy, evaluating tumor response to treatment, and eval-uating indeterminate masses discovered on CT, MRI and US. Many decisions regarding medical and/or surgical inter-ventions are largely based on functional metabolic information gathered from the PET/CT. It is, therefore, critical for the interpreting physician to be aware of potential pitfalls that may lead to an erroneous diagnosis.

As the name implies, FDG is an an-alog of glucose that is beneficial in de-tecting a variety of malignancies. The relative increased uptake of FDG by many malignancies compared to back-ground tissues is due to the increased expression of glucose transporters by cancer cells, as well as variations of intracellular enzyme activity with increased activity of hexokinase and decreased activity of glucose-6-phos-phatase.1 Ultimately, this leads to in-creased accumulation of FDG in many malignant cells as, unlike regular glu-cose, FDG does not become further me-tabolized after initial phosphorylation.

Unfortunately for interpreting physi-cians, a major limitation of FDG is that it is not specific for neoplastic cells. In addition to the variations of normal human metabolism within organs and tissues that universally rely on glucose as a substrate, a variety of nonmalig-nant inflammatory processes can also demonstrate significant FDG uptake. In fact, FDG is increasingly used clinically for nononcological purposes, including neurodegenerative disorders, cardiac viability, cardiac sarcoid, as well as replacing traditional radiolabeled leu-kocyte imaging for detecting infection. There is also an overlap in the amount of FDG uptake between many benign and malignant lesions. This problem is common in evaluating solitary pul-monary nodules and incidental adrenal nodules, for example. Furthermore, certain benign lesions such as Warthin’s tumors may also display a high degree of FDG uptake.

Additionally, whole-body FDG PET/CT is a technically challenging exam-ination compared to many standard radiology studies. Patient preparation, radiotracer injection, uptake period, image acquisition, and processing all

have potential for problems that can af-fect image interpretation.

This article is a pictorial review of a variety of pitfalls in interpreting FDG PET/CT scans. After discussing a vari-ety of general considerations, details of pitfalls related to specific body regions will be presented. With familiarity and understanding of these processes, the reading physician increases the likeli-hood of diagnostic pitfall recognition, thus avoiding incorrect interpretations.

General ConsiderationsAlthough patient preparation can

vary by institution, practice guidelines from the Society of Nuclear Medicine and Molecular Imaging suggest that patients fast 4 to 6 hours prior to PET imaging to ensure optimal insulin lev-els.2 Injection of FDG and subsequent imaging in nonfasting patients can re-sult in a so-called altered biodistribu-tion, in which there is relative increased FDG uptake throughout the body’s skeletal muscles largely due to insulin effect (Figure 1). Similar findings can be seen in patients on insulin and corti-costeroids, as well as in those who have recently exercised. Regardless of cause,

Common Pitfalls in Oncologic FDG PET/CT Imaging

Benjamin L. Viglianti, M.D., Ph.D.,1,2 Ka Kit Wong, M.B.B.S.,1 Milton D. Gross, M.D.,1,2 Daniel J. Wale D.O.1,2

1Department of Radiology, University of Michigan, Ann Arbor, MI; 2Nuclear Medicine Service, Veterans Affairs (VA) Medical Center, Ann Arbor, MI



FIGURE 1. Altered biodistribution. FDG PET MIP image demonstrates diffuse increased muscular uptake, most consistent with insulin effect in this nonfasting patient.

FIGURE 2. Extravasation at the injection site. FDG PET MIP image demonstrates a large focus of uptake in the right upper extremity (solid arrow) with adjacent lymphatic uptake (dashed arrow) due to extravasation at the injection site. Not only does this create an optical distraction for the interpreter, it also decreases the amount of radiotracer in the blood pool and can lead to inaccurate SUV measurements.

FIGURE 3. Misregistration artifact. Axial FDG PET (A) and fused PET/CT (B) images demonstrate myocardial FDG uptake erroneously localizing to the left lung (arrow, B). The patient changed position between CT and PET acquisition resulting in this artifact.

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FIGURE 4. Brown fat uptake. FDG PET MIP image in a pediatric patient demonstrates bilateral uptake in cervical, supraclavicular, and paraspinal fat, as well as additional foci in the upper abdomen (arrows) in a classic pat-tern of brown fat uptake.

FIGURE 5. Normal pediatric red marrow dis-tribution. FDG PET MIP image in a pediatric patient demonstrates heterogenous FDG uptake in the proximal humeri, proximal and distal femurs, and proximal tibias (arrows) reflecting normal FDG uptake in red bone marrow. This uptake is usually minimal or absent in adults due to the conversion of red marrow to yellow marrow, which is typically less metabolically active.



an altered biodistribution can obscure underlying disease and potentially af-fect tumor-to-background conspicuity.3

Similarly, artifacts can be related to suboptimal injection technique of the radiopharmaceutical. A small amount of extravasation at the injection site is common, and correlation with in-jection site documentation is advised when identifying a small focus of ab-normal uptake in the subcutaneous tissues of the upper extremities or in draining lymph nodes. However, oc-casionally a greater amount of the ra-diotracer extravasates, causing more significant artifacts (Figure 2). The interpreting physician must use cau-tion when reporting such cases and may need to repeat the study to ensure diagnostic accuracy. Specifically, the calculated standardized uptake values (SUVs) of the lesions of concern may not be accurate as the documented in-jected dose (one parameter for deter-mining SUV) likely does not reflect the true dosage of FDG in the blood pool due to the extravasation.

In addition to the usual motion ar-tifacts present throughout imaging modalities, PET/CT is susceptible to potentially problematic artifacts when patient position changes between CT and PET acquisition, resulting in mis-registration. This is common near the diaphragm, as most PET acquisition is not done with a breath-hold, although respiratory gating can help minimize this misregistration. With more significant motion, FDG uptake can project over the

incorrect anatomic structures and may lead to incorrect localization (Figure 3). Some software packages allow the user to adjust registration to align data to cor-rect the error, although these are usually limited to rigid realignments in 3 axes. Patient motion between the PET and CT portion of the studies can also cause an incorrect attenuation map to be applied to the PET region, thus affecting the at-tenuated corrected data set.

In addition, metal or other high-den-sity implants, as well as oral and in-travenous contrast, can create a false area of relative increased uptake due to attenuation correction artifacts. Attenu-ation correction works well in the range of tissue densities within the human body; however, it is prone to falsely overestimate the degree of attenuation correction in regions of higher density materials. As this activity is usually

FIGURE 6. Thymus activity. FDG PET MIP image in a pediatric patient demonstrating normal uptake in the thymus (solid arrow) including a lower cervical component (dashed arrow), a variant of normal.

FIGURE 7. Windowing pitfall. FDG PET MIP images (A, B) at two window levels demon-strate a hypermetabolic left cerebellar mass (arrow, B) confirmed in fused PET/CT image (arrow, C). The mass is obscured in the default window (A) due to the relatively high physiologic uptake in the brain.

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not associated with anatomic masses, it is usually discounted by the interpreter by noting the CT findings. However, review of the nonattenuation corrected data set can confirm the artifact, as this activity should disappear on nonattenu-ation-corrected images.4

Lymphoma is one of the more com-mon indications for oncological PET/CT. Some of the most common histo-logical subtypes, including Hodgkin disease and diffuse large B-cell lym-phoma, are extremely PET-avid, and PET can be used for staging and assess-

ing treatment response. However, other histological subtypes are less likely to be FDG-avid. These include pri-mary cutaneous anaplastic large T-cell lymphoma, extranodal marginal zone lymphoma, and small lymphocytic lym-phoma.5 When performing initial stag-ing PET/CT on patients with a known lymphoma, occasionally a non-FDG avid lymphoma will be encountered. It is important to alert the referring phy-sician that the disease being evaluated is not FDG-avid and a follow-up FDG PET/CT for determining treatment

response may not be useful. Knowl-edge of neoplasms that have low FDG avidity is important to prevent inappro-priate action regarding false-negative findings, including hepatocellular car-cinoma, renal cell carcinoma, neuro-endocrine tumors, well-differentiated endocrine malignancy, prostate cancers and some genitourinary cancers.

Pediatric Variants, Pitfalls and Artifacts

PET imaging for childhood cancers is predominately performed for lym-phoma, osteosarcoma, Ewing sarcoma, and soft-tissue sarcomas including rhabdomyosarcoma and malignant pe-ripheral nerve sheath tumors. Imaging children requires specific knowledge of changes in the physiological processes of maturation; the more frequent need for sedation; and awareness of the spec-trum of childhood cancers, genetic pre-disposition syndromes, and secondary cancers after treatment.6

Brown FatBrown fat contains metabolically ac-

tive mitochondria that burn energy and release heat. Brown fat uptake has been reported in one-third of children im-aged with PET, and is more frequent in children than adults. It is more common in cold climates and can be reduced by

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FIGURE 8. Photopenic brain metastasis. Axial FDG PET (A) and contrast-enhanced CT (B) images demonstrate a metastasis from lung carcinoma (arrows) appearing relatively photopenic com-pared to the high background uptake throughout the brain.

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FIGURE 9. Prior infarct. Axial FDG PET image (A) demonstrates a wedge-shaped region of pho-topenia in the right parieto-occipital lobe (arrow), correlating to a prior infract with a region of encephalomalacia noted on CT (arrow, B).

FIGURE 10. Focal nasopharyngeal uptake. Axial fused FDG PET/CT image demonstrates focal uptake in the right fossa of Rosenmuller (arrow) in a patient with metastatic lung car-cinoma. This uptake was inflammatory and resolved on follow-up imaging.



warming techniques.6 Common loca-tions include the supraclavicular fossa, cervical and axillary soft tissues, me-diastinum, thoracic parascapular and paraspinal soft tissues, and the upper ab-domen (Figure 4).7

MarrowRed marrow is more metabolically

active than yellow marrow and, there-fore, demonstrates relatively increased FDG uptake. In neonates, the distribu-tion of red marrow involves the distal

long extremities. As infants grow, the red marrow shifts from the skull and extremities to the axial skeleton (spine, pelvic bones, ribs and sternum) with yellow fatty marrow replacement oc-curring earlier at the epiphyses and di-aphysis (Figure 5). By around 15 years of age, this process is largely complete. In adults, only a little hemopoietic red marrow remains in the proximal me-taphysis of the femur and humerus. Additionally, the skeleton in children is rapidly growing at the physes and syn-chondroses, which can appear relatively “hot” on PET imaging.8

ThymusChildren, adolescents, and young

adults have a greater incidence of thy-mus visualization on PET imaging, with hyperplasia occurring in the set-ting of severe stress or chronic disease,

FIGURE 11. Unilateral decreased left vocal cord uptake. Axial FDG PET image (A) shows decreased uptake in the left vocal cord (arrow). Fused PET/CT image (B) of the chest demonstrates a hyper-metabolic left suprahilar mass extending into the aortopulmonary window (arrow), likely impress-ing and/or infiltrating the left recurrent laryngeal nerve.

FIGURE 12. Diffuse thyroid uptake. Axial FDG PET/CT image demonstrates diffuse uptake in the thyroid gland (arrows) in a patient with Hashimoto’s thyroiditis.

FIGURE 13. Focal uptake in a thyroid nodule. Axial FDG PET (A) and fused PET/CT (B) images demonstrate focal FDG uptake in a benign right thyroid nodule (arrows). As both benign and malignant nodules can demonstrate focal FDG uptake, further evaluation with ultrasound is recommended when this finding is encountered.

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FIGURE 14. Muscle uptake. Axial FDG PET (A) and fused PET/CT (B) images demonstrate increased FDG uptake in the muscles of mastication in a patient presenting for restaging of head and neck carcinoma. Gum chewing during uptake led to this unusual appearance.



termed thymic rebound when found after chemotherapy. With maturity, the thymus varies considerably in shape, and often can be difficult to distinguish from an anterior mediastinal mass. Neonates have a large thymus, which increases up to 2 years of age. It can cover both the left and right aspects of the heart, and has been described as quadrangular. Gradually, the thymus assumes the more classic sail or spin-naker sign. On PET imaging, the thy-mus should have uniform FDG uptake and smooth convex margins. Cervical thymic extension is an important vari-ant to recognize, wherein thymic tissue extends into the superior mediasti-num and lower neck (Figure 6). This represents an embryologic remnant

along the track of descent. It may oc-casionally appear as a lower cervical mass, discontinuous with the thymus, and can be mistaken for a tumor or en-larged lymph node.9

Lymphoid TissueChildren have prominent lymphoid

tissue compared to adults, including the above-described thymus and in bone marrow. They also have prominent sec-ondary lymphoid tissue, including the adenoid, palatine, and lingual tonsils. Furthermore, they are more prone to symmetric low-grade FDG uptake in re-active lymph nodes due to inflammation or infection in common sites, including cervical, axillary, mesenteric, and in-guinal lymph nodes.

Head and NeckEvaluation for brain masses is po-

tentially problematic, largely due to the high physiologic FDG uptake in the gray matter structures. It is critical for the interpreting physician to adjust the win-dow to detect potential hypermetabolic brain masses, such as those resulting from lymphoma, metastatic melanoma, or lung cancer (Figure 7). On the other hand, brain lesions with significant cystic and/or necrotic components may appear relatively photopenic (Figure 8). When encountering subtle foci, it is best to correlate with contrast-enhanced, diag-nostic quality CT or MR. Other causes of photopenic defects in the brain include postoperative changes and prior infarcts (Figure 9).

In patients with no history of head and neck cancer, incidental asymmetric uptake in the pharynx poses a diagnos-tic dilemma, as both malignancy and in-fection/inflammation can result in focal asymmetric uptake (Figure 10).10 Focal uptake at the midline of the nasophar-ynx has also been described in inflamed Thornwaldt’s cysts. Despite a variety of attempts to find a reliable prospective means to differentiate benign from ma-lignant uptake,11-13

there is no clinical consensus for a reliable absolute or rel-ative SUV to differentiate inflammation

FIGURE 15. Incidental intraparotid focus. Axial FDG fused PET/CT image demonstrates an incidental focus of uptake in the left parotid gland (arrow). The focus was stable for several years and presumed benign.

FIGURE 16. Benign sinus uptake. Axial FDG fused PET/CT image demonstrates a hypermetabolic focus in the left maxillary sinus (arrow). Tissue sampling revealed an inverted papilloma.

FIGURE 18. Sarcoidosis. Coronal FDG fused PET/CT image demonstrates mild increased FDG uptake in bilateral hilar adenopathy and adjacent peribronchovascular interstitial changes (arrows) in a woman with sarcoidosis.

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FIGURE 17. Non-FDG avid pulmonary nodule. Axial FDG PET (A) and fused PET/CT (B) images demonstrate a 2-cm right upper lobe nodule demonstrating minimal FDG uptake (arrows). Con-tinued CT follow-up is required, as certain malignancies, including adenocarcinoma in situ and carcinoid, can be PET negative.



from malignancy. Ultimately, clinical and/or endoscopic evaluation will likely be needed to exclude malignancy.14

Recent phonation will increase FDG uptake in the vocal cords. When this is symmetric, no diagnostic challenge is present. Focal asymmetric uptake in the vocal cords, however, likely requires further investigation. A common cause of asymmetric uptake is unilateral vocal cord paralysis. Vocal cord paralysis will result in decreased FDG uptake in the affected cord and a search for an under-lying cause, such as a thoracic mass im-pinging the recurrent laryngeal nerve, cervical mass involving the course of the vagus nerve, or history of neck sur-gery (Figure 11). In the absence of an underlying cause, laryngoscopy will likely be necessary.

As with pediatric patients, brown fat FDG uptake is a common cause of focal uptake in adult necks, and is potentially problematic when evaluating patients with head and neck cancers as well as lymphoma.15 The key for identifying this pitfall is localization of the uptake to fat density on CT and lack of corre-sponding soft-tissue mass. At times, however, it can be difficult to separate this activity from closely adjacent lymph nodes. This entity occurs more in colder climates. Because brown fat is sympathetically innervated, patient anxiety at the time of the PET scan may contribute to its visualization. A vari-ety of means can help minimize this brown fat uptake, the simplest of which is to ensure adequate warming prior to injection and uptake.16 Several drugs,

including propranolol,17 diazepam,18 and fentanyl,19 have also shown to de-crease brown fat uptake; however, the routine clinical implementation of these medications is challenging in the outpa-tient setting. Although uncommon, hi-bernomas, which are benign neoplasms composed of brown fat, can demon-strate increased FDG uptake.

Incidental uptake in the thyroid gland is often encountered on PET imaging. Diffuse increased FDG up-take throughout the thyroid gland is usually benign; correlation can be made for diffuse thyroid diseases, in-cluding Graves’ disease or chronic lymphocytic (Hashimoto’s) thyroiditis (Figure 12).20 Although rare, diffuse FDG uptake has been associated with malignancy, including cases of thyroid lymphoma21 and metastatic non-small cell lung carcinoma.22 Focal thyroid FDG uptake, on the other hand, re-quires additional evaluation with ul-trasound and possible tissue sampling, as there is a significant association with malignancy. In one study, Choi et al demonstrated malignancy in 18 of 49 focal thyroid lesions detected on FDG PET/CT and it is generally accepted that one-third of FDG-avid thyroid nodules are malignant, with the remainder being benign thyroid adeno-mas (Figure 13).23

Muscle uptake in the neck is variable and mostly related to recent use, pain,

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FIGURE 19. Postoperative inflammation in an aortic graft. FDG PET MIP (A) and axial fused PET/CT (B) images demonstrate mild FDG uptake along the course of a recently placed aortic graft (arrows).

FIGURE 20. Radiation inflammation. Axial CT (A) and fused FDG PET/CT (B) images demonstrate increased FDG uptake within bilateral medial upper lobe airspace opacities (arrows) in a patient undergoing radiation therapy of the thoracic spine. Findings are asymmetric and worse on the left.

FIGURE 21. Myocardial infarct. Axial FDG PET image demonstrates a focal photopenic defect corresponding to an apical left ventric-ular infarct (arrows).



anxiety or inflammation. As with brown fat uptake, this muscular uptake can be readily localized to muscle with CT correlation and the lack of a correlating mass lesion. Regardless, this should be minimized, particularly when evaluat-ing patients with head and neck cancer, as this uptake may obscure small dis-ease foci. Most patient protocols request withholding eating and chewing gum prior to the exam, as this can result in in-tense FDG uptake throughout the mus-cle of mastication (Figure 14).

Additional hypermetabolic lesions may be encountered incidentally in the head and neck. Most commonly, these include incidental foci in the sal-ivary glands (Figure 15) and sinuses (Figure 16). When encountering such lesions, it is appropriate to suggest ad-ditional work-up with imaging and/or tissue sampling. Seo et al documented focal FDG uptake in the parotid gland in 2.1% of patients with head and neck malignancy, of which 33.3% were met-astatic foci disease and 66.7% demon-strated a variety of benign pathologies.24

ThoraxEvaluation of the solitary pulmonary

nodule is one the most common indica-tions for FDG PET/CT, which aids char-acterizaion of indeterminate pulmonary nodules. In a study evaluating 89 patients with solitary pulmonary nodules, FDG PET/CT demonstrated a sensitivity of 92% and speficity of 90% for detecting

FIGURE 22. Cardiac melanoma metastases. Axial CT (A) and fused FDG PET/CT (B) images demonstrate multiple hypermetabolic cardiac masses (arrows) in a patient with widely metastatic melanoma.

FIGURE 23. Adrenal nodular hyperplasia. Axial FDG PET (A) and fused PET/CT (B) images demon-strate low-level FDG uptake, equal to slightly less than liver background, and nodular thickening of the adrenals (arrows) in a patient with lung carcinoma. These findings correspond to benign nodular adrenal hyperplasia.

FIGURE 24. Fibroid uptake. Sagittal CT (A) and fused FDG PET/CT (B) images show intense FDG uptake in a large fundal fibroid (arrow, B). FDG PET cannot readily distinguish leiomyomas from leiomyosarcomas.

FIGURE 25. Physiologic ovarian uptake. Fused FDG PET/CT image in a young woman with lymphoma demonstrates focal uptake in the right ovary (arrow), a normal finding repre-senting functional changes in a premeno-pausal female.

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malignancy.25 However, smaller nodules pose potential problems given the spatial resolution of PET (7 to 8 mm).26 Both the 2013 American College of Chest Physi-cians practice guidelines for pulmonary nodules and the 2017 Fleischner Society guideines for incidental pulmonary nod-ules have indications for FDG PET/CT for nodules > 8 mm.27,28 In routine clin-ical practice, any non-FDG avid nodule < 8 mm should be considered too small to accuretely characterize by PET, and continued CT followup should be con-sidered to ensure stability.

In addition to issues with small pul-monary nodules, PET/CT has been shown to be less sensitive for several types of pulmonary malignancy. Adeno-carcinoma in situ (formerly called bron-choalveolar carcinoma) and carcinoid are classically associated with being falsely PET negative, although other low-grade or early broncogenic ma-lignancies have also been shown to be falsely PET negative.29 Given the rela-tively low metabolic rate of these malig-nancies, it is necessary to continue CT surveilance of pulmonary nodules that demonstrate low (less than mediastinal vascular blood pool) FDG uptake (Fig-ure 17). Continued follow-up is rec-ommended, as the referring physician may not be aware of these potentially significant false negatives. The 2017 Fleischner Society guidelines provide generally accepted follow-up intervals

FIGURE 26. Occult bladder mass. Fused FDG PET/CT (A) and unfused CT (B) images demonstrate a subtle polypoid bladder mass (arrows) that is largely obscured on fused imaging due to the physiologic FDG uptake in the urine.

FIGURE 27. Renal cell carcinoma. Contrast-enhanced coronal CT image (A) demonstrates a small enhancing exophytic right lower pole renal mass consistent with renal cell carcinoma (arrow). However, on FDG PET/CT (B), the lesion is metabolically indistinguishable from high physiologic background uptake of the kidney.

FIGURE 28. Crohn’s disease. Axial CT (A) and fused PET/CT (B) images show focal FDG uptake localizing to a short segment of small bowel in the right lower quadrant with wall thickening (arrows).

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for indeterminate pulmonary nodules. If a non-FDG avid nodule demon-strates enlargement at follow-up, tissue sampling should be considered.

A variety of infectious or inflam-matory processes can be incidentally detected on PET/CT. Unfortunately, there is no reliable SUV threshold that can routinely differentiate infection/in-flammation from malignancny with cer-tain infectious/inflammatory processes being hypermetabolic and certain malignancies being non-FDG avid, in-cluding cystic or necrotic neoplasms.30

Additionally, measured SUVs depend on numerous factors independent of the target lesion of concern, including body fat composition, uptake time, and pa-tient blood glucose levels.31 In the chest, pneumonia, tuberculosis, mycobacteria avium complex, aspergiollosis, sarcoid-

osis, rheumatoid nodules, postsurgical inflammatory changes, talc pleurodesis, esophagitis, and postradiation inflam-mation are common (Figures 18-20). The sequelae of chronic granulomatous infections often include FDG-avid lung nodules and mediastinal lymph nodes that are often calcified.

Cardiac uptake is highly variable in fasting FDG PET/CT, ranging from essentially background to diffuse, in-tense FDG uptake. This is largely due to the heart’s ability to metabolize car-bohydrates or fatty acids with a switch to glucose in the presence of insulin or glucose loading.32 Unfortunately, this makes interpreting PET findings challenging. Occasionally, an infarct

may be encountered as a focal area of photopenia (Figure 21). Although un-common, malignancies can occasion-ally involve the heart with regions of hypermetabolic activity, most often due to metastases with primary cardiac neo-plasms being rare (Figure 22).33

Abdomen and PelvisThe adrenal glands are common lo-

cations for metastases and, therefore, should be closely evaluated on onco-logical PET/CT. Studies have shown PET/CT to be reasonably sensitive and specific for differentiating benign from malignant lesions.34 However, one must be careful not to misdiagnose a variety of common benign adrenal processes

FIGURE 29. Metformin-related bowel uptake. MIP image from FDG PET shows intense bowel uptake, most conspicuously in the distal small bowel and right colon (arrows) in a diabetic patient on metformin with a hypermetabolic right lung mass.

FIGURE 30. Urostomy with ileal conduit. MIP images from an FDG PET study in the frontal (A) and lateral (B) projections in a patient with hypermetabolic head and neck cancer demonstrate intense FDG uptake in the right lower abdomen (arrows) related to FDG-avid urine being diverted into a urostomy with an ileal conduit in a patient with a history of cystectomy.

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as metastases (eg, adrenal adenomas, hyperplasia, myelolipomas, benign pheochromocytomas, oncocytomas, hemorrhage, and cysts), as some of these benign entities can demonstrate mild FDG uptake (Figure 23).35 Al-though no absolute SUV threshold exists for differentiating benign from malignant uptake, Boland et al suggest a combination of CT characteristics (< 10 HU indicating a benign adenoma) and ratio of adrenal lesion to liver back-ground PET activity (with a ratio of > 1 suspicious for malignancy) to be a rea-sonable means to characterize adrenal lesions as malignant with a sensitivity of 100% and specificity of 99%.36

Expected uptake in the uterus and ova-ries depends on a patient’s menopausal status. Uptake in the endometrium can vary during the menstrual cycle, with greatest levels during menstrual flow and ovulatory phases.37 This can pose particular diagnostic problems when evaluating women with cervical carci-noma. Consideration may be given to coordinating PET/CT with menstrual cycle phase to perform the PET/CT in the late secretory or early proliferative phases (just before or after menstrua-tion).38 Increased FDG uptake can also be seen in uterine fibroids; however, PET cannot reliably distinguish leiomyomas from leiomyosarcomas (Figure 24).39,40

FIGURE 31. Focal FDG uptake in a benign rib fracture. Axial-fused FDG PET/CT image demonstrates focal FDG uptake in a non-pathological traumatic left rib fracture (arrow).

FIGURE 32. Bone metastases and bone marrow stimulation. FDG PET MIP image (A) demon-strates innumerable hypermetabolic osseous metastases. After treatment (B), there is evidence of marrow stimulation with diffuse increased uptake throughout the red marrow as well as the spleen, hampering treatment assessment.

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FIGURE 33. Chronic radiation changes. FDG sagittal PET (A) and fused PET/CT (B) images demon-strate relative decreased uptake in the thoracic spine (arrows) due to chronic radiation changes.



Similarly, ovarian activity in premeno-pausal women can be physiologic and related to ovulation (Figure 25).37

In postmenopausal women, focal in-creased FDG uptake in either the endo-metrium or the ovary should be further evaluated to exclude malignancy.

Other portions of the genitourinary system may pose difficulty for the in-terpreting physician, largely due to the high physiologic FDG uptake in the urine, which can obscure small disease foci. It is advisable to adjust PET win-dow and fusion level to avoid missing subtle lesions (Figure 26). Similarly, due the relatively high background uptake in the kidneys, FDG PET/CT has questionable utility in charac-terizing renal masses (Figure 27),41 although higher-grade, clear-cell and papillary subtypes have been shown to have greater activity than renal background.42 Additionally, pooling of radioactive urine in the ureters can often be difficult to distinguish from retroperitoneal or pelvic lymph nodes, often at the pelvic brim where the ure-ters cross the psoas muscles.

FDG uptake in the bowel continues to present a diagnostic challenge, as the uptake is highly variable. When focal FDG uptake is identified, fur-ther investigation (usually with en-doscopy) is recommended, as there is an association with malignant and premalignant conditions.43 Addition-ally, correlation with CT findings is warranted, as this may reveal an un-derlying infectious or inflammatory process such as appendicitis, divertic-ulitis, or inflammatory bowel disease (Figure 28).44 Metformin, an oral diabetic medication, results in diffuse intense uptake in the colon as well as the small bowel (Figure 29).45 This can unfortunately obscure metabolic activity from foci of malignancy, war-ranting consideration of holding the medication prior to FDG PET/CT im-aging. Postsurgical changes from cer-tain urinary diversion procedures also can result in intense bowel activity as FDG-avid urine enters the bowel (Figure 30).

MuskuloskeletalFocal FDG uptake can be identified

in both pathological and nonpatholog-ical fractures (Figure 31). Some stud-ies indicate that relatively high SUVs suggest malignant pathological frac-tures,46,47 although no absolute SUV can be used in routine clinical practice to reliably differentiate benign from ma-lignant fractures.48 Correlation with the co-acquired CT for features suggesting a benign or malignant process is sug-gested. If the focus of uptake remains indeterminate, consideration can be given to MR if it would change clinical management. Alternatively, attention should be given on follow-up PET/CT, as the activity from benign post-trau-matic or postsurgical fractures should normalize over several months.49

Diffuse red marrow uptake on FDG PET/CT is another common pattern of normal variant uptake. This is most often related to bone marrow stimulation with drugs such as filgrastim and pegfilgras-tim. Given the marrow stimulation, this may also result in increased uptake in the spleen.50 Given the history of marrow stimulation, the interpreting physician can readily identify this marrow uptake as benign. However, occasionally the diffuse uptake can obscure previously present hypermetabolic osseous foci, making it difficult to evaluate response to treatment (Figure 32). Waiting sev-eral weeks after discontinuation of such drugs will help decrease this uptake, but must be balanced with the need for timely clinical results.

Patients who have undergone prior radiation therapy may have relative de-creased marrow uptake in affected areas (Figure 33).51 Knowledge of treatment history and location is beneficial in PET interpretation to identify this unusual pattern of uptake. The interpreting phy-sician must be mindful to not misinter-pret the normal, nonirradiated marrow as pathologic.52

ConclusionOncologic FDG PET/CT is prone to

many pitfalls and incidental findings, largely related to whole-body imaging

and the nonspecific mechanism of FDG. This article reviewed a variety of processes that can lead to potential false-positive and false-negative find-ings. Interpreting radiologists must maintain constant vigilance for these common pitfalls.

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