Benign Causes of FDG Activity
Todd M. Blodgett, MD
Alex Ryan, MD
Key Facts
Terminology
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Nonmalignant areas of increased metabolism
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Benign nonphysiologic uptake of FDG may be encountered in as many as 25% of studies
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As many as 75% of those lesions will be inflammatory
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Imaging Findings
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Similar imaging findings may be present for malignant and various benign processes
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History is critical for reducing misinterpretation
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FDG activity in a typical distribution suggests a benign process
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Sarcoidosis, fungal infections, post-radiation, postsurgical, and other benign processes may have recognizable patterns of involvement
Top Differential Diagnoses
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Malignancy
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Benign Masses
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Iatrogenic
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Inflammation
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Infection
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Granulomatous Disease
Pathology
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Activated inflammatory cells have greatly elevated levels of glycolysis
Diagnostic Checklist
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Accurate differentiation between malignant and benign disease can reduce unnecessary surgical explorations
TERMINOLOGY
Abbreviations and Synonyms
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Nonmalignant areas of increased metabolism
Definitions
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Benign nonphysiologic uptake of FDG may be encountered in as many as 25% of studies
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As many as 75% of those lesions will be inflammatory
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IMAGING FINDINGS
General Features
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Best diagnostic clue
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FDG activity in a typical distribution suggests a benign process
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Sarcoidosis, fungal infections, post-radiation, postsurgical and other benign processes may have recognizable patterns of involvement
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Location: Varies
Nuclear Medicine Findings
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Tuberculoma and tuberculous lymphadenopathy
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Tuberculoma well-known cause of intense FDG uptake
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Appears as discrete nodule or mass with central caseous necrosis and surrounding inflammatory mantle
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Sarcoidosis
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Typical distribution is bilateral hilar and right paratracheal
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FDG uptake secondary to accumulation of Tlymphocytes and mononuclear phagocytes and noncaseating epithelioid granulomas
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Intensity of FDG uptake may reflect activity of disease
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Multisystem disease
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Easily misinterpreted as malignancy
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Thus FDG PET most useful for response to treatment and evaluation of extent of disease
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Cryptococcosis
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Paragonimiasis
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Endemic to southern Asia
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Parasitic disease with larval damage ultimately in lungs and brain
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Reported cause of high FDG uptake
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Abscesses
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Glycolytic metabolism elevated in association with leukocytic infiltration
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Usually has central photopenia secondary to necrosis or pus
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Pneumocystis
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Associated with high FDG uptake
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Other infections
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Sinusitis, pneumonia, radiation-induced pneumonitis, pancreatitis
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Each may show elevated FDG uptake
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Radiation pneumonitis/fibrosis
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FDG uptake caused by infiltration of leukocytes and macrophages
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Radiation leads to production of local cytokines including IL-6, TNF, and TGF-beta, which provoke inflammatory morphologic changes
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Early after radiation to the lung, PET may be positive (up to several months); may not be able to interpret effect on underlying tumor until resolution
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Pneumoconiosis
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Parenchymal reaction to presence of foreign substances in lungs
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May present with massive fibrosis and associated FDG uptake
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Peri-tumoral granulation tissue
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Granulation tissue surrounding tumor and inflammatory cells within necrotic areas of tumor contribute to FDG uptake in tumors
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As much of 24% of concentration may be due to non-tumor tissue
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Chemotherapy
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FDG uptake generally decreases after chemotherapy, correlating with clinical response
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Splenic uptake
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In the setting of infection, splenic uptake can be intense
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Spleen has multiple roles in the immune response, reflected in increased FDG activity in patients with infection or inflammation
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AIDS
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This patient group is vulnerable to a wide range of infections and malignancies
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Difficult to distinguish infection from tumor
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Toxoplasmosis can be differentiated from lymphoma because it is much less FDG avid, with virtually no overlap in SUV
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Fever of undetermined origin
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Diagnosis entails 3 weeks duration, episodic fever exceeding 38.3° C, and no diagnosis after standard workup
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Causes include infection, neoplasms, collagen vascular disease, granulomatous disease, pulmonary emboli, CVA, and drug fever
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FDG PET provides helpful information in 41% of cases
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Negative FDG PET makes it very unlikely that a morphologic origin of the fever will be identified
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In spite of normal cardiac uptake, FDG PET aids in identification of sites of infective endocarditis
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Post-operative uptake
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Several weeks should elapse prior to imaging to reduce likelihood of positives due to post-operative changes
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Good sensitivity for identification of infection in post-operative patients
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Wound healing, such as tracheostomy and colostomy sites or indwelling stents, commonly show elevated FDG uptake
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Osteomyelitis
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Useful for detection of osteomyelitis
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Inflammatory arthritis, acute fracture, and normal healing bone may also cause positive signal
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Prosthetic joint infection
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Commonly seen due to high prevalence of hip and knee arthroplasties
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Joint infection vs. aseptic loosening is a difficult differentiation
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FDG PET does not effectively distinguish the two conditions, as they are both inflammatory
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Bone fractures
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Degree of FDG accumulation usually modest in rib fractures, but may closely mimic malignancy
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FDG uptake in healing bone can be present as late as 6 months after the injury
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Arthritis
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FDG uptake seen especially in acromioclavicular, sternoclavicular, and glenohumeral joints
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Uptake can be intense and asymmetric, leading to misinterpretation as neoplasm
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Spinal osteomyelitis
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Usually confined to vertebral body and intervertebral disk
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MR is imaging modality of choice for diagnosis
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FDG PET has similarly high sensitivity and specificity
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Vasculitis
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FDG uptake in giant cell arteritis, Takayasu disease, aortitis, and unspecified large vessel vasculitis has been described
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Lymph Nodes
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Uptake in lymph nodes is not specific for malignant neoplasm
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Granulomatous diseases such as tuberculosis and sarcoidosis may provoke intense FDG uptake in lymph nodes
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Necrotic lymph nodes may show poor accumulation
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DIFFERENTIAL DIAGNOSIS
Malignancy
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When in doubt, consider short term follow-up exam to differentiate
Benign Masses
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Adenomas can have focal intense FDG activity
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Indistinguishable from malignancy
Iatrogenic
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History is imperative for reducing misinterpretation
Inflammation
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Almost any inflammatory process may cause false positives on FDG PET
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Consider dual-phase PET imaging
Infection
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Clinical symptoms often helpful for differentiating malignancy from benign process
Granulomatous Disease
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Sarcoidosis and other granulomatous processes can often mimic malignancy
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Look for other clues such as distribution, calcifications, and lack of features suggesting malignancy
PATHOLOGY
General Features
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General path comments
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Inflammatory cells such as neutrophils and activated macrophages at site of inflammation or injection show increased FDG accumulation
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Active granulomatous disease, other infectious processes, and active fibrosis may also show FDG uptake and cause false positives
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Activated inflammatory cells have greatly elevated levels of glycolysis
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20-30x increased in hexose monophosphate shunt, which accounts for high FDG uptake
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DIAGNOSTIC CHECKLIST
Consider
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Accurate differentiation between malignant and benign disease can reduce unnecessary surgical explorations
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Dual-phase or delayed-phase PET imaging may be helpful for distinguishing between malignancy and benign processes
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Hyperglycemia promotes greater glucose utilization in inflammatory cells
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Leads to more false positives in the setting of elevated blood glucose
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SELECTED REFERENCES
1. Chryssikos T et al: FDG-PET imaging can diagnose periprosthetic infection of the hip. Clin Orthop Relat Res. 466(6):1338-42, 2008
2. Chundru S et al: Granulomatous disease: is it a nuisance or an asset during PET/computed tomography evaluation of lung cancers? Nucl Med Commun. 29(7):623-7, 2008
3. Nigg AP et al: Tuberculous Spondylitis (Pott’s Disease). Infection. 36(3):293-4, 2008
4. Saleem BR et al: Periaortic endograft infection due to Listeria monocytogenes treated with graft preservation. J Vasc Surg. 47(3):635-7, 2008
5. Balink H et al: Diagnosis of abdominal aortic prosthesis infection with FDG-PET/CT. Vasc Endovascular Surg. 41(5):428-32, 2007
6. Helleman JN et al: Mycotic aneurysm of the descending thoracic aorta. Review and case report. Acta Chir Belg. 107(5):544-7, 2007
7. Inoue K et al: Diagnosing active inflammation in the SAPHO syndrome using 18FDG-PET/CT in suspected metastatic vertebral bone tumors. Ann Nucl Med. 21(8):477-80, 2007
8. Kang K et al: Positron emission tomographic findings in a tuberculous brain abscess. Ann Nucl Med. 21(5):303-6, 2007
9. Maldonado F et al: Focal organizing pneumonia on surgical lung biopsy: causes, clinicoradiologic features, and outcomes. Chest. 132(5):1579-83, 2007
10. Sheehy N et al: Acute varicella infection mimics recurrent Hodgkin’s disease on F-18 FDG PET/CT. Clin Nucl Med. 32(10):820-1, 2007
11. Lustberg MB et al: FDG PET/CT Findings in Acute Adult Mononucleosis Mimicking Malignant Lymphoma. Eur J Haematol. (In Press)
Image Gallery
![]() (Left) Axial CECT shows slight asymmetrical fullness in the left false vocal cord
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