Benign Causes of FDG Activity

Todd M. Blodgett, MD

Alex Ryan, MD

Key Facts

Terminology

Nonmalignant areas of increased metabolism
Benign nonphysiologic uptake of FDG may be encountered in as many as 25% of studies
- As many as 75% of those lesions will be inflammatory

Imaging Findings

Similar imaging findings may be present for malignant and various benign processes
History is critical for reducing misinterpretation
FDG activity in a typical distribution suggests a benign process
Sarcoidosis, fungal infections, post-radiation, postsurgical, and other benign processes may have recognizable patterns of involvement

Top Differential Diagnoses

Malignancy
Benign Masses
Iatrogenic
Inflammation
Infection
Granulomatous Disease

Pathology

Activated inflammatory cells have greatly elevated levels of glycolysis

Diagnostic Checklist

Accurate differentiation between malignant and benign disease can reduce unnecessary surgical explorations

Multiple images (A, B, C) show inflammation

from talc pleurodesis. PET may be positive indefinitely.

Graphic shows a representation of talc pleurodesis

. The talc is often discontinuous.

TERMINOLOGY

Abbreviations and Synonyms

Nonmalignant areas of increased metabolism

Definitions

Benign nonphysiologic uptake of FDG may be encountered in as many as 25% of studies
- As many as 75% of those lesions will be inflammatory

IMAGING FINDINGS

General Features

Best diagnostic clue
- FDG activity in a typical distribution suggests a benign process
- Sarcoidosis, fungal infections, post-radiation, postsurgical and other benign processes may have recognizable patterns of involvement
Location: Varies

Nuclear Medicine Findings

Tuberculoma and tuberculous lymphadenopathy
- Tuberculoma well-known cause of intense FDG uptake
- Appears as discrete nodule or mass with central caseous necrosis and surrounding inflammatory mantle
Sarcoidosis
- Typical distribution is bilateral hilar and right paratracheal
- FDG uptake secondary to accumulation of Tlymphocytes and mononuclear phagocytes and noncaseating epithelioid granulomas
- Intensity of FDG uptake may reflect activity of disease
- Multisystem disease
- Easily misinterpreted as malignancy
  - Thus FDG PET most useful for response to treatment and evaluation of extent of disease
Cryptococcosis
- Caused by Cryptococcus neoformans
- Infection occurs by inhaling fungus into lung
- Lung lesions generally demonstrate intense granulomatous inflammation
- Several reports have shown false positives due to high FDG uptake
Paragonimiasis
- Endemic to southern Asia
- Parasitic disease with larval damage ultimately in lungs and brain
- Reported cause of high FDG uptake
Abscesses
- Glycolytic metabolism elevated in association with leukocytic infiltration
- Usually has central photopenia secondary to necrosis or pus
Pneumocystis
- Associated with high FDG uptake
Other infections
- Sinusitis, pneumonia, radiation-induced pneumonitis, pancreatitis
- Each may show elevated FDG uptake
Radiation pneumonitis/fibrosis
- FDG uptake caused by infiltration of leukocytes and macrophages
- Radiation leads to production of local cytokines including IL-6, TNF, and TGF-beta, which provoke inflammatory morphologic changes
- 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
Pneumoconiosis
- Parenchymal reaction to presence of foreign substances in lungs
- May present with massive fibrosis and associated FDG uptake
Peri-tumoral granulation tissue
- Granulation tissue surrounding tumor and inflammatory cells within necrotic areas of tumor contribute to FDG uptake in tumors
- As much of 24% of concentration may be due to non-tumor tissue
Chemotherapy
- FDG uptake generally decreases after chemotherapy, correlating with clinical response
Splenic uptake
- In the setting of infection, splenic uptake can be intense
- Spleen has multiple roles in the immune response, reflected in increased FDG activity in patients with infection or inflammation
AIDS
- This patient group is vulnerable to a wide range of infections and malignancies
- Difficult to distinguish infection from tumor
- Toxoplasmosis can be differentiated from lymphoma because it is much less FDG avid, with virtually no overlap in SUV
Fever of undetermined origin
- Diagnosis entails 3 weeks duration, episodic fever exceeding 38.3° C, and no diagnosis after standard workup
- Causes include infection, neoplasms, collagen vascular disease, granulomatous disease, pulmonary emboli, CVA, and drug fever
- FDG PET provides helpful information in 41% of cases
  - Negative FDG PET makes it very unlikely that a morphologic origin of the fever will be identified
- In spite of normal cardiac uptake, FDG PET aids in identification of sites of infective endocarditis
Post-operative uptake
- Several weeks should elapse prior to imaging to reduce likelihood of positives due to post-operative changes
- Good sensitivity for identification of infection in post-operative patients
- Wound healing, such as tracheostomy and colostomy sites or indwelling stents, commonly show elevated FDG uptake
Osteomyelitis
- Useful for detection of osteomyelitis
- Inflammatory arthritis, acute fracture, and normal healing bone may also cause positive signal
Prosthetic joint infection
- Commonly seen due to high prevalence of hip and knee arthroplasties
- Joint infection vs. aseptic loosening is a difficult differentiation
- FDG PET does not effectively distinguish the two conditions, as they are both inflammatory
Bone fractures
- Degree of FDG accumulation usually modest in rib fractures, but may closely mimic malignancy
- FDG uptake in healing bone can be present as late as 6 months after the injury
Arthritis
- FDG uptake seen especially in acromioclavicular, sternoclavicular, and glenohumeral joints
- Uptake can be intense and asymmetric, leading to misinterpretation as neoplasm
Spinal osteomyelitis
- Usually confined to vertebral body and intervertebral disk
- MR is imaging modality of choice for diagnosis
- FDG PET has similarly high sensitivity and specificity
Vasculitis
- FDG uptake in giant cell arteritis, Takayasu disease, aortitis, and unspecified large vessel vasculitis has been described
Lymph Nodes
- Uptake in lymph nodes is not specific for malignant neoplasm
- Granulomatous diseases such as tuberculosis and sarcoidosis may provoke intense FDG uptake in lymph nodes
- Necrotic lymph nodes may show poor accumulation

DIFFERENTIAL DIAGNOSIS

Malignancy

When in doubt, consider short term follow-up exam to differentiate

Benign Masses

Adenomas can have focal intense FDG activity
Indistinguishable from malignancy

Iatrogenic

History is imperative for reducing misinterpretation

Inflammation

Almost any inflammatory process may cause false positives on FDG PET
Consider dual-phase PET imaging

Infection

Clinical symptoms often helpful for differentiating malignancy from benign process

Granulomatous Disease

Sarcoidosis and other granulomatous processes can often mimic malignancy
Look for other clues such as distribution, calcifications, and lack of features suggesting malignancy

PATHOLOGY

General Features

General path comments
- Inflammatory cells such as neutrophils and activated macrophages at site of inflammation or injection show increased FDG accumulation
  - Active granulomatous disease, other infectious processes, and active fibrosis may also show FDG uptake and cause false positives
- Activated inflammatory cells have greatly elevated levels of glycolysis
  - 20-30x increased in hexose monophosphate shunt, which accounts for high FDG uptake

DIAGNOSTIC CHECKLIST

Consider

Accurate differentiation between malignant and benign disease can reduce unnecessary surgical explorations
Dual-phase or delayed-phase PET imaging may be helpful for distinguishing between malignancy and benign processes
Hyperglycemia promotes greater glucose utilization in inflammatory cells
- Leads to more false positives in the setting of elevated blood glucose

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

DDx: Focal Intense FDG Activity

(Left) Axial CECT shows left maxillary sinus mucosal thickening

and a subtle air-fluid level

, compatible with acute sinusitis. (Right) Axial fused PET/CT shows mild to moderately increased FDG activity within the left maxillary sinus

, compatible with sinusitis. Also note physiologic FDG activity within both palatine tonsils

(Left) Axial CECT (top) and PET/CT (bottom) show moderately increased FDG activity

in the thyroidectomy bed in a patient who had a left hemithyroidectomy approximately 3 weeks prior to this scan. (Right) Axial CT (top) and fused PET/CT (bottom), 16 weeks following thyroidectomy, show resolution of the inflammatory activity in the thyroidectomy bed

(Left) Coronal PET (A), axial CT (B) and fused PET/CT (C) demonstrate a hypermetabolic right upper lobe mass

, compatible with primary lung cancer, and an incidental focal area of moderately increased FDG activity

, corresponding to facet arthrosis in the cervical spine. (Right) Coronal PET (A), axial CT (B) and fused PET/CT (C) demonstrate focally increased FDG activity

in the right maxillary molar, compatible with patient’s history of a dental abscess.

(Left) Axial CECT shows no obvious abnormalities. However, there is some subtle infiltration of the subcutaneous tissues in the anterior jaw

. (Right) Axial fused PET/CT shows a focal area of intense FDG activity

in this patient with jaw pain and a history of a dental abscess being treated with antibiotics.

(Left) Approximately 8 weeks after tracheostomy tube placement, coronal PET (A), axial CT (B) and PET/CT (C) demonstrate intense FDG activity surrounding the tube

, compatible with inflammation. (Right) Coronal PET (A), axial CT (B) and PET/CT (C) demonstrate focal intense FDG activity surrounding this patient’s tracheostomy

, compatible with inflammation &/or granulation tissue. Almost all tracheostomies will have some degree of increased FDG due to inflammation.

(Left) Axial CECT shows slight asymmetrical fullness in the left false vocal cord

. This patient had a history of thyroid carcinoma, status post thyroidectomy, and damage of the left recurrent laryngeal nerve. (Right) Axial fused PET/CT shows focal intense FDG activity in the region of left false vocal cord fullness

. Additional history revealed a thyroplasty procedure for paralyzed vocal cord. Teflon may cause a chronic granulomatous reaction, creating intense FDG activity indefinitely.

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