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DOI:10.2214/AJR.04.1896
AJR 2006; 186:639-648
© American Roentgen Ray Society

Pictorial Essay

Focal Parenchymal Lung Lesions Showing a Potential of False-Positive and False-Negative Interpretations on Integrated PET/CT

Sung Shine Shim1, Kyung Soo Lee1, Byung-Tae Kim2, Joon Young Choi2, Myung Jin Chung1 and Eun Jeong Lee2

1 Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-dong, Kangnam-gu, Seoul 135-710, Korea.
2 Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Received December 13, 2004; accepted after revision February 16, 2005.

 
Address correspondence to K. S. Lee (kyungs.lee{at}samsung.com).


Abstract
Top
 Abstract
Introduction
 Mechanism of 18F-FDG Uptake
 Summary
 References
 
OBJECTIVE. We describe a number of benign focal lung lesions with increased 18F-FDG uptake that simulate lung cancer and malignant lesions that lead to false-negatives due to little 18F-FDG uptake on integrated PET/CT images.

CONCLUSION. The integration of clinical history, morphologic findings of lung parenchymal lesions on the CT component, and metabolic activities on the PET component of integrated PET/CT can help reduce false interpretation of the study. A lung biopsy may be needed for lesions showing increased 18F-FDG uptake on PET for tissue confirmation irrespective of their morphology on CT.

Keywords: 18F-FDG uptake • lung • lung cancer • lung diseases • PET/CT


Introduction
Top
 Abstract
 Introduction
Mechanism of 18F-FDG Uptake
 Summary
 References
 
PET using 18F-FDG has been reported to increase the diagnostic accuracy of benign and malignant lesion differentiation. Moreover, integrated PET/CT—that is, combining morphologic CT and functional PET data—provides both morphologic and functional information. However, because PET or integrated PET/CT also shows increased uptake in lung tissues with active inflammation or benign nodules, interpretation should be approached with caution [1]. In this pictorial essay, we describe a number of benign focal lung lesions with increased 18F-FDG uptake that simulate lung cancer and malignant lesions that lead to false-negatives due to little 18F-FDG uptake on integrated PET/CT images.


Mechanism of 18F-FDG Uptake
Top
 Abstract
 Introduction
 Mechanism of 18F-FDG Uptake
Summary
 References
 
In malignant tissues, 18F-FDG uptake depends on the metabolic activity of the lesion. In other words, the extent of uptake is proportional to the number of malignant cells and their proliferative activity. However, increased 18F-FDG uptake has also been reported in pulmonary inflammatory lesions; in that setting, increased uptake is not thought to represent increased metabolic activity but, rather, the presence and activity of leukocytes. The rationale underlying this belief is that activated macrophages and neutrophils in inflammatory tissue use glucose as an energy source for chemotaxis and phagocytosis, whereas fibroblasts use glucose for proliferation [1].

Inflammatory or Infectious Lung Lesions Simulating Lung Cancer with Increased 18F-FDG Uptake
Active tuberculosis or tuberculoma, acute and chronic pneumonia, abscess, fungal infection, sarcoidosis, parasitic infestation, and pneumoconiosis are frequent causes of increased 18F-FDG uptake.

Active tuberculous pneumonias and granulomas have been reported to show avid 18F-FDG uptake on PET (Figs. 1A and 1B) and to be associated with satellite lesions adjacent to a dominant nodule (tuberculoma) on CT [2]. In tuberculosis, granulomatous lesions are mainly composed of lymphocytes and macrophages, which use 18F-FDG as an energy source.


Figure 1
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  		Fig. 1A —Pulmonary tuberculosis in 44-year-old man. Mediastinal window of enhanced CT scan (5.0-mm collimation) obtained at level of suprahepatic inferior vena cava shows masslike consolidation in left lower lobe.

 

Figure 2
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  		Fig. 1B —Pulmonary tuberculosis in 44-year-old man. Markedly increased 18F-FDG uptake (arrow) is observed in lesion on PET image (peak standardized uptake value = 22.0).

 
Pneumonias usually present with a lobular, segmental, or lobar pattern on CT, which is atypical for cancer and may suggest benign disease on integrated PET/CT. However, the intensity of 18F-FDG uptake shown by some masslike consolidations is sufficient to simulate a malignant lesion (Figs. 2A, 2B, and 2C). Moreover, in this situation, standardized uptake values (SUVs) indicating the intensity of 18F-FDG uptake are not helpful in differentiating benignancy from malignancy [1, 3]. Lung abscess also shows increased 18F-FDG uptake in the surrounding inflammatory tissue with little or no uptake in the central necrotic area (Figs. 3A and 3B).


Figure 3
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  		Fig. 2A —Actinomycosis in 48-year-old man. Lung window of thin-section CT scan (2.5-mm collimation) obtained at level of great vessels shows 5.6-cm masslike consolidation in left upper lobe.

 

Figure 4
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  		Fig. 2B —Actinomycosis in 48-year-old man. Significantly increased 18F-FDG uptake (peak standardized uptake value = 16.5) is noted in lesion of left upper lobe on PET (B) and integrated PET/CT (C) images. Small focus of activity (arrow, B) medial to main lesion is also portion of inflammatory lesion, which could be connected to main lesion on inferior images.

 

Figure 5
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  		Fig. 2C —Actinomycosis in 48-year-old man. Significantly increased 18F-FDG uptake (peak standardized uptake value = 16.5) is noted in lesion of left upper lobe on PET (B) and integrated PET/CT (C) images. Small focus of activity (arrow, B) medial to main lesion is also portion of inflammatory lesion, which could be connected to main lesion on inferior images.

 

Figure 6
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  		Fig. 3A —Lung abscess in 72-year-old woman. Mediastinal window of enhanced CT scan (5.0-mm collimation) obtained at subcarinal level shows 4-cm subpleural necrotic mass in right upper lobe. Also note right hilar lymph node enlargement (arrow).

 

Figure 7
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  		Fig. 3B —Lung abscess in 72-year-old woman. Markedly increased 18F-FDG uptake in parenchymal right upper lobar lesion (peak standardized uptake value [SUV] = 13.5) and in right hilar lymph node (arrow) (peak SUV = 6.5) is noticed on PET image.

 
Previous reports have suggested intermediate increased 18F-FDG uptake in fungal infections [4]. However, we encountered two cases of fungal infections (aspergillosis and coccidioidomycosis, respectively) that showed intense 18F-FDG uptake, thereby mimicking lung cancer (Figs. 4A and 4B). Watanabe et al. [5] described a case of pulmonary paragonimiasis with increased 18F-FDG uptake that simulated lung cancer, and we also encountered an almost identical case (Figs. 5A, 5B, and 5C).


Figure 8
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  		Fig. 4A —Coccidioidomycosis in 58-year-old man. Lung window of CT scan (4.0-mm collimation, 80 mA) obtained at level of left lower lobar bronchus shows masslike consolidation in right middle and lower lobes. Also note enlarged lymph nodes (arrow) in subcarinal area.

 

Figure 9
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  		Fig. 4B —Coccidioidomycosis in 58-year-old man. Integrated PET/CT scan clearly shows high 18F-FDG uptake (peak standardized uptake value [SUV] = 9.6) in parenchymal lung lesions and in subcarinal (peak SUV = 10.4) lymph nodes (arrow).

 

Figure 10
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  		Fig. 5A —Paragonimus westermani infestation in 46-year-old man. Mediastinal window of CT scan (5.0-mm collimation) obtained at subcarinal level shows 2.6-cm low-attenuation nodule (arrow) at bottom of right upper lobe.

 

Figure 11
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  		Fig. 5B —Paragonimus westermani infestation in 46-year-old man. Increased 18F-FDG uptake (peak standardized uptake value = 8.1) (arrow, C) is noted in nodule both on PET (B) and integrated PET/CT (C) images.

 

Figure 12
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  		Fig. 5C —Paragonimus westermani infestation in 46-year-old man. Increased 18F-FDG uptake (peak standardized uptake value = 8.1) (arrow, C) is noted in nodule both on PET (B) and integrated PET/CT (C) images.

 

Although glucose metabolism increases in patients with sarcoidosis, it is variable; therefore, 18F-FDG uptake in sarcoidosis is inconsistent. 18F-FDG uptake in sarcoidosis depends on the presence of actively dividing inflammatory cells, particularly the macrophages, lymphocytes, and epithelioid monocytes that comprise sarcoid granulomas. Actively granuloma-forming parenchymal lesions or nodes show increased 18F-FDG uptake because activated lymphocytes and macrophages contribute to increased glucose use in the corresponding lesions [6]. In our experience, 18F-FDG uptake in hilar lymph nodes of sarcoidosis was significantly increased (Figs. 6A and 6B).


Figure 13
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  		Fig. 6A —Sarcoidosis in 48-year-old man. Mediastinal window of unenhanced CT scan (7.0-mm collimation) obtained at level of bronchus intermedius shows 13-mm hilar lymph nodes (arrows) bilaterally.

 

Figure 14
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  		Fig. 6B —Sarcoidosis in 48-year-old man. Areas of increased 18F-FDG uptake (arrows) are seen on PET image (peak standardized uptake value = 4.8 in right hilum, 3.5 in left hilum).

 

Bandoh et al. [7] described the 18F-FDG PET findings of a patient with lung cancer arising from pneumoconiosis-associated progressive massive fibrosis. In that case, 18F-FDG PET enabled clear distinction to be drawn between lung cancer and progressive massive fibrosis, thus illustrating the potential usefulness of 18F-FDG PET for cancer screening among pneumoconiosis patients: The cancer tissue showed increased 18F-FDG uptake, whereas progressive massive fibrosis showed little uptake. However, in our experience, progressive massive fibrosis showed increased 18F-FDG uptake (Figs. 7A, 7B, and 7C), precluding clear distinction between progressive massive fibrosis and lung cancer.


Figure 15
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  		Fig. 7A —Pneumoconiosis and progressive massive fibrosis in 59-year-old man who worked in coal mine for 20 years. Lung window of CT scan (5.0-mm collimation) obtained at level of aortic arch shows two poorly defined masses, one each in right and left upper lobes. Also note right pneumothorax caused by percutaneous needle biopsy of mass in right upper lobe.

 

Figure 16
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  		Fig. 7B —Pneumoconiosis and progressive massive fibrosis in 59-year-old man who worked in coal mine for 20 years. Areas of increased 18F-FDG uptake (arrows) (peak standardized uptake value [SUV] = 11.1) are noted in masses of both upper lobes on transaxial (B) and coronal (C) images of integrated PET/CT. Also note increased uptake in right paratracheal node (arrowhead, B) (peak SUV = 11.0).

 

Figure 17
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  		Fig. 7C —Pneumoconiosis and progressive massive fibrosis in 59-year-old man who worked in coal mine for 20 years. Areas of increased 18F-FDG uptake (arrows) (peak standardized uptake value [SUV] = 11.1) are noted in masses of both upper lobes on transaxial (B) and coronal (C) images of integrated PET/CT. Also note increased uptake in right paratracheal node (arrowhead, B) (peak SUV = 11.0).

 


Figure 18
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  		Fig. 8A —Sclerosing hemangioma in 40-year-old woman. Mediastinal window of enhanced CT scan (5.0-mm collimation) obtained at level of right middle lobar bronchus shows 2.2-cm enhancing nodule (arrow) in right middle lobe.

 


Figure 19
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  		Fig. 8B —Sclerosing hemangioma in 40-year-old woman. High 18F-FDG uptake (arrow) (peak standardized uptake value = 5.3) is seen on PET image.

 


Figure 20
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  		Fig. 9A —Inflammatory pseudotumor in 70-year-old-woman. Lung window of CT scan (5.0-mm collimation) obtained at level of basal segmental bronchus shows 2.5-cm well-defined nodule in left lower lobe.

 


Figure 21
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  		Fig. 9B —Inflammatory pseudotumor in 70-year-old-woman. Abnormally increased 18F-FDG uptake (arrow, C) (peak standardized uptake value = 6.4) is seen on both PET (B) and integrated PET/CT (C) images.

 


Figure 22
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  		Fig. 9C —Inflammatory pseudotumor in 70-year-old-woman. Abnormally increased 18F-FDG uptake (arrow, C) (peak standardized uptake value = 6.4) is seen on both PET (B) and integrated PET/CT (C) images.

 
Benign Neoplasms with Increased 18F-FDG Uptake Simulating Malignancy
Benign tumors such as sclerosing hemangioma, leiomyoma, and inflammatory pseudotumor may show increased 18F-FDG uptake.

Sclerosing hemangioma of the lung is considered a low-grade malignant epithelial tumor that occasionally shows regional lymph node metastases. Previous reports suggest that the disease shows little or only mild 18F-FDG accumulation [8]. However, in our experience, this tumor shows increased uptake (Figs. 8A and 8B) and contains epithelial cells with focal moderate to severe nuclear atypism.

Moreover, according to a single report, inflammatory pseudotumor shows increased 18F-FDG and rubidium-82 (a marker of flow) uptake, suggesting a high degree of metabolic activity and increased perfusion [9]. We also encountered a similar case showing increased 18F-FDG uptake (Figs. 9A, 9B, and 9C).


Figure 23
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  		Fig. 10A —Adenocarcinoma with predominantly mucinous bronchioloalveolar carcinoma component in 48-year-old man. Lung window of thin-section CT scan (2.5-mm collimation) obtained at level of azygous arch shows 2.1-cm nodule (arrow) containing internal bubble radiolucencies with lobulated and spiculated margin in left upper lobe.

 


Figure 24
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  		Fig. 10B —Adenocarcinoma with predominantly mucinous bronchioloalveolar carcinoma component in 48-year-old man. Little 18F-FDG uptake (straight arrows) in lesion shown in A is noted on PET (B) and integrated PET/CT (C) images. Mediastinal node uptakes (curved arrows) were due to benign node uptake: follicular hyperplasia with fibrotic nodule formation and anthracotic change on histopathologic examination. Small focus of activity (arrowhead, B) medial to lung cancer in B corresponds to vascular uptake in left upper lobar pulmonary artery branch.

 


Figure 25
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  		Fig. 10C —Adenocarcinoma with predominantly mucinous bronchioloalveolar carcinoma component in 48-year-old man. Little 18F-FDG uptake (straight arrows) in lesion shown in A is noted on PET (B) and integrated PET/CT (C) images. Mediastinal node uptakes (curved arrows) were due to benign node uptake: follicular hyperplasia with fibrotic nodule formation and anthracotic change on histopathologic examination. Small focus of activity (arrowhead, B) medial to lung cancer in B corresponds to vascular uptake in left upper lobar pulmonary artery branch.

 
Lung Neoplasms with Reduced 18F-FDG Uptake Simulating Benignancy
Mucinous and nonmucinous bronchioloalveolar carcinomas (BACs), adenocarcinomas with BAC components, carcinoids, and mucoepidermoid carcinomas are all tumors that may show little 18F-FDG uptake and thus may simulate benign tumors. Kim et al. [10] showed that BAC, which often contains abundant mucin, has significantly lower peak SUVs than squamous cell carcinoma, adenocarcinoma, and other cell types and can thus lead to false-negative interpretations on PET images. Higashi et al. [11] reported a correlation between 18F-FDG uptake and the degree of cell differentiation in adenocarcinomas of the lung. They found that the mean SUV of well-differentiated adenocarcinomas was significantly lower than that of moderately differentiated adenocarcinomas (Figs. 10A, 10B, and 10C).

Moreover, it is well known that carcinoids show little 18F-FDG uptake [12] (Figs. 11A and 11B). Somatostatin receptor imaging with indium-111 DTPA pentetreotide (Octreoscan, Mallinkrodt) can help identify bronchial carcinoid with increased radionuclide uptake [13]. Based on our experience, mucoepidermoid carcinomas also show marginal 18F-FDG uptake (Figs. 12A, 12B, and 12C).


Figure 26
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  		Fig. 11A —Carcinoid tumor in 56-year-old man. Mediastinal window of enhanced CT scan (5.0-mm collimation) obtained at level of left atrium shows 41-mm moderately enhancing homogeneous mass in right lower lobe.

 

Figure 27
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  		Fig. 11B —Carcinoid tumor in 56-year-old man. Mass shows little 18F-FDG uptake (arrows) on PET image.

 

Figure 28
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  		Fig. 12A —Mucoepidermoid carcinoma in 64-year-old woman. Coronal reformation image of enhanced CT scan (2.5-mm collimation) shows nonenhancing endobronchial nodule (arrow) in left lower lobar bronchus.

 

Figure 29
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  		Fig. 12B —Mucoepidermoid carcinoma in 64-year-old woman. No 18F-FDG uptake (arrow, C) is noted on coronal PET (B) and integrated PET/CT (C) images.

 

Figure 30
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  		Fig. 12C —Mucoepidermoid carcinoma in 64-year-old woman. No 18F-FDG uptake (arrow, C) is noted on coronal PET (B) and integrated PET/CT (C) images.

 


Summary
Top
 Abstract
 Introduction
 Mechanism of 18F-FDG Uptake
 Summary
References
 
Benign focal lung lesions can simulate lung cancer with increased 18F-FDG uptake and malignant lesions can lead to a false-negative interpretation due to little 18F-FDG uptake on integrated PET/CT images. Thus, an awareness of the various 18F-FDG uptakes of parenchymal lung lesions is crucial for the correct interpretation of integrated PET/CT images. The integration of clinical history, morphologic findings of lung parenchymal lesions on the CT component, and metabolic activities on the PET component of integrated PET/CT can help reduce false interpretation of the study. A lung biopsy may be needed for lesions showing increased 18F-FDG uptake on PET for tissue confirmation irrespective of their morphology on CT.


References
Top
 Abstract
 Introduction
 Mechanism of 18F-FDG Uptake
 Summary
 References
 

  1. Bakheet SM, Saleem M, Powe J, Al-Amro A, Larsson SG, Mahassin Z. F-18 fluorodeoxyglucose chest uptake in lung inflammation and infection. Clin Nucl Med 2000;25 : 273-278[CrossRef][Medline]
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  8. Hara M, Iida A, Tohyama J, et al. FDG-PET findings in sclerosing hemangioma of the lung: a case report. Radiat Med2001; 19:215 -218[Medline]
  9. Slosman DO, Spiliopoulos A, Keller A, et al. Quantitative metabolic PET imaging of a plasma cell granuloma. J Thorac Imaging 1994; 9:116 -119[Medline]
  10. Kim BT, Kim Y, Lee KS, et al. Localized form of bronchioloalveolar carcinoma: FDG PET findings. AJR 1998;170 : 935-939[Abstract/Free Full Text]
  11. Higashi K, Ueda Y, Seki H, et al. Fluorine-18-FDG PET imaging is negative in bronchioloalveolar lung carcinoma. J Nucl Med 1998; 39:1016 -1020[Abstract/Free Full Text]
  12. Lee KS, Jeong YJ, Han J, Kim BT, Kim H, Kwon OJ. T1 non-small cell lung cancer: imaging and histopathologic findings and their prognostic implications. RadioGraphics 2004;24 : 1617-1636[Abstract/Free Full Text]
  13. Goldsmith SJ, Kostakoglu LA, Somrov S, Palestro CJ. Radionuclide imaging of thoracic malignancies. Thorac Surg Clin2004; 14:95 -112[CrossRef][Medline]

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