March 2012, VOLUME 198
NUMBER 3

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March 2012, Volume 198, Number 3

Women???s Imaging

Pictorial Essay

False-Positive Lesions Mimicking Breast Cancer on FDG PET and PET/CT

+ Affiliations:
1 Department of Diagnostic Radiology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1350, Houston, TX 77030.

2 Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX.

3 Department of Nuclear Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX.

Citation: American Journal of Roentgenology. 2012;198: W304-W314. 10.2214/AJR.11.7130

ABSTRACT
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OBJECTIVE. Incidental 18F-FDG-avid breast lesions are commonly encountered in patients with cancer who undergo staging PET/CT. This pictorial essay discusses breast lesions that show increased FDG activity, mimicking breast cancer, with biopsy-confirmed benign diagnosis.

CONCLUSION. Acute and chronic inflammation, physiologic lactation, and benign breast masses, including silicone granuloma, fat necrosis, fibroadenoma, and postsurgical changes, may show increased FDG uptake on PET/CT. These conditions can often be differentiated from malignancy by correlative imaging, including mammography, sonography, or MRI.

Keywords: breast, mammography, neoplasm, PET/CT, ultrasound

Whole-body 18F-FDG PET/CT is not currently indicated for primary breast cancer detection because of high false-negative rates for the detection of early breast cancer. Low sensitivity was described for the detection of small nonpalpable (> 1.0 cm) and low-grade malignancies in 116 patients with breast cancer who underwent staging FDG PET [1]. FDG PET/CT in breast cancer imaging has an adjunctive role in the detection of locoregional recurrence or distant metastases in locally advanced breast cancer when results of other standard imaging techniques are equivocal or suspicious [2]. FDG PET???positive lesions in the breast generally have high positive predictive value for breast cancer. The diagnostic value of FDG PET for the diagnosis of primary breast cancer was analyzed in a study of 144 patients with 185 masses and reported a positive predictive value of 96.6% for the diagnosis of breast cancer, with only three of 53 benign breast masses presenting with intense tracer uptake [3]. It is not rare to encounter an incidental finding of an FDG PET???positive lesion in oncologic imaging. Acute and chronic inflammation, physiologic lactation, and benign focal breast masses, including silicone granuloma, fat necrosis, fibroadenoma, and postsurgical changes, may show increased FDG uptake on PET/CT [4???7]. We present a pictorial essay of biopsy-confirmed benign lesions with increased FDG PET activity that may mimic breast malignancy.

General Principles of FDG PET
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The use of FDG PET in oncology is based on the premise that malignant cells have high metabolic rates and take up more glucose and FDG than the surrounding tissue [8]. Glucose uptake is enhanced in malignant cells because they express more specific transporter proteins with a greater affinity for glucose than those expressed by normal cells [8]. Malignant cells have also been shown to have an overall increased number of glucose transporters [9]. FDG is a radio- pharmaceutical analog of glucose that is taken up by metabolically active tumor cells, also via the glucose transporter proteins. The degree of uptake is related to the cellular metabolic rate and the number of glucose transporters [10]. Glucose undergoes intracellular degradation by the process of glycolysis. IV-administered FDG is transported into the cells by glucose transporter proteins, just as unlabeled deoxyglucose would be. However, unlike glucose, further degradation via the glycolysis pathway is not possible, and FDG-6-phosphate becomes trapped in metabolically active cells [10]. FDG PET images are assessed qualitatively or quantitatively for increased radiotracer uptake. The standardized uptake value, a semiquantitative measurement, is the most commonly used measurement, and its value tends to be higher with malignant lesions when compared with benign lesions [8].

FDG PET/CT Technique
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FDG PET/CT was performed using a camera (Discovery ST, GE Healthcare) in combination with the CT component of an 8-MDCT scanner (LightSpeed, GE Healthcare) in our institution. Patients were positioned supine in the scanner with their arms raised after fasting for at least 6 hours, and with a fasting blood glucose level of less than 150 mg/dL. An IV injection of 555???629 MBq (15???17 mCi) of FDG was administered in the arm or central venous catheter, and 2D emission scans were acquired at 3 minutes per FOV approximately 60 minutes after injection. PET images were reconstructed using standard vendor-provided reconstruction algorithms. Unenhanced CT images were acquired in helical mode (speed, 13.5 mm/rotation) from the base of the skull to the mid thigh during suspended mid expiration at 3.75-mm slice thickness, 120 kVp, 300 mA, and 0.5-second rotation.

Causes of False-Positive Breast Lesions on FDG PET/CT
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Breast Infection

Acute or chronic infection is a common cause of false-positive FDG uptake in PET/CT in breast cancer (Figs. 1A, 1B, 1C, 1D, and 1E). Activated inflammatory cells, such as neutrophils and macrophages, have increased expression of glucose transporters (as do malignant cells), resulting in trapping of IV-administered FDG [8]. Therefore, noncancerous tissues that are involved in processes of infection or inflammation may have increased FDG activity on PET. Increased FDG uptake in acute bacterial mastitis or abscesses, tuberculosis, and fungal infections of the breast is documented in the literature [7, 8].

Silicone Granuloma

Silicone granulomas have been reported to show increased uptake on PET/CT [7, 9, 10] (Figs. 2A and 2B). Silicone granulomas may appear as dense or calcified masses anterior to or superior to the implant on mammography [11] (Fig. 2B). Free extracapsular silicone may have variable appearances on ultrasound that include homogeneous low-level echogenicity, with a well-defined anterior margin and loss of detail posteriorly, representing silicone gel leakage that is described as echogenic noise (Fig. 2C), or a hypoechoic mass representing conglomerates of silicone gel with or without surrounding echogenic noise [11]. Alternately, a highly echogenic area is seen anterior to the implant with marked posterior acoustic shadowing [10]. MRI remains the imaging modality of choice for the detection of implant rupture. On MRI, free silicone has low signal intensity on fat-suppressed T1-weighted MRI and appears hyperintense on T2-weighted MRI [12]. On high-resolution fast spin-echo T2- weighted imaging, silicone looks bright (isointense to fat), and water looks brighter, thus enabling evaluation of internal implant integrity. Special sequences that can be used to evaluate silicone gel implant integrity are designed to make silicone look bright (such as the 3-point Dixon method or silicone-selective techniques) but have diminished spatial resolution. The axial inversion recovery sequence with water saturation is a ???silicone-only??? sequence in which silicone is bright, and fat and water are dark [13].

Fat Necrosis

Fat necrosis is a sterile inflammatory process that may result in increased FDG uptake due to the presence of metabolically active inflammatory cells [14] (Figs. 3A, 3B, 3C, 3D, 3E, 3F, 3G, and 3H). Histopathologically, there is an infiltration of partially necrotic adipose tissue by foamy macrophages, multinucleated giant cells, and fibroblasts. Breast trauma, diagnostic interventions, and surgical procedures are the main causes of fat necrosis in the breast [14]. The radiologic appearances of fat necrosis vary with the age of the lesion. On mammography, fat necrosis can present as lipid cysts, coarse calcifications, focal asymmetries, microcalcifications, or spiculated masses [15]. The ultrasound appearances of fat necrosis are variable (Figs. 3B and 3C) and have been described as increased echogenicity of the subcutaneous tissues, with or without small cysts (27%), anechoic masses with posterior acoustic enhancement (27%), anechoic masses with posterior acoustic shadowing (16%), solid masses (14%), cystic masses with internal echoes (11%), and cystic masses with mural nodules (4%) [16]. Fat necrosis shows decreased signal intensity on T1- and T2-weighted images on MRI as a result of iron- containing siderophages, surrounded by a rim of variable signal intensity that may represent surrounding edema (Figs. 3D and 3E). Non- fat-suppressed unenhanced T1-weighted images can be extremely helpful in confirming the impression of fat necrosis by revealing bright fat signal centrally within the enhancing lesion (Fig. 3D). The appearance of fat necrosis on T1-weighted contrast-enhanced images is variable because of the various stages in development, maturation, and resolution of fat necrosis [17]. The MRI finding of a central stellate nonenhancing irregular mass with a thick irregular rim of enhancement may necessitate biopsy to differentiate it from malignancy [17] (Fig. 3F). A history of trauma and mammographic correlation of characteristic oil cysts and calcifications may be helpful in distinguishing this condition from malignancy.

Lactation

Increased FDG PET/CT uptake may be seen in the lactating breast (Figs. 4A, 4B, 4C, 4D, 4E, and 4F). Hicks and colleagues [18] evaluated the breast uptake of FDG in seven women: six were lactating, and one was in the early postpartum period but had not commenced breast-feeding. They found significantly increased FDG breast uptake in all lactating breasts except for one breast consistently refused by the nursing infant and in one woman who had not begun breast-feeding after delivery of her child, suggesting that high uptake of FDG in the lactating breast is likely related to suckling. The high uptake and retention of FDG in the breast even after expression of breast milk suggests intracellular trapping of the radiotracer in active glandular tissue.

Benign Breast Masses

FDG uptake may occur in fibroadenomata, as a consequence of their rapid growth and high proliferation, and also in areas of fibrocystic disease or inspissated cysts [19] (Figs. 5A, 5B, 5C, 5D, 5E, 6A, 6B, 6C, and 6D). Simple cysts generally do not demonstrate FDG activity.

Surgery and Radiotherapy

Increased FDG uptake may be observed in the early postoperative period as a consequence of leukocyte infiltration of granulation tissue involved in wound repair and resorption of necrotic debris and hematoma [8] (Figs. 7A and 7B). Radiotherapy, by virtue of its ability to cause inflammation of normal structures, may cause increased FDG uptake in the breast [8].

Conclusion
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Incidental FDG-avid lesions seen in the breast on whole-body PET/CT may cause diagnostic dilemmas in oncologic imaging and may be misinterpreted as a primary breast cancer in women with extramammary malignancies, more extensive disease in patients with known breast cancer, or recurrence in women with treated cancer. In many instances, these false-positive lesions can be differentiated from cancer by correlation with characteristic imaging appearances on conventional breast imaging modalities. Biopsy can be performed for tissue diagnosis when needed.

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Fig. 1A???50-year-old woman with recurrent squamous cell carcinoma of cervix who presented for further evaluation of FDG-avid lesion seen on staging PET/CT. A,Axial fused PET/CT image shows focal area of increased FDG activity (arrow) in left breast, with maximum standardized uptake value of 4.5, suspicious for metastasis or primary breast neoplasm. Color intensity scale included on left side of image applies to images in Figures 2A, 4B, 5A, 6A, 7A, and 7B.
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Fig. 1B???50-year-old woman with recurrent squamous cell carcinoma of cervix who presented for further evaluation of FDG-avid lesion seen on staging PET/CT. B,Lateromedial mammogram shows small mass (arrow) in central breast.
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Fig. 1C??? 50-year-old woman with recurrent squamous cell carcinoma of cervix who presented for further evaluation of FDG-avid lesion seen on staging PET/CT. C,Gray-scale ultrasound shows poorly defined solid hypoechoic avascular mass (arrows) with indistinct margins.
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Fig. 1D??? 50-year-old woman with recurrent squamous cell carcinoma of cervix who presented for further evaluation of FDG-avid lesion seen on staging PET/CT. D,Core needle biopsy stains show nodular area of abscess formation (D, ??40), with immunohistochemical stain for cytokeratin (inset, D; ??100) highlighting presence of benign breast ducts, and numerous neutrophils (E, ??200), features of abscess formation with reactive reparative changes on histopathology.
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Fig. 1E??? 50-year-old woman with recurrent squamous cell carcinoma of cervix who presented for further evaluation of FDG-avid lesion seen on staging PET/CT. E,Core needle biopsy stains show nodular area of abscess formation (D, ??40), with immunohistochemical stain for cytokeratin (inset, D; ??100) highlighting presence of benign breast ducts, and numerous neutrophils (E, ??200), features of abscess formation with reactive reparative changes on histopathology.
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Fig. 2A???62-year-old woman with bilateral prepectoral silicone gel breast implants who underwent staging PET/CT for mantle cell lymphoma. A,Axial fused PET/CT image shows two FDG-avid masses (arrows), with maximum standardized uptake value of 3, in right upper outer quadrant, adjacent to underlying breast implant, presumed to represent progressive active lymphoma.
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Fig. 2B???62-year-old woman with bilateral prepectoral silicone gel breast implants who underwent staging PET/CT for mantle cell lymphoma. B,Mediolateral oblique right mammogram shows two hyperdense circumscribed round masses (short arrow) in superior breast anterior to prepectoral silicone implant, consistent with extravasated silicone. Long arrow indicates port projecting over right chest wall.
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Fig. 2C???62-year-old woman with bilateral prepectoral silicone gel breast implants who underwent staging PET/CT for mantle cell lymphoma. C,Extended-FOV gray-scale ultrasound of right breast shows focal masses (arrows) with ???snowstorm appearance??? and marked posterior acoustic shadowing.
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Fig. 2D???62-year-old woman with bilateral prepectoral silicone gel breast implants who underwent staging PET/CT for mantle cell lymphoma. D,Ultrasound-guided fine-needle aspiration Papanicolaou stains show multinucleated giant cells (arrow, D; ??200) and benign ductal epithelium (arrow, E; ??100), consistent with reactive process such as granuloma formation.
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Fig. 2E???62-year-old woman with bilateral prepectoral silicone gel breast implants who underwent staging PET/CT for mantle cell lymphoma. E,Ultrasound-guided fine-needle aspiration Papanicolaou stains show multinucleated giant cells (arrow, D; ??200) and benign ductal epithelium (arrow, E; ??100), consistent with reactive process such as granuloma formation.
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Fig. 3A???44-year-old woman with history of right invasive ductal carcinoma treated with mastectomy who presented with palpable abnormality in lower outer quadrant of right reconstruction. A,Axial FDG PET image shows increased FDG activity (arrow) in inferolateral aspect of right reconstruction.
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Fig. 3B???44-year-old woman with history of right invasive ductal carcinoma treated with mastectomy who presented with palpable abnormality in lower outer quadrant of right reconstruction. B,Gray-scale ultrasound shows large heterogeneous area (arrows) with mixed hyper- and hypoechogenicity.
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Fig. 3C???44-year-old woman with history of right invasive ductal carcinoma treated with mastectomy who presented with palpable abnormality in lower outer quadrant of right reconstruction. C,Gray-scale ultrasound shows circumscribed anechoic mass (arrows) consistent with oil cyst adjacent to large heterogeneous area.
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Fig. 3D???44-year-old woman with history of right invasive ductal carcinoma treated with mastectomy who presented with palpable abnormality in lower outer quadrant of right reconstruction. D,Axial T1-weighted non-fat-suppressed image of right breast shows T1-hyperintense mass (arrow) at inferior lateral margin of reconstruction.
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Fig. 3E???44-year-old woman with history of right invasive ductal carcinoma treated with mastectomy who presented with palpable abnormality in lower outer quadrant of right reconstruction. E,Axial STIR image of right breast shows signal loss (arrow) within mass.
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Fig. 3F???44-year-old woman with history of right invasive ductal carcinoma treated with mastectomy who presented with palpable abnormality in lower outer quadrant of right reconstruction. F,Axial contrast-enhanced fat-suppressed T1-weighted MRI of right breast shows thick irregular rim enhancement (arrow) of mass.
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Fig. 3G???44-year-old woman with history of right invasive ductal carcinoma treated with mastectomy who presented with palpable abnormality in lower outer quadrant of right reconstruction. G,Fine-needle aspiration biopsy Papanicolaou stains of mass show abundant degenerated adipose tissue (G, ??100), myospherulosis (inset, G; ??100), and histiocytes with multinucleated giant cell (arrow, H; ??200), features characteristic of fat necrosis.
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Fig. 3H???44-year-old woman with history of right invasive ductal carcinoma treated with mastectomy who presented with palpable abnormality in lower outer quadrant of right reconstruction. H,Fine-needle aspiration biopsy Papanicolaou stains of mass show abundant degenerated adipose tissue (G, ??100), myospherulosis (inset, G; ??100), and histiocytes with multinucleated giant cell (arrow, H; ??200), features characteristic of fat necrosis.
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Fig. 4A???43-year-old lactating woman diagnosed with palpable invasive ductal right carcinoma showed increased uptake in both breasts at PET, raising possibility of synchronous left breast cancer.

A,Coronal maximum-intensity-projection PET image shows FDG-avid right breast mass (long thick arrow) with adjacent satellite nodules (short thick arrow); regional right adenopathy (short thin arrows) involving axillary, infraclavicular, internal mammary, supraclavicular regions, and parasternal soft tissue; and increased FDG uptake in left retroareolar region (long thin arrow).

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Fig. 4B???43-year-old lactating woman diagnosed with palpable invasive ductal right carcinoma showed increased uptake in both breasts at PET, raising possibility of synchronous left breast cancer.

B,Axial PET image shows FDG-avid right breast mass (left arrow), with maximum standardized uptake value of 9.9, and increased FDG uptake (right arrows) in left retroareolar region (standardized uptake value, 4.3), suspicious for synchronous left breast cancer.

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Fig. 4C???43-year-old lactating woman diagnosed with palpable invasive ductal right carcinoma showed increased uptake in both breasts at PET, raising possibility of synchronous left breast cancer.

C,Left mediolateral oblique mammogram shows heterogeneous calcifications (arrow) in upper outer left breast. Stereotactic biopsy showed fibroadenoma with microcalcifications (data not shown).

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Fig. 4D???43-year-old lactating woman diagnosed with palpable invasive ductal right carcinoma showed increased uptake in both breasts at PET, raising possibility of synchronous left breast cancer.

D,Gray-scale ultrasound reveals solid oval hyperechoic mass in periareolar left breast. Image of ultrasound-guided biopsy shows needle shaft (arrows) within hyperechoic mass.

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Fig. 4E???43-year-old lactating woman diagnosed with palpable invasive ductal right carcinoma showed increased uptake in both breasts at PET, raising possibility of synchronous left breast cancer.

E,Core needle biopsy stains show adenosis (E, ??40) and epithelial cells (F, ??200) with vacuolated cytoplasm and secretions in lumen of glands, typical of lactational change.

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Fig. 4F???43-year-old lactating woman diagnosed with palpable invasive ductal right carcinoma showed increased uptake in both breasts at PET, raising possibility of synchronous left breast cancer.

F,Core needle biopsy stains show adenosis (E, ??40) and epithelial cells (F, ??200) with vacuolated cytoplasm and secretions in lumen of glands, typical of lactational change.

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Fig. 5A???35-year-old woman with metastatic supraclavicular lymph nodes from unknown primary tumor had suspicious lesion in left lung and indeterminate mass in right breast on staging PET/CT.

A,Axial fused PET/CT image shows irregular focus (arrow) of increased FDG activity in medial right breast.

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Fig. 5B???35-year-old woman with metastatic supraclavicular lymph nodes from unknown primary tumor had suspicious lesion in left lung and indeterminate mass in right breast on staging PET/CT.

B,Craniocaudal mammograms of both breasts show focal asymmetry (arrow) in medial right breast.

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Fig. 5C??? 35-year-old woman with metastatic supraclavicular lymph nodes from unknown primary tumor had suspicious lesion in left lung and indeterminate mass in right breast on staging PET/CT.

C,Gray-scale ultrasound shows heterogeneous predominantly hyperechoic mass (arrows) that underwent ultrasound-guided biopsy.

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Fig. 5D??? 35-year-old woman with metastatic supraclavicular lymph nodes from unknown primary tumor had suspicious lesion in left lung and indeterminate mass in right breast on staging PET/CT.

D,Bilateral axial T1-weighted contrast-enhanced MRI shows heterogeneous clumped enhancement (long arrow) in right breast with blooming artifact (short arrow) from postbiopsy clip placed at time of ultrasound-guided biopsy. Histopathology at ultrasound-guided core needle biopsy showed proliferative fibrocystic change.

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Fig. 5E??? 35-year-old woman with metastatic supraclavicular lymph nodes from unknown primary tumor had suspicious lesion in left lung and indeterminate mass in right breast on staging PET/CT.

E,Photomicrograph shows microscopic partially sclerosed papilloma (??40) and florid usual ductal hyperplasia (inset, ??100).

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Fig. 6A???72-year-old woman with right lung cancer who presented for staging PET/CT. A,Axial fused PET/CT image shows increased FDG uptake (arrow) in outer right breast.
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Fig. 6B???72-year-old woman with right lung cancer who presented for staging PET/CT. B,Right craniocaudal mammogram shows lobular mass (arrow) with circumscribed margins and associated coarse calcifications in lateral right breast.
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Fig. 6C???72-year-old woman with right lung cancer who presented for staging PET/CT. C,Gray-scale ultrasound shows lobular circumscribed hypoechoic mass (arrow) suggesting inspissated cyst.
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Fig. 6D???72-year-old woman with right lung cancer who presented for staging PET/CT. D,Ultrasound-guided fine-needle aspiration biopsy of cystic mass shows degenerated cyst contents with no cells (Papanicolaou staining, ??40).
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Fig. 7A???46-year-old woman with history of left breast angiosarcoma who presented for surveillance. A,Axial fused PET/CT image performed 2 weeks after resection of left breast tumor shows diffused increased FDG uptake consistent with inflammatory postsurgical change.
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Fig. 7B???46-year-old woman with history of left breast angiosarcoma who presented for surveillance. B,Axial fused PET/CT image performed 6 months after resection of left breast tumor shows resolution of previously seen increased FDG uptake.

CME

This article is available for CME credit.

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Address correspondence to W. T. Yang ().

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