key: cord-0812186-0zyxpia6
authors: Li, Yan; Behr, Spencer
title: Acute Findings on FDG PET/CT: Key Imaging Features and How to Differentiate Them from Malignancy
date: 2020-09-12
journal: Curr Radiol Rep
DOI: 10.1007/s40134-020-00367-x
sha: 28b8bc5733366da7e5230c4888cc773aa90009a6
doc_id: 812186
cord_uid: 0zyxpia6

PURPOSE OF REVIEW: To review acute findings commonly encountered during routine clinical FDG PET/CT studies and present key imaging features to differentiate them from malignant counterparts. RECENT FINDINGS: FDG PET/CT is extensively used in routine clinical practice for oncology patients. Incidental acute findings in patients undergoing FDG PET/CT are increasingly common, and awareness of these findings and their mimics are important in delivering a clinically relevant and accurate radiological report for directing further management. SUMMARY: This article will review examples of common acute findings encountered during routine FDG PET/CT scans, compare them against examples of FDG-avid malignancy that can mimic these findings and emphasize key imaging findings to differentiate acute findings from their malignant mimics.

18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is a routinely performed imaging study in oncology patients. However, FDG uptake is not limited to neoplastic processes, as infections and inflammation can also result in focal FDG uptake, which may lead to false-positive results. Interpreting physicians must be aware of these potential pitfalls in order to avoid misdiagnosis. Patient history, concurrent CT finding, and knowledge of typical patterns of metastatic spread can guide interpretation of the abnormal FDG uptake. 18 F-FDG, a glucose analogue, has been used for the detection and evaluation of a wide range of solid and hematological malignancies due to the increased rate of glucose utilization in cancer cells. However, increased glucose uptake and utilization is not specific for malignant cells. Inflammatory cells such as neutrophils, activated macrophages, and lymphocytes also demonstrate increased 18 F-FDG accumulation through a shared mechanism [1, 2] . Therefore, infectious and inflammatory processes have the potential to be misinterpreted as metastatic disease. Metser et al. reviewed greater than one thousand 18 F-FDG PET/ CTs and found one-quarter of these examinations contained incidental foci of benign FDG uptake [3] . The majority of these were related to infection and inflammation. Pneumonia, upper respiratory tract infections, and wound infections were among the most common etiologies identified incidentally on 18 F-FDG PET/CT done for oncologic indications [4] . In addition, numerous additional common and uncommon benign causes of FDG uptake have been described [5] .

In this review, we will present examples of common infectious and inflammatory processes encountered in oncologic 18 F-FDG PET/CT, compare them with potential mimics of FDG-avid malignancy of these findings, and emphasize key imaging features to differentiate acute findings from their malignant mimics.

A wide variety of pulmonary infections can be 18 F-FDGavid, including typical and atypical organisms such as bacterial, fungal, TB, nocardia, and pneumocystis [6 • , 7-9] . Bacterial pneumonia is one of the most commonly encountered scenarios during routine 18 F-FDG PET/CT scan. Key differentiating considerations are CT appearance a Non-contrast CT of the chest shows ill-defined consolidation in the left lower lobe. b Fusion of PET with CT shows hypermetabolism associated with left lower lobe consolidation, compatible with bacterial pneumonia. c Non-contrast CT of the chest shows bilateral peripheral ground-glass opacities. d Fusion of PET and CT shows hypermetabolism associated with ground-glass opacities, highly suggestive of COVID-19 infection. e Non-contrast CT of the chest shows a well-defined, round mass in the left lower lobe. f Fusion of PET with CT shows hypermetabolism associated with left lower lobe mass, compatible with lung malignancy and clinical symptoms. If the FDG uptake is diffuse and corresponding to ill-defined consolidation and patient has clinical symptom of infection, bacterial pneumonia is likely the underlying cause. On the other hand, if the focal FDG uptake corresponds to a solid nodule/mass on CT and is round or oblong in appearance, then malignancy should be highly considered. In the current COVID-19 pandemic, there have been case reports of PET-CT findings in COVID patients [10, 11] . The characteristic CT appearance of peripheral ground-glass opacities in combination with high FDG uptake is highly suggestive of COVID-19 infection (Fig. 1) . Occasionally, pulmonary edema can be confused with lymphangitic spread of tumor since both conditions can show interlobular septal thickening and ground-glass opacities [12] . Key differentiating features are that in pulmonary edema, the septal thickening is symmetric and smooth, and without associated hypermetabolism, while in lymphangitic spread of tumor, the septal thickening tends to be irregular and nodular, and is often associated with increased FDG uptake (Fig. 2) .

Hypercoagulability in cancer patients predispose them to develop thrombosis. Incidental pulmonary embolism can sometimes be seen in FDG PET/CT scan and some of the emboli are associated with increased FDG uptake [13] . CT appearance and location of the FDG uptake are key. If the FDG uptake is low level, along a vessel, has a curvilinear configuration, and corresponding to filling defect in pulmonary artery on post-contrast CTs, then PE is likely the culprit of FDG uptake. The most common scenario this can be confused with is hypermetabolic perihilar lymph nodes given both of them are central in location and close attention should be paid to differentiate them (Fig. 3 ). In addition, PE-associated hypermetabolism can also mimic pulmonary artery sarcoma. SUV max value can distinguish these two entities as pulmonary artery sarcoma demonstrates much higher SUV max compared to that of pulmonary embolism [14] .

Some inflammatory conditions including organizing pneumonia, sarcoidosis, Wegener granulomatosis, immunotherapy-induced pneumonitis, as well as post-radiation changes can also demonstrate 18 F-FDG avidity Fusion of PET with CT shows no associated hypermetabolism, compatible with pulmonary edema. c Non-contrast CT of the chest shows right lower lobe mass, irregular and nodular thickening of interlobular septa, and small right pleural effusion. d Fusion of PET with CT shows hypermetabolism associated with the right lower lobe mass as well as the interlobular septa, compatible with lymphangitic spread of tumor [6, [15] [16] [17] [18] [19] [20] [21] [22] . Radiation therapy-induced inflammation in lung parenchyma is often geographical and diffuse or linear configuration, distinguishing it from more focal uptake from malignancy. Additionally, FDG uptake related to radiation-induced inflammation should slowly resolve over time and nearly completely resolve 12 weeks after radiation. Conversely, talc pleurodesis performed for management of malignant and benign pleural effusions is associated with intense inflammatory foreign body response and also demonstrates high FDG uptake, which can be present for many years after the procedure [23, 24] . Thus, clinical history of prior talc pleurodesis should be correlated so that it is not confused with pleural spread of malignancy.

Extra-pulmonic infectious and inflammatory foci are also routinely encountered. Esophagitis can be various patterns of FDG uptake. For example, low-level liner FDG uptake at gastroesophageal junction can be seen in the setting of reflux esophagitis [25] , as well as prior radiation, recent nasogastric tube, or other causes of esophagitis.

However, intense, focal esophageal uptake, especially in the mid-thoracic esophagus, is worrisome for malignancy and further evaluation with endoscopy should be considered. Breast uptake on FDG PET/CT can be secondary to variety of processes including malignancy, inflammation, as well as benign breast masses, including silicone granuloma, fat necrosis, fibroadenoma, and postsurgical changes [26, 27] . Symmetric ill-defined low-level uptake in a premenopausal woman is usually physiological. Conversely, rounded, focal uptake should be followed up with a mammogram as it is challenging to differentiate benign versus malignant masses on PET/CT [28] . Cardiac uptake is relatively common on oncologic PET/CTs, most of which are related to increased circulating glucose or insulin level. However, if there is clinical concern for myocardial inflammation, specific tailored exam such as sarcoid PET/ CT should be performed. Moreover, pericarditis, myocarditis, as well as uptake in the adjacent great vessels due to vasculitis can demonstrate increased FDG uptake 

Many acute intra-abdominal infectious or inflammatory process demonstrate increased FDG uptake and can mimic malignancy. Bowel uptake of FDG is relatively common and can be physiologic, infectious/inflammatory, or neoplastic in origin. Physiologic uptake is usually low level, linear and the CT appearance of the bowel is normal (Fig. 4) . Focal FDG uptake in bowel can be related to abscesses, appendicitis, diverticulitis, infectious and inflammatory colitis, as well as immunotherapy-related colitis [31] [32] [33] [34] [35] [36] [37] . Moreover, it is well known that metformin can lead to intense FDG uptake in the colon [38] . Figure 4 demonstrates examples of physiologic uptake, immunotherapy-induced colitis, diverticulitis, and colon cancer. If there is diffuse FDG uptake corresponding to inflammatory changes around diverticula, diverticulitis is more likely. Immunotherapy-induced colitis demonstrates diffuse bowel wall thickening, surrounding fat stranding, and diffuse FDG uptake. Conversely, focal, rounded uptake in the colon regardless of CT correlate should raise concerns for colon cancer, especially if it persists over multiple exams, and colonoscopy should be considered.

Visceral organs can also demonstrate increased FDG uptake. For example, acute pancreatitis shows increased FDG uptake [39] [40] [41] . CT appearance, FDG uptake pattern, and clinical symptoms are key. If patient has acute onset of epigastric pain, CT shows diffuse pancreatic enlargement, and peripancreatic fat stranding with associated lab shows increased lipase, then pancreatitis is more likely. On the other hand, pancreatic cancer will show soft tissue mass with focal FDG uptake resulting in distal main pancreatic ductal dilatation (Fig. 5) . Any focal pancreatic abnormality, whether on the PET or CT, should be handled with care. Follow-up dedicated pancreatic imaging should be seriously considered. Like acute pancreatitis, acute cholecystitis will show intense FDG uptake [42, 43] . CT appearance, FDG uptake pattern, and clinical symptoms are key. If patient has acute onset of right upper quadrant pain and CT shows circumferential gallbladder wall thickening with diffuse FDG uptake, acute cholecystitis is highly likely. Conversely, gallbladder cancer will show soft tissue mass in the gallbladder wall with possible direct invasion into the adjacent liver parenchyma (Fig. 6) . The patient can be asymptomatic or has persistent, long-term right upper quadrant pain. Tumefactive sludge can be a mimic of gallbladder cancer on CT; however, this will demonstrate no FDG uptake.

Both hepatic metastases and infection/abscess can demonstrate intense FDG uptake [44, 45] . CT appearance, clinical history, and time course are key to differentiate them from metastatic lesions (Fig. 7) . If patient has clinical symptoms and lab evidence of infection, infectious etiology should be high on differential. Also, if the patient has other signs of infection, especially intra-abdominal infection, or recent interventions such as ERCP or percutaneous biopsy, then abscesses should be considered. On imaging, larger abscesses (greater than 1 cm) can be centrally photopenic on FDG PET. Sometimes, systemic antibiotics or chemotherapy treatment and short-term follow-up are necessary to differentiate abscess versus metastases. Similarly, focal renal infections like renal tuberculosis, acute pyelonephritis, xanthogranulomatous pyelonephritis, and renal abscesses have all been encountered on 18F-FDG PET/CT and may be mistaken for a neoplastic process [46] [47] [48] [49] . Gonadal infection such as tubo-ovarian abscesses and orchitis has been mistaken for neoplasm on 18F-FDG PET/CT [50] [51] [52] .

In addition to the above-mentioned infectious or inflammatory process in the abdominal and pelvic organs, hernias can also demonstrate increased FDG uptake due to incarceration of fat and/or bowel, which can mimic tumor [53] . Figure 8 shows a case of FDG-avid inguinal hernia and a companion case of local tumor recurrence. CT is key. If the FDG uptake corresponds to bowel-containing inguinal hernia without adjacent soft tissue mass, do not mistake it for local recurrence. An additional potential mimic of tumor is inguinal hernia repair with prolene mesh, which can show increased FDG uptake [54] . CT can help differentiate local recurrence from prolene mesh as mesh will have lower Hounsfield units compared to local recurrence, which usually demonstrates attenuation similar to that of muscle. In equivocal cases, surgical history will be helpful. Additionally, FDG uptake can be seen along the tract of a surgical intervention due to granulation tissue. However, these regions should not be dismissed because these are common sites of recurrence after surgical resections. Any focal or new soft tissue masses should be considered suspicious for tumor and ultrasound-guided biopsy should be considered. Some other miscellaneous conditions such as acute portal venous thrombosis, peritonitis, idiopathic mesenteric necrotizing granuloma, and sclerosing mesenteritis have also been reported to show increased FDG uptake [55] [56] [57] , which can potentially mimic peritoneal carcinomatosis. The location, clinical history, and CT findings can be helpful to differentiate inflammatory from malignant changes; however, often times, it is evolution of time and changes in tumor markers that differentiate them. Musculoskeletal Low-level physiologic FDG uptake can be seen in the axial and proximal appendicular skeleton. Maximum intensity projection (MIP) images can delineate the diffuse physiologic skeletal uptake nicely. Meanwhile, a variety of musculoskeletal processes can lead to focal uptake on FDG PET/CT. Incidental inflammatory uptake in joints from degenerative osteoarthritis is almost ubiquitously visualized. Acute processes such as herniated discs, discitis, osteomyelitis, and septic arthritis can also demonstrate focal FDG uptake and may be mistaken for osseous metastases [58, 59] . Focal FDG uptake in the muscles can be related to tendinous insertion, myositis, or intramuscular infection and mistaken for sites of malignancy [60] [61] [62] .

Most times, the pattern of FDG uptake can distinguish the two scenarios as metastasis are usually focally rounded or oblong in appearance, while infectious/inflammatory uptake is usually more diffuse and linear (Fig. 9 ). MRI may be used for ambiguous cases. In addition, osseous remodeling after fracture will show increased FDG uptake and should be differentiated from osseous metastasis [63] . CT and FDG patterns are key to differentiate these two etiologies. If the FDG uptake is less intense and extends linearly along the fracture line, then insufficiency fracture is likely. Conversely, if the FDG uptake is more intense with a corresponding sclerotic or lytic osseous lesion on CT, then osseous metastasis should be considered (Figs. 10, 11 ). In cases of no CT correlate, the pattern of FDG uptake can be helpful. Multiple areas of FDG uptake make metastasis more likely. However, an isolated FDGavid lesion can be due to both benign and malignant etiologies. For example, case report that pigmented villonodular synovitis and solid aneurysmal bone cyst can contrast CT of the pelvis shows subtle lesions in the right gluteus maximum and left iliopsoas muscle. d Fusion of PET and CT shows focal intense FDG uptake associated with these lesions, compatible with intramuscular metastatic disease demonstrate increased FDG uptake and mimic malignancy [64, 65] . In these situations, MRI would be helpful to differentiate. Many cutaneous and subcutaneous lesions can demonstrate increased 18F-FDG uptake, including common processes such as sebaceous cysts and acne vulgaris to less common entities such as hidradenitis suppurativa [66 • ,67] . Fortunately, direct inspection of the skin is easily done clinically and can assist to determining the etiology of abnormal uptake; thus, these scenarios rarely cause diagnostic conundrum.

18 F-FDG PET/CT is a routinely performed imaging modality for cancer staging and evaluation of treatment response. A variety of conditions other than malignancy can cause increased FDG uptake and should be always be considered when reviewing these complex patients. Ways to differentiate acute findings from cancer including time course of change, co-existing findings on CT, patient's symptom and lab values, primary tumor type, and intensity c Non-contrast CT of the pelvis shows diffuse sclerosis of the sacrum and bilateral iliac bones. d Fusion of PET and CT shows hypermetabolism in the right sacrum; given diffuse sclerosis, this is compatible with pathological fracture

FDG PET/CT in infection and inflammation-current and emerging clinical applications

FDG PET of infection and inflammation

Benign nonphysiologic lesions with increased 18F-FDG uptake on PET/CT: characterization and incidence

Clinically important detection of infection as an' incidental' finding during cancer staging using FDG-PET/CT

Benign causes of 18-FDG uptake on whole body imaging

Enlisted variety of benign neoplasms and inflammatory lesions that can mimic pulmonary malignancy, discussed their metabolic and morphologic characteristics and provided a pathophysiological basis for their FDG uptake

PET imaging of cerebral and pulmonary Nocardia infection

Fluorine-18-fluorodeoxyglucose uptake in pneumonia

FDG PET imaging in pneumocystis pneumonia

18 F-FDG PET/CT findings of COVID-19: a series of four highly suspected cases

The potential added value of FDG PET/CT for COVID-19 pneumonia

FDG PET/CT in assessment of pulmonary lymphangitic carcinomatosis

The incidence of pulmonary embolism and associated FDG-PET Findings in IV contrast-enhanced PET/CT

Diagnostic usefulness of 18 F-FDG PET/CT in the differentiation of pulmonary artery sarcoma and pulmonary embolism

Imaging features of toxicities by immune checkpoint inhibitors in cancer therapy

Ipilimumab-induced organizing pneumonia on 18F-FDG PET/CT in a patient with malignant melanoma

Cancer immunotherapy: imaging assessment of novel treatment response patterns and immune-related adverse events

18F-FDG uptake in focal organising pneumonia mimicking bronchial carcinoma

Uptake of fluorine-18-fluorodeoxyglucose in sarcoidosis

Sarcoidosis mimicking metastatic breast cancer on FDG PET/CT

Imaging features of sarcoidosis on MDCT, FDG PET, and PET/CT

Disseminated multisystem sarcoidosis mimicking metastases on (18)F-FDG PET/ CT

Talc pleurodesis mimics pleural metastases differentiation with positron emission tomography/computed tomography

Positive FDG-PET/CT of the pleura twenty years after talc pleurodesis: three cases of benign talcoma

Bowel hot spots at PET-CT

Falsepositive lesions mimicking breast cancer on FDG PET and PET/ CT

Fat necrosis may mimic local recurrence of breast cancer in FDG PET/CT

Incidental breast lesions identified by 18 F-FDG PET/CT: which clinical variables differentiate between benign and malignant breast lesions?

Reviewed the variations of normal cardiac 18F-FDG uptake observed in oncology patients and the appearances of other patterns of pathologic metabolic activity, such as post-therapeutic effects after radiation therapy, systemic diseases

Spectrum of physiological and pathological cardiac and pericardial uptake of FDG in oncology PET-CT

18-F fluorodeoxyglucose positron emission tomography indicating unsuspected infections in two patients with dermatomyositis

Abnormal colonic accumulation of fluorine-18-FDG in pseudomembranous colitis

Colonic parasitic infection mimicking peritoneal seeding on 18F-FDG PET/CT

A unique presentation of appendicitis: f-18 FDG PET/CT

Unsuspected active ulcerative colitis in a patient with dermatomyositis: a rare association detected on (18)F-FDG PET/CT during the search for an occult malignancy

18F-FDG uptake in ischemic colitis during follow-up of a patient with lung cancer

Radiologic manifestations of immune-related adverse events in patients with metastatic melanoma undergoing anti-CTLA-4 antibody therapy

Metformin may be associated with false-negative cancer detection in the gastrointestinal tract on PET/CT

Localized autoimmune pancreatitis mimicking pancreatic cancer: case report and literature review

Focal autoimmune pancreatitis mimicking pancreatic cancer on FDG PET/CT imaging

Hypermetabolic lesions of the pancreas on FDG PET/CT

FDG PET imaging of acute cholecystitis

Chronic cholecystitis detected by FDG-PET

Hepatosplenic Candidiasis Detected by (18)F-FDG-PET/CT, Asia Ocean

Multiple liver amoebic abscesses detected on FDG PET/CT

FDG PET/CT and MRI findings in a patient with focal xanthogranulomatous pyelonephritis Curr Radiol Rep (2020) 8:22 Page 13 of 14 22 mimicking cystic renal malignancy

A case of septic pulmonary embolism associated with renal abscess mimicking pulmonary metastases of renal malignancy

PET/CT appearance of acute pyelonephritis

Dual time point (18)F-FDG PET/CT imaging identifies bilateral renal tuberculosis in an immunocompromised patient with an unknown primary malignancy

Ovarian mass mimicking malignancy: a case report

False Positive FDG PET/CT of recurrent testicular tumor due to orchitis

Bilateral tubo-ovarian abscess mimics ovarian cancer on MRI and (18)F-FDG PET/CT

Hiatal hernia mimics centrally necrotic cancer in the lung on FDG positron emission tomographic imaging

Multitechnique imaging findings of prolene plug hernia repair

Acute portal vein thrombosis: an important mimic of malignancy on FDG PET/CT

Large idiopathic mesenteric necrotizing granuloma mimicking metastatic disease on FDG PET/CT

Progressing sclerosing mesenteritis (Mesenteric Panniculitis) mimics progression of malignancy after neoadjuvant chemotherapy for gastri adenocarcinoma on serial 18 F-FDG PET/ CT

Incidental diagnosis of sternoclavicular septic arthritis with Moraxella nonliquefaciens. IDCases

Pyogenic vertebral osteomyelitis in a breast cancer patient: report of a case

Detection of multiple muscle involvement in eosinophilic myositis with (1)(8)F-FDG PET/CT

Focal inflammatory myositis on 18F-FDG PET/CT

A case of intramuscular cryptococcosis mimicking a malignant tumor on FDG PET/CT

MS 18 F-FDG PET/CT in a patient with pregnancy and lactation-associated osteoporosis

Pigmented villonodular synovitis mimics metastases on fluorine 18 fluorodeoxyglucose position emission tomography-computed tomography

Solid aneurysmal bone cyst of the humerus mimics metastasis or brown tumor

Reviewed various benign cutaneous and subcutaneous conditions encountered in routine clinical practice and discussed morphologic features of the lesion on CT to help differentiate them from malignancy

Multiple hypermetabolic subcutaneous lesions from hidradenitis suppurativa mimicking metastases on 18F-FDG PET/CT

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