How Do Oncologists Deal With IncidentalAbnormalities on Whole-Body Fluorine-18Fluorodeoxyglucose PET/CT?

Guohui Wang, MD1

Eddie W. F. Lau, MB, BS2,3

Ramdave Shakher, MB, BS2

Danny Rischin, MB, BS3,4

Robert E. Ware, MB, BS2

Emily Hong, ANMT2

David S. Binns, ANMT2

Annette Hogg, PhD2

Elizabeth Drummond, MSc2

Rodney J. Hicks, MD2,3

1 Department of Nuclear Medicine, Cancer Cen-ter, Sun Yat-sen University, Guangdong, P.R.China.2 Centre for Molecular Imaging, The Peter Mac-Callum Cancer Center, Melbourne, Australia.

3 University of Melbourne, Melbourne, Australia.

4 Division of Hematology and Oncology, The PeterMacCallum Cancer Center, Melbourne, Australia.

BACKGROUND. Combined positron emission tomography (PET)/computed tomo-

graphy (CT) using fluorine-18 fluorodeoxyglucose (FDG) is an exciting technique

for cancer evaluation, but false-positive results are a recognized limitation. The

aim of the study was to evaluate how oncologists deal with focal extrathyroidal

FDG abnormalities considered by imaging specialists to be unrelated to the refer-

ral indication.

METHODS. PET scan reports from a 12-month period from August 2002 to July

2003 in 1727 consecutive patients (mean age, 63 years) were reviewed. Incidental,

nonphysiologic FDG abnormalities were classified based on the report conclu-

sion. The frequency with which such abnormalities were investigated by oncolo-

gists and the final diagnosis were compared with the imaging diagnosis with a

minimum potential follow-up of 2 years (mean, 27.5 months).

RESULTS. Incidental FDG abnormalities were reported in 199 (12%) of 1727

patients, including 181 with adequate follow-up. Of 59 cases with a suspected

second malignancy, 34 (58%) were actively investigated, with 14 confirmed, 7

unexpected metastatic sites, and 10 other active pathologies. Only 1 further can-

cer was subsequently detected in the 25 (42%) patients not actively investigated.

Conversely, of 122 sites presumed to be benign, only 10 (8%) were actively inves-

tigated. Only 2 were proven to relate to malignancy.

CONCLUSION. Although incidental abnormalities were common, most were be-

nign and appropriately categorized by experienced readers. For actively investi-

gated extrathyroidal abnormalities, a neoplastic basis was confirmed in over 60%

of cases. Conversely, for cases deemed most likely benign by the PET/CT report

or after review of readily available clinical information by the referring oncologist,

the rate of malignancy was less than 2%. Cancer 2007;109:117–24.

� 2006 American Cancer Society.

KEYWORDS: incidental lesions, PET/CT, FDG, oncology, synchronous primary.

F luorine-18 fluorodeoxyglucose (FDG), an analog of glucose, has

high uptake in a variety of tumors related to enhanced glycolytic

metabolism. Consequently, positron emission tomography (PET)

using FDG has proven to be an accurate functional imaging tech-

nique in the diagnosis, staging, restaging, and therapeutic monitor-

ing of many common cancers.1 However, uptake of FDG is not

specific for cancer, being seen also in inflammatory and granuloma-

tous processes, as well as in normal tissues.2 This has led to the

impression that this technology is somewhat flawed as a method of

cancer staging because of a propensity for false-positive results.3

In research studies assessing the diagnostic performance of

FDG PET, focal areas of abnormal tracer uptake identified on

Address for reprints: Prof. Rodney Hicks, Director,Centre for Molecular Imaging, The Peter MacCal-lum Cancer Centre, 12 Cathedral Place, East Mel-bourne VIC 3002, Australia; Fax: (011) 61-3-9656-1826; E-mail: Rod.Hicks@petermac.org

Received August 18, 2006; revision receivedOctober 8, 2006; accepted October 9, 2006.

ª 2006 American Cancer SocietyDOI 10.1002/cncr.22370Published online 28 November 2006 in Wiley InterScience (www.interscience.wiley.com).

117

blinded reading that prove to be unrelated to the

cancer being evaluated are usually designated as

false-positive results. However, in clinical practice

imaging specialists often consider additional infor-

mation in establishing the most likely differential di-

agnosis of FDG uptake abnormalities. Moreover,

cancer staging is not limited to the results of a single

test, but rather involves an integrative process coor-

dinated by the managing oncologist. In this process

the results of the clinical history and examination are

combined with the results of laboratory and imaging

findings to assign a likely stage, or to determine

which further investigations are required to reach a

level of diagnostic certainty sufficient to define a

management strategy. Although this selective order-

ing of validation tests potentially introduces posttest

selection bias in the research setting, it is a necessary

and appropriate use of resources in clinical practice.

The aims of this study, therefore, were to ass-

ess how oncologists deal with incidental areas of

increased FDG uptake reported on routine clinical

PET/CT reporting, to assess how influenced they are

by the clinical PET/CT report, and to determine the

outcome of patients with incidental PET/CT find-

ings as a result of this process. We used a con-

secutive cohort of patients scanned over a period of

12 months.

MATERIALS AND METHODSPatient PopulationThe study included 1727 consecutive patients (980

men and 747 women: mean age, 63 years) referred

for FDG PET/CT evaluation of known or suspected

cancer from August 2002 to July 2003. All patients

were included in a prospective evaluation of the clin-

ical impact of PET in cancer care on a protocol

approved by our institutional ethics committee and

provided written consent for the scan and subse-

quent follow-up. Our PET facility was established in

1996 and the 4 nuclear medicine specialists involved

with clinical reporting in this series had a collective

experience of over 15,000 oncological PET studies by

the time the study began. This included over

6 months experience with PET/CT. Accordingly, both

our referral base and the reporting specialists had a

relatively long experience with this imaging modality

before the beginning of this study.

Imaging ProtocolPatients were imaged on a GE Discovery LS PET/CT

(General Electric Medical Systems, Milwaukee, WI)

combining a 4 slice multidetector CT scanner with a

dedicated, full-ring PET scanner with bismuth ger-

manate crystals. The CT transmission scan was

acquired using a low-dose protocol (140 kVp and 40–

120 mA). Patients were not routinely given oral or in-

travenous CT contrast for the CT scan. Total imag-

ing time was approximately 30 minutes. Attenuation-

corrected PET images were reconstructed with an

iterative reconstruction (ordered-subset expectation

maximization algorithm). Orthogonal CT, PET, and

fused PET/CT images were displayed simultaneously

on a GE Xeleris Workstation. The PET data were also

displayed in a rotating maximum-intensity projec-

tion.

Definition of Incidental PET/CT AbnormalitiesAn incidental finding was defined as any focal extra-

thyroidal accumulation of FDG considered by the

reporting clinician to be unrelated to the primary

malignancy being evaluated. This decision was gen-

erally based on the abnormality having an atypical

location, pattern, or intensity for metastasis. Scan

results were based only on the clinical report issued

and not reinterpreted in light of subsequent findings

nor reread blinded to clinical information that was

available at the time of reporting. The most likely dif-

ferential diagnosis raised by the imaging specialist

was recorded as being either benign, or malignant,

recognizing that these assignments were made with

varying degrees of certainty. Incidental thyroid

abnormalities were not included in this analysis

because our previous experience has demonstrated

that such abnormalities can represent either benign

or malignant thyroid nodules and therefore we routi-

nely perform thyroid ultrasound and perform a fine-

needle aspiration biopsy (FNAB) of all solitary

nodules with enhanced FDG uptake.

Assessment of Investigation of Incidental Findingsby Referring CliniciansResults of imaging and biopsy obtained in the month

after the PET scan result were used to ascertain

whether oncologists acted to further investigate inci-

dental abnormalities. Thereafter, the outcome of

patients was ascertained from the medical record,

pathologic reports, reports of other imaging modal-

ities, and clinical follow-up. Clinical follow-up ranged

from 9 to 37 months, with a mean of 27.5 months.

The imaging diagnosis indicated by the reporting

specialist was compared with the final diagnosis. Bi-

opsy or surgical results were considered definitive.

Focal abnormalities at any site that resolved on the

subsequent FDG PET/CT scan without specific treat-

ment were classified as benign. Cases with focal bowel

uptake but negative endoscopic findings and no fur-

ther evidence of colonic disease during a follow-up

118 CANCER January 1, 2007 / Volume 109 / Number 1

period of at least 12 months were considered to repre-

sent sites of physiologic FDG uptake.

RESULTSOn the basis of the intensity and pattern of uptake

and other clinical information, including correlation

with the low-dose, noncontrast CT performed as part

of the examination, incidental FDG PET/CT abnorm-

alities thought to be independent of the primary dis-

ease process being evaluated were reported in 199

(12%) of 1727 patients. There was complete follow-

up for 181 (91%) of these patients. The results are

summarized in Table 1. Of these, 15 (8%) were pro-

ven to represent second malignancies (Table 2). This

represented a rate of incidental, nonthyroidal cancer

of 0.9% in the entire study population.

Of the 181 evaluable sites, 59 (33%) were sus-

pected to be a second primary malignancy. Further-

more investigation was recommended to evaluate

these abnormalities subject to the degree of suspi-

cion, including the clinical circumstances of the indi-

vidual patient. The remaining 122 (67%) foci were

considered more likely to represent a benign than a

malignant process. Generally, further evaluation of

these abnormalities was not recommended except

when confirmation of malignancy would have signifi-

cantly altered curative potential.

Final Diagnosis of FDG Foci Reported as a PossibleSecond MalignancyThe referring oncologist instigated active investiga-

tion in 34 (58%) of the 59 sites reported as suspicious

of second malignancy (Table 1). Of these 34 lesions,

14 (41%) were confirmed to be a synchronous or

metachronous primary malignancy (Table 2) (Fig. 1),

whereas another 7 (21%) sites were deemed to be

metastases of the known malignancy based on histo-

pathology. Although incorrect regarding the most

likely differential diagnosis, in all cases these sites of

disease had previously been unrecognized and fur-

ther evaluation was appropriate to determine further

management. ‘‘Benign’’ lesions on histology account-

ed for 5 (15%) lesions (2 colonic polyps, 1 tubular ad-

enoma, 1 pituitary adenoma, 1 breast fibroadenoma).

Active inflammatory processes were confirmed in a

further 5 (15%) lesions (proctitis, fat necrosis, divertic-

ular abscess, 2 reactive follicular lymph node hyper-

plasia). The remaining 3 (9%) patients who were

actively investigated had focal large bowel uptake,

suggesting a possible primary tumor, but had negative

colonoscopy and negative follow-up of at least 12

months.

In 25 (42%) of 59 cases of suspected second

malignancy, either the relatively low level of suspi-

TABLE 1Summary of Results

Parameter LesionsPercentageof subgroup

Suspected second malignancy 59

Actively investigated (34)

Confirmed second malignancy 14 41

Metastasis from known primary 7 21

‘‘Benign’’ tumor on biopsy 5 15

Alternative pathology 5 15

Presumed physiological uptake 3 9

Not actively investigated (25)

Confirmed second malignancy 1 4

Alternative pathology 1 4

Presumed physiological uptake 16 64

Not relevant to clinical management 7 28

Suspected benign process 122

Mediastinal nodes (38)

Benign 34 90

Confirmed malignancy 2 5

Not confirmed 2 5

Non-mediastinal lesions (84)

Benign 79 94

Not confirmed 5 6

Total 181

Data in parentheses indicates the subgrouping of patients within each major group.

TABLE 2Pathology-Proven Second Malignancies

Patient

no. Age Sex

Indication

for PET

IncidentalFDG

abnormality Histology

1 83 W NHL Cervix SCC Cervix

2 61 W SCC tonsil LUL Adenocarcinoma lung

3 73 W Lymphoma Left breast Ductal breast cancer

4 40 W Adenocarcinoma

lung Pancreas

Adenocarcinoma

pancreas

5 51 M Undiff cancer lung Stomach Gastric adenocarcinoma

6 77 M Adenocarcinoma

lung Prostate Prostate adenocarcinoma

7 50 W Melanoma Multinodal IV stage: NHL

8 82 M SCC esophagus Colon Duke A adenocarcinoma

9 55 M Gastric

adenocarcinoma Mesentery Spindle cell sarcoma

10 61 M SCC anus Right hilum Undiff cancer lung

11 53 W SCC esophagus Tonsil SCC tonsil

12 57 W Cancer lung Colon Dysplastic villous

adenoma

13 56 W Adenocarcinoma

esophagus Colon Dysplastic adenoma

14 64 W SCC lung Left breast Ductal breast cancer

15* 77 M SCC esophagus Lung Lung adenocarcinoma

PET indicates positron emission tomography; FDG, fluorine-18 fluorodeoxyglucose; W, women; M, men;

SCC, squamous cell carcinoma; Undiff, undifferentiated; NHL, non-Hodgkin lymphoma; LUL, left upper

lobe (lung).

* This patient was confirmed only on the basis of serial PET and biopsy at 2 years.

Whole-Body FDG PET/CT/Wang et al. 119

cion expressed by the reporting imaging specialist or

the clinical circumstances of the patient led to the

FDG uptake not being actively investigated at the

time of the initial PET/CT (Table 1). In 7 patients of

these patients no final confirmation of the nature of

the FDG abnormality was achieved because all were

elderly and had aggressive primary malignancies (4

lung cancers, 2 diffuse large B-cell lymphoma, and a

metastatic rectal cancer) that rendered further inves-

tigation irrelevant. In the remaining 18 patients no

active investigation other than clinical correlation

was performed but follow-up information allowed

definition of the likely nature of the lesion. A patho-

logical basis for the FDG abnormality was confirmed

in only 2 of these patients on follow-up. In 1 case a

focus of FDG activity in the lung was deemed likely

to be benign on an early follow-up CT, but progres-

sive PET abnormality 2 years later led to biopsy and

confirmation of a primary adenocarcinoma of the

lung. Another lesion was characterized as being most

likely an inflammatory lung process rather than a

lung cancer based on rapidly evolving parenchymal

lung abnormalities consistent with pneumonia. The

remaining 16 foci of increased FDG uptake were in

regions known to be associated with physiologic

uptake but which were either more intense or asym-

metrical than considered normal by the reporting

physician. There were 7 cases of asymmetric uptake

in the head and neck (4 oropharynx, 3 larynx). Clini-

cal examination was able to quickly exclude a muco-

sal lesion at these sites and subsequent follow-up

confirmed absence of disease. In 6 patients focal

bowel uptake was not actively investigated but spon-

taneous resolution on follow-up PET/CT or lack of

clinical manifestations of disease on follow-up of at

least 24 months indicated a likely physiological basis.

Finally, 3 patients had focal uptake in the kidney

thought not to definitely relate to focal urinary stasis

in the calyceal system. Lack of abnormality on cor-

relative diagnostic CT or ultrasound and lack of pro-

gression of abnormality at the site identified on

follow-up of at least 12 months excluded disease.

Slight misregistration due to respiratory movement

may have accounted for these abnormalities.

Including all cases, irrespective of whether they

were investigated or not, the rate of confirmed

malignancy in those incidental abnormalities that

were considered suspicious for malignancy by the

reporting imaging specialist, malignancy was con-

firmed in 22/59 (37%), with 15 second primaries and

7 sites of unexpected metastasis.

Final Diagnosis of FDG Foci Reported as Probably BenignOf the 122 sites considered to be most likely benign,

this impression was confirmed in 113 (93%) (Table 1),

primarily by clinical follow-up. Overall, only 10 (8%)

FIGURE 1. In this patient (Patient 6) with a primary lung cancer (crosshairs in left panels), the presence of focal uptake in bone of the pelvic girdle combinedwith focal uptake in the prostatic bed (crosshairs, right panels) raised the possibility of an incidental prostatic cancer. Ultrasound-guided biopsy of the prostate

showed an adenocarcinoma, Gleason score 7. In view of the patient’s age and the presence of metastatic bone involvement, the patient received palliative

rather than radical radiotherapy for his lung cancer and was commenced on androgen blockade with a good response on bone scan and prostate-specific anti-

gen (PSA) (decreased from 18 to 2 mg/L after 6 months of treatment).

120 CANCER January 1, 2007 / Volume 109 / Number 1

patients were actively investigated, primarily by PET-

guided biopsy including endoscopic ultrasound of

equivocal mediastinal nodal stations. This was spe-

cifically performed in patients in whom the pattern

of uptake was interpreted as being most likely related

to granulomatous disease but in patients with a dis-

ease process potentially associated with mediastinal

nodal metastasis, malignancy was subsequently

demonstrated in only 2 (2%) cases. A further 7 (5%)

cases could not be characterized because of progres-

sion of the primary disease being evaluated. The me-

diastinum was the most common site of increased

uptake identified on PET as being of probable benign

etiology. Overall, 38 (2.2%) patients were reported as

having incidental abnormalities in the mediastinum

on FDG PET/CT scan. A benign etiology was gener-

ally assigned based on a pattern of symmetrical, low

to moderate FDG uptake in bilateral hilar, subcarinal,

and right paratracheal nodal stations (Fig. 2). Of

these, 89% (34/38) were proven to be interpretative

true-negatives by mediastinal lymph node sampling

(n ¼ 8), clinical follow-up, or lack of progression on

subsequent PET/CT scan. Two patients were incor-

rectly assumed to have benign mediastinal lymphad-

enopathy. These were both diagnosed on biopsy that

had been recommended by the imaging specialist to

exclude a malignant basis for abnormalities display-

ing an uptake pattern that was atypical of, but not

definitely excluding, malignant involvement. The ba-

sis of the focal uptake remained uncharacterized in 2

patients at the end of follow-up. Excluding mediast-

inal sites, there were 84 other incidental lesions

reported as most likely being benign. Of such lesions,

94% (79/84) were proven to be interpretative true-

negative by follow-up. The remaining 6% (5/84)

remain uncharacterized. Thus, no malignant sites

beyond the mediastinum appear to have been misin-

terpreted as being a benign process.

DISCUSSIONWhen assessing the diagnostic performance of FDG

PET for cancer evaluation, a dichotomous characteri-

zation of focal FDG accumulation as benign or ma-

lignant is generally used to determine the true-

positive and false-positive rate. In clinical practice,

the posttest probability of malignancy for each site

of FDG abnormality needs to be considered to

appropriately guide further investigation and man-

agement. In clinical practice, the interpretation of

focal FDG accumulation is usually based on the pat-

tern and intensity of FDG uptake. More important,

oncologists also place these findings in the clinical

context of other clinical and investigation findings.

Because of its whole-body scanning capability

and high sensitivity, FDG PET/CT scanning not infre-

quently detects additional lesions compared with

conventional imaging techniques. In the majority of

cases these lesions are metastases from a known pri-

mary tumor and are reported as such. However,

unexpected synchronous and metachronous primary

malignant lesions can occur and may be suspected

by imaging specialists because the pattern or inten-

sity of uptake differs from that expected for the

known primary disease. Although traditional medical

teaching encourages the formulation of a single, uni-

fying diagnosis, in cancer patients multiple comor-

bidities frequently exist. Indeed, there is a significant

prevalence of second primary neoplasms in cancer

patients. Dong et al4 reported that 8.5% of 633,964

patients with known cancers were subsequently pro-

ven to have other and previously unrecognized types

of primary cancer during follow-up. Ueno et al5

reported that 5.2% of 24,498 cancer patients had

multiple documented cancers. Recently, detection of

incidental second primary tumors by whole-body

FDG PET/CT imaging has been reported.6,7 However,

because of the nonspecific accumulation of FDG

both in benign and malignant lesions, the detection

of such malignancies occurs against the background

of many more abnormalities that are not due to sec-

ond malignancy. In our study the overall the rate of

detection of second malignancies was 0.9%, similar

to that reported by Ishimori et al.8 However, this rep-

resented less than 1 in 10 of those with a reported

incidental PET/CT abnormality. Despite the potential

advantages of early detection of second cancers, er-

roneous interpretation of such lesions may adversely

impact patient management. Possible consequences

include unnecessary patient anxiety, increased use of

noninvasive and invasive techniques to establish a

firm diagnosis, and inappropriately altered treatment

planning. In our population, the majority (34 of 59,

58%) of the patients suspected of having a potential

second malignancy were actively investigated. These

results suggest that referring clinicians use other clini-

cal factors in addition to the PET result in determining

the need for investigation. In those actively investi-

gated, 41% were confirmed to have a second malig-

nancy, and in 21% to be unexpected metastatic site of

the cancer prompting referral. A nonmalignant but

pathologic process was confirmed in 30% with either

‘‘benign’’ tumors or active inflammatory processes.

Only 9% of those sites actively investigated yielded no

pathology and presumably represented physiologic

FDG uptake (all focal bowel accumulations). Conver-

sely, in the 25 (42%) patients not actively investigated

by other than clinical examination and review of previ-

Whole-Body FDG PET/CT/Wang et al. 121

FIGURE 2. Adenocarcinoma of rectum (oblique arrow) and mediastinal lymphadenopathy on CT scan. On the basis of the pattern of symmetrical hilar and mediastinalnodal uptake, PET suggested granulomatous disease rather than metastatic disease. Sarcoidosis involving the mediastinum was confirmed. An isolated upper abdominal

node (horizontal arrow) in the absence of pelvic, lower para-aortic or mesenteric nodal involvement was considered more likely to be benign than malignant, although

this is a slightly atypical location for sarcoidosis. Neoadjuvant chemoradiation including only the pelvic tumor led to a complete metabolic response locally and no change

in the mediastinal and upper abdominal sites. The patient remains well with no evidence of metastatic disease more than 2 years after the scan.

ous radiology investigations, a physiological basis was

demonstrated in 64% and a pathological basis in only

8%, with only 1 further second malignancy documen-

ted. The interpretative false-positive cases were pre-

sumably of a physiological nature and were all in

regions of high physiologic uptake including the upper

airways, large bowel, and kidney. In 7 cases (28%) fur-

ther investigation was deemed inappropriate in the

context of the primary disease being evaluated by PET

and the patients’ clinical circumstances. Although it

remains possible that these sites also represented syn-

chronous malignancies, the progression of disease

elsewhere prevented confirmation of the nature of

these abnormalities.

It should be noted that semiquantitative measure-

ment of FDG uptake using the standardized uptake

value (SUV) was not used for the basis of dichotomiz-

ing lesions into benign and malignant groupings, but

rather the qualitative appearances including the pattern

of uptake. However, all studies were calibrated to allow

SUV determination and individual clinicians variably

assess the SUV of suspicious lesions as part of the

reporting process. The SUV has been considered by

some to be a useful tool for differentiating between ma-

lignant and benign etiologies of FDG foci.9,10 However,

this view remains controversial. Recently, Israel et al11

found that there was no statistical difference between

the SUV of premalignant, malignant, benign, and physi-

ologic lesions in an evaluation of unexpected gastroin-

testinal foci of FDG detected by PET/CT.

It is increasingly recognized that granulomatous

disease can cause ‘‘false-positive’’ results on FDG PET.

In our experience, there is a pattern of mediastinal

nodal tracer uptake that is characterized by symmetric

low to intermediate intensity FDG uptake both hilar

regions, and extending into the paratracheal and sub-

carinal nodal stations, which is similar to the pattern of

Ga-67 citrate uptake termed the lambda sign12 in

patients with sarcoidosis. This pattern is also observed,

not infrequently, in patients undergoing high-dose Ga-

67 SPECT, even in the absence of known malignancy.

On the basis of this, we elected to interpret such

abnormalities on FDG PET as being likely to be benign

and have not routinely recommended biopsy confirma-

tion. A recent report by Xiu et al13 supports this view.

This interpretative schema improves the specificity of

FDG but at a risk of degrading the sensitivity of PET for

the detection of malignant mediastinal nodal involve-

ment. Whereas mediastinal nodal sampling may be

indicated to ascertain the true nature of such abnorm-

alities, this involves procedures with considerable cost,

potential morbidity, and that may still fail to diagnose a

specific pathology due to sampling errors. Encoura-

gingly, of 38 incidental cases of abnormal FDG uptake

in mediastinal lymph nodal stations that were inter-

preted as being most likely to be benign, only 2 (5%)

were proven to be malignant. In both cases with con-

firmed malignancy, mediastinal uptake was accompa-

nied by atypical nodal sites, including a supraclavicular

node and posterior mediastinal nodes. Biopsy was

therefore recommended to exclude a malignant basis.

Overall, 10 (26%) patients with incidental med-

iastinal abnormalities that were suspected to be be-

nign by the imaging specialist underwent nodal

sampling. A benign basis was confirmed in 8 (80%)

of patients who were sampled. None of the patients

who were not actively investigated have progressed

in the mediastinum during follow-up. Thus, no

patient appears to have been denied appropriate

investigation or treatment when our interpretative

approach was followed. Furthermore, these patients

avoided the attendant management consequences

being upstaged, including the cost and morbidity of

unnecessary nodal sampling. To our knowledge, the

outcome of patients with incidental mediastinal

nodal abnormalities that have not been biopsied has

not been previously reported. Excluding mediastinal

nodal sites, there were 84 other sites classified as

being of a likely benign nature. Of these, 94% (79 of

84) were confirmed to be benign by follow-up. None

were confirmed to be malignant. These data suggest

that such abnormalities are correctly categorized by

experienced PET/CT readers and do not warrant rou-

tine biopsy, nor even necessarily further investigation

unless otherwise clinically indicated. Including the

mediastinum, only 2 of 122 (1.6%) of sites inter-

preted as being likely to be benign were subse-

quently proven to be malignant. This further justifies

a conservative approach to the investigation of such

abnormalities. The decision to further investigate

and characterize focal FDG abnormalities should,

however, always be based on the clinical conse-

quences of inappropriate assignment of etiology and,

therefore, cancer stage.

ConclusionAlthough incidental abnormalities are relatively com-

monly identified on whole-body FDG PET/CT, most

can be appropriately interpreted as being benign by

experienced readers. This allows oncologists to avoid

unnecessary investigations in the majority of cases

and, thereby, minimizes unwarranted patient anxiety,

and reduces the cost and potential morbidity asso-

ciated with aggressive investigation. The detection of

second malignancies in our series (0.9%) was compa-

rable to previous reports, suggesting that a strategy

of not actively investigating all incidental abnormal-

ities does not significantly compromise the sensitiv-

Whole-Body FDG PET/CT/Wang et al. 123

ity of FDG PET for the detection of malignant

lesions. Conversely, the frequency of neoplastic

lesions, or other active pathology that may be rele-

vant to the management of oncology patients, when

a second malignancy was suspected by experienced

PET readers is sufficient to warrant further investiga-

tion and appropriate follow-up. This is particularly

the case in patients who would otherwise be consid-

ered to have curable disease.

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