soft - tissue sarcomas ( stss ) are mesenchymal - origin neoplasms characterized by locally aggressive behavior and a propensity for metastases 1 .
intra - lesional heterogeneity , a well - documented phenomenon in stss 2 - 8 , can lead to imaging characteristics on us , ct , mri , and f - fluorodeoxyglucose ( fdg ) pet that can be confused with those of benign fluid collections ( bfs ) , such as hematomas , abscesses , and post - operative fluid collections 3 , 9 - 33 .
this overlap in imaging appearance leads to diagnostic dilemmas in two main clinical situations : at initial diagnosis of a soft - tissue mass , and in differentiation of recurrent sts from a bf on post - operative imaging . in either setting , the clinician must decide between biopsy and short - term follow - up imaging , each with its own limitations and important implications for patient care .
biopsy of all suspected lesions would not only be costly , but sampling error can lead to equivocal results .
follow - up imaging can avoid this issue by demonstrating growth , stability , or regression , but can delay the diagnosis and appropriate treatment of malignant lesions .
f - fdg pet - ct offers the potential of non - invasively helping to make this distinction .
however , previous studies of differentiating stss from benign lesions have met with variable success and have included few or no bfs 2 , 13 , 34 - 36 .
in addition , the majority of these studies have used the degree of f - fdg avidity , as assessed by metrics such as standardized uptake values ( suvs ) , while ignoring other data available in f - fdg pet examinations , such as the spatial pattern of f - fdg avidity ( sp ) .
sp has not been as extensively investigated as suv 36 - 42 , and may provide additional information about the biological behavior of soft - tissue lesions on f - fdg pet 37 .
this study will test two hypotheses about the use of f - fdg pet - ct in differentiation of stss and bfs .
we hypothesized that 1 ) f - fdg pet - ct can differentiate stss from bfs , and 2 ) sp can provide useful information in differentiating stss from bfs in addition to that provided by suvmax .
a retrospective study was performed using a search of fdg - pet / ct reports from 1/1/2006 to 12/31/2011 using keywords " hematoma , " " seroma , " " abscess , " and " sarcoma . " reports were reviewed for all 3,938 cases .
images were reviewed when a report was unclear or indicated the presence of an sts or bf in the extremity .
a total of 100 cases ( 44 bfs and 56 primary , recurrent , or metastatic stss ) met our inclusion criteria ( table 1 ) .
we limited the study to lesions in the extremities in order to decrease the likelihood of interpretation errors caused by normal adjacent structures such as bowel .
when multiple studies were available from the same patient , the study on which the finding first appeared was selected . in cases of multiple lesions ,
only a single representative lesion from the patient was selected in order to avoid the bias toward malignancy when a large numbers of lesions were present .
the readers were directed to the specific lesion in question prior to opening the study .
the reference standard for bf was biopsy , decrease in size , or stability for at least 6 months off treatment as per imaging , or development immediately following surgery ( too quickly for a malignancy to typically develop ) .
all f - fdg pet / cts were performed at our institution according to standard guidelines and uniform image acquisition and processing protocols .
patients were instructed to fast for at least 6 hours prior to imaging and had a measured blood glucose level of less than 150 mg / dl at the time of radiopharmaceutical administration .
patients received 10 to 20 mci of f - fdg , and were allowed to rest quietly in a darkened room for about 60 minutes before images were acquired on a pet / ct scanner ( discovery , ge healthcare , milwaukee , wi ) .
ct images were acquired without oral or intravenous contrast , and used for attenuation correction of pet data .
four readers with 7 years , 6 years , 6 years , and 3 years of experience in interpretation of f - fdg pet / ct at a large cancer center that specializes in the care of sts underwent a 30-minute training session using cases not included in the subsequent imaging review .
the readers were told that the lesions that they would be assessing would either be stss ( primary , recurrent , or metastatic ) or bfs ( post - operative collection , hematoma , or abscess ) .
the readers independently reviewed the images on dedicated workstations ( advantage workstation ( aw ) , ge healthcare , milwaukee , wi ) and were allowed to review all pet and ct images in the selected study using custom and adjustable window settings , but were blinded to historical data , other studies , and the final diagnoses .
the readers were asked to 1 ) assess the sp of a specific lesion on a 4-point scale ( thin , moderate , thick , or solid ) independently of the degree of f - fdg avidity on a score sheet ( fig .
1 ) , and 2 ) make a subjective determination based on their experience as to whether each lesion represented an sts . standardized uptake value ( suv ) was calculated as where a is the tissue tracer activity in microcuries per gram , i is the injected radiotracer dose in millicuries , and m is the patient mass in kilograms .
the maximum suv ( suvmax ) for each lesion was measured by placing a 3d volume of interest around each lesion .
kruskal - wallis tests were used to compare the 4-point ordered avidity scale by reference standard diagnosis , and wilcoxon rank - sum tests were used to compare suvmax .
agreement was classified by convention based on kappa values as slight ( 0.00 - 0.2 ) , fair ( 0.21 - 0.40 ) , moderate ( 0.41 - 0.60 ) , substantial ( 0.61 - 0.80 ) , and almost perfect ( 0.81 - 1.00 ) 43 .
logistic regression analysis was used to evaluate the diagnostic utility of using suvmax alone and combined with sp for differentiation of sts from bf . the resultant receiver operating characteristic ( roc ) curves are provided .
the discrimination analysis for suvmax alone used frequentist inference with delong 's 95% confidence interval ( ci ) 44 for the area under the roc curve ( auc ) .
the bootstrapping approach provided in the proc library was used to compute 95% pointwise cis for the roc shape .
youden 's optimal threshold using suvmax alone is reported 45 . because independent variable sp is assessed with uncertainty among the four readers , a joint model was used to conduct inference using all of the observed information .
the combined inference used a bayesian hierarchical model to integrate over the inherent inter - reader variability for evaluating sp . for each patient ,
let i denote the probability that the i patient presents thick or solid sp ( i = 1 ,  , n ) .
a conditional multiple logistic regression model was used to adjust the i patient 's log - odds ratio for presence of sts as a linear combination of an intercept , a partial effect modifying suvmax , and a partial effect modifying i .
beta ( 1 , 1 ) prior distributions were assumed for the is reflecting maximum entropy .
results are reported to reflect discrimination of sts in the presence of the estimated inter - reader variability for evaluating sp in the form of marginal 95% pointwise posterior credible intervals ( pci ) for the auc and roc shape .
a retrospective study was performed using a search of fdg - pet / ct reports from 1/1/2006 to 12/31/2011 using keywords " hematoma , " " seroma , " " abscess , " and " sarcoma . " reports were reviewed for all 3,938 cases .
images were reviewed when a report was unclear or indicated the presence of an sts or bf in the extremity .
a total of 100 cases ( 44 bfs and 56 primary , recurrent , or metastatic stss ) met our inclusion criteria ( table 1 ) .
we limited the study to lesions in the extremities in order to decrease the likelihood of interpretation errors caused by normal adjacent structures such as bowel .
when multiple studies were available from the same patient , the study on which the finding first appeared was selected . in cases of multiple lesions ,
only a single representative lesion from the patient was selected in order to avoid the bias toward malignancy when a large numbers of lesions were present .
the readers were directed to the specific lesion in question prior to opening the study .
the reference standard for bf was biopsy , decrease in size , or stability for at least 6 months off treatment as per imaging , or development immediately following surgery ( too quickly for a malignancy to typically develop ) .
all f - fdg pet / cts were performed at our institution according to standard guidelines and uniform image acquisition and processing protocols .
patients were instructed to fast for at least 6 hours prior to imaging and had a measured blood glucose level of less than 150 mg / dl at the time of radiopharmaceutical administration .
patients received 10 to 20 mci of f - fdg , and were allowed to rest quietly in a darkened room for about 60 minutes before images were acquired on a pet / ct scanner ( discovery , ge healthcare , milwaukee , wi ) .
ct images were acquired without oral or intravenous contrast , and used for attenuation correction of pet data .
four readers with 7 years , 6 years , 6 years , and 3 years of experience in interpretation of f - fdg pet / ct at a large cancer center that specializes in the care of sts underwent a 30-minute training session using cases not included in the subsequent imaging review .
the readers were told that the lesions that they would be assessing would either be stss ( primary , recurrent , or metastatic ) or bfs ( post - operative collection , hematoma , or abscess ) .
the readers independently reviewed the images on dedicated workstations ( advantage workstation ( aw ) , ge healthcare , milwaukee , wi ) and were allowed to review all pet and ct images in the selected study using custom and adjustable window settings , but were blinded to historical data , other studies , and the final diagnoses .
the readers were asked to 1 ) assess the sp of a specific lesion on a 4-point scale ( thin , moderate , thick , or solid ) independently of the degree of f - fdg avidity on a score sheet ( fig .
1 ) , and 2 ) make a subjective determination based on their experience as to whether each lesion represented an sts . standardized uptake value ( suv ) was calculated as where a is the tissue tracer activity in microcuries per gram , i is the injected radiotracer dose in millicuries , and m is the patient mass in kilograms .
the maximum suv ( suvmax ) for each lesion was measured by placing a 3d volume of interest around each lesion .
kruskal - wallis tests were used to compare the 4-point ordered avidity scale by reference standard diagnosis , and wilcoxon rank - sum tests were used to compare suvmax .
agreement was classified by convention based on kappa values as slight ( 0.00 - 0.2 ) , fair ( 0.21 - 0.40 ) , moderate ( 0.41 - 0.60 ) , substantial ( 0.61 - 0.80 ) , and almost perfect ( 0.81 - 1.00 ) 43 .
logistic regression analysis was used to evaluate the diagnostic utility of using suvmax alone and combined with sp for differentiation of sts from bf . the resultant receiver operating characteristic ( roc ) curves are provided .
the discrimination analysis for suvmax alone used frequentist inference with delong 's 95% confidence interval ( ci ) 44 for the area under the roc curve ( auc ) .
the bootstrapping approach provided in the proc library was used to compute 95% pointwise cis for the roc shape .
youden 's optimal threshold using suvmax alone is reported 45 . because independent variable sp is assessed with uncertainty among the four readers , a joint model was used to conduct inference using all of the observed information .
the combined inference used a bayesian hierarchical model to integrate over the inherent inter - reader variability for evaluating sp . for each patient ,
let i denote the probability that the i patient presents thick or solid sp ( i = 1 ,  ,
a conditional multiple logistic regression model was used to adjust the i patient 's log - odds ratio for presence of sts as a linear combination of an intercept , a partial effect modifying suvmax , and a partial effect modifying i .
beta ( 1 , 1 ) prior distributions were assumed for the is reflecting maximum entropy .
results are reported to reflect discrimination of sts in the presence of the estimated inter - reader variability for evaluating sp in the form of marginal 95% pointwise posterior credible intervals ( pci ) for the auc and roc shape .
there were 100 patients , ranging from 9 to 89 years of age ( median age 54 years ) , with 42 females and 58 males .
there were 100 lesions ( table 2 ) , of which 56 were stss and 44 were bfs .
of the 56 stss , 38 ( 68% ) were primary , 14 ( 25% ) were recurrences , and 4 ( 7% ) were metastases .
of the 44 bfs , 32 ( 72.8% ) were post - operative fluid collections , 9 ( 20.5% ) were hematomas , and 3 ( 6.8% ) were abscesses .
of the 9 hematomas 3 were of unknown etiology , 3 related to catheter placement , 2 were related to surgery , and 1 was related to anticoagulation . the abscesses were associated with immunocompromised status in patients receiving chemotherapy , either related to direct inoculation following minor injury or in the setting of systemic bacteremia . the diagnostic performance of f - fdg pet - ct using the subjective assessments of the 4 readers is shown in table 3 .
the mean sensitivity of the readers for detection of stss was 93% ( range : 91% - 98% ) and the mean specificity was 77% ( range : 59% - 91% ) .
we next assessed the data available in f - fdg pet studies , including suvmax and sp .
the median suvmax for all lesions was 5.5 ( range : 1.1 - 33.7 ) .
the stss had a significantly higher suvmax ( median 10.7 , range : 2.0 - 33.7 ) than bfs ( median 2.8 , range : 1.1 - 12.3 ) ( p<0.0001 ) .
the median suvmax of abscesses ( 11.6 , range 4.3 -12.3 ) was higher than that of the other bfs ( 2.7 , range 1.1 - 8.4 ) ( p=0.009 ) .
the readers scored the sp of the stss and bfs on the 4-point avidity scale ( fig .
61 ) and varied among the different sps , being highest for the thin sp (  = 0.70 ) and lowest for the thick sp (  = 0.46 , table 4 )
the sp of stss was more likely to be assessed as thick or solid by all readers ( p<0.0001 ) .
modeling the diagnostic efficacy of a system that classified lesions with a thick or solid sp as an sts yielded an inter - reader averaged sensitivity and specificity of 69% and 98% , respectively .
the presence of thick or solid sp resulted in an estimated 14.1-fold increase in the partial odds of sts with 95% pci=(3.74 , 54.1 ) .
moreover , each unit increase in suvmax was associated with a 1.35-fold increase in the partial odds of sts with 95% pci=(1.18 , 1.60 ) .
4 , red curve ) produced an auc=0.89 ( 95% ci 0.83 - 0.96 ) .
4 , red dot ) , yielding a sensitivity of 84% and specificity of 89% . classification using both suvmax and sp ( fig .
4 , blue curve ) resulted in an auc=0.96 ( 95% pci = 0.94 - 0.98 ) .
comparing the two interval estimates of auc revealed that the resultant improvement in the discriminability of sts from bf using both suvmax and sp did not achieve statistical significance at the 0.05 level .
4 , see open circle ) were contained within the 95% interval estimates of both roc shapes .
our results showed that f - fdg pet - ct is a sensitive ( mean 93% , range : 91% - 98% ) modality for the differentiation of stss from bfs ( table 3 ) .
the mean specificity of 77% ( range : 59% - 91% ) was lower than the sensitivity .
however , given the importance of making a prospective diagnosis of a sarcoma , the high sensitivity affirms the value of f - fdg pet - ct in the early diagnostic workup of patients suspected of having a primary or recurrent sarcoma , especially given that the studies were interpreted in the absence of historical and clinical data .
our results are in the range of sensitivity ( 91% - 100% ) and specificity ( 73% - 100% ) reported in the literature on differentiating sts from benign soft - tissue lesions 5 , 6 , 16 , 35 , 36 , 46 , although these studies included few or no bfs .
we found statistically significant differences in the suvmax of stss ( 10.7 , range : 2.0 - 33.7 ) and bfs ( 2.8 , range : 1.1 - 12.3 ) .
in addition , suvmax was significantly independently associated with sts in the presence of sp .
sp has not been as extensively investigated as suv 36 - 42 , and may provide additional information about the biological behavior of soft - tissue lesions on f - fdg pet 37 .
qualitative assessments of heterogeneity , degree of peripheral nodularity , and apparent peripheral thickness of lesions have been used in the past to differentiate benign from malignant lung 38 and peripheral nerve sheath 39 tumors , and to distinguish between high - grade and low - grade stss 36 . quantitative algorithms for objective characterization of sp
have been used to estimate prognosis in patients with stss 37 , 40 , 41 and to assess treatment response in patients with head and neck cancers 42 .
widespread adoption of these quantitative methods has likely been hampered by practical concerns such as time constraints in busy clinical practices .
we chose to focus on a qualitative assessment of sp to provide a more readily applied clinical method using an intuitive 4-point scale ( fig .
agreement among the readers in scoring the sps had a mean  = 0.61 ( range 0.46 - 0.70 ) .
stss were more likely to be assessed as thick or solid across all readers ( p<0.0001 ) , and we found that sp was significantly independently associated with sts in the presence of suvmax .
the shape of the roc curves may suggest that the incorporation of sp ( fig .
4 , blue curve ) improves discrimination of sts from bf compared to suvmax alone ( fig .
4 , red curve ) ; however , the difference between the aucs lacked statistical significance , and the shapes of the 95% intervals overlapped .
4 , open circle ) were contained within the 95% interval estimates of both roc shapes , suggesting that the sensitivity / specificity tradeoffs derived from the subjective assessments of the 4 readers are similar to the tradeoffs provided by the quantitative methods .
first , it was retrospective and f - fdg pet - ct is not routinely used for detecting abscesses or hematomas in our clinical practice .
this likely introduced a selection bias regarding our patient population , which tended to include large numbers of simple post - operative fluid collections ( 72.8% ) detected on routine surveillance , and relatively few hematomas ( 20.5% ) and abscesses ( 6.8 ) , which are usually characterized by mri or ultrasound at our institution . given that inflammatory lesions such as hematomas and abscesses tend to have higher suvmax and present greater diagnostic challenges
we found an " optimal " suvmax threshold of 5.15 for classification of sts using suvmax alone , arbitrarily assuming equal costs for misclassification of a lesion as an sts and a bf . in clinical practice , the implications of a false negative diagnosis of an sts would likely outweigh those of a false positive diagnosis ; however , in the interest of objectivity we adopted the more conventional assumption of equal costs in our analysis , avoiding specification of subjective utility weights .
in addition , this suvmax threshold should be used with caution , given the variability that exists in suv measurements across institutions 47 .
an apparent limitation of our study concerns the inclusion of lesions with the solid sp .
it can be argued that these cases present little or no diagnostic challenge , since they would be expected to represent stss .
given the degree of inter - observer variability for the solid sp (  = 0.63 , table 4 ) , our results indicate that this sp is not necessarily straightforward .
this may be secondary to the  blooming  effect that is evident when fdg uptake is indicated on fused images .
f - fdg pet - ct is a sensitive modality for the differentiation of stss from bfs .
classification schemes based upon suvmax , alone or augmented with sp are expected to help effectively discriminate sts .
 objective : to assess the diagnostic performance of 18f - fdg pet - ct in differentiating soft tissue sarcomas ( stss ) from benign fluid collections ( bfs).materials and methods :   four readers independently reviewed 100 lesions on 18f - fdg pet - ct and subjectively classified each lesion as an sts or bf and scored the spatial pattern of 18f - fdg avidity ( sp ) of each on a 4-point ordered scale ( thin , moderate , thick , solid).results : subjective assessment by readers allowed sensitive ( 91%-98% ) differentiation of stss from bfs , with lower specificity ( 59%-91% ) . 
 the stss had significantly higher suvmax ( median 10.7 , range : 2.0 - 33.7 ) than bfs ( median 2.8 , range : 1.1 - 12.3 ) . 
 reader agreement in assessment of sp had average  = 0.61 ( range 0.46 - 0.70 ) . 
 classification of thick or solid sp as sts yielded an inter - reader averaged sensitivity and specificity of 69% and 98% , respectively . 
 the presence of thick or solid sp resulted in 14.1-fold increase in partial odds of sts . each unit increase in suvmax resulted in 1.35-fold increase in partial odds of sts . 
 the receiver operating characteristic ( roc ) curves and 95% intervals for suvmax alone and suvmax + sp overlapped . 
 the average subjective assessments for the four readers and estimated performance of using sp alone were both contained within the 95% intervals of the two roc curves.conclusions : 
 18f - fdg pet - ct is a sensitive modality for differentiating stss from bfs . 
 suvmax and sp are significantly associated with sts . 
 classification schemes based upon suvmax alone or augmented with sp can be useful for distinguishing sts from bf . 