Keywords
ADC value - diffusion-weighted imaging - soft tissue sarcoma
Introduction
Soft tissue sarcomas/tumors (STSs) are a variegated group of disorders that have remarkable
diagnostic and therapeutic challenges for clinical care. The evaluation of posttreatment
response in STS is one of the most important aspects of patient care, as therapeutic
options may change depending on the success of response.[1]
Following surgery, the main mantle of magnetic resonance imaging (MRI) is to evaluate
the surgical site for recurrent tumors. MRI is the modality of choice for differentiation
between a residual or a recurrent tumor and postoperative fibrosis or inflammation.[2]
Differentiating residual or a recurrent tumor from treatment-related tissue changes
after surgical resection is a common dilemma because of nonspecific signal abnormalities
by standard MRI as there is overlap in the imaging features of benign postsurgical
reaction and subtle residual or recurrent disease.[3],[4]
The aim of the study was to evaluate the efficacy of gadolinium-enhanced MRI and quantitative
diffusion-weighted imaging with apparent diffusion coefficient (ADC) mapping in the
detection of residual/recurrent postoperative soft-tissue sarcomas and to define the
cut-off ADC values of residual/recurrent tumors.
Materials and Methods
This prospective study included 36 patients (16 women and 20 males); their ages ranged
from 17 to 73 years with a median age of 38 years. The study was performed in a specialized
oncology centre between March 2015 and November 2016.
We included patients of postoperative follow-up who were candidates for MRI after
resection of soft-tissue sarcoma in isolation or with radiation and/or chemotherapy.
MRI was performed on a high-field system (1.5 Tesla) closed magnet unit (Phillips
Achieva XR). Conventional MRI, diffusion-weighted imaging (DWI), and post-gadolinium
DTPA MRI were performed. First blind characterization and detection of lesions were
performed, following which diffusion images with ADC values were reviewed.
The morphological features of each lesion were recorded including size, shape, margin,
signal characteristics, and pattern of enhancement. The provisional diagnosis was
then reported. We reviewed the diffusion images with ADC values measured for each
lesion by two different regions of interest. The first region of interest included
the average of the whole lesion, whereas the second included the most restricted diffusion
area on the ADC map (least ADC value/maximum restricted diffusion; MRDA).
Measurements of the ADC value was made using an electronic cursor applied for each
lesion three times when possible, and then the mean ADC value for the lesion was calculated.
ADC of the minimum, maximum, and average values was obtained and expressed as mean
and standard deviation.
In statistical analysis, features considered positive for recurrent disease included
mass-like abnormality of hypo- or isointense signal at T1-weighted imaging, hyperintense
signal at T2-weighted imaging, identification of a mass on conventional imaging, mass-like
contrast enhancement, and the presence of a low-signal-intensity mass at ADC mapping.
Results
Preoperative histologic diagnoses in the patients included in our study were:
Synovial sarcoma (n = 12), myxoid liposarcoma (n = 9), pleomorphic sarcoma (n = 7), myxofibrosarcoma (n = 3), malignant peripheral nerve sheath tumor (MPNT) (n = 2), spindle cell sarcoma (n = 1), infantile fibrosarcoma (n = 1), high-grade fibrosarcoma (n = 1).
Out of 36 patients, 27 patients (75%) were proven to have postoperative recurrent/residual
soft tissue sarcomas, and 9 patients (25%) had benign postoperative changes (inflammation/fibrosis).
There were 27 proven recurrences and residuals having the following histologic diagnoses:
synovial sarcoma (n = 11), myxoid liposarcoma (n = 5), pleomorphic sarcoma (n = 5), myxofibrosarcoma (n = 2), malignant peripheral nerve sheath tumour (MPNT) (n = 2), spindle cell sarcoma (n = 1), infantile fibrosarcoma (n = 1), and 9 cases with postoperative inflammation/fibrosis.
Most tumors were in the lower extremity (30 out of 36) and the remaining 6 were in
the upper extremity.
The interval between the surgery and the MRI exam was variable, ranging from 1 month
up to 10 years after surgery, with an average of 18 months of follow-up duration.
Detailed analysis of mean ADC (mm2/s) values and MDRA of recurrent/residual nonmyxoid, myxoid lesions, and benign postoperative
changes is shown in the [Table 1], including the average ADC±standard deviation.
Table 1
Detailed analysis of mean ADC (mm2/s) values and MDRA of recurrent/residual nonmyxoid, myxoid lesions, and benign postoperative
changes
|
Pathology
|
Recurrent/Residual (Nonmyxoid)
|
Recurrent/Residual myxoid lesions
|
Benign postoperative changes
|
|
No. of cases
|
21
|
6
|
9
|
|
Mean ADC (±standard deviation)
|
1.1±0.2
|
1.71±0.69
|
1.9±0.3
|
|
MRDA (±standard deviation)
|
0.81±0.25
|
1.39±0.67
|
1.4±0.26
|
Static postcontrast T1-weighted MRI achieved 87.5% sensitivity and specificity of
only 55.6% because mass-like enhancement was observed in many cases without recurrence
(5 of 9 patients with benign postoperative changes).
Decreased signal intensity mass at ADC mapping raised specificity to 100% in the detection
of recurrence/residual (absent in all 9 patients with postoperative changes), yet
this feature does not always exist in all cases (70.37% sensitivity; 19 of 27 patients).
The diagnostic performance of each imaging feature in the detection of recurrent/residual
disease is illustrated in [Table 2]; sensitivity and specificity calculated according to positivity for malignancy.
Table 2
The diagnostic performance of each imaging feature
|
Parameter
|
Sensitivity
|
Specificity
|
Accuracy
|
P
|
|
Hypo- or isointensity at Tl-weighted imaging
|
81.48%
|
11.11%
|
63.88%
|
1.0 (insignificant)
|
|
Hyperintensity at T2-weighted imaging
|
81.48
|
11.11
|
63.88%
|
1.0 (insignificant)
|
|
Mass at conventional imaging
|
59.26
|
88.89
|
66.66
|
0.0198 (significant)
|
|
Mass at T1-weighted postcontrast imaging
|
87.5
|
55.56
|
78.78
|
0.0962 (not quite significant)
|
|
Low-signal-intensity mass at ADC mapping (including myxoid tumors)
|
70.37
|
100
|
77.77
|
0.0003 (significant)
|
|
Low-signal-intensity mass at ADC mapping (excluding myxoid tumours)
|
85.71
|
100
|
90
|
0.0001 (significant)
|
|
Minimum ADC ≤1.2
|
88.89
|
88.89
|
88.88
|
<0.0001 (significant)
|
|
Average ADC ≤1.4
|
85.19
|
100
|
88.88
|
<0.0001 (significant)
|
|
Minimum ADC ≤1.2 (in nonmyxoid tumors)
|
95.24
|
88.89
|
93.33
|
<0.0001 (significant)
|
|
Average ADC ≤1.3 (in nonmyxoid tumors)
|
90.48
|
100
|
93.33
|
<0.0001 (significant)
|
Regarding the lesion size, the ADC map performance was comparable to contrast-enhanced
sequences in detecting small recurrent/residual lesions. Lesions as small as 0.6 cm
were depicted as low signal intensity within the surgical bed at the ADC map [Table 3].
Table 3
Lesion sizes detected at postcontrast images and ADC map
|
Recurrent/Residual lesion size
|
Postcontrast images (area of mass-like enhancement)
|
ADC map low signal intensity lesion)
|
|
Minimum
|
0.6 cm
|
0.6 cm
|
|
Maximum
|
9 cm
|
7 cm
|
|
Mean
|
2.8 cm
|
2.3 cm
|
Similar to the findings of the qualitative assessment of the ADC maps, the quantitative
ADC measures of recurrent/residual disease (mean, 1.23 × 10−3 mm2/s ± 0.46) were different than those of postoperative changes (mean, 1.9 × 10−3 mm2/s ± 0.3) (P< 0.0001).
Receiver operator curve analysis was conducted to establish a cut-off ADC value for
detecting recurrent/residual lesions with high specificity [given the relatively high
observed sensitivity (87.5%) yet low specificity (55.6%) of the post-contrast sequences].
The cut-off average ADC value for detecting recurrent/residual lesions was found to
be ≤1.4 × 10−3 mm2/s with 100% specificity and 85.19% sensitivity, and the cut-off minimum ADC value
were found to be ≤1.2 × 10−3 mm2/s with 88.89% specificity and 88.89% sensitivity.
All nine patients with postoperative changes showed high average ADC values >1.4 ×
10−3 mm2/s (the estimated cut-off for recurrence/residual), whereas 23 out of 27 patients
with recurrent/residual tumors showed ADC values ≤1.4 × 10−3 mm2/s. Only 4 out of 27 patients with recurrent/residual tumors representing 14.8% showed
high ADC values >1.4 × 10−3 mm2/s, imitating recorded values for benign changes; all these 4 cases were of myxoid
pathologies. [Table 4] shows how excluding the recurrent myxoid lesions affected the minimum and average
ADC values statistical parameters.
Table 4
Minimum and mean ADC cut-off values with inclusion and after exclusion of recurrent
myxoid lesions
|
Parameter
|
Cut-off
|
Sensitivity
|
Specificity
|
Accuracy
|
P
|
|
Cut-off ADC value (positive malignancy if less than or equal to)
|
|
Minimum ADC (MRDA)
|
|
|
|
|
|
|
In all recurrent cases
|
1.2
|
88.89
|
88.89
|
88.88
|
<0.0001
|
|
In non-myxoid recurrences
|
1.2
|
95.24
|
88.89
|
93.33
|
<0.0001
|
|
Mean ADC
|
|
|
|
|
|
|
In all recurrent cases
|
1.4
|
85.19
|
100
|
88.88
|
<0.0001
|
|
In non-myxoid recurrences
|
1.3
|
90.48
|
100
|
93.33
|
<0.0001
|
Discussion
Early detection of postoperative soft tissue sarcoma residual/recurrence allows a
larger variegation of treatment choices and results in better prognosis than late
identification of recurrence.[5] Therefore, early detection of recurrence is crucial to treat sarcomas, making it
the main goal of postoperative MRI.
The differentiation of postoperative changes from a recurrent tumor with conventional
MR sequences is challenging.[3]
In our study, most recurrences were hypo or isointense to muscle on T1-weighted sequences
and hyperintense to muscle on T2-weighted and STIR sequences with a sensitivity of
81.48% and specificity 11.11%. This was a nonspecific feature for recurrence as 8
out of 9 cases (89%) with benign operative bed changes presented with areas of isointense
T1 and high T2 and STIR signal intensities.
Approximately 59.3% of recurrent masses in our series (16 of 27 cases) were identified
as suspicious masses on T1- or T2-weighted images. However, subtle recurrences were
disregarded in approximately 40.47% (11 of 27 patients) of cases with unenhanced conventional
sequences. This matches the findings in other studies by Fayad et al. and Grande et al., and points out that intravenous contrast material should be administered for evaluating
tumor recurrence.[2],[3]
In the study by Afonso et al., incorporating gadolinium MRI resulted in significant improvement in reader’s overall
accuracy and sensitivity. It also better distinguished solid from cystic masses and
improved lesion conspicuity.
Enhancement in the surgical bed is nonspecific as it also occurs in areas of postsurgical
and/or post radiation inflammation and fibrosis.[2]
The sensitivity of the static post contrast T1-weighted sequence in the detection
of a recurrent/residual tumor is high (87.5%, 21 of 24 patients). However, a mass-like
region of enhancement was observed in almost half of the patients without recurrence
[44.4% (4 of 9 patients)], resulting in only 55.56% specificity for detecting recurrence.
Such a high false-positive rate may lead to an unnecessary biopsy of a mass-like region
of postoperative scar tissue.
Unlike T1-weighted and fluid-sensitive imaging which depends on the signal intensity
and morphologic features, DWI is a technique of functional imaging.[3]
Quantitative DWI with ADC mapping is an established technique that has been used throughout
the body to distinguish lesions according to their cellularity, with advantages being
rapid acquisition and good reproducibility.[6],[7]
The part played by quantitative ADC mapping in the discrimination of benign from malignant
soft-tissue lesions has been debatable. Einarsdóttir et al. reported notable overlap in their ADC values, whereas Razek et al. and Pekcevik et al. reported that ADCs can discriminate malignant from benign soft-tissue masses.[8],[9],[10]
In our study, ADCs of recurrent nonmyxoid sarcomas (mean, 1.2 × 10−3 mm2/s ± 0.46) were significantly dissimilar from those of postoperative changes (mean,
1.9 × 10−3 mm2/s ± 0.3) (P< 0.0001), and the addition of qualitative and quantitative assessment
of the ADC maps gave 100% specificity in recurrence detection.
This is comparable to the study by Grande et al. were the mean ADC values of recurrent disease and postoperative fibrosis were 1.08
× 10−3 mm2/s ± 0.19 and 0.9 × 10−3 mm2/s ± 0.0; P = 0.03, respectively [Figure 1].
Figure 1 (A-F): MRI images 10 months postsurgical excision of left thigh liposarcoma: (A-C) T1, T2,
and STIR weighted images showing an operative bed ill-defined irregular lesion, eliciting
a low signal in T1 and T2 with a bright signal in STIR. (D) Homogeneous post-contrast
enhancement (arrows) (E and F) DWI and ADC show facilitated diffusion and high ADC
measurements (Mean 2.2 x 10-3 mm2/s, Minimum 1.5 x 10-3 mm2/s) in keeping with benign postoperative changes (circle). Wide excision revealed
granulation tissue negative for residual malignancy
However, our study showed limited diagnostic value of the use of DWI with ADC mapping
in the assessment of myxoid sarcomatous tumor recurrences as they showed relatively
high ADC map signals and high-recorded ADC values mimicking postoperative changes.
Our study included 6 cases of recurrent malignant myxoid tumors showing areas of high
ADC values in the recurrent lesions, 5 of which showed homogeneously high mean ADC
values, with an average of about 1.71 × 10−3 mm2/s compared to a mean ADC of approximately 1.1 × 10−3 mm2/s in nonmyxoid tumors (P< 0.0003).
This matches the results of Nagata et al. who showed that the ADC (mean + SD) in myxoid-containing tumors was 1.92 ± 0.41
× 10−3 mm2/s, whereas that in nonmyxoid tumors was 0.97 ± 0.33 × 10−3 mm2/s (P< 0.01) [Figure 2].[11]
Figure 2 (A-F): MRI images 8 months postsurgical excision of right vastus intermedius synovial sarcoma:
(A-C) Axial T1, axial T2, and coronal STIR weighted images showed hardly detectable
mass-like area of signal abnormality (arrow) within the right vastus intermedius muscle
bed eliciting an isointense signal in T1, high signal in T2 and STIR. (D) Homogeneous
enhancement (arrow). (E and F) DWI and ADC restricted diffusion (Mean, 1.2 x 10-3 mm2/s; Minimum, 0.86 x 10-3 mm2/s). Wide excision of the operative bed mass revealed recurrent monophasic synovial
sarcoma
This reflects overlap in the ADC values within benign and malignant soft-tissue tumors
particularly, myxoid lesions, and rendering use of DWI for soft tissue lesion characterization
or recurrence detection [Figure 3].[12]
Figure 3 (A-F): MRI images 8 months postsurgical excision of a left gluteal myxoid liposarcoma: Axial
T1 (A) and axial T2 (B) images showed dense surgical bed scarring of isointense signal
intensity in T1 and low signal intensity in T2. (C) Fat-suppressed contrast-enhanced
T1 weighted image showed avidly enhancing deep left pre-sacral nodule (circle). (D-F)
Restricted diffusion (Mean, 1 x 10-3 mm2/s; minimum 0.75 x 10-3 mm2/s). Wide excision confirmed the presence of microscopic recurrent myxoid lipo-sarcoma
within the scar tissue
In nonmyxoid tumors, if the mean ADC value exceeds 1.3 × 10−3 mm2/s, the possibility of malignancy (residual/recurrence) is low. The specificity of
ADC values is dependent on the cut-off value that determines the differentiation between
benign and malignant lesions. In our study, we obtained cut-off mean ADC value of
1.3 × 10−3 mm2/s (in nonmyxoid lesions) with 90.48% sensitivity and 100% specificity (P< 0.0001).
This is higher than the results of Nagata et al. who found that there was a difference in mean ADC between malignant (1.08 ± 0.30
× 10−3 mm2/s) and benign (1.76 ± 0.53 × 10−3 mm2/s) tumors with sensitivity and specificity of 76.3% and 76.7%, respectively, achieved
when an ADC value threshold of 1.35 × 10−3 mm2/s was used.
Our results showed high specificity of mean ADC (100%) yet lower sensitivity (85.19%
and 90.48% in nonmyxoid tumors) compared to the minimum ADC sensitivity measurements
(88.89% and 95.24% in nonmyxoid tumors), indicating that mean ADC measurements alone
are highly specific but not sensitive in the detection of residual tumors. Thus, average
ADC should be accompanied with measuring peripheral maximum restricted areas as well.
Excluding the category of recurrent/residual myxoid tumors from the analysis of the
recorded ADC values increased the sensitivity and accuracy of qualitative and quantitative
ADC observations (both mean and minimum ADC measurements), showing a cut-off average
ADC value for detecting recurrent/residual lesions of ≤1.3 × 10−3 mm2/s with 90.48% sensitivity and a cut-off minimum ADC value of ≤1.2 × 10−3 mm2/s with 95.24% sensitivity. This denotes the poor diagnostic performance of ADC maps
in the detection of recurrent/residual myxoid soft tissue sarcomas compared to other
pathological subtypes.
Among the 37 cases included in our study, preoperative MRI was available for 12 cases;
10 were diagnosed with postoperative recurrent/residual masses and 2 with postoperative
benign changes. The recurrent/residual masses showed no obvious difference in the
recorded ADC values in the pre-and postoperative examinations [Figure 4], [Figure 5], [Figure 6].
Figure 4 (A-H): Coronal STIR, axial THRIVE, DWI (b = 800) and ADC MR images of a case of right mid-thigh
synovial sarcoma pre (A-D) and 3 months postsurgical excision (E-H). Showing operative
bed nodular signal abnormality eliciting high STIR signal (E) avid homogenous post-contrast
enhancement (F), and restricted diffusion pattern (G and H) with Mean ADC value of
1.26 x 10-3 mm2/s; minimum 1.15 x 10-3 mm2/s) compared to initial preoperative ADC values of (Mean 1.2 x 10-3 mm2/s; minimum 0.94 x 10-3 mm2/s) (F). Wide excision of the operative bed lesion was positive for residual malignancy
Figure 5 (A-F): Axial THRIVE, DWI (b = 800) and ADC MR images of a case of left popliteal fossa synovial
sarcoma pre (A-C) and 2 months post-surgical excision (D-F). Operative bed diffuse
post-contrast enhancement (D), facilitated pattern of diffusion (E) and diffuse high
signal at the ADC map (F), and recording high ADC measurements (Mean 2.6 x 10-3 mm2/s; minimum 2 x 10-3 mm2/s) compared to the initial preoperative ADC values of (Mean 1.2 x 10-3 mm2/s; minimum 0.98 x 10-3 mm2/s) (C). Wide excision revealed granulation tissue negative for residual malignancy
Figure 6 (A-H): Axial T2WI, THRIVE, DWI (b = 800), and ADC MR images of a case of right upper thigh
myxoliposarcoma, pre (A-D), and 4 months post-surgical excision (E-H). Operative bed
abnormal mass-like area eliciting high T2 WI signal (E) heterogeneous peripheral post-contrast
enhancement (F), and high DWI and ADC signal (G and H) with mean ADC value of 2.8
x 10-3 mm2/s; minimum 1.7 x 10-3 mm2/s) compared to initial preoperative ADC values of (mean 2.8 x 10-3 mm2/s; minimum 2.5 x 10-3 mm2/s) (D). Wide excision of the operative bed lesion revealed residual myxoliposarcoma
Restrictions in our study were the absence of some pathological types of soft tissue
sarcomas and the limited number of cases, making it difficult to know if our results
can be applied to all soft tissue sarcomas in addition to the lack of all preoperative
MRI examinations for all patients.
In conclusion, the inclusion of contrast-enhanced and DWI showed a notable role in
postoperative recurrence detection. They increased both the diagnostic sensitivity
and specificity for discriminating tumoral recurrence from postoperative nodular scar
tissue.
