|Year : 2022 | Volume
| Issue : 1 | Page : 91-96
Sonoelastography in differentiation between metastatic and tuberculous lymphadenitis
Renu Yadav1, Amita Malik1, Rajni Prasad2
1 Department of Radiodiagnosis, VMMC and Safdarjung Hospital, New Delhi, India
2 CIO Lab, Department of Pathology VMMC and SJH, New Delhi, India
|Date of Submission||26-Dec-2021|
|Date of Decision||11-Jan-2022|
|Date of Acceptance||14-Jan-2022|
|Date of Web Publication||23-Jun-2022|
Department of Radiodiagnosis, VMMC and Safdarjung Hospital, New Delhi
Source of Support: None, Conflict of Interest: None
Introduction: The purpose of this study was to evaluate the diagnostic accuracy of sonography including Doppler and sonoelastography in differentiation between metastatic and tuberculous cervical lymphadenopathy. Materials and Methods: This single-center observational study was undertaken with 86 study subjects after defined inclusion and exclusion criteria as per study needs and imaging limitations. Sonographic and sonoelastographic examinations were done by two examiners, and the diagnosis was reached in consensus. Sonographic features assessed were size, short/long axis ratio, the presence or absence of echogenic hilum, and intranodal necrosis including pattern of vascularity. With ultrasonoelastography, color-coded elastograms and strain ratio (SR) were evaluated. Then, the accuracy of individual sonographic and sonoelastographic parameters as well as combined sonographic and sonoelastographic evaluation was evaluated against HPE diagnosis. Cutoff for all the combined evaluations was determined from receiver observing curve. Results: Out of 127 nodes examined, 100 were tuberculous and 27 were metastatic on histopathology. Among all ultrasound features, intranodal necrosis showed maximum sensitivity, i.e., 39% and specificity 96%. SR had highest sensitivity (95.6%) and specificity (96.3%) among all US and elastographic parameters. Conclusion: Sonoelastographic assessment has good diagnostic accuracy for differentiation between metastatic and tuberculous cervical lymphadenopathy and adds to sonographic assessment, thereby further increasing the diagnostic confidence.
Keywords: Metastasis, sonoelastography, sonography, tuberculous lymphadenitis
|How to cite this article:|
Yadav R, Malik A, Prasad R. Sonoelastography in differentiation between metastatic and tuberculous lymphadenitis. J Head Neck Physicians Surg 2022;10:91-6
|How to cite this URL:|
Yadav R, Malik A, Prasad R. Sonoelastography in differentiation between metastatic and tuberculous lymphadenitis. J Head Neck Physicians Surg [serial online] 2022 [cited 2022 Jun 28];10:91-6. Available from: https://www.jhnps.org/text.asp?2022/10/1/91/347997
| Introduction|| |
Forty percent of the body's lymph nodes (LNs) are located in the head-and-neck region, comprising 20% of the body's volume. Cervical lymphadenopathy is a common clinical entity with varied causes. Tuberculous and metastatic lymphadenopathy comprises majority of the causes of cervical LN enlargement. Tuberculous lymphadenitis is the most common form of extrapulmonary tuberculosis. It frequently involves posterior triangle and upper deep cervical group of LNs. Three patterns of LN involvement are seen in tuberculosis with imaging findings depends upon the stage of the disease at the time of examination. Metastatic nodes are site-specific and are secondary to the head-and-neck cancer sixth most common malignancy worldwide. Lymph nodal staging decides treatment protocol and assesses prognosis. Imaging confirms the presence of enlarged nodes characterize them plus reveals related head-and-neck abnormalities aiding diagnosis.
Imaging modalities available for assessment of LNs are ultrasound (US), including color Doppler and sonoelastography, computed tomography (CT), and magnetic resonance imaging (MRI).
Ultrasonography being noninvasive, easily available has been the first line of imaging assessment. It evaluates various US features such as size, shape, echogenic hilum, intranodal necrosis or calcification, and nodal borders for characterization. On color Doppler, intranodal vascular patterns were evaluated.
CT and MRI helps to further characterize the sonographic abnormalities, confirm LNs situated in deeper locations, with superior anatomical localization. However, CT is associated with risk of radiation, and magnetic resonance studies are time-consuming and require sedation in pediatric population.
Ultrasound elastography (USE) with principle similar to palpation employs the fact that neoplastic tissues are generally harder than benign ones due to associated desmoplastic reaction; hence, assessment of tissue stiffness can helps in differentiating benign from malignant tissues. Sonoelastographic assessment can be either qualitative or quantitative. Qualitative assessment done with color-coded elastograms maps. For quantitative assessment, strain ratio (SR) is obtained.,
The current study aims to evaluate the diagnostic accuracy of sonoelastography in differentiating metastatic from tuberculous lymphadenitis.
| Materials and Methods|| |
This single-center observational study was conducted with the approval of the institutional ethical committee. Prior written informed consent was taken from all study patients. Eighty-six patients with palpable cervical lymphadenopathy were included in the study. Patients with age <5 years, LN with >50% cystic area or macrocalcifications or with inadequate surrounding reference muscle tissue were excluded from the study protocol.
After proper history and clinical examination, ultrasonographic and sonoelastographic assessments were done by two examiners in unison, one having 25-year experience in sonography including Doppler and 7-year experience in sonoelastography, whereas the second one having 6-year experience in sonography including Doppler and 4-year experience in sonoelastography using an US scanner Philips iU22 equipped with linear array transducer of frequencies 5–17MHz and 3–9MHz. In patient with multiple cervical lymphadenopathy, LN with necrosis <50%, calcification <50%, and where superficial LN along with normal surrounding muscle tissue could be incorporated in single frame and at same level were chosen. US parameters assessed were distribution, size, shape, the presence or absence of echogenic hilum, nodal borders, echogenicity, intranodal calcifications and necrosis, and pattern of vascularity.
With USE, color-coded elastogram and SR were calculated. Five patterns defined by Alam et al. were used in the study. Hard area is displayed as red, soft as blue, and intermediate strain as green. For calculation of SR, region of interest (ROI) was placed at same levels as tissue at different depths develops different strains on compression. Moreover, ellipse ROI was chosen to measure SR, as it can be used even in small LNs. Cutoff for SR was calculated from receiver observing curves (ROCs).
After histopathological examination, metastatic and tuberculous LNs were selectively evaluated for diagnostic accuracy of US and elastography against histopathological examination.
| Results|| |
Hundred twenty-seven lymph nodes in 86 patients were included in the study. Of all the LNs included 100 tuberculous LNs while 27 were metastatic. (And among malignant nodes twenty-six were metastatic from head-and-neck malignancy and 1 from papillary carcinoma thyroid).
The mean age of patients with metastatic lymphadenopathy was 49.5 years compared to 24 years for tuberculous enlargement. The difference in age distribution was significant P < 0.0005.
B-Mode sonography and sonoelastographic parameters
Calcification was seen in 69% of tuberculous lymphadenitis, whereas 33% of metastatic LNs show calcification [Table 1].
|Table 1: Ultrasound and ultrasonoelastographic characteristics of examined nodes|
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All sonographic parameters show low sensitivity and good specificity. However, no single sonographic parameter shows a balanced high sensitivity and specificity for accurate characterization. Among all sonographic parameters, best diagnostic accuracy is seen with intranodal necrosis followed by the presence of echogenic hilum [Table 2].
|Table 2: Diagnostic performance of various ultrasound and ultrasonoelastographic parameters in the examined nodes|
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Cutoff value >1.99 for SR was obtained from ROC for differentiation between benign and malignant LNs was applied to differentiate tuberculous and metastatic LNs.
Color-coded elastograms pattern 2 was seen in 13% of tuberculous LNs and 78% show pattern 3. Whereas all metastatic LNs show color-coded patterns >3 except 2.
All metastatic LNs show SR >1.99 except 1. Representative cases are shown in [Figure 1],[Figure 2],[Figure 3],[Figure 4],[Figure 5].
|Figure 1: Color Doppler (a) and elastographic (b) images of 22 years male with tuberculous lymphadenits. The node has SAD = 0.8cm, S/L ratio 0.56 and show peripheral vascularity Elastographic images (c) of lymph nodes with color-coded elastograms pattern 2 and strain ratio 1.1|
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|Figure 2: Color Doppler (a) and elastographic images (b) of a tuberculous lymph nodes in a 17-year-old male. The lymph nodes are well defined, have SAD 0.67cm, S/L ratio 0.62, and show necrotic areas within. No calcification is seen in the node. On color Doppler, lymph nodes shows avascular pattern. On ultrasound elastography, color-coded elastogram shows pattern 3 and strain ratio = 0.9|
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|Figure 3: Color Doppler (a) and elastographic images (b) of a tuberculous lymph nodes in a 23-year-old male. The lymph nodes are well defined, have SAD 0.8cm, S/L ratio 0.74, and show necrotic areas within. Few calcific foci are seen in the node. On color Doppler, lymph nodes shows avascular pattern. On ultrasound elastography, Color-coded elastogram shows pattern 4 and strain ratio = 0.8|
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|Figure 4: Color Doppler (a) images of 56-year-old male with metastatic cervical lymphadenopathy. The lymph nodes are well defined have SAD 1.47cm, S/L ratio 0.7, appears heteroechoic with hypoechoic areas representing necrosis. On color Doppler, lymph nodes shows avascular pattern. Ultrasound elastography (b) shows color-coded pattern 4 and strain ratio = 5.43|
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|Figure 5: Color Doppler (a) images of 47-year-old male with metastatic cervical lymphadenopathy. The lymph nodes are well defined have SAD 1.3cm, S/L ratio 0.78, appears heteroechoic with hypoechoic areas representing necrosis. On color Doppler, lymph nodes shows peripheral pattern ultrasound elastography (b) shows color-coded pattern 4 and strain ratio = 3.9|
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Combined Ultrasound and sonoelastographic evaluation
For assessment of diagnostic accuracy of sonography, various US features were scored as size >8 mm = 2, size <8 mm = 0; S/L ratio >0.5 = 2, S/L ratio <0.5 = 0; intranodal necrosis present = 2, absent = 0; absence of echogenic hilum = 2, presence of echogenic hilum = 0; peripheral or mixed vascularity = 2, avascular or hilar vascularity = 0. ROC curve was plotted using the total score, and cutoff value of 4 was obtained for differentiation of tuberculous from metastatic LNs.
For assessment of combined elastographic examination using both SR and color-coded elastogram, scoring was done as: SR >1.99 = 2, SR <1.99 = 0, and color-coded elastogram pattern >2 = 2 and <2 = 0. ROC curve was plotted which yielded cutoff value >2 suggestive of malignancy.
Comparison between sonography and sonoelastography
Sonography has poor diagnostic accuracy (34%) to differentiate tuberculous from metastatic LNs, while sonoelastography has good diagnostic accuracy (96.3%)for the same. Adding sonoelastographic assessment to sonographic evaluation can significantly increase diagnostic accuracy [Table 3].
|Table 3: Diagnostic accuracy of sonographic and combined sonographic and sonoelastographic examination|
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| Discussion|| |
The mean age of patients with metastatic lymphadenopathy (49.5 years) was significantly older compared to one with tuberculous enlargement (24 years); similar findings were observed between benign and malignant lymphadenopathy by Moharram et al. and Yadav et al.
Hundred twenty-seven LNs in 86 patients were included in the study. There were 51 men and 35 women. One hundred nodes were proven to be tuberculous and 27 were metastatic. Out of which, 26 were from rsoral cancer, whereas 1 was from papillary carcinoma thyroid.
Thirty percent of tuberculous LNs are from the level V group of cervical lymphadenopathy.
Available literature on various US criteria to differentiate benign and malignant cervical lymphadenopathy were applied to differentiate tuberculous from metastatic LNs. Sensitivity of sonographic variables ranged from 0% to 39%, whereas specificity was from 77% to 96.3% for grayscale parameters. Maximum accuracy of 70% was obtained with intranodal necrosis and followed by echogenic hilum individually. Similar observations were made with respect to reactive versus metastatic differentiation.
Size >8 mm cannot be used to differentiate the two as 100% of tuberculous, and metastatic LNs were >8 mm in size. It has poor sensitivity.
Shape is assessed by short axis-to-long axis ratio (S/L ratio). Round nodes or those with S/L ratio >0.5 are considered suspicious of malignancy. S/L ratio >0.5 was observed in 74% of tuberculous LNs and 81% of metastatic LNs, hence it cannot be reliably used to differentiate the two. Ying et al. in their study including 315 tuberculous nodes reported that 79% had increased S/L ratio >0.5, however, the percentage was less than that in metastatic nodes. Sensitivity of 26% and specificity of 81% were obtained with S/L ratio >0.5 to differentiate tuberculous from metastatic LNs.
The absence of echogenic hilum indicates infiltration by malignant cells but tubercular nodes also exhibit similar appearance due to necrosis. Absent echogenic hilum was seen in 78% of tuberculous and 97% of metastatic LNs. Sensitivity of 23%while high specificity 93% was obtained using sonographic criteria. Evans et al. observed that the presence of echogenic hilum does not indicate benignity.
Intranodal necrosis is common in metastatic nodes and benign tubercular enlargement. In our study was seen in 60% of tuberculous and 97% of metastatic LNs. Among all sonographic criteria, maximum accuracy was seen with intranodal necrosis 70%. Yadav et al. found that intranodal necrosis has high sensitivity but low specificity since it is a feature of both metastasis and tuberculosis. It was seen in 80.5% of malignant nodes, 93% of which were metastatic. It was seen in 41.2% of benign nodes, all of which were tubercular.
Intranodal calcification was seen in 69% of tuberculous lymphadenitis, it is a common feature of tuberculous enlargement whereas 33% of metastatic LNs show calcification secondary to metastasis from papillary carcinoma thyroid or postradiotheraphy. Similar observations were noted by Giacomini et al.
Peripheral or mixed vascular pattern was observed in 77% of malignant nodes and 87% of tubercular nodes. Hence, this pattern cannot be used for differentiation of malignant from tubercular nodes. Ahuja et al. concluded significant overlap between tuberculous nodes and metastatic nodal vascular pattern.
Combined sonography and Doppler evaluation
Combination of multiple sonographic variables seen to increase diagnostic accuracy. Wang et al. while evaluating different causes of cervical lymphadenopathy did not found significant imaging difference between metastatic and tuberculous lymphadenopathy similar to our study.
Color-coded elastogram is qualitative assessment. In our study, 91% of tuberculous LNs show color-coded elastogram <3, whereas 85% of metastatic LNs show >3. Balasubrmaniam S et al. in their study considered <2 benign patterns whereas >2 malignant patterns. They stated that tuberculous LNs cannot be diagnosed on elastography due to overlapping features with both benign and malignant nodes. Tuberculous lymphadenitis with scarring calcification and necrosis may demonstrate stiffer areas. Similar findings were also observed by Ying L et al., Teng D K et al. and. Hasan D I et al. If similar criteria were applied to our data, it demonstrates poor diagnostic accuracy as 78% of tuberculous LNs show color-coded elastogram pattern 3. However, using color-coded elastogram >3 as big divide to differentiate tuberculous from metastatic lymphadenopathy it shows high sensitivity 91% and specificity 85%.
SR with semiquantitative assessment shows the best diagnostic accuracy among all sonographic and sonoelastographic parameters. SR <1.99 was seen in 95% of tuberculous LNs, whereas 96% metastatic LNs show SR >1.99. All metastatic LNs except metastasis from papillary carcinoma thyroid show SR >1.99 which show false-negative results to cystic areas within. 82.6% of tubercular LNs show SR <.5, this number increases to 95% with SR <1.99. Available literature on strain elastography in cervical lymphadenopathy shows SR between 1.5 and 2.39 to differentiate benign from malignant lymphadenitis with no specific data on tubercular LNs which are considered part of benign spectrum.,
Combined sonographic and sonoelastographic evaluation
Grey scale including doppler evaluation has limited role to differentiate to tuberculous from metastatic cervical lymphdenopathy. Sonoelastography shows promising results. It increases the diagnostic accuracy beyond sonography.
History and clinical examination were followed by sonographic and sonoelastographic examination, leading to observer bias. Sonoelastographic evaluation of cervical LNs is affected by internal vibration produced by pulsation of great vessels. LNs with >50% necrosis and calcification were excluded, as being limitation of elastography producing spuriously low or high stiffness values, respectively. Moreover, data are skewed toward single diagnosis with all malignant LNs are from head-and-neck malignancy except one; hence result cannot be extrapolated to other malignant LNs causes.
| Conclusion|| |
Individual sonographic parameters have poor sensitivity but good specificity to characterize cervical lymphadenopathy. Among all sonographic parameters, intranodal necrosis shows the best diagnostic accuracy. Sonoelastographic variables color-coded elastogram and SR characterization have high sensitivity and specificity, better than sonographic variables. SR being semiquantitative has higher diagnostic accuracy compared to color-coded elastograms.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
This material has never been published and is not currently under evaluation in any other peer reviewed publication.
The permission was taken from Institutional Ethics Committee prior to starting the project. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3]