Role of sonoelastography beyond sonography for differentiation between reactive and metastatic lymphadenopathy

Renu Yadav; Amita Malik; Rajni Prasad

doi:10.4103/jhnps.jhnps_40_20

ORIGINAL ARTICLE

Year : 2020 | Volume : 8 | Issue : 2 | Page : 109-113

Role of sonoelastography beyond sonography for differentiation between reactive and metastatic lymphadenopathy

Renu Yadav¹, Amita Malik¹, Rajni Prasad²
¹ Department of Radiology and Imaging, VMMC and Safdarjung Hospital, New Delhi, India
² Department of Pathology, CIO Laboratory, VMMC and Safdarjung Hospital, New Delhi, India

Date of Submission	09-Aug-2020
Date of Acceptance	12-Aug-2020
Date of Web Publication	8-Dec-2020

Correspondence Address:
Renu Yadav
Department of Radiodiagnosis, VMMC and Safdarjung Hospital, New Delhi
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jhnps.jhnps_40_20

Abstract

Purpose: To evaluate the diagnostic accuracy of sonography including Doppler and sonoelastography in differentiation between reactive and metastatic cervical lymphadenopathy. Materials and Methods: A cross-sectional study was undertaken with 50 study participants after defined inclusion and exclusion criteria as per the study needs and imaging limitations. Sonographic and sonoelastographic examination was done by two examiners and diagnosis was reached in consensus. Sonographic features assessed were size, short/long axis ratio, presence or absence of echogenic hilum, intra-nodal 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 were evaluated against histopathological examination diagnosis. Cutoff for all the combined evaluation was determined from the receiver operating characteristic curve. Results: Sensitivity of individual sonographic parameters ranged from 81% to 96.3%, whereas specificity was from 50% to 96.3%. Maximum accuracy of 94.3% was obtained with intra-nodal necrosis and echogenic hilum individually. Color-coded elastograms with pattern >3 suggesting metastatic showed sensitivity of 100% but specificity of 75%. Maximum accuracy was achieved by SR >1.99 with 96.3% sensitivity and 93.02% specificity. Combined ultrasonography evaluation had sensitivity of 70.4% and specificity of 87.5%, whereas combined sonographic plus elastographic evaluation increased sensitivity and specificity to 92.6% and 100%, respectively. Conclusion: Combined sonographic and sonoelastographic assessment is better than individual assessment; hence, elastographic findings complement sonographic assessment and further increases the diagnostic confidence.

Keywords: Cervical lymphadenopathy, histopathological examination, sonoelastography, ultrasonography

How to cite this article:
Yadav R, Malik A, Prasad R. Role of sonoelastography beyond sonography for differentiation between reactive and metastatic lymphadenopathy. J Head Neck Physicians Surg 2020;8:109-13

How to cite this URL:
Yadav R, Malik A, Prasad R. Role of sonoelastography beyond sonography for differentiation between reactive and metastatic lymphadenopathy. J Head Neck Physicians Surg [serial online] 2020 [cited 2021 Apr 18];8:109-13. Available from: https://www.jhnps.org/text.asp?2020/8/2/109/302629

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.^[1] Cervical lymphadenopathy is a common clinical entity with varied causes. Imaging confirms the presence of enlarged nodes, characterize them plus reveals related head and neck abnormalities aiding diagnosis. Malignant nodes are site specific and are secondary to metastases from the head and neck cancer sixth-most common malignancy worldwide.^[2] Metastatic nodes at an unexpected site indicates advanced disease.^[3],[4],[5] Lymph nodal staging decides treatment protocol and assesses the prognosis.^[6] The presence of ipsilateral metastatic node in head and neck malignancies reduces 5-year survival by 50%, whereas contralateral metastasis reduces it further to 75%,^[7] hence requiring differentiation between reactive and malignant nodes.

Ultrasonography (USG) being noninvasive, easily available has been the first line of imaging assessment. Various ultrasound (US) features such as size, shape, echogenic hilum, intranodal necrosis or calcification, and nodal borders are being evaluated for differentiation between benign and metastatic cervical LNs. On Color Doppler intra-nodal vascular patterns evaluated as either-Hilar, spotted, avascular, and mixed. Benign LNs show either an avascular pattern or a hilar vascular pattern,^[8] whereas metastatic LNs usually have peripheral or mixed vascularity.

US has far greater accuracy than clinical. However, no single criterion or combination of US criteria has a balanced high sensitivity and specificity for the diagnosis of metastatic lymphadenopathy emphasizing the need of combining various US signs to increase the sensitivity and specificity of the method.

Ultrasound elastography (USE) is a relatively new-imaging modality which is being put to use to increase the sensitivity and specificity of USG. It 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.^[9]

The current study aims to evaluate the role of sonoelastography beyond sonography in the differentiation of reactive from malignant LNs as noninvasive assessment can significant impact treatment strategy.

Materials and Methods

A cross-sectional observation study was conducted with the approval of Institutional Ethical Committee. Prior written informed consent was taken from all study patients. Fifty patients with palpable cervical lymphadenopathy were included in the study. Patients with age <5 years, LN with >50% cystic area or macro-calcifications, or with inadequate surrounding reference muscle tissue were excluded from the study protocol.

After proper history and clinical examination, ultrasonographic and sonoelastographic assessment was done by two examiners in unison one having 25 years’ experience in sonography including Doppler and 7-year experience in sonoelastography, while 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 5–17 MHz and 3–9 MHz. Ultrasound parameters assessed are distribution, size, shape, presence or absence of echogenic hilum, nodal borders, echogenecity, intranodal calcifications, and necrosis and pattern of vascularity.

With USE color-coded elastogram and SR were calculated. Five patterns defined by Alam et al.^[10] were used in the study. Hard area is displayed as red, soft as blue, and intermediate strain as green. Diagnostic accuracy of ultrasound and elastography was compared with histopathological examination. Cutoff for strain ration, combined sonographic, sonoelastographic and combined evaluation were calculated from receiver operating characteristics (ROCs).

Results

The age of the patients included in the study ranged from 6 to 70 years, with a mean age of 37 years.

[Table 1] shows the distribution of LNs according to various sonographic criteria.

Table 1: Distribution of lymph nodes according to various sonographic criterias

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[Table 2] shows distribution of LNs according to sonoelastographic criteria.

Table 2: Distribution of lymph nodes according to sonoelastographic criteria

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[Table 3] shows the diagnostic accuracy of various sonographic and elastographic parameters to differentiate reactive from metastatic LNs.

Table 3: Diagnostic accuracy of various sonographic and elastographic parameters to differentiate reactive from metastatic lymph nodes

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[Table 4] shows diagnostic accuracy of combined elastographic and sonographic evaluation.

Table 4: Diagnostic accuracy of combined elastographic and sonographic evaluation

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Discussion

Demographic distribution

The mean age of patients with metastatic lymphadenopathy (49.5 years) was significantly older compared to one with reactive enlargement (16.2 years); similar findings were observed by Moharram et al.^[11]

Cohort characteristics

Fifty neck nodes in thirty patients were included in the study. The age of the patients ranged from 6 to 70 years with a mean age of 37 years. There were 17 men and 13 women. Twelve nodes were proven to be reactive and 38 were metastatic. Out of which 36 were from oral cancer, whereas 2 were from papillary carcinoma thyroid.

B-mode sonography

All the patients included in the study underwent gray scale sonography with color Doppler assessment followed by sonoelastographic evaluation. Data collected were analyzed and cut-off for different variables was calculated from the ROC curves. Final diagnosis was made on histopathological examination or US-guided fine-needle aspiration cytology (FNAC) of nodes.

Of all the nodes included in the study, 77.1% were metastatic. Sensitivity ranged from 81% to 96.3%, whereas specificity was from 50% to 96.3% for gray scale parameters. Maximum accuracy of 94.3% was obtained with intranodal necrosis and echogenic hilum individually. Alam et al.^[10] and Moharram et al.^[11] also achieved best accuracy with the later. Kanagaraju et al.^[12] reported 100% sensitivity and negative predictive value with echogenic hilum. Size > 8 mm had sensitivity, specificity, and accuracy of 85%, 62.5%, and 77.1%, respectively. This accuracy is well within 65% and 84% as reported by Lyshchik et al.^[13] and Alam et al.^[10]

Shape with short/long axis (S/L) ratio >0.5 had 81% sensitivity and 50% specificity. Most metastatic LNs have S/L ratio >0.5.^[10],[13] However, few reactive LNs also had S/L ratio >0.5. In our study, single cutoff S/L ratio >0.5 was taken which might not be optimal for all group of LNs. The cutoff diameter for level II nodes has been suggested to be two times higher than that for level 3.^[10]

Intranodal necrosis had sensitivity of 92.6% and specificity of 100%. This is in concordance with literature that the presence of necrosis is never a feature of reactive LN. Furthermore, metastatic LN may not show necrosis as it is a late event in tumor invasion of LNs [Figure 1] and [Figure 2].^[7],[14]

Figure 1: Gray scale (a) and color Doppler (b) images of 18-year-old male with reactive cervical lymphadenopathy. The node has short-axis diameter = 7 mm, short/long axis ratio 0.46 and hilar vascularity. Elastographic images (c) of lymph node with color-coded elastograms pattern 2 and strain ratio = 1.51

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Figure 2: Grey-scale (a) and color Doppler (b) images of a metastatic node in a 60-year-old male. The lymph node is well defined, has short-axis diameter = 0.9 cm, short/long axis ratio 0.75 and has heterogeneous echogenecity with hyperchoic areas representing coagulative necrosis. No calcification is seen in the node. On color Doppler lymph node shows avascular pattern. On ultrasound (c) Color-coded elastogram shows pattern 5 and strain ratio = 7.42. Final diagnosis was metastatic squamous cell carcinoma

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Color Doppler had sensitivity of 66.7% and was 100% specific. Vascularity of LN is 70% accurate in predicting malignancy in a study by Kanagaraju et al.^[12] Similar accuracy was determined by Misra et al.^[15] Six out of 27 metastatic nodes showed hilar or avascular pattern resulting in lower sensitivity. Hilar vascularity may be seen in early stages when malignant cells are not sufficient to destroy hilum.

Strain elastography

Color-coded elastograms with pattern >3 suggesting malignancy showed sensitivity of 100% but specificity of 75%. Similarly, Alam et al.^[10] reported sensitivity and specificity of 83% and 100%, respectively.

Cutoff calculated for SR in our study was >1.99. This value is well within the range of 2.39 and 1.5 described in previous studies.^[16],[17] Maximum accuracy was achieved by SR >1.99 with 96.3% sensitivity and 93.02% specificity. Among all metastatic LNs only LN which was falsely negative was metastasis from papillary carcinoma thyroid [Figure 3]. This node had few cystic areas within. USE has its inherent limitation that it gives spurious results with cystic and calcified LNs.

Figure 3: Grey-scale (a) and color Doppler (b) images of 25-year-old female with metastatic papillary carcinoma thyroid. The lymph node is well defined has short-axis diameter = 1.67cm, short/long axis ratio = 0.47, appears heteroechoic with hypoechoic areas representing necrosis. Multiple fine calcific foci are seen within the node. On color Doppler lymph node shows peripheral vascularity. Ultrasound elastography (c) shows color-coded pattern 4 and strain ratio = 1.81

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Combined sonography and sonoelastography

Combined USG evaluation had sensitivity of 70.4% and specificity of 87.5%, whereas combined sonographic plus elastographic evaluation increased sensitivity and specificity to 92.6% and 100% respectively. This is in concordance with the observation made by Alam et al.^[10] that B-mode sonography and elastography are complementary and the diagnostic power of the combined evaluation is better than that of individual evaluation.

Conclusion

In conclusion, combined elastographic and sonographic assessment is better than sonographic assessment. In a patient with known malignancy high diagnostic accuracy of combined evaluation helps in appropriate characterization of LNs. Furthermore, it is helpful in the selection of suspicious node that can be further examined by FNAC or biopsy for accurate staging.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Disclosure

This material has never been published and is not currently under evaluation in any other peer reviewed publication.

Ethical approval

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

Informed consent was obtained from all individual participants included in the study.

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