Differentiating Benign from Malignant Cervical Lymph Nodes with Sonoelastography

In the clinical practice, there is many overlap in diagnostic criteria between benign and malignant lymph nodes by grayscale and Doppler sonography. This study was carried out on 30 patients who suffered from enlarged cervical lymph nodes examined with B-mode US, Doppler US and Sonoelastography in the Sonoelastography unit of the Radiology department of Tanta university hospitals to prospectively estimate the accuracy of sonoelastography in the differentiation between benign and malignant cervical lymph nodes. Sonoelastography had the highest sensitivity (92.1%), specificity (95.5%) and accuracy (93.3%) in the differentiation between benign and malignant cervical lymph nodes, so Sonoelastography is a promising technique that is easy and rapid non-invasive to perform and help identifying cervical lesions that are likely to be malignant to avoid hazards that found in tissue biopsy especially in patients with bleeding disorders.


Introduction
Of the 450 lymph nodes inside the human body, the head and neck contain 60 -70. Those nodes display reactive enlargement in response to infection (e.g., infection of upper aero-digestive tract). They also go through expansion while they are secondarily involved in head and neck cancer. Differentiation between reactive and metastatic lymphadenopathy is important [1].
Diverse imaging modalities are used to evaluate the possible etiology of neck nodes enlargement which include CT, MRI and ultrasonography. Among them, sonography is the least expensive and time consuming exam and ultrasound guided fine needle aspiration (US-FNA) can be done simultaneously to achieve cloth for cytological assessment.
A few characteristics have been documented to assist expect malignant cervical lymphadenopathy. However, no single criterion had satisfactory sensitivity and specificity for predicting this disease entity [2].
One of the differentiating criteria among benign and malignant lymph nodes is hardness (elasticity) [1] Elasticity (hardness) varies in different types of tissue (fat, collagen, and so forth) and within the same tissue in different pathologic states (inflammatory, malignant) [1].
Amongst different imaging modalities, ultrasound has the very best sensitivity in the evaluation of malignant cervical nodes, whereas PET/CThas the highest specificity in the diagnosis [3].
Among different imaging modalities, ultrasound has the highest sensitivity in the assessment of malignant cervical nodes, whereas PET/CT has the highest specificity in the Nodes with Sonoelastography diagnosis [3].

Methods
The study was conducted on 30 patients who suffered from enlarged cervical lymph nodes (13 male and 17 female), they were referred from Tanta university hospital clinics within 10 months period from May 2015 to February 2016, after obtaining their informed consent and within the approved protocol of Tanta Faculty of medicine ethical committee.
All patient names were hidden and replaced by code numbers to maintain privacy of the patients. Real time Bmode ultrasonography, Doppler US and Elastographic examination of the cervical lymph nodes was done for the study patients in the Sonoelastography unit of the Radiology department of Tanta university hospitals.
The study included patients with enlarged cervical lymph nodes, diagnosed by clinical examination. However, any patient with known cause of cervical lymphadenopathy was excluded from the study.
All patients were subjected to detailed history taking, full clinical examination and radiological imaging including Real-time B-mode ultrasonography, Doppler US and Elastographic examination of the cervical lymph nodes was done using Toshiba Aplio 500 Machine in the Sonoelastography unit of the Radiology department of Tanta university hospitals and they underwent laboratory investigations e.g. Total leukocyte count with differential leukocyte count, platelet count, prothrombin time and activity. Confirmatory Lymph node biopsy of the enlarged cervical lymph nodes was finally made.
In the case of suspected cases of metastatic cervical lymph nodes, they underwent abdomino-pelvic, neck and breast ultrasound, chest X-ray, mammography and contrast enhanced computed tomography of thehead, neck, chest, abdomen and pelvis.

Results
This study was prospectively carried on 30 patients (13 male and 17 female). The mean age for both benign and malignant cervical lymph nodepatients was (56.24 years ± 12.45 SD); the mean age washigher for malignant LNs (59.37 years ± 9.68 SD) than for benign LNs (42.78 years ± 10.36 SD), (P < 0.003). Their ages ranged from 28 to 72 years.
Detailed description of the number and percentage for each pathological cervical lymph nodes entity within benign and malignant categories are illustrated in Table 1. For assessment of the elastographic Strain ratio (Strain index), it wasfound that; the mean strain ratio for both malignant and benign LNs was 4.14 ± 3.19 with a range of (0.89 -7.33). We found that the mean strain ratio for malignant LNs (4.61 ± 2.52; range: 1.46 ± 7.33) was significantly greater than that for benign LNs (mean, 1.19 ± 0.24; range: (0.89-1.48).
In this study, the assessment of the lymph node strain ratio was according to Lyshchik, et al., (2007) [9]. So, it was considered LNs with strain ratio less than 1.5 as benign and LNs with strain ratio more than or equal 1.5 as malignant.
After revising the pathological results; it was found that 12/30 (40%) of LNs were diagnosed as benign by elastography strain ratio; out of which 11/12 (91.7%) were confirmed to bebenign (true negative) by pathology and 1/12 (8.3%) were proved to be malignant by pathology (false negative). On the other hand, 18/30 (60%) of LNs were diagnosed as malignant by strain ratio and all of them (100%) were confirmed to be malignant by pathology (truepositive). These results revealed that the calculated sensitivity of elastography strain ratio was 94.7% and specificity was 100%, PPV and NPV were 100% and 91.7%, respectivly and the total accuracy was 96.7%, Table 2. The diagnostic performance of the cervical lymph nodes B-Mode sonography, elastographic pattern (score) and elastography strain ratio are shown in Table 3 and Figure 1.

Figure 1. Comparison between the diagnostic performance of the Lymph node B-Mode sonography, Elastography Score and Strain ratio.
Elastography strain ratio shows the highest sensitivity, specificity and accuracy. Elastography score and strain ratio show higher sensitivity, specificity and accuracy compared to B-Mode sonography.

Discussion
Sonoelastography visualizes the hardness of the lesion by reflecting the biological characteristics. The palpation results vary with the experience of the examiners. If the stiffness of the tissues can be visualized through some instrument and quantitatively measured, the elasticity information of the tissues will be reflected more objectively [4].
Two different methods could be obtained for sonoelastography evaluation; qualitative elastography by the scoring method and quantitative elastography by strain ratio measurement. By means of scoring system, operator should score the target lesion according to the proportion of blue areas in the lesions. It is semi-objective and it depends on different factors such as the operator's experience and scoring system (5 or 4 point) [5].
Strain ratio (SR) measurement has been considered to be more accurate than scoring method because it could estimate the difference between stiffness of the lesions and the surrounding tissue [6].
One of the advantages of the SR method is being quantitative, in cases that the scores are the same visually, the SR could be different [6,7].
In this study we found that benign cervical lymphadenopathy gives strain ratio that ranges from 0.89 to 1.48, whereas malignant cervical lymph nodes give strain ratio that ranges from 1.46 to 7.33. The mean strain ratio of malignant cervical LNs is significantly higher than the mean strain ratio of malignant cervical LNs.
There was a significant difference in the mean strain ratio between the benign and malignant cervical lymph nodes; 1.19 ± 0.24 versus 4.61 ± 2.52, respectively (P < 0.01). Also, we found that all the benign cervical lymph nodes were less than 1.5 times stiffer than the surrounding muscles; however, 94.7% of the malignant cervical lymph nodes were more than 1.5 times stiffer than the surrounding muscles, (P < 0.01). When the diagnostic accuracy of a strain ratio greater than 1.5 was calculated, results showed that this criterion had 94.7% sensitivity, 100% specificity, 100% positive predictive value, 91.7% negative predictive value and the highest overall accuracy (96.7%) of all the diagnostic criteria examined.
Our  [9,10,11] who found that the diagnostic accuracy of the muscle-to-lymph node strain index was high. There was a significant difference in mean strain index between the benign and metastatic lymph nodes: 0.8 ± 0.5 versus 4.4 ± 3.6, respectively (P < 0.01). Among the numerous cut-off values tested, the strain index cut-off value of 1.5 enabled the best distinction between metastatic and benign lymph nodes. The majority (98%) of the benign lymph nodes were less than 1.5 times stiffer than the surrounding muscles; however, 85% of the metastatic lymph nodes were more than 1.5 times stiffer than the surrounding muscles (P < 0.01). When the diagnostic accuracy of a strain index greater than 1.5 was calculated, results showed that this criterion had 85% sensitivity, 98% specificity, 96% positive predictive value, 90% negative predictive value and the highest overall accuracy (92%) of all the diagnostic criteria examined.

Conclusion
Finally, the study concluded that Sonoelastography can improve the performance of conventional sonography in the diagnosis of enlarged cervical lymph nodes by increasing the overall sensitivity, specificity and accuracy of cervical lymph node ultrasonography.
Sonoelastography is a rich and rapidly developing technique that promises to improve diagnosis of many different lymph node diseases. As with most new technologies, diagnostic criteria and quality control mechanisms are still being established. Interested Radiologists are encouraged to begin training themselves on the properuse of this emerging methodology as most new ultrasound machines will have this option.