Lymphadenopathy is one of the common daily clinical encounters, and it holds high clinical significance as it could be a manifestation of a number of pathological entities [1]. A detailed knowledge of the differential diagnosis of localized or generalized lymphadenopathy is important as lymphadenopathy can be caused by serious conditions such as malignancy.
B-mode sonography, color Doppler sonography, and ultrasound elastography were used in our study to differentiate between benign and malignant cervical lymph nodes in the light of clinical data, follow-up, and histopathological results.
Owing to the multiplicity of lymph nodes, the most suspicious nodes were chosen as the clinical concern was whether the nodal masses are benign or malignant. Choosing the most suspicious nodes resulted in 84 lymph node groups in 55 patients. Statistical data showed male predominance as 60% of patients were males and 40% were females.
Histopathological results showed that 69% of the lymph nodes (58 lymph nodes) were malignant. This high percentage of malignant lymph nodes in the current study can be attributed to the selection of the most suspicious lymph nodes because physician were worried about metastatic disease in patients with primary malignancy and about being malignant lymphadenopathy such as lymphoma in patients without known primary. This was also observed by Alam et al. [6] and Shi et al. [8], the studies of whom were conducted on 85 lymph nodes, 62% of which were malignant. However, in some other studies such as that performed by Lyshchik et al. [9], only 43% of the total of 114 examined lymph nodes were found to be malignant.
The B-mode ultrasonographic diagnosis of lymph nodes has been the topic of many studies in the literature [10, 11].
Unlike Teng et al. [12] found that the best B-mode criterion was short-axis diameter with sensitivity of 94% and accuracy of 71.9%, the current study results showed that the best conventional ultrasound criterion was the presence or absence of a hyperechoic hilum. In the current study, we observed a lost hilum in 100% of malignant lymph nodes and 27% of benign nodes. On the other hand, some authors have reported that a hyperechoic hilum can be visualized in up to 51.5% of metastatic nodes [13], regarding short-axis diameter, results showed that it was statistically insignificant in differentiation between benign and malignant cervical lymph nodes, with a P value of 0.315.
In the current study, the shape of lymph nodes was not a sufficient reliable indicator for identifying malignant lymph nodes (P 0.121). In contrast, the observations of Toriyabe et al. [14] and Lyshchik et al. [9] showed that 68% and 82% of benign nodes respectively were oval and 81% and 75% of malignant nodes respectively were round in shape
Normal and reactive nodes were predominantly hypoechoic when compared to the adjacent muscles, however, metastatic nodes from papillary carcinoma of the thyroid are usually hyperechoic. The hyperechogenicity of the lymph nodes is believed to be due to the intra-nodal deposition of thyro-globulin originating from the thyroid primary tumor [15, 16].
Regarding color Doppler US, it has been shown that benign lymph nodes tend to show hilar vascularity (73% of benign lymph nodes). In contrast, malignant lymph nodes had peripheral (56.8%) or mixed (both peripheral and hilar) vascularity (8.6%). In their study, Teng et al. [12] reported sensitivity 67%, specificity 76%, and accuracy 71% for Doppler in differentiating benign and malignant LNs. Also, in Lyshchik et al. [10] had found that specificity of Doppler was higher than its sensitivity recording 99% and 47%, respectively.
Ultrasound elastography corresponds to clinical palpation as a method to assess how stiff lymph nodes are. In general, metastatic lymph nodes are hard and lymph nodes of TB are of tough texture.
Elastography is a technique that uses ultrasound to analyze the stiffness of lymph nodes by measuring the amount of distortion that occurs when the lymph node is subjected to external pressure. The stiffness of the lymph node is closely related to biological characteristics. Malignant lymph nodes often are infiltrated by tumor cells, necrosis, and calcification. Benign lymph nodes, not containing metastatic deposits, have a similar stiffness to normal tissue. According to this theory, malignant lymph nodes are mostly stiffer than benign ones (Bhatia et al. [17]).
Elasticity score is used for the interpretation of elastographic findings [17]. The elasticity scoring system initially proposed by Itoh et al. [18] was useful for comparing breast ultrasound elastographic results, by using five pattern elasticity scores. The four patterns scoring system is the most frequently ES used in detecting lymph nodes abnormalities due to its simplicity [17]. So, we used it in the present study.
Furukawa et al. [19], Iagnocco et al. [20], and Choi et al. [21] carried out studies on lymph nodes and classified the elastographic findings into four patterns. Their results revealed that malignant lymph nodes were found to exhibit patterns 3 and 4 and benign lymph nodes patterns 1 and 2.
Findings observed in the current study were similar to those of Furukawa et al. [19]. Eighty-two percent of benign lymph nodes that we examined were classified as patterns 1 and 2, while 94% of malignant ones were classified as patterns 3 and 4.
Scores 3 and 4 were present in 72.4% and 22.4% of the malignant lymph nodes, respectively, 7.72% and 0% of the benign lymph nodes, respectively. On the other hand, 5.1% (3/58) of the malignant nodes had score 2 (false negative).
Ying et al. [7] concluded that even though elasticity score measurement had a good diagnostic accuracy, it had significant inter-observer variability. Thus, a quantitative method such as strain ratio measurement was needed for analysis of elasticity of the lymph node.
Different cut-off values of strain index were suggested to differentiate between benign and malignant nodes (1.5 and 1.78) [6, 9], while the cut-off value used in Arda et al. [22] was 2.5. In the present study, the cut-off value was 1.9 and after revising the histopathological results, the calculated sensitivity for strain ratio greater than 1.9 was 94.8%, specificity was 88.5%, PPV was 94.8%, NPV was 88.5%, and accuracy was 92.8%. High specificity is the greatest advantage of elastography, which has been found not only in the current study but also in other studies [7, 9, 22, 23]. So, ultrasound elastography can reduce the number of unnecessary biopsy in the diagnosis of metastatic cervical lymph nodes. In a study carried out on 32 enlarged lymph nodes, the authors stated that ultrasound elastography showed sensitivity, specificity, and accuracy of 83.3%, 90%, and 87.5%, respectively [24].
The specificity of ultrasound elastography has varied widely among different reports. Some studies showed high specificity of elastography as in the studies performed by Alam et al. [6] and Hefeda et al. [25] (100% and 95.6%, respectively), who studied the difference between reactive and metastatic lymph nodes. In the current study, sensitivity of elasticity score was 96.4% and sensitivity of strain ratio was 94.8%. Alam et al. [6] reported the highest accuracy for sonoelastography (89%) in agreement with our results that showed 94.4% accuracy for elasticity score and 92.8% accuracy for strain ratio
On the other hand, Lo et al. [23] in a study included 131 patients, found that the elasticity pattern system had sensitivity of 67%, specificity of 57%, positive predictive value of 52%, and negative predictive value of 71%. They concluded that elastography offers no additional value over conventional ultrasound in predicting malignancy in cervical lymph nodes.
The sonoelastography technique is helpful in differentiating reactive from metastatic lymph nodes, but it did not show the ability to distinguish other situations such as TB. Two patients in our study were diagnosed with TB lymphadenitis. The first one took score 3 (false positive), and the second one score 2. So, ultrasound elastography was equivocal in our results in such situations.
The characteristics of TB on ultrasonography are variable according to clinical stage. The appearance of TB on ultrasonography was classified into four types: acute inflammation type, cheesy necrosis type, cold abscess type, and calcification type according to some authors such as Zhao et al. [26]. The differential diagnosis between TB and malignant disease of lymph node is always the diagnostic dilemma of ultrasound and sonoelastography. In a study done by Teng et al. [12], only 5 out of 16 lymph nodes of TB were diagnosed correctly by ultrasound elastography, whereas the whole diagnostic accuracy of elastography was 66% in 89 lymph nodes which were suspected to be malignant.
The current study has some limitations such as the small number of studied nodes. Sonoelastography is a user-dependent technique related to experience of the radiologists. A low-quality elastogram can result in problems in interpretation. A poor-quality elastogram may result from pulsation of neighboring vessels. The shape of the neck may result in sliding motion during compression.
A lot of research is still needed to fully understand the varied appearance of diseases and to standardize its application. It is possible that it will become a part of the routine diagnostic sonographic procedure in the near future.