| Abstract|| |
Aims: To assess the diagnostic accuracy of color doppler ultrasonography (CDUS) in differentiating metastatic from reactive lymph nodes in oral cancer patients.
Material And Methods: Study comprised 80 adult subjects with oral cancer, divided in two groups based on clinical criteria. Group I included 40 patients with clinically suspected metastatic cervical lymph nodes, Group II included 40 patients with clinically suspected reactive cervical lymph nodes. Study population was evaluated with CDUS for color flow signals and intranodal vascular resistance (Pulsatility Index and Resistivity Index), followed by Fine Needle Aspiration Cytology, used as a standard, to confirm the etiology of the lymph node enlargement.
Statistical Analysis Used: Chi-Square Test (SPSS 15.0 version) was used to evaluate the significance of the parameters used between the two study groups.
Results: Sensitivity of CDUS by vascular flow pattern was 94.1%, specificity of 100%, with accuracy of 95.4% and by vascular indices the sensitivity was 81.4%, specificity of 100%, and accuracy of 85.5%, with statistically significant correlation.(P < 0.05)
Conclusion: CDUS plays a definitive role as an adjunct to clinical evaluation of differentiating metastatic from reactive cervical lymph involvement in patients with oral cancer as it aid in grading and staging of oral cancer and can determine the treatment plan prognosis and morbidity by diminishing the possibility nodal dissection.
Keywords: Cervical lymph node, color doppler ultrasonography, oral cancer
|How to cite this article:|
Jayachandran S, Sachdeva SK. Diagnostic accuracy of color doppler ultrasonography in evaluation of cervical lymph nodes in oral cancer patients. Indian J Dent Res 2012;23:557-8
The presence of regional lymph node metastasis in oral cancer patients substantially influences treatment and prognosis, as presence of isolated metastatic node reduces survival rate by 50% and the presence of bilateral metastatic lymph nodes further reduces the survival rate by 25%. , The management of oral cancer is based on the status of cervical lymph nodes so there is a need for an appropriate investigative procedure which can differentiate between metastatic and reactive lymph nodes. There are alterations in vascular morphology in metastatic nodes by neoplastic infiltration and neo-vascularisation induced by angiogenesis factor, whereas inflammation causes dilatation of intranodal vessels due to local humoral agents, which provide the potential for diagnosis, if these changes can be reliably detected. Color Doppler Ultrasound (CDUS) is advancement in ultrasonography which helps in differentiating metastatic from reactive nodes based on these vascular changes.  CDUS may direct the surgeons to convert the treatment plan to choose a more conservative neck dissection or to a more radical neck dissection depending on the improved preoperative staging of the oral cancer.  Studies have shown that there is a general tendency of the clinician to over-diagnose the cervical lymph nodes as metastatic in patients with oral cancer as traditionally each and every lymph node is considered metastatic in these patients. CDUS can also avoid this over-diagnosis and can prevent the unnecessary removal of nodes in each and every patient with oral cancer. , The use of fine needle aspiration cytology (FNAC), which is a minimally invasive technique,  still remains the most acceptable, cheap, and easily accessible modality for the diagnosis of metastatic lymphadenopathy. Therefore, this study was conducted to evaluate the possibility of using CDUS as an alternative investigative procedure in differentiating metastatic nodes from reactive nodes in patients with oral cancer. This study also showed the importance of CDUS in discovery of clinically non-palpable cervical lymph nodes. Objective of this study was to assess the diagnostic accuracy of CDUS in differentiating metastatic from reactive lymph nodes in oral cancer patients, to evaluate the status of clinically not-palpable lymph nodes and to correlate these findings with and FNAC findings.
|How to cite this URL:|
Jayachandran S, Sachdeva SK. Diagnostic accuracy of color doppler ultrasonography in evaluation of cervical lymph nodes in oral cancer patients. Indian J Dent Res [serial online] 2012 [cited 2019 Oct 18];23:557-8. Available from: http://www.ijdr.in/text.asp?2012/23/4/557/104976
| Materials and Methods|| |
This study was conducted in the Department of Oral Medicine and Radiology, Tamil Nadu Government dental college and hospital, Chennai-3.This study was carried out after obtaining approval from Institutional Ethical Committee and informed written consent from each patient. Study comprised 80 Adult Subjects with clinically and histopathologically diagnosed Oral cancer of either gender with age range of 20-60 years (50 male and 30 female), Study population was divided into two groups, Group-I included 40 patients (26 male and 14 female) with clinically suspected metastatic cervical lymph nodes, Group-II included 40 patients (24 males and 16 females) with clinically suspected reactive cervical lymph nodes. Inclusion criteria were patients with oral cancer diagnosed on the basis of thorough history and clinical examination followed by histopathological confirmation. Exclusion criteria were those patients with acute cervical lymph node enlargement due to infections; with malignancies of lymph nodes like lymphoma, lymphocytic leukemia; with generalized lymphadenopathy; in cases where FNAC was inconclusive. The clinical stage and location of primary tumor was determined according to the recommendations of American Joint Committee on Cancer Staging.  Initially, the cervical lymph nodes were assessed based on clinical criteria to differentiate metastatic lymph nodes from reactive nodes. Clinical criteria used for differentiating metastatic lymph nodes were (i) lymph node size larger than 1 cm in diameter, (ii) a hard or stony hard in consistency, (iii) fixity to underlying structures. , After getting the informed consent; the same patients with oral cancer were evaluated with CDUS for cervical lymph node involvement. The CDUS was performed by an experienced radiologist by using Linear Multi-frequency Transducer with range of 5MHz-13MHz (ACUSON ANTARES MODEL PREMIUM EDITION, SIEMENES MEDICAL).The radiologist had not been given any clinical data or pathological diagnosis in any of the cases and the findings were recorded in a tabular format. Different criteria considered in CDUS of the lymph nodes were color flow signals and intranodal vascular resistance (Pulsatility Index and Resistivity Index). The vascular pattern of the enlarged lymph nodes was classified into the following four groups, according to the location of the vascularity, (1) Peripheral: flow signal at the periphery of lymph node [Figure 1]. (2) Central: flow signal in the centre of the lymph node [Figure 2]. (3) Mixed: flow signal in the centre as well as periphery of the lymph node [Figure 3]. (4) No flow: absence of flow signal in the lymph node  [Figure 4]. The presence of blood flow signals in the centre of node suggests that the node is reactive. The presence of peripheral, mixed, or no flow suggests a metastatic nature. On-board software was used for the evaluation of the vascular resistance, Resistive index (RI) and Pulsatility index (PI). Metastatic nodes have high PI and RI values as compared to low PI and RI values for Reactive nodes. Cut-off values used for PI was 1.5 and for RI was 0.7 as suggested by Wu et al. PI and RI more than cut-off values [Figure 1] and [Figure 3] suggested metastatic node, whereas PI and RI less than cut-off suggested a reactive node.[Figure 2]
|Figure 1: Metastatic lymph node with peripheral color flow pattern. Spectral wave form showing high values of vascular indices.|
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|Figure 2: Reactive lymph node with central flow pattern. Spectral wave form showing low values of vascular indices.|
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|Figure 3: Metastatic lymph node with mixed flow pattern. Spectral wave form showing high values of vascular indices.|
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|Figure 4: Metastatic lymph node with no color flow pattern. LT SUB MAND: Left submandibular lymph node.|
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Cytological diagnosis of the same lymph nodes was made from FNAC. In patients with many lymph nodes belonging to the same group of lymph nodes with similar CDUS appearance, the most prominent and accessible node was subjected to FNAC. In all oral cancer patients, FNAC was suggestive of either metastatic or reactive lymph node involvement [Figure 5] and [Figure 6]. A comparative study was done between the clinical features, CDUS, and the cytological features of cervical lymph nodes. Chi-Square Test (SPSS 15.0 version) was used to evaluate the significance of the parameters used between the two study groups.
|Figure 5: Photomicrograph showing metastatic lymph node with deposits of malignant squamous cells at multiple sites and rudimentary lymphoid tissue in sub-capsular area (Hematoxylin and eosin, x10) .|
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|Figure 6: Photomicrograph showing reactive lymph node with centroblasts, centrocytes, and small lymphocytes with nuclear fragments (Hematoxylin and eosin, x100)|
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| Results and Analysis|| |
Clinical examination detected total 112 palpable lymph nodes (67 Group-I and 45 in Group-II). Number of nodes ranged from 1 to 3 in Group-I and from 1 to 2 in Group-II. Size of nodes ranged from 5 x 6cm in Group-I to 6x8mm in Group-II. Thirteen (16.2%) patients had bilateral lymph node involvement. During CDUS examination an additional 19 (17 in Group-I and 2 in Group-II) lymph nodes were discovered with a significant correlation from clinical examination (P < 0.05), which were also included in the overall CDUS study. So total lymph nodes evaluated by CDUS were 131.Clinically as well as by CDUS, most commonly evaluated nodes were Level I lymph nodes followed by Level II and Level III [Figure 7]. No lymph node was evaluated at Level IV or Level V. On the basis of color flow pattern out of 131 lymph nodes 96(73.3%) showed features of metastasis. There was a significant difference between Group-I and Group-II regarding flow pattern. (P < 0.05) [Table 1] On the basis of intranodal vascular resistance indices, out of 131 lymph nodes 83(63.4%) showed features of metastasis and 48 (36.6%). This study showed statistically significant differences between two groups regarding PI and RI values. (P < 0.05) [Table 2] There was statistically significant differences between the mean values of PI and RI for metastatic and reactive (P < 0.05 for PI and RI) [Figure 8].
|Figure 8: Mean values of intranodal vascular indices (PI and RI) in metastatic and reactive lymph nodes. PI - Pulsatility Index RI -Resistivity Index|
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|Table 1: Correlation of color doppler flow patterns of in 131 lymph nodes in 80 oral cancer patients|
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|Table 2: Correlation of vascular indices of CDUS in131 lymph nodes in 80 oral cancer patients|
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Comparison of the results between clinical, CDUS, and FNAC to find out the efficacy of CDUS: A comparison of clinical findings with cytological findings showed that all lymph nodes of Group-I were confirmed to be metastatic deposits (no false positive) and in Group-II, 28 lymph nodes proved reactive and 17 proved metastatic (false negative) by cytology. So, total 84 (75%) nodes were diagnosed as metastatic and 28(25%) as reactive by FNAC. [Table 3] There was statistically significant difference between clinical diagnosis and FNAC findings (P < 0.05), accordingly a sensitivity of 79.8%, specificity of 100% with accuracy of 84.82% for clinical evaluation was found in patients with oral cancer. FNAC confirmation of those 131 lymph nodes, the result was 102 (84 in Group-I and 18 in Group-II) were metastatic and 29(all in Group-II) were reactive. CDUS study of those 131 lymph nodes 96(73.3%) had features of metastatic lymph nodes and the remaining 35(26.7%) lymph nodes had features of reactive lymph nodes. On the basis of vascular indices on CDUS of 131 nodes 83 (63.4%) showed features of metastatic nodes and 48(36.6%) showed features of reactive nodes. On comparison with FNAC findings, there was no statistical difference between CDUS flow pattern and FNAC (P > 0.05), but statistically significant difference was found between CDUS vascular indices findings and FNAC (P < 0.05) [Table 4].
|Table 3: Comparison of clinical examination Vs FNAC of cervical lymph nodes in 80 oral cancer patients(112 lymph nodes)|
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|Table 4: Comparison of color doppler findings vs cytological examination of cervical lymph nodes in 80 oral cancer patients (131 Lymph nodes)|
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| Discussion|| |
Recent studies have shown that there is a tendency to over-diagnose nodes as metastatic in patients with oral cancer and have suggested that all clinically palpable cervical lymph nodes in oral cancer patients cannot be assumed to be metastatic but there should be a re-evaluation of the clinical criteria for suspicion of cervical lymph nodes in patients with oral cancer. , So based on these studies, we divided study population into two groups, based on clinical criteria for differentiating metastatic nodes from reactive nodes. , CDUS correctly identified 112 cervical lymph nodes and additional 19 lymph nodes. This resulted in a false negative rate of 14.5% by clinical examination as those nodes were totally missed during clinical evaluation. By FNAC confirmation, 18 out of 19 cervical lymph nodes had metastatic deposits so rate of occult metastasis were 94.7% which is different as compared to reported by Ahmed et al.,  and Dangore et al. as they found it to be 33%.  This study showed that in patients with oral cancer, highest risk for early metastasis to lymph nodes were to Level I followed by Level II, Level III. These findings were comparable to the findings of Ying and Ahuja.  No nodes were palpated at Level IV or Level V. These findings were similar to the findings of Ying  and Ahuja and Dangore et al. In this study, out of total 131 lymph nodes evaluated by CDUS, 81 showed peripheral color flow signal, and further confirmed as metastatic nodes by FNAC. This study again supported the fact that peripheral flow is suggestive of metastatic nodes, which is similar to previous studies. , Reason for peripheral flow can be, destruction of hilar vascularity by tumor cells may result in the induction of vascular supply from the peripheral pre-existing vessels or from vessels in the peri-nodal soft tissue.  A total of 35 nodes showed central vascular flow, 33 nodes proved to be reactive and 2 metastatic, by FNAC. Reason for central flow may be due to the increase in vessel diameter and blood flow.  This finding was consistent with other studies, suggesting that presence of central flow is indicator of reactive nodes. ,,, Presence of central flow in two metastatic lymph nodes was contradictory finding. This finding was comparable to the study by Sato et al.,  and Steinkamp et al. The reason for this could be the presence of micro-metastases at the early stage of lymph node involvement, which could not be detected by CDUS as intranodal vascular alterations take place at a relatively late stage of metastasis.  Twelve lymph nodes showed mixed vascularity, which were confirmed as metastatic nodes by FNAC. This finding was consistent with the findings of Chih-Hsiu Wu et al.,  and Dangore et al. Mixed vascular flow of the metastatic node can be explained, as the tumor nests replace the node, the pre-existing nodal vessels may be proliferated and transformed into feeding vessels by tumor angiogenesis, resulting in central aberrant nodal vessels and advanced tumoral infiltration of a node will destroy the hilar blood supply, resulting in induction of the vascular supply from the peripheral pre-existing vessel or vessels in peri-nodal connective tissue. This study showed no flow in 3 (2.3%) FNAC proved metastatic cervical lymph nodes. This finding was consistent with the previous studies. , Reason for no flow in metastatic nodes could be the total replacement of the whole node by necrosed and keratinized tumor tissue leading to absence of vascular patterns. , On the basis of the presence of color flow pattern, the sensitivity and specificity were 94.1% and 100%, respectively, with a accuracy of 95.4%.As compared with a previous study, the present study showed comparable sensitivity but high specificity and high accuracy. , Overall results of color doppler flow criteria were highly statistically significant in this study (P < 0.001). In the present study, higher values for both PI and RI were found in patients with metastatic lymph nodes, and lower values than the cut-off values for reactive nodes. These findings were consistent with most of the previous studies. ,, Reason for higher values is that vascular compression by infiltrating tumor cells increases vascular resistance. , The lower values found in reactive node are because of dilatation of blood vessels in reactive nodes. In our study, we applied the cut-off points suggested by Wu et al.,  and found that the sensitivity and specificity in our population were 81.4% and 100%, respectively, with an accuracy of 85.5%.
As in this study, we used the clinical criteria to differentiate metastatic lymph nodes from reactive nodes in patients with oral cancer, the specificity of clinical criteria 100%, with a sensitivity of 79.8% and accuracy of 84.8%.The sensitivity of CDUS by vascular flow pattern was 94.1%, specificity of 100%, with accuracy of 95.4% and by vascular indices the sensitivity was 81.4%, specificity of 100%, and accuracy of 85.5%. According to this study, the overall rate of metastatic cervical nodes in oral cancer was 77.9% (102 out of 131 nodes were metastatic). This finding was comparable to study of Dietmar Koischwitz et al.,  they reported lymph node metastatic rate of 80% in patients with squamous cell carcinoma. However, Spiro JD, et al.,  and Dangore et al.,  reported a lower rate of lymph node metastasis (18.57%).
| Summary and Conclusion|| |
In summary, this study support the fact that each node involved in patient with oral cancer should not be considered as metastatic, which can lead to unnecessarily treatment of neck. Thorough evaluation for lymph node involvement in oral cancer patients is not possible clinically. In this study, all the findings suggested superiority of CDUS over clinical evaluation. In CDUS evaluation, flow pattern is more accurate than the vascular indices. From the present study we conclude that CDUS plays a definitive role as an adjunct to clinical evaluation of differentiating metastatic from reactive cervical lymph involvement in patients with oral cancer. However, results of this study can be validated with more studies involving large number of oral cancer patients.
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Department of Oral Medicine and Radiology, Tamil Nadu Government Dental College and Hospital, Chennai, Tamil Nadu
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
[Table 1], [Table 2], [Table 3], [Table 4]