Role of ultrasound and color doppler in evaluation of cervical lymphadenopathy.
Background: Cervical lymphadenopathy is a commonly encountered clinical problem. Patients either present with palpable neck masses or with malignancy of the head and neck where the preoperative detection of the involved nodes is essential. Ultrasound and color/power Doppler are used to localize the node and evaluate their multiplicity, size, shape (roundness index), hilum status, margin, calcification, necrosis (>3 mm), and perilymphnodal edema. Color and power Doppler is used to know the pattern of vascularity and doppler indices [resistive index (RI) and pulsatility index (PI)].
Aims and Objective: To determine the role of ultrasound and color/power Doppler in the differentiatiation of benign and malignant nodes and in tapering the differential diagnosis.
Materials and Methods: Eighty lymph nodes were evaluated with ultrasound and color Doppler and correlated later with histopathology reports over a period of 18 months (May 2013 to November 2014) referred to Department of Radiology at Katuri Medical College and Hospital. Roundness index (<2), ill-defined margins, absence of hilum, peripheral/mixed vascularity, RI > 0.8 ,and PI > 1.5 were the criteria taken to diagnose the malignant involvement of the lymph node.
Results: Of the 80 lymph nodes examined, 22 are proved to be malignant on histopathology examination. Features such as roundness index, absence of hilum, and vascular pattern demonstrated sensitivities of 91%, 86%, and 86% and positive predictive values (PPVs) of 71%, 73%, and 86%, respectively. Among these features, pattern of vascularity and Doppler indices showed high PPV.
Conclusions: Ultrasound and color Doppler findings of roundness index, absence of hilum, vascular pattern, and impedance values revealed good PPV, sensitivity, specificity, and accuracy reaching 90% in differentiating benign from malignant lymph nodes.
KEY WORDS: Ultrasound, color doppler, cervical lymphadenopathy, benign, malignant
Lymph nodes are secondarily involved in a variety of systemic diseases, local injuries, and infections. They are also the site of some important primary neoplasms and metastasis. Causes of cervical lymphadenopathy are inflammatory, infective (viral, bacterial, and protozoan), and neoplastic.
The diagnosis of malignant lymphadenopathy is crucial for therapeutic planning in patients with suspected malignant neoplasm and for pretreatment staging in patients with primary malignant tumors of the head and neck. In patients with proven head and neck carcinomas, the presence of a unilateral metastatic node reduces the 5-year survival rate by 50%, whereas the presence of bilateral metastatic nodes reduces the 5-year survival rate to 25%. [1-3]
The histologic variations observed in lymph nodes in patients with nodal diseases are used to describe the morphologic changes in lymph nodes shown by gray-scale sonography.  High-resolution ultrasound is a useful imaging tool for the assessment of cervical lymph nodes because of its high image resolution and high sensitivity (98%) and specificity (95%) when combined with fine-needle aspiration cytology (FNAC). [5-7] Moreover, ultrasound is noninvasive and easily available. Therefore, it is suitable for both monitoring disease progression and follow-up assessment after treatment. In proven metastatic nodes, size reduction on serial examinations is a useful indicator for monitoring patient's response to treatment. 
In addition to the gray-scale changes, both the angioarchitecture and the hemodynamics differ among various cervical nodal diseases. Neoplastic infiltration destroys the internal nodal architecture, which leads to the deranged morphology of the blood vessels in metastatic nodes, whereas local humoral agents causes dilatation of intranodal vessels in inflammation.
All these intranodal vascular changes help to differentiate benign and malignant lymph nodes. [8,9] The presence of intranodal vascularity, its distribution, and estimates of the intravascular resistance and spectral Doppler analysis are evaluated with color Doppler.
Cervical lymph nodes, which have the advantage of being located superficially, can be studied with even better spatial resolution. These classical criteria to differentiate the benign and malignant nodes described in Table 1 are applicable everywhere but they are studied on neck nodes. [1,5,10-16]
MATERIAL AND METHODS
This is a prospective study involving 80 lymph nodes from 72 patients of which 8 were known cases of head and neck carcinomas who were evaluated with ultrasound and color Doppler over a period of 18 months (May 2013 to November 2014) referred to Department of Radiology at Katuri Medical College and Hospital and later correlated with histopathology. In seven of the eight known malignancies, more than one lymph node was sampled, that is, 15 lymph nodes were sampled. Totally, 80 lymph nodes were studied. Patients aged 18 to 75 years of both sexes were included in this study. Ultrasound of the neck was performed after obtaining informed consent by using PHILIPS Envisor-C, high-resolution linear array probe at 3-12 MHz.
Ultrasound features documented included lymph node site, number, size, roundness index, presence and absence of hilum, margins of lymph node (i.e., well defined, ill defined, and matted), infiltration to adjacent structures, calcification, necrosis and cystic change, and perilymphnodal edema. Color Doppler and power Doppler features documented were the absence of vascularity, central vascularity, peripheral vascularity, and mixed vascularity. Spectral waveforms were taken from the intranodal vessel to document the Doppler indices: resistive index (RI) and pulsatility index (PI).
The criteria for the diagnosis of malignancy are size more than 10 mm, round lymph node (roundness index is calculated by the maximum dimension of lymph node to the minimum dimension no <2),[10,11] and absence of hilum. Color and power Doppler criteria for the diagnosis of maligancy are peripheral and mixed vascularity of the lymph node, RI more than 0.8, and PI more than 1.5.
Other features documented were necrosis, calcification, and perilymphnodal edema. However, the significance of these findings in relation to malignancy is questionable becasue India is an endemic area to tuberculosis and to other infections and there has been an increasing incidence of infections among the immunocompromised patients. Acute suppurative involvement may be associated with perilymphnodal edema.
These features were compared with the histopathology reports obtained by FNAC or from the specimens of surgical dissection. From the data obtained, the positive predictve value (PPV), negative predictive value (NPV), sensitivity, specificity, and accuracy of the each finding was calculated.
The individual criteria for malignancy on ultrasound and color Doppler were compared with the histopathological findings (Table 2).
Short axis diameter of more than 10 mm was taken as the criteria for enlarged lymph node. Of the 80 lymph nodes studied, 70 were greater than 10 mm, of which 20 were found to be malignant on histopathology examination. Of the remaining 10 nodes, two turned out to be malignant on histopathology. When considered alone, size criteria showed a PPV of 28%, NPV 80%, sensitivity 91%, specificity 14%, and accuracy 35%.
Benign nodes are either oval or elongated, and malignant nodes are often described as round in shape. To define the nodal shape, the ratio between the longitudinal axis (L) of the node and the nodal transverse or short axis (S) is used, which is also known as axial diameter. The long axis of an oval benign node will be at least two times greater than the axial diameter, where the value of ratio will be L/S > 2 or S/L < 0.5. [10,11] In malignant (rounded) nodes, the value of L/S is less than 2 or even <1.5 or S/L> 0.5. [1,11,14] This ratio of long axis diameter to short axis diameter is called the roundness index.
Twenty-eight of the 80 lymph nodes showed a roundness index of less than 2, of which 20 lymph nodes were positive for malignancy. Rest of the 52 lymph nodes revealed a roundness index of more than 2, of which 2 lymph nodes were positive for malignancy. Roundness index criteria possesed a high PPV of 71%, NPV 96%, sensitivity 91%, specificity 86%, and accuracy 87%.
Normal and reactive nodes show a central echogenic hilum interrupting the continuity of the cortex and continuing with the perinodal fat tissue (Figure 1). This appearance is because of the interface created by the subsurface of multiple medullar sinuses[1,11,14] It has been shown that an echogenic hilum can be observed in about 90% of benign cervical nodes with a diameter more than 5 mm.  Malignant nodes generally show no visible hilum [1,11,14,17] The absence of an echogenic hilum owing to replacement or effacement is considered to represent diagnostic criteria of abnormality and is significantly greater in malignancies than in benign lesions [18,19] In malignant infiltration of lymph node, hilum is distorted and absent. Among the 26 lymph nodes that showed absence of hilum, 19 were positive for malignancy on histopathology examination and 3 of the 54 lymph nodes with normal hilum showed malignancy. Absence of hilum has a high NPV of 94%. The PPV, sensitivity, specificity, and accuracy were 73%, 86%, 88%, and 88%, respectively.
Acute inflammatory nodes possess blurred margins. Irregular or angular nodal margins lead to suspicion of metastasis.  Similar to Frank invasive contour, irregular and blurred margins indicate extracapsular and extranodal spread of malignancy and bear a severe prognosis [1,11] Malignant nodes with sharp margins can also be observed. In these cases, tumor infiltration leads to high impedance mismatch.  Six of the eight lymph nodes with ill-defined margins were malignant on histopathology findings. Of the remaining, 68 showed well-defined margins and 4 matted margins; of these, 16 were positive for malignancy on histopathology examination. Ill-defined margins as criteria showed a high specificity of 96% and low sensitivity of 27%. The PPV, NPV, and accuracy were 75%, 76%, and 76%, respectively.
Both papillary and medullary thyroid carcinomas show punctuate and peripheral microcalcifications, which appear as shadows only at high resolution[1,11] They result because of calcification of infarcted tips of malignant papillae or intravascular tumor thrombi by psammoma bodies. [21,22]. Secondary carcinomas from papillary carcinoma of thyroid will show punctate calcifications in lymph nodes. Chronic infectious diseases such as tuberculosis and lymphomas after treatment will reveal calcifications in lymph nodes. In our study, only six lymph nodes showed calcifications. Assuming the presence of calcification to be malignant will have a low PPV of 0% and sensitivity 0% and high specificity 90%, whereas taking the criteria for benignity will have a high PPV of 100% and specificity 100% and low sensitivity 21%.
Necrosis and Cystic Change
Intranodal necrosis is of two types: coagulative and cystic necrosis. On ultrasound examination, a necrotic focus of more than 3 mm can be detected. Differentiation between the two types of necrosis is possible only when the focus of necrosis is large. Coagulation necrosis can be seen as an echogenic focus with no shadow, and it reveals no contact with the hilum or continuity with perinodal fat. [1,11] This necrosis can be observed in tuberculous nodes as well. Hence, it is just a sign of certainty for pathologic changes but without disease specificity. Cystic or liquefaction necrosis forms areas of eccentric fluid inside the lymph node structure. In the cases of papillary thyroid carcinoma, a cystic lymph node detection by ultrasonography suggests the presence of locally metastatic disease [21,23] In this study, seven lymph nodes showed necrosis on ultrasound of which only two were positive for malignancy. Necrosis as a criteria for malignancy revealed a PPV of 28%. In developing countries such as India where the prevalence of infectious disease is high, necrosis can be seen as a part of infections. In this regard, considering necrosis as benignity will have PPV of 71%.
Perilymphnodal edema is usually the result of inflammatory reaction around the lymph node or caused by aggressive spread of lymphomatous/cancerous cells beyond the lymph node to the surrounding structures. In our study, five lymph nodes showed perilymphnodal edema of which only one lymph node revealed malignant deposits on histopathology examination. Assuming perilymphnodal edema as criteria of malignancy gives a PPV of 20%, whereas considering it as a criteria for inflammation, that is, benignity, results in a PPV of 80%.
Pattern of Vascularity
Lymph nodes possess a central main stump of vascularity in the hilum and small branches that taper near to hilum itself (Figure 2). In reactive hyperplasia of nodes, this pattern of vascularity is maintained.  Malignant deposits will reach the lymph node through the afferent lymphatics, which enters through the cortex; so, these deposits will rest near the cortex with neovasculrisation, resulting in peripheral or mixed vascurlarity (Figure 3). In our study, 21 lymph nodes showed peripheral vascularity and 2 lymph nodes showed mixed vascularity. Of these, 19 were positive for malignancy on histopathology examination. Peripheral and mixed vascularity has a PPV of 86%, NPV 95%, sensitivity 86%, specificity 95%, and accuracy 92%.
Resistive Index: Malignant cells infiltrate the lymph node, distorting its normal architecture and blood vessel morphology, thereby causing high-resistance flow patterns with RI of more than 0.8. In our study, 24 lymph nodes revealed a RI of more than 0.8, of which 19 were positive for malignancy on histopathology examination. RI possesed a PPV of 79%, NPV 95%, sensitivity 86%, specificity 91%, and accuracy 90%.
Pulsatility Index: Similarly, along with RI, PI also increases in malignant nodes. PI of more than 1.5 is taken as a criteriion for malignancy. In our study, 21 lymph nodes showed a PI of more than 1.5 of which 18 were positive for malignancy. PI possesed a PPV of 86%, NPV 93%, sensitivity 82%, specificity 95%, and accuracy 90%.
Lymphadenopathy results from a variety of causes such as malignant deposits, lymphomas, infections, and other unusal causes such as autoimmune diseases. Accurate detection is helpful for staging and treatment planning.
A total of 80 lymph nodes from 72 patients were evaluated using gray-scale and colour Doppler ultrasound and compared with the histopathology findings. Of the 72 patients, 8 cases were known cases of malignancy of the upper aerodigestive tract and thyroid. In seven of the eight patients with known malignancies, more than one lymph node was sampled, that is, 15 lymph nodes were sampled, of which 12 turned out to be malignant on histopathology.
Of the 80 lymph nodes, 22 lymph nodes showed malignant deposits on histopathology examination. No case of lymphoma was observed in our study. Of the 58 benign lymph nodes, 33 were diagnosed as tuberculosis and 13 as reactive hyperplasia, and the rest were because of nonspecific inflammatory causes.
The criteria of roundness index, absence of hilum, ill-defined margins, peripheral and mixed vascularity, and high-resistance Doppler indices revealed significant specificity and sensitivity of more than 90%.
Dangore-Khasbage et al.  in a prospective study evaluated 70 cervical lymph nodes in 30 patients with known primary oral cancer using color Doppler ultrasound (CDUS) during a period of 8 months and the CDUS evaluation was found to be highly significant with a sensitivity of 92.9% and a specificity of 84.21%, after comparing the CDUS findings with Histopathological examination (HPE) results. 
Tschammler et al.  in their study found a specificity of 77% and a sensitivity of 96% of CDUS examination. In the study by Genes et al.,  the shape of lymph node and vascular pattern revealed a sensitivity of 84.21% and 97.37% and PPV of 82.05% and 82.84%, respectively. 
In our study, the features such as roundness index, absence of hilum, and vascular pattern demonstrated sensitivities of 91%, 86%, and 86% and PPV of 71%, 73%, and 86%, respectively. Among these features, pattern of vascularity and Doppler indices showed highest PPV. All these features show good reliability on kappa statistics (Table 3).
This prospective study showed good correlation between ultrasound and color Doppler with histopathology findings in differentiating benign and malignant lymph nodes, especially from roundness index, absence of hilum, vascular pattern, and Doppler indices. All these revealed good PPV, sensitivity, specificity, and accuracy, reaching 90%.
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Naganarasimharaju Jukuri (1), Ramakrishna Narra (1), Murali Mohan V Kuppili (2), Sivakanth Nalubolu (1), Bhimeswararao Pasupuleti (1)
(1) Department of Radiology, Katuri Medical College and Hospital, Guntur, Andhra Pradesh, India. (2) Department of Pathology, Katuri Medical College and Hospital, Guntur, Andhra Pradesh, India.
Correspondence to: Naganarasimharaju Jukuri, E-mail: email@example.com
Received January 13, 2015. Accepted January 27, 2015
How to cite this article: Jukuri N, Narra R, Kuppili MMV, Nalubolu S, Pasupuleti, B. Role of ultrasound and color Doppler in evaluation of cervical lymphadenopathy. Int J Med Sci Public Health 2015;4:520-526
Source of Support: Nil, Conflict of Interest: None declared.
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Table 1: Classical criteria for differentiating malignant and benign lymphnodes B scan criteria Benign malignant Size Small Large Shape Oval Rounded Hilum Present Absent Echogenicity Moderate or low hypoechoic Marked Margins Sharp Irregular,blurred, angular, invasive Structural changes Focal cortical nodules - - Intranodal necrosis Absent Present Reticulation - - Calcification - - Matting - - Soft tissue edema May be present Absent Doppler criteria Flow Absent Present Vessel location Central Peripheral Vascular pedicles Single Multiple Vascular pattern Regular Chaotic Impedance values Low High Table 2: Different criteria and their significance Ultrasound and No. of Patients color Doppler Criteria having ultrasound Positive characteristics and color Doppler features Size < 1.0 cm 10 2 > 1.0 cm 70 20 Roundness index (L/T) > 1.5 52 2 <1 .5 28 20 Hilum Present 54 3 Absent 26 19 Well defined 68 16 Margins Ill defined 8 6 Matted 4 0 Calcification Absent 74 22 Present 6 0 Perilymphnodal edema Absent 75 21 Present 5 1 Necrosis Absent 73 20 Present 7 2 Absent/central 57 3 Pattern of vascularity Peripheral 21 18 Mixed 2 1 Doppler indices (RI) <0.8 56 3 >0.8 24 19 Doppler indices (PI) <1.4 59 4 >1.4 21 18 Histopathology for malignancy Ultrasound and Positive Negative color Doppler Negative Predictive Predictive Sensitivity characteristics Value Value Size 8 28 80 91 50 Roundness index (L/T) 50 71 96 91 8 Hilum 51 73 94 86 7 52 75 76 27 Margins 2 4 Calcification 52 0 70 0 6 100 (a) 70 21 Perilymphnodal edema 54 20 72 5 4 80 (a) 72 16 Necrosis 53 28 73 09 5 71 (a) 72 20 54 86 95 86 Pattern of vascularity 3 1 Doppler indices (RI) 53 79 95 86 5 Doppler indices (PI) 55 86 93 82 3 Histopathology for malignancy Ultrasound and color Doppler Specificity Accuracy characteristics Size 14 35 Roundness index (L/T) 86 87 Hilum 88 88 96 76 Margins Calcification 90 65 100 72 Perilymphnodal edema 93 68 98 72 Necrosis 91 68 96 68 95 92 Pattern of vascularity Doppler indices (RI) 91 90 Doppler indices (PI) 95 90 (a) Sensitivity, specificity, and other values for calcification, necrosis, and perilymphnodal edema are calculated for both presence and absence for diagnosis of malignancy and benignity. Table 3: Reliability of ultrasound and color Doppler based on kappa statistics Property under study k value Strength of agreement Size 0.046 Poor Roundedness 0.711 Good Hilum 0.703 Good Margins 0.297 Fair Calcifications 0.134 Worse than that expected to be seen by chance alone Perilymph Node 0.031 Worse than that expected to Edema be seen by chance alone Necrosis 0.006 Poor Pattern Of Vascularity 0.784 Good R.I 0.756 Good P.I 0.777 Good
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|Title Annotation:||Research Article|
|Author:||Jukuri, Naganarasimharaju; Narra, Ramakrishna; Kuppili, Murali Mohan V.; Nalubolu, Sivakanth; Pasupu|
|Publication:||International Journal of Medical Science and Public Health|
|Date:||Apr 1, 2015|
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