N e u r o r a d i o l o g y / H e a d a n d N e c k I m a g i n g • C l i n i c a l Pe r s p e c t i ve Ludwig et al. Cervical Lymphadenopathy Imaging in the Young

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Neuroradiology/Head and Neck Imaging Clinical Perspective

Imaging of Cervical Lymphadenopathy in Children and Young Adults Benjamin J. Ludwig1 Jimmy Wang1 Rohini N. Nadgir 1 Naoko Saito 2 Ilse Castro-Aragon1 Osamu Sakai1 Ludwig BJ, Wang J, Nadgir RN, Saito N, CastroAragon I, Sakai O

OBJECTIVE. This article describes the role of imaging in evaluating cervical lymphadenopathy in patients from birth to their mid-20s, illustrates imaging features of normal and abnormal lymph nodes, and highlights nodal imaging features and head and neck findings that assist in diagnosis. CONCLUSION. Cervical lymph node abnormalities are commonly encountered clinically and on imaging in children and young adults. Although imaging findings can lack specificity, nodal characteristics and associated head and neck imaging findings can assist in determining the underlying cause.

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Keywords: cervical lymphadenopathy, head and neck imaging, head and neck infection, head and neck malignancy, lymph nodes, pediatrics DOI:10.2214/AJR.12.8629 Received January 17, 2012; accepted after revision April 18, 2012. 1 Department of Radiology, Boston University Medical Center, Boston University School of Medicine, 820 Harrison Ave, FGH Bldg, 3rd Flr, Boston, MA 02118. Address correspondence to B. J. Ludwig ([email protected]). 2 Department of Radiology, Saitama International Medical Center, Saitama Medical University, Saitama, Japan.

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ervical lymph node abnormalities are a common reason for pediatric and otolaryngology office visits and may be related to benign processes, such as reactive nodes, or to aggressive processes, including malignancy. Although often considered nonspecific, cervical lymph node imaging features, in conjunction with clinical presentation and related head and neck imaging findings, can aid in determining the cause of the abnormality. Ultrasound, CT, and MRI may be used to confirm the presence of lymphadenopathy, distinguish nodal abnormalities from congenital head and neck lesions, and further characterize lymph nodes. In the pediatric population, ultrasound is the most appropriate initial imaging modality because of the lack of ionizing radiation. CT and MRI are complementary and can further characterize nodal abnormalities and related head and neck imaging findings. It is critical for the interpreting radiologist to recognize the appearance of normal cervical lymph nodes and to report nodal features typical of specific infections, inflammatory conditions, and neoplasms to assist clinicians in subsequent management. Clinical Approach to Cervical Lymph Nodes Clinical evaluation of cervical lymph nodes in the pediatric population can be difficult because palpable lymph nodes are common in healthy children. Previous studies have docu-

mented palpable cervical lymph nodes in up to 90% of children 4–8 years old [1]. Clinicians rely on history and physical examination to determine the possible causes of and the diagnostic workup for lymphadenopathy. Physical examination findings of tender, mobile, soft nodes suggest reactive adenopathy, whereas nontender, firm, nonmobile nodes raise concern for neoplastic causes. Because infectious causes are most common, patients are often treated empirically with antibiotics [2]. When nodes fail to resolve after 4–6 weeks of therapy, progress in size or number, or are accompanied by systemic symptoms, further workup is necessary, which often includes imaging. Role of Imaging Imaging may be performed to evaluate nodes lacking clinical features of benign causes, confirm lymph nodes as the cause of palpable abnormalities, and evaluate the remainder of the head and neck (including areas not amenable to clinical examination, such as the deep fascia–defined spaces). Ultrasound may be used to confirm the presence of an abnormal lymph node and characterize its size, shape, borders, internal architecture, vascularity, and perinodal soft tissues [3]. Benefits of ultrasound include the lack of ionizing radiation and the ability to characterize the nature of lymph nodes as either cystic or solid. Both contrast-enhanced CT and MRI may be used to further characterize the extent of

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Ludwig et al. sonographic abnormalities and to confirm deep nodal abnormalities, if suspected [4]. Benefits include superior anatomic localization; determination of size, number, shape, borders, internal architecture, and enhancement characteristics of nodes; and evaluation of perinodal soft tissues and related head and neck findings. Diffusion-weighted imaging has been shown to increase conspicuity of subcentimeter lymph nodes due to suppression of background tissue and can aid in detection of lymph nodes relative to conventional sequences [5]. These benefits must be weighed against the radiation risks of CT, and the need for sedation must also be considered before CT and MRI in infants and young children. Currently, the American College of Radiology (ACR) Appropriateness Criteria support the use of ultrasound (rating, 9/9), contrast-enhanced neck CT (rating, 8/9), and contrastenhanced neck MRI (rating, 7/9) for evaluation of children up to 14 years old who have solitary or multiple neck masses, both with and without fever [4]. The ACR Appropriateness Criteria rate PET/CT evaluation of a solitary neck mass in a febrile child less than 14 years old and solitary or multiple neck mass in both febrile and afebrile children less than 14 years old as “usually not appropriate” (both rated 1/9) [4]. In contrast, the role of PET/CT is evolving in the setting of known malignancy, with studies showing superior accuracy of PET/CT in initial staging, response to therapy, and follow-up of Hodgkin lymphoma relative to other imaging modalities, with a significant (26.8%) change in initial staging based on PET/CT findings [6]. Normal Lymph Nodes Anatomic localization of cervical lymph nodes has been established on the basis of the previous description of metastatic adenopathy by Som et al. [7]. In adults, the upper limit of normal lymph node size is 10 mm when measured in terms of greatest long-axis dimension in the axial plane, with the exception of nodal stations IB and IIA, for which the upper limit of normal is 15 mm in adults; this size allowance is because levels IB and IIA drain common sites of infection, including the teeth, gums, tonsils, and pharynx and thus are often enlarged [8, 9]. The upper limit of normal for retropharyngeal nodes has been proposed as 8 mm [8–10]. No specific size criteria have been defined for lymphadenopathy in the pediatric population, although the preceding criteria are commonly used. Thus, additional imaging features including

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Fig. 1—7-year-old boy with normal lymph node. Gray-scale ultrasound shows circumscribed, ovoid node with cortical hypoechogenicity (arrowhead) and relatively hyperechoic hilum (arrow).

nodal morphology, internal architecture, and perinodal soft tissues are complementary in lymph node evaluation. On ultrasound, normal or reactive lymph nodes are well defined and reniform in shape, with fatty echogenic hila and a hypoechoic cortex relative to muscle (Fig. 1). Color Doppler sonography may show avascularity or radial symmetric hilar vascularity with low pulsatility index and low resistive index [3]. On CT, nodes are iso- or hypoattenuating relative to muscle and show mild homogeneous enhancement after contrast administration. Normal nodes are circumscribed, with preserved fat planes with adjacent structures [8–10] (Fig. 2). On MRI, nodes show low to intermediate signal on T1-weighted images, intermediate to high signal on T2-weighted images relative to muscle, and homogeneous enhancement after IV contrast administration [8, 9] (Fig. 3). Clinical Entities Reactive Lymph Nodes Reactive lymph nodes may result from viral, bacterial, fungal, or protozoal pathogens. Such nodes are typically slightly enlarged and may show mild enhancement on CT or MRI and vascularity radiating from the hilum on Doppler ultrasound (Fig. 4). Viral infections are the most common cause of reactive adenopathy [11] and typically result in bilateral mildly enlarged cervical lymph nodes without periadenitis. Cytomegalovirus infection, herpes simplex virus infection, varicella, rubeola (measles), and rubella are common viral causes but typically require correlation with clinical or laboratory data to reach a definitive diagnosis. Infectious mononucleosis and HIV infection have associated imaging findings and will be described in detail later. Staphylococcus aureus and group A Streptococcus infections [12] are common bacterial

causes of reactive lymph nodes, although any bacteria can cause lymphadenopathy. They are seen as enlarged nodes with perinodal inflammatory change [10]. Fungal infections may be seen in endemic regions or immunocompromised patients and include cryptococcosis, coccidiomycosis, and histoplasmosis. The single protozoal cause of lymphadenitis is toxoplasmosis. Bacterial Infections Staphylococcus aureus and group A Streptococcus—Staphylococcus aureus and group A Streptococcus are the most common bacterial causes of cervical lymphadenitis and account for 53–89% of cases of unilateral cervical adenitis [12]. These infections commonly occur in children 1–4 years old. They often produce enlarged nodes with perinodal inflammatory change and may progress to suppurative adenopathy, defined as infection resulting

Fig. 2—18-year-old woman with normal lymph nodes. Contrast-enhanced axial CT image shows multiple ovoid, circumscribed left level II nodes with fatty hila (arrow), which are hypo- to isoattenuating relative to muscle.

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Cervical Lymphadenopathy Imaging in the Young

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Fig. 3—21-year-old man with normal lymph nodes. A, Axial T1-weighted MR image shows ovoid right level IIA node with low to intermediate T1 signal relative to muscle (arrow). B, Axial T2-weighted MR image shows intermediate to high T2 signal within same node (arrow).

in necrosis within lymph nodes (also referred to as intranodal abscess formation) [8, 10]. On ultrasound, features of suppurative adenopathy include anechoic regions, peripheral vascularity, and possibly septations and posterior acoustic enhancement [13] (Fig. 5). On CT, suppurative nodes are hypoattenuating centrally, with peripheral rim enhancement and perinodal inflammatory change. MRI shows central T1 hypo- and T2 hyperintensity, with peripheral enhancement. The associated perinodal inflammatory change can assist in differentiation from central nodal necrosis due to

metastatic disease, which otherwise can have a similar imaging appearance. It is also important to differentiate between suppurative retropharyngeal lymph nodes and true retropharyngeal abscesses in children. Both medial and lateral retropharyngeal nodes are present until about the age of 6 years and can exhibit intranodal abscess formation (Fig. 6). The peripheral enhancement on cross-sectional imaging in intranodal abscesses conforms to the nodal border, whereas true retropharyngeal abscesses show retropharyngeal fluid with enhancement corresponding to the borders of the

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Fig. 4—8-year-old boy with reactive lymph node due to Streptococcus pharyngitis. A, Gray-scale ultrasound shows increased cortical echogenicity (arrow) and lack of echogenic hilum. B, Axial contrast-enhanced CT image in same patient shows enhancing, round, enlarged level II node (arrowhead) with perinodal inflammatory change. Note reactive retropharyngeal edema (arrow).

retropharyngeal space. Differentiation is critical because intranodal abscesses are usually managed with antibiotics, whereas retropharyngeal abscesses often require surgical drainage [14, 15]. Mycobacterial infection—Head and neck involvement with Mycobacterium tuberculosis infection accounts for 12–15% of cases of extrapulmonary tuberculosis [8, 16–18]. In the acute phase, tuberculous granulomas may produce nodal enlargement and enhancement. Subacute disease is characterized by formation of suppurative nodes and intranodal abscesses [10, 18]. Nodal calcification can be seen in the chronic phase or after treatment, although calcification within cervical nodes is much less common than in mediastinal or hilar lymph nodes [19]. Levels II and V nodes are most commonly involved [8, 10, 16–18]. Ultrasound, CT, and MRI can depict all stages of disease. Subacute disease is most commonly encountered on imaging and characterized by intranodal abscess formation, which classically lacks perinodal inflammatory change [10, 18] (Fig. 7). Because of the lack of periadenitis in tuberculosis, metastatic adenopathy is the main differential diagnosis and fine-needle aspiration may be required for diagnosis. When tuberculous adenitis is suspected, imaging of the chest should be performed to assess whether active pulmonary disease is present [8, 10, 18]. Atypical, nontuberculous mycobacterial infection may also result in cervical lymphadenitis. In children less than 5 years old, the most

Fig. 5—6-year-old boy with suppurative lymph node due to Staphylococcus aureus. Gray-scale color Doppler ultrasound shows enlarged cervical lymph node with central hypoechogenicity and peripheral Doppler vascularity.

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Ludwig et al.

Fig. 6—6-year-old boy with intranodal abscess within lateral retropharyngeal lymph node. Axial contrast-enhanced CT image shows central fluid attenuation and peripheral enhancement within enlarged left lateral retropharyngeal lymph node (arrow) with surrounding phlegmon.

Fig. 7—18-year-old boy with tuberculous adenitis. Axial contrast-enhanced CT image shows multiple enlarged bilateral level II lymph nodes with central fluid attenuation and thick, irregular peripheral enhancement (arrows). Lack of perinodal fat stranding is characteristic finding of tuberculous adenitis.

Fig. 8—2-year-old boy with nontuberculous mycobacterial infection. Axial contrast-enhanced CT image shows enlarged, hypoattenuating left intraand periparotid, level V, and lateral retropharyngeal nodes with thick irregular enhancement and septations (arrows). Note perinodal inflammatory change posteriorly.

common cause of nonmycobacterial TB is Mycobacterium avium-intracellulare. Affected children usually do not have a history of tuberculosis exposure, and the tuberculin skin test is usually normal or only minimally indurated [10]. Children present with an isolated enlarging neck mass with overlying skin discoloration. On imaging, the most common findings include a dominant centrally necrotic peripherally enhancing neck mass, typically in the parotid or submandibular region (Fig. 8). Multiple separate adjacent nodal masses and minimal periadenitis have also been described [20]. Distinction between tuberculous and nontuberculous mycobacterial adenitis has important treatment implications. Whereas tuberculous mycobacterial adenitis responds to antituberculosis therapy [8], medical therapy is not effective in nontuberculous mycobacterial adenitis and the treatment of choice is surgical excision [21]. Cat-scratch disease—Regional lymphadenitis secondary to Bartonella (formerly Rochalimaea) henselae infection, also referred to as cat-scratch disease, most commonly affects children and young adults. The majority of cases are related to cat scratches or bites, with regional lymphadenopathy identified approximately 3 weeks after inoculation. Cervical lymphadenopathy is the third most common site of involvement after axillary and epitrochlear nodes [22]. Isolated head and neck nodal involvement occurs in 25% of cases, often with solitary nodal involvement [23].

Because exposure history is often not recalled, children may undergo imaging for the evaluation of a new solitary neck mass. Unfortunately, the imaging findings in catscratch disease are variable, ranging from enhancing to necrotic lymphadenopathy. The diagnosis can be confirmed by an enzyme immunoassay (EIA), polymerase chain reaction, skin or nodal biopsy [22].

suggests underlying HIV infection when seen in conjunction with generalized cervical lymphadenopathy [8, 10, 24] (Fig. 10). Lymphoid hyperplasia and adenoid hypertrophy can be seen but may not be present in patients with low CD4 counts due to inability to mount an immune response. Upon recognizing such imaging findings, the radiologist may be the first to raise suspicion for HIV infection and can facilitate early diagnosis before disease progression and development of associated complications [8, 10, 24].

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Viral Infections Infectious mononucleosis—Infectious mononucleosis is caused by Ebstein-Barr virus [8], but illnesses that clinically simulate mononucleosis may result from other viruses. Children present with pharyngitis, fatigue, and fevers. Heterophile antibody (monospot) tests may be diagnostic when clinical suspicion is high. However, imaging may also be used when the clinical course is less characteristic. Lymphadenopathy is classically diffuse and lacks perinodal inflammatory change. Associated head and neck findings can aid in diagnosis, particularly adenoid and palatine tonsil enlargement [13] (Fig. 9). The disease is typically self-limiting with resolution after 3–4 weeks. HIV—Diffuse lymphadenopathy is present in nearly all patients with HIV infection or AIDS and is a common initial presentation [8, 10, 24]. Lymphadenopathy is present in 40– 70% of children who are HIV-positive [12]. On imaging, findings are typical of reactive viral-infected nodes. Identification of multiple, bilateral parotid lymphoepithelial lesions (cysts)

Lymphadenopathy Associated with Clinical Syndromes Cervical lymphadenopathy is a component of many clinical syndromes. Entities in which associated head and neck imaging findings may aid in determining potential causes are discussed in this section. Unfortunately, many disease processes, including systemic lupus erythematosus, juvenile rheumatoid arthritis, posttransplantation lymphoproliferative disorder, and sickle cell disease, lack distinguishing imaging findings but may be considered on the basis of patient history and demographics. Kawasaki disease—First described in Japanese children, Kawasaki disease (febrile mucocutaneous lymph node syndrome) is now recognized in infants and young children of all demographics [25]. The most common age of onset is 6 months in Japan and between 13 and 24 months in North America [26]. Diagnostic criteria include fever lasting at least 5 days; lack

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Cervical Lymphadenopathy Imaging in the Young

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Fig. 9—16-year-old boy with infectious mononucleosis. Axial contrast-enhanced CT image shows enlarged palatine tonsils bilaterally (arrows) and enlarged left level IIA lymph node (arrowhead).

Fig. 10—25-year-old woman with HIV infection. A, Axial contrast-enhanced CT image shows multiple, mildly enlarged nonspecific level II nodes (arrow). B, Additional image shows multiple left parotid lymphoepithelial cysts (arrow).

of evidence of concurrent disease to explain clinical features; and meeting at least four of five clinical components, one of which is cervical lymphadenopathy (> 1.5 cm in diameter), usually unilateral [27]. Even though cervical adenopathy is the least often fulfilled diagnostic criterion and is present in less than 50% of confirmed cases [28], it has been described as the dominant manifestation of the disease in its early stages [26]. The presence of lymphadenopathy

may be confused with bacterial lymphadenitis early in the course of Kawasaki disease; differentiation between the two entities has been described on ultrasound, in which nodal involvement consists of a coalescent nodal mass resembling a cluster of grapes formed by multiple hypoechoic nodes as opposed to mildly enlarged or centrally cystic vascular nodes in bacterial infection [29]. Head and neck findings of mucositis, including tonsillar enlargement and retropharyngeal edema,

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Fig. 11—4-year-old girl with Kawasaki disease. A, Axial contrast-enhanced CT image shows bilateral palatine tonsil hypertrophy (arrows) and retropharyngeal edema (arrowhead). B, Additional image in same patient shows multiple enlarged right level II nodes, including conglomerate adenopathy (arrow) with periadenitis. Findings are consistent with mucositis and reactive lymphadenopathy.

may also be observed in Kawasaki disease (Fig. 11). Early recognition facilitated by imaging and treatment with IV immunoglobulin can reduce the risk of cardiac complications, including coronary artery aneurysms and associated devastating consequences. Kikuchi-Fujimoto disease—Kikuchi-Fujimoto disease, or histiocytic necrotizing lymphadenitis, is a self-limiting disease of unknown cause. There is a slight female predominance, and patients are typically less than 30 years old. Patients present with cervical lymphadenopathy, often with systemic symptoms, including fever, fatigue, nausea, vomiting, diarrhea, and weight loss [30]. Because no laboratory tests are diagnostic of the entity, imaging plays a crucial role in diagnosis, surgical planning, and follow-up. Imaging findings in Kikuchi-Fujimoto disease have been described with great variability. Unilateral cervical nodal involvement or asymmetric bilateral nodal involvement is most typical, with levels II, V, and III nodes most often involved. Most nodes show homogeneous attenuation, enhancement, and perinodal inflammatory change (Fig. 12), and some show intranodal necrosis. Because the differential diagnosis includes both infection and malignancy, definitive diagnosis relies on biopsy. The natural history of the disease is usually benign, with spontaneous resolution occurring 1–6 months after symptom onset [31]. Castleman disease—Castleman disease, or angiofollicular lymphoid hyperplasia, commonly presents with cervical lymphadenopathy.

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Ludwig et al. Fig. 13—9-year-old boy with Castleman disease. Axial contrast-enhanced fatsaturated T1-weighted MR image shows markedly enlarged, homogeneously enhancing, nonnecrotic, intermediate-signal left level II and lateral retropharyngeal lymph nodes (arrows). 

Fig. 12—22-year-old woman with KikuchiFujimoto disease. Axial contrast-enhanced CT shows homogeneously enhancing mass in right submandibular space (arrow) with surrounding inflammatory change.

Isolated cervical lymphadenopathy is more common in the hyaline vascular subtype, in which younger patients tend to present with asymptomatic cervical nodal masses. Overall, the mediastinum is the most common site followed by the head and neck [8, 10]. On ultrasound, marked nodal enlargement is present, typically with Doppler hypervascularity. Moderate to intense enhancement has been described on CT [32]. Nodal calcification has been described including punctate and “arborizing” calcifications within pelvic lymph nodes [33]. On MRI, lesions are typically T1 hypointense relative to muscle and T2 hyperintense with linear, stellate T2 hypointensity centrally. The finding of central T2 hypointensity correlates with sinusoidal fibrosis, vessels, and

calcification on histopathology [34] (Fig. 13). Central lack of enhancement, indicative of fibrosis, within an enhancing nodal mass on CT has been described as suggestive of Castleman disease [32]. Surgery is typically curative; however, lesions can recur if incompletely excised. Kimura disease—Kimura disease is a chronic inflammatory disorder that affects the subcutaneous tissues, lymph nodes, and salivary glands. This entity is most common in boys and men of Asian descent during the 2nd and 3rd decades of life [35]. Patients present with nontender soft-tissue masses, most frequently within the submandibular or parotid regions, with involvement of adjacent lymph nodes or salivary glands [35]. Peripheral eosinophilia and elevated serum IgE levels are characteristic laboratory features. On ultrasound, focal hypervascular hypoechoic lesions within the subcutaneous tissues are characteristic (Fig. 14A). Similarly, involved lymph nodes are enlarged and hypervascular.

Contrast-enhanced CT depicts enhancing subcutaneous masses, regional cervical lymphadenopathy, and often focal or infiltrative salivary gland lesions. On MRI, involved nodes show low to intermediate signal on T1-weighted images, intermediate to high signal on T2-weighted images relative to muscle, and enhancement after contrast administration [35] (Fig. 14B). Kimura disease usually follows a benign course with surgical excision performed for both diagnosis and treatment. Imaging findings are not diagnostic of Kimura disease, but the entity should be considered, particularly in young adults of Asian descent with enhancing subcutaneous head and neck lesions, nodal and salivary gland involvement, cervical lymphadenopathy, and peripheral eosinophilia.

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Neoplasia Malignancy is the most feared cause of cervical lymphadenopathy. Suspicious clinical features—including hard, nonmobile, painless

Fig. 14—14-year-old boy with Kimura disease involving right parotid gland and intraparotid lymph nodes. A, Gray-scale color Doppler ultrasound image shows hypoechoic parotid mass (arrow) with increased vascularity. B, Axial STIR MR image shows hyperintense right parotid lesion (arrow).

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Cervical Lymphadenopathy Imaging in the Young

Fig. 15—21-year-old man with Hodgkin lymphoma. Axial contrast-enhanced CT image shows multiple, markedly enlarged homogeneous left level II lymph nodes (arrow) without necrosis or periadenitis.

Fig. 16—20-year-old man with nodal metastasis due to oral tongue cancer. Axial contrast-enhanced CT shows large left level II node (arrow) with intranodal necrosis and irregular, peripheral enhancement. Biopsy revealed squamous cell carcinoma, and primary tongue neoplasm was subsequently identified on physical examination.

lymph nodes; progressive nodal enlargement; lack of response to antibiotic therapy; or systemic symptoms—most often lead to imaging. Sonographic features of malignant lymphadenopathy include nodal enlargement, round shape, absent or eccentric echogenic hilum, hypoechoic parenchyma, and tendency of nodes to aggregate into a mass [36]. Color Doppler features, including subcapsular vessels, displacement of hilar vasculature, and absent segments of nodal vessels, have been suggested to be related to tumor infiltration [37]. Increased pulsatility and resistive indices have also been described as secondary to compression of nodal vasculature by infiltrative tumor [37]. Nodal enlargement, enhancement, and intranodal necrosis without periadenitis are common on CT or MRI. Diffusion-weighted MRI has been reported to differentiate between enlarged benign and malignant lymph nodes on the basis of decreased apparent diffusion coefficient values in some malignancies [38]. When imaging features suspicious for malignancy are identified in pediatric and young-adult patients, leukemia, lymphoma, and metastasis should be considered. Lymphoma—Lymphoma accounts for 10– 15% of all childhood malignances and is divided into two main subtypes: Hodgkin and non-Hodgkin lymphoma. In young adults, the most common age of onset of Hodgkin lymphoma is in the mid to late 20s. In these patients, cervical lymphadenopathy is the most

common manifestation of the disease [36]. Non-Hodgkin lymphoma is the more common of the two subtypes and increases in prevalence with age. Extranodal disease is more common in non-Hodgkin lymphoma and is present at the onset of disease [36]. Imaging cannot reliably distinguish between Hodgkin lymphoma and non-Hodgkin lymphoma, and biopsy remains the primary means of definitive diagnosis. Nevertheless, it remains critical for the interpreting radiologist

to be familiar with characteristics of the disease and associated head and neck findings to raise suspicion of lymphoma and guide clinical management. Involved nodes show the characteristic features of malignant adenopathy, typically with homogeneous density and mild enhancement (Fig. 15). Nodal calcification may be seen in both subtypes of lymphoma and is a hallmark of treated disease, although calcification has also been reported in lymphomatous nodes before treatment. Associated head and neck findings of Waldeyer ring involvement may be seen in Hodgkin lymphoma but is rare in children [36]. Leukemia—Leukemia is the most common childhood malignancy; however, diagnosis relies on clinical evaluation, laboratory tests, and bone marrow biopsy. Cervical lymphadenopathy is a common presentation of acute lymphocytic leukemia [13] but is commonly seen in all forms of childhood leukemia. On imaging, nodal involvement is very similar to lymphoma [8, 10] and thus requires correlation with clinical data. Metastatic disease—Approximately 25% of malignant childhood tumors occur in the head and neck, and cervical lymph nodes are common sites of metastatic disease [11]. Neuroblastoma, leukemia, rhabdomyosarcoma, and non-Hodgkin lymphoma are the most common primary malignancies associated with cervical lymph node involvement in children up to 6 years old [11]. After the age of 6 years, Hodgkin lymphoma is most common, followed by rhabdomyosarcoma and nonHodgkin lymphoma [11].

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Fig. 17—26-year-old woman with cystic nodal metastases secondary to papillary thyroid cancer. A, Axial T2-weighted MR image shows enlarged hyperintense left level II/III node (arrow). B, Coronal T1-weighted MR image shows hyperintensity within enlarged node (arrow), which may be related to thyroglobulin content or hemorrhage.

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Ludwig et al. Identification of malignant lymphadenopathy is critical to diagnosis, staging, and clinical management and can be facilitated through imaging. Unfortunately, current imaging techniques are not able to resolve microscopic nodal disease, and metastasis may be present in lymph nodes that are normal by imaging criteria. The most accurate criterion for the diagnosis of nodal metastasis is central nodal necrosis [8, 9]. Ultrasound, CT, and MRI depict central nodal necrosis with a lack of periadenitis (Fig. 16). Extracapsular tumor spread is suggested by ill-defined nodal margins and enhancement extending into the perinodal soft tissues and is associated with an increased risk of distant metastasis and a poor prognosis [8–10]. When CT or MRI of potential metastatic lymphadenopathy is undertaken, it is also important to evaluate for the primary malignancy in the head and neck. In particular, on the basis of a recent increase in incidence in young adults, nodal metastases from oropharyngeal neoplasms and thyroid cancer should be considered [39, 40]. Oropharyngeal neoplasms, specifically tonsillar and oral tongue cancers, have increased in incidence from 2.1% in 1973 to 3.9% in 2001 among patients 20–44 years old [39]. This increase has been attributed to infection by human papillomavirus (HPV), specifically type 16, which is hypothesized to be sexually transmitted [40]. Although established as causative, HPV positivity is a favorable prognostic factor with improved response to induction chemotherapy and chemoradiation [40]. Thyroid cancer is currently the fourth most common malignancy in young adults 15–29 years old with the most common age of diagnosis between 20 and 24 years [41]. The majority of cases presenting before age 30 years are well-differentiated carcinomas, either papillary or medullary, and are more common in women [41]. The incidence has increased steadily from 1975 to 2000 [41]. Nodes related to metastatic papillary thyroid cancer range in appearance from mimicking reactive nodes to enhancing, cystic, or necrotic nodes. Fine calcifications on CT or punctate hyperechogenicities on ultrasound may be seen secondary to psammoma bodies in papillary thyroid metastases [8, 9, 13]. MRI features include T1 nodal hyperintensity, thought to be due to thyroglobulin or intranodal hemorrhage [8–10] (Fig. 17). Conclusion Enlarged cervical lymph nodes are commonly encountered in the pediatric population, both

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clinically and on imaging. Clinicians and radiologists often struggle with the nonspecific features of such nodes, which are most commonly reactive secondary to infection but can also be related to more aggressive processes, including malignancy. Appropriate clinical evaluation is paramount in the assessment of enlarged lymph nodes. Imaging plays an important role, particularly when lymph nodes lack benign features or fail to resolve with treatment. Imaging can characterize nodal features including size, distribution, internal architecture, vascularity, and enhancement. Ultrasound is an excellent initial modality because of the lack of ionizing radiation, and CT and MRI may add additional detail regarding deep spaces of the neck and evaluation of associated head and neck pathology. It is important for the radiologist to be familiar with nodal pathology, particularly nodal features that aid in distinguishing between causes and related head and neck imaging findings to guide clinical management. References 1. Park YW. Evaluation of neck masses in children. Am Fam Physician 1995; 51:1904–1912 2. Nield LS, Kamat D. Lymphadenopathy in children: when and how to evaluate. Clin Pediatr (Phila) 2004; 43:25–33 3. Ahuja AT, Ying M. Sonographic evaluation of cervical lymph nodes. AJR 2005; 184:1691–1699 4. American College of Radiology. ACR Appropriateness Criteria: neck mass/adenopathy. American College of Radiology Website. www.acr.org/~/ media/ACR/Documents/AppCriteria/Diagnostic/ NeckMassAdenopathy.pdf. Accessed June 27, 2012 5. Vandecaveye V, De Keyzer F, Vander Pooten V, et al. Head and neck squamous cell carcinoma: value of diffusion-weighted MR imaging for nodal staging. Radiology 2009; 251:134–146 6. Riad R, Omar W, Kotb M, et al. Role of PET/CT in malignant pediatric lymphoma. Eur J Nucl Med Mol Imaging 2010; 37:319–329 7. Som PM, Curtin HD, Mancuso AA. Imagingbased nodal classification for evaluation of neck metastatic adenopathy. AJR 2000; 174:837–844 8. Som PM, Brandwine-Gensler MS. Lymph nodes of the neck. In: Som PM, Curtin HD, eds. Head and neck imaging, 5th ed. St. Louis, MO: Mosby, 2011:2287–2384 9. Som PM. Detection of metastasis in cervical lymph nodes: CT and MR criteria and differential diagnosis. AJR 1992; 158:961–969 10. Som PM, Curtin HD, Mancuso AA. An imagingbased classification for the cervical nodes designed as an adjunct to recent clinically based nodal classifications. Arch Otolaryngol Head Neck Surg 1999; 125:388–396

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