Benign and Malignant Nodes in the Neck: Magnetic

Resonance Microimaging Misa Sumi and Takashi Nakamura

Introduction

The presence of metastatic lymph nodes in the neck of patients with head and neck cancer is an important prog- nostic determinant in staging the cancer and in planning the patient's surgery and chemo- and radiotherapy. Therefore, metastatic nodes should be effectively differentiated from benign lymphadenopathies. The cervical lymph nodes are also the sites where other benign and malignant diseases occur, including infectious diseases and malignant lympho- mas. Imaging examinations are expected to provide clues to differentiate between the benign and malignant nature in order to determine treatment planning.

We propose a high-resolution MR technique using a microscopy coil (MR microimaging) to differentiate between malignant and benign nodes in the neck. Detailed assessment of the affected nodes using high-resolution MR images could greatly improve the diagnostic performance of MR imaging in terms of detecting metastatic cervical nodes. Furthermore, assessment of the structural changes in the nodes by using the MR microimaging technique may be use- ful in differentiating between metastatic lymph nodes, nodal lymphomas, and benign lymphadenopathies.

Technical Details

The MR microimaging system used in this study is com- posed of a 1.5-T MR imager (Gyroscan Intera 1.5T Mas- ter; Philips Medical Systems) and a microscopy coil with a diameter of 47 mm. The 47-mm microscopy allows local acquisition of the MR signals with a high signal-to-noise ratio. This critical property of the microscopy coil, coupled with a field-of-view (FOV) of a small size and thin image sections, allows the achievement of high-resolution MR images. For example, when a 160 × 128 matrix size for a 7- cm FOV, 2-mm image thickness, and 0.2-mm interslice gap are used, MR images with a 0.438 mm x 0.547 mm x 2 mm measured voxel size can be obtained. This resolution is much higher than those ranging from 0.7 mm x 0.7 mm x 4 mm to 1 mm x 1 mm x 6 mm that are obtained using other coils.

An inherent property of these coils of a small size is a low signal yield at increasingly greater distances from them. To overcome the image intensity inhomogeneity, the contrast- level appearance (CLEAR) postprocessing technique (Phil- ips Medical Systems) is routinely used. This technique uses the premeasured sensitivity profile of the coil to calculate the compensation needed to apply to the pixel intensities so that

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432 Iil Applications to Specific Cancers

even image intensity can be achieved. The 47-mm micros- copy coil is positioned so that the nodes remain under the coil; the coil is secured using an adhesive tape and a band.

Axial fat-suppressed spectral presaturation with inversion recovery (SPIR) T2 images and axial Tl-weighted spin-echo images, both obtained using the CLEAR technique, are use- ful for assessing the internal nodal architecture. T 1-weighted imaging after an intravenous injection of a gadolinium-based contrast agent, such as gadopentetate dimeglumine, can pro- vide additional information regarding the changes to the nodal vascularity. The acquisition time for each sequence is < 4 min for 15 slices.

Anatomy of the Lymph Node

A lymph node consists of four structural and functional components: (1) the cortex with its germinal center, where the B-cell system develops; (2) the medullary zone in which most of the plasma cells reside and the B-cell system exerts its secretory functions; (3) the paracortex lying between the germinal centers in which most T-cells reside; and (4) the sinuses, which contain macrophages and other mononuclear phagocytes.

The capsule of the lymph node is interrupted at various places by afferent lymphatics that transport lymph into the marginal sinus. The marginal sinus continues into the corti- cal or trabecular sinuses that traverse the paracortex and then enter the medullary cords; here the sinus (medullary sinus) becomes wider and more tortuous.

Almost all blood vessels enter lymph nodes through the hilum. The larger arterial branches initially run within the trabeculae; then they abruptly enter the medullary cords to supply their capillary network. Next, the arteries reach the cortex where they distribute to capillary plexuses of the cor- tical parenchyma and the germinal centers. In the paracor- tex, the capillary branches give rise to the high endothelial venules, which are characteristic of this region, and transport circulating lymphocytes, predominantly T-cells, to the para- cortex.

Metastatic Nodes

Metastatic Focus and Nodal Necrosis

Cervical lymph node metastasis may occur in patients with both squamous and nonsquamous cell carcinomas of the head and neck. Lymph node metastasis leads to drastic changes in the components and structures of the nodes. A metastatic focus first appears in the cortical portion of the node. The focus continues to grow and gradually displaces the surrounding lymphoid tissues of the node. In conjunc- tion with the growth of the metastatic focus, the metastatic

node becomes larger, and the metastatic cancer cells rupture the nodal capsule and, eventually, extend outward beyond the capsule (extranodal spread, ENS). The extranodal can- cer cells may occasionally invade the surrounding structures such as the blood vessels, muscles, and skin, worsening the patient's prognosis.

Nodal necrosis may associate with nodal metastasis as cancer cells infiltrate into the medullary portion of the nodes and surpass the available blood supply, and is considered to be a pathognomonic feature of metastatic nodes in patients with squamous cell carcinomas of the head and neck. The nodal necrosis is also one of the most reliable imaging findings of metastatic nodes. It was reported to occur in 56-63% and 10-33% of metastatic nodes > 1.5 cm and < 1 cm in diameter, respectively (King et al., 2004b). Conventional MR imaging is unable to detect the necrotic foci that were < 3 mm (van den Brekel et al., 1990). In addition, small metastatic foci do not always cause enlargement of the affected nodes. In fact, 71% of metastatic nodes were smaller than 1 cm in minimal axial diameter (Castelijns and van den Brekel, 2002). There- fore, a small metastatic node with a necrotic focus that is < 3 mm may often be misinterpreted as a nonmetastatic node on conventional MR images.

Metastatic foci may exhibit, in addition to cancer cell nests and keratinization, either liquefaction necrosis or coagula- tion necrosis, or both (Nakamura and Sumi, 2007). On gado- linium-enhanced T 1-weighted images, necrosis in the node is identified as a noncontrast-enhancing area (focal defect). On fat-suppressed T2-weighted images, the metastatic focus is most frequently identified as an area with high signal inten- sity; this corresponds to liquefaction necrosis. However, the metastatic focus may contain coagulation necrosis, which is demonstrated on fat-suppressed T2-weighted images as an area with lower signal intensity when compared with the residual normal lymphoid tissue (Fig. 1).

Keratinization is depicted as areas with remarkably low signal intensity on fat-suppressed T2-weighted and contrast- enhanced T 1-weighted images. On T 1-weighted images, however, keratinization may often be depicted as high signal intensity areas reflected in keratin protein. Cancer cell nests can be observed as low signal intensity areas on fat-sup- pressed T2-weighted images when compared with the resid- ual normal lymphoid tissue. However, they are enhanced on gadolinium-enhanced Tl-weighted images.

Magnetic resonance microimaging using a microscopy coil can potentially facilitate the detection of a metastatic lymph node in its early stages. Using MR microimaging, we were able to effectively distinguish metastatic nodes that har- bored metastatic foci as small as 1.5 mm in diameter (Sumi et al., 2006). Magnetic resonance microimaging can be coupled with other magnetic resonance imaging sequences; for example, diffusion-weighted imaging is used to evaluate water diffusibility in nodes with or without metastasis. In this regard, the apparent diffusion coefficients (ADCs) are

21 Beniqn and Malignant Nodes in the Neck: Magnetic Resonance Microimaging 433

A B

Figure 1 56-year-old man with tongue squamous cell carcinoma. (A) Axial fat-suppressed T2-weighted images shows a metastatic node (arrowhead) at level II of the neck. The node contains hyperintense focus (arrow) in a relatively hypointense area (*). SMG, submandibular gland. Scale bar = 10mm. (B) Photomicrograph of the excised metastatic node in (A) shows large cancer nests (*) associated with liquefaction necrosis (arrow), which corresponds to the hyperintense focus in (A). Cancer nests consist mainly of proliferating cancer cells and coagulation necrosis.

significantly greater in the metastatic nodes than those in the benign nodes of the patients with head and neck carcinoma (Sumi et al., 2006). Therefore, a combined use of these mag- netic resonance microscopic criteria on nodal architectures and ADCs may be a promising technique for discriminating metastatic nodes.

Loss of Hilar Structure

As the metastasized cancer cell nest continues to increase in size and volume, the hilum becomes obliterated and the node eventually loses its bean-shaped contour. The presence of a normal hilum, and parenchymal homogeneity is sug- gestive of nonmetastatic nodes. The hilum is best depicted by ultrasonography (US) and can be identified as a highly echogenic structure in the central part of the node. The lack of the normal hilar echogenicity is one of the US criteria for the diagnosis of metastatic lymph nodes (Sumi et al., 2001).

With regard to conventional MR imaging, little has been dis- cussed on the appearance of the hilar structure; this is mainly because of the low spatial resolution.

High-resolution MR microimaging, on the other hand, can readily depict the normal hilum structure as a concav- ity of the nodes that is filled with fatty tissue. The hilar fat is depicted as a high-intensity area on T 1-weighted images and as a low-intensity area on fat-suppressed T2-weighted images. The vessels in the hilum may also be depicted as a high-intensity area on both fat-suppressed T2- and contrast- enhanced T 1-weighted images. The hilar fat is lost at a high rate in the metastatic lymph nodes (92%); however, such absence may also be noted in nodal lymphomas (79%) and even in benign lymphadenopathy (46%) (Sumi et al., 2006). In the early stages of nodal metastasis, when the metastatic cancer nest is still very small, the hilar structures are intact. Missing hilar structure can also be observed in benign nodes as stated above. Therefore, although the findings on the hilar

434 III Applications to Specific Cancers

structures are helpful in differentiating between metastatic and benign nodes, they are not as predictive as the findings on focal defects with or without nodal necrosis.

Extranodal Spread

Extranodal spread (ENS) is a significant factor affect- ing the treatment plan and patients' prognosis. Therefore, sensitive detection of the ENS is mandatory for predicting poor treatment outcome and deciding whether regional and systemic adjuvant therapy should be considered. For detec- tion of the advanced stages of ENS, we strongly recommend investigating the presence of lymph edema around the meta- static node. The nodes with ENS are frequently associated with high-intensity signals in the interstitial tissues. These signals can be observed around the metastatic nodes and appear to extend from them (flare sign) (unpublished obser- vation).

The detection of ENS in its early stages by conventional MR imaging is difficult owing to its low spatial resolution. Even with MR microimaging, it is very hard to detect slight changes in the nodal capsule or minimal extensions of cancer cells into the surrounding fatty tissues. However, in relatively advanced stages, MR microimaging can depict an irregular margin blending into the surrounding tissues as an important finding suggestive of the ENS (Sumi et al., 2006). There- fore, MR microimaging could detect early stages of ENS in the neck more readily than conventional MR imaging.

Nodal Lymphomas and Infectious Lymphadenopathy

Nodal Lymphomas

When a patient with an unknown primary neoplasm has cervical lymphadenopathy, differential diagnosis between metastatic lymph node and nodal lymphoma should be con- sidered. Nodal lymphomas are generally well circumscribed and exhibit a homogeneous parenchyma on both T 1- and fat- suppressed T2-weighted images (Fig. 2). Furthermore, the ADC of the lymphomas is significantly lower than that of the benign nodes and metastatic nodes (Sumi et al., 2006). Therefore, it is not difficult to differentiate nodal lymphoma from nodal metastasis.

However, nodal necrosis is never uncommon in Hodg- kin's and non-Hodgkin's Lymphomas, in particular, the dif- fuse large B-cell lymphomas (King et al., 2004a; Sumi et al., 2006). In such cases, nodal lymphomas may be reminiscent of metastatic nodes with a necrotic focus, and the differen- tiation between these two entities may be difficult. In addi- tion, the presence of a necrotic area within the lymphoma would affect the ADC levels of the lesion. It is noteworthy that the nodal necrosis in lymphomas seems to differ from

Figure 2 43-year-old man with non-Hodgkin's Lymphoma (mantle cell lymphoma). Axial fat-suppressed T2-weighted image shows multiple, enlarged nodes (arrowheads) with homogeneous areas of high signal inten- sity at level IA of the neck. Narrowed hilum (arrow) is seen in one of the nodal lymphomas. Scale bar = 10mm.

that in metastatic nodes in that the former frequently occu- pies almost the entire node with minimal loss of the hilar structures. Moreover, it may appear as a hypointense focus on fat-suppressed T2-weighted images.

Infectious Lymphadenopathy

Infectious lymphadenopathies are very common and are in most cases caused by bacterial, mycobacterial, or viral infection. The presence of a normal hilum and homogeneous parenchyma suggests benign lymphadenopathy. However, in the inflammatory nodes, such as those in bacterial adenitis and cat-scratch disease, the nodal parenchyma is heteroge- neous on MR microimages. This may be due to the pus forma- tion, which is pathognomonic of the condition; it may also be due to the dilated blood vessels and the increased number of blood vessels. On fat-suppressed T2-weighted images, hyper- intense radiating streaks representing blood vessels (Fig. 3), or a central hypointense core representing the flow-void phe- nomenon, are highly indicative of inflammatory nodes.

Imaging Strategy for Diagnosing Lymphadenopathy in the Neck

MR microimaging has some disadvantages. First, MR microimaging requires additional time for examina- tion. Second, the small field-of-view makes observing

21 Benign and Malignant Nodes in the Neck: Magnetic Resonance Microimaging 435

in the whole of the neck before undertaking MR micro- imaging. When nodes are superficially located (within 6-7 cm from the neck surface) and a detailed examination of the nodes is required for purposes such as differential diagnosis of metastatic lymph nodes, nodal lymphomas, or benign lymphadenopathies, or for examining the presence or absence of extranodal spread, MR microimaging is recom- mended.

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Figure 3 16-year-old girl with lymphadenitis in parotid nodes. Axial fat-suppressed T2-weighted image shows enlarged nodes (arrowheads) in and around the parotid gland (PG). Some of the nodes contain hyperintense areas (arrows) suggestive of enlarged blood vessels. Scale bar = 10mm.

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