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1 Head and Neck Imaging Kapoor et al. 18F FDG PET/T of Head and Neck ancers Downloaded from by on 12/01/17 from IP address opyright RRS. For personal use only; all rights reserved Pictorial Essay Role of 18F FDG PET/T in the Treatment of Head and Neck ancers: Principles, Technique, Normal Distribution, and Initial Staging H ead and neck cancers constitute approximately 2 3% of all cancers in the United States [1], with approximately 50,000 new cases diagnosed Received pril 15, 2004; accepted after revision July 26, Kapoor V, Fukui M, Mcook M every year. Treatment of head and neck tumors is challenging. multidisciplinary approach that includes medical oncology, radiation therapy, surgery, and radiology results in optimal Fig. 1. Diagram illustrates principle of PET with 18F FDG: annihilation reaction. Positrons (β+) released spontaneously from decaying fluorine-18 component of 18F FDG nucleus annihilate with electrons (β-), releasing two coincident 511-keV photons (γ) that are detected by scintillation crystals (blue rectangles). P = protons (red), N = neutrons (blue). Source: Kapoor V, Mcook M, Torok FS. n introduction to PET-T imaging. RadioGraphics 2004;24: Reprinted with permission. Vibhu Kapoor 1,2, Melanie. Fukui 3, arry M. Mcook 1 patient care. lthough the superficial extent of most primary carcinomas on the head and neck is evident by clinical examination, depth of tumor invasion, lymph node status, and other 1 Department of Radiology, Division of PET/T Imaging, University of Pittsburgh Medical enter, Pittsburgh, P Present address: 301 Frank ushing Way, Suite 501, Tuman, GU ddress correspondence to V. Kapoor (ajr@kapoorv.us). 3 Department of Radiology, llegheny General Hospital, Pittsburgh, P JR 2005;184: X/05/ merican Roentgen Ray Society JR:184, February

2 Kapoor et Fig. al. 2. Diagram illustrates mechanism of action of 18F FDG, in which glucose analog 18F FDG is taken up in facilitated transport by metabolically active cells via glucose transporters (Glut) in cell membrane. In cell cytoplasm, 18F FDG undergoes phosphorylation to form FDG-6-phosphate (FDG-6-P) that, unlike glucose, cannot undergo further metabolism and becomes trapped in cell with only negligible amount of FDG- 6P diffusing from cells. Source: Kapoor V, Mcook M, Torok FS. n introduction to PET-T imaging. RadioGraphics 2004;24: Reprinted with permission. Downloaded from by on 12/01/17 from IP address opyright RRS. For personal use only; all rights reserved Fig. 3. Standardized uptake value (SUV) is semiquantitative method to determine 18F FDG uptake by tissues and may help in distinguishing malignant from benign processes as illustrated by these fused 18F FDG PET/T images., In 45-year-old man with left tonsil lymphoma, coronal fused 18F FDG PET/T image obtained at level of oropharynx shows marked asymmetry of 18F FDG uptake in tonsils with hypermetabolism in left tonsil (arrowhead) extending into soft palate. Visualization of asymmetric uptake and maximal SUV of 9.07 in left tonsil helped direct biopsy that revealed mantle cell lymphoma., In 50-year-old man with benign parapharyngeal cyst, axial fused 18F FDG PET/T image obtained at level of mandible shows cystic mass (straight arrow) in left parapharyngeal (prestyloid) space with negligible 18F FDG uptake, suggestive of benign lesion. On resection, mass proved to be infected congenital second branchial cleft cyst. rrowhead marks increased uptake by infected molar, and curved arrow marks physiologic uptake by pharyngeal mucosa. Fig year-old woman with non-hodgkin s lymphoma evaluated for restaging showing coregistration advantage of fused 18F FDG PET/T over 18F FDG PET., xial 18F FDG PET image of neck shows focal areas of hypermetabolism in posterior neck bilaterally (arrowheads), with maximal uptake of 4.19 standardized uptake value that suggests malignant lymphadenopathy. rrows mark increased uptake anteriorly in midline that is due to physiologic tongue muscle or hard palate mucosa uptake. and, orresponding axial fused 18F FDG PET/T () and T () images show posteriorly located hypermetabolic areas to be in brown fat around muscles (arrowheads) and anteriorly located hypermetabolic areas to be in hard palate mucosa (arrows). Hence, T helps in accurate localization of 18F FDG uptake. ox in center of gives attenuation data. 580 JR:184, February 2005

3 18F FDG PET/T of Head and Neck ancers Fig year-old man with squamous cell tongue cancer. Sagittal images of neck show differential PET/T weighting possible with fused 18F FDG PET/T. Images may be viewed as only T scans (left image), only PET scans (right image), or varying combination of both (middle image) by dragging vertical bar at the bottom of the image (arrow). Physiologic and anatomic fusion is possible as scanning is performed without moving patients from gantry table between T and PET portions of examination. Voluntary or involuntary patient motion may result in misregistration artifact. rrowheads mark abnormal 18F FDG uptake at base of tongue. Downloaded from by on 12/01/17 from IP address opyright RRS. For personal use only; all rights reserved D Fig. 6. Fused PET/T images in several patients depict areas of normal 18F FDG uptake in head and neck., Sagittal fused 18F FDG PET/T image of 40-year-old man shows 18F FDG uptake (arrows) in normal brain. D, xial 18F FDG PET/T images show normal 18F FDG uptake in lymphoid tissues of nasopharynx (straight arrows, ), and of palatine (arrowheads, ) and lingual (curved arrows, D) tonsils. E and F, oronal fused 18F FDG PET/T images show normal 18F FDG uptake in parotid (straight arrows, E and F), and submandibular (curved arrows, E) salivary glands and vocal cords (arrowheads, F). (Fig. 6 continues on next page) E F JR:184, February

4 Kapoor et al. Downloaded from by on 12/01/17 from IP address opyright RRS. For personal use only; all rights reserved synchronous and metachronous primary lesions are best evaluated on imaging. urrently the most widely accepted cross-sectional imaging technique is T (and in some institutions MRI) for the initial evaluation and follow-up of these patients. n additional imaging technique in the evaluation of patients with head and neck cancers is 18F FDG PET. G J Fig. 6. (continued) Fused PET/T images in several patients depict areas of normal 18F FDG uptake in head and neck. G, oronal fused 18F FDG PET/T image obtained in 60-year-old man shows 18F FDG uptake in hard palate mucosa (arrowhead) and genioglossus muscle (arrows). H, xial fused 18F FDG PET/T image obtained in 52-year-old man at nasopharyngeal level shows normal 18F FDG uptake in right lateral pterygoid muscle (arrow). I, oronal fused 18F FDG PET/T image of neck in 41-year-old woman shows normal 18F FDG uptake in neck muscle (arrows) due to physical activity after 18F FDG injection. J, xial 18F FDG PET image obtained at level of parotid glands (arrows) in 57-year-old man shows 18F FDG uptake in normal parotid gland with standardized uptake value (SUV) of lthough SUV of normal parotid gland (and other normal structures depicted in I) may be in malignant range, symmetric distribution of 18F FDG uptake and typical locations of physiologic uptake help in differentiation between physiologic and abnormal metabolisms. oxed area is region in which SUV was measured. Molecular imaging using radiopharmaceuticals that are incorporated into metabolic pathways of normal and abnormal cells for diagnosis and treatment of cancers is an area of ongoing research. Various radiopharmaceuticals are being currently investigated for clinical use such as 18F FDG, 11 methionine, 11 tyrosine, 11 thymidine, H and 18F fluroide [2]. The most extensively studied and clinically utilized diagnostic radiopharmaceutical is 18F FDG. PET using 18F FDG has been approved by Medicare for diagnosis, staging, and follow-up (restaging) of numerous malignancies such as lymphoma, melanoma, and head and neck, non-small cell lung, colorectal, breast, thyroid, and Fig year-old man with metastatic squamous cell carcinoma of neck evaluated on 18F FDG PET/T for nodal staging., xial image from 18F FDG PET portion of examination shows hypermetabolism (arrows) in right supraclavicular region consistent with malignant lymph nodes. However on PET alone, it is not possible to determine number and size of nodes or presence of extracapsular tumor spread information that is important for staging and prognosis., xial contrast-enhanced image from T portion of examination obtained at same level as shows more than three nodes (arrowheads) in right supraclavicular region, all smaller than 6 cm in greatest diameter with extracapsular spread (arrow). Such findings aid in accurate staging and prognostication. I 582 JR:184, February 2005

5 18F FDG PET/T of Head and Neck ancers Downloaded from by on 12/01/17 from IP address opyright RRS. For personal use only; all rights reserved Fig year-old man with poorly differentiated laryngeal carcinoma evaluated on 18F FDG PET/T for local and nodal extent of disease., xial image from 18F FDG PET portion of examination shows intense hypermetabolism (arrowheads) at site of primary tumor and right neck, consistent with malignancy. However, local extent of primary tumor cannot be evaluated on PET alone. and, xial contrast-enhanced T () and fused 18F FDG PET/T () images show large laryngeal mass (arrowheads, and ) invading adjacent structures hyoid bone (H, ) and ipsilateral pyriform sinus and crossing midline (straight arrow, ). Large metastatic level 2a-III jugulodigastric lymph node (N, ) is also seen at same level as extracapsular spread (curved arrow, ) and necrotic center (focal central area of less intense 18F FDG uptake, ), compressing adjacent internal jugular vein (IJV, ). esophageal cancers. ancer detection on T and MRI is dependent on changes in morphology (size, shape), electron density (attenuation on T), or proton environment and density (signal intensity on MRI) in abnormal tissue. With 18F FDG PET, cancer detection is based on changes in glucose metabolism in tumor cells [3]. It is intuitive that abnormal metabolic changes at a cellular level should be detectable before macroscopic morphologic changes and that PET may be more accurate than T or MRI for staging tumors and evaluation for recurrent Fig year-old man with nasopharyngeal squamous cell carcinoma; advantage of fused 18F FDG PET/ T in evaluating local extent of tumor., xial image from 18F FDG PET portion of examination obtained at level of nasopharynx shows focal hypermetabolism (arrowheads) anteriorly at site of primary tumor. Evaluation of local invasion is not possible on PET alone. urved arrows mark normal 18F FDG uptake in cerebellum., xial image from T portion of examination obtained at same level as shows advanced nasopharyngeal cancer (arrowheads) with local invasion of adjacent bones in skull base (arrowheads). Patient thereafter underwent chemoradiation therapy. tumors that have undergone treatment changes. lthough no large studies comparing PET/T to T or MRI alone in staging head and neck cancer have been published, some reports have suggested that PET/T may be a better examination for the staging of patients with lung and colorectal cancers [4, 5]. PET is limited by poor spatial resolution that may make it difficult to accurately localize 18F FDG uptake to an anatomic structure. This limitation has been significantly reduced by combined PET T, a technique in which both PET and T are performed sequentially during a single visit on a hybrid PET/T scanner [6]. The PET and T images thus obtained are coregistered using fusion software, thereby enabling accurate designation of physiologic data obtained on PET to anatomic structures visualized on T. We have found that using PET/T increases our level of confidence in staging and evaluating tumor recurrence in patients with head and neck cancers. t our institution, patients with neck carcinoma are routinely evaluated on PET/T for initial staging and followup after treatment. One must, however, be aware JR:184, February

6 Kapoor et al. Downloaded from by on 12/01/17 from IP address opyright RRS. For personal use only; all rights reserved of certain pitfalls of this technique that may lead to both false-positive and false-negative results. This pictorial essay addresses the principles of 18F FDG PET/T, normal FDG uptake in the neck tissues, and the role of 18F FDG PET/T in the diagnosis and initial staging of head and neck tumors. Principle of 18F FDG PET/T The technique of 18F FDG PET is based on the detection of coincident annihilation Fig year-old woman with squamous cell carcinoma metastatic to cervical lymph node and unknown primary site that was correctly identified on 18F FDG PET/T., oronal fused 18F FDG PET/T image of neck shows focus of increased uptake (arrowhead) in right neck corresponding to metastatic level 2 lymph node., xial T image obtained at level of oropharynx shows mild asymmetry of tonsils with larger left tonsil (arrow) contralateral to metastatic lymph node. Source: Kapoor V, Mcook M, Torok FS. n introduction to PET-T imaging. RadioGraphics 2004;24: Reprinted with permission., Fused 18F FDG PET/T image obtained at same level as shows asymmetric 18F FDG uptake with intense hypermetabolism (arrows) in left tonsil that on biopsy was found to be primary tumor site for contralateral metastatic nodal disease. Source: Kapoor V, Mcook M, Torok FS. n introduction to PET-T imaging. RadioGraphics 2004;24: Reprinted with permission. photons released during decay of 18F DG [4] (Fig. 1). Neovascularization is essential to the proliferation of malignant cells; however, even in the presence of oxygen, these cells have a high rate of glycolysis. The glycolysis phenomenon was first described by Otto Warburg in 1924 and is known as the Warburg effect [7]. Metabolically active cells use a facilitated transport system for glucose uptake. 18F FDG is a glucose analogue that competes with glucose for the same transport system. Unlike glucose, however, after initial phosphorylation into FDG-6-phosphate, FDG cannot undergo further metabolism and thus it accumulates in metabolically active tumor cells [8] (Fig. 2). ecause glucose competes with 18F FDG for uptake into metabolically active cells, it is important to have adequate blood glucose control to improve the sensitivity of the examination. The standardized uptake value (SUV) is a semiquantitative method for assessing Fig year-old man with extensive nodal and distant metastatic disease from unknown primary tumor detected on fused 18F FDG PET/T., xial contrast-enhanced T image obtained at level of angle of mandible shows multiple large necrotic metastatic (squamous cell carcinoma) level 1 and 2 lymph nodes (arrowheads) on right., orresponding axial fused 18F FDG PET/T image shows hypermetabolism in right cervical lymph nodes (arrowheads) and in right palatine tonsil (arrows) that was found to be site of primary tumor at biopsy., xial fused 18F FDG PET/T image of thorax shows increased uptake in right axillary (arrow) and hilar (arrowheads) lymph nodes due to metastatic disease. 584 JR:184, February 2005

7 18F FDG PET/T of Head and Neck ancers Downloaded from by on 12/01/17 from IP address opyright RRS. For personal use only; all rights reserved Fig year-old man with laryngeal squamous cell carcinoma and second primary tumor in lung who underwent resection and radiation of metastatic squamous cell carcinoma of lymph node from unknown primary tumor 4 years prior to this study., oronal fused 18F FDG PET/T image of neck shows intense supraglottic hypermetabolism (arrows) consistent with cancer (squamous cell cancer on biopsy) having transglottic spread., xial fused 18F FDG PET/T image of thorax shows large right lower lobe lung mass (arrows) with cavitation (arrowhead). Increased 18F FDG uptake is seen in this mass that proved to be primary squamous cell carcinoma. 18F FDG uptake in tissues and is determined using the following formula: Standardized uptake value = Tracer ctivity in Tissue (ui/g) [Injected radiotracer dose (mi) / Patient weight (kg)] t our institution, we consider an SUV of greater than 3.0 (Fig. 3) suggestive of malignancy in the appropriate clinical setting. SUV has also been used to follow up response to therapy. ecause SUV is dependent on a patient s body weight and the radiotracer injected, corrections for residual activity in the syringe and tubing and for the dose of 18F FDG at time of injection are required to prevent Fig year-old man with primary anaplastic thyroid carcinoma with metastatic nodal, liver, and bone disease., oronal fused 18F FDG PET/T image of neck shows intense hypermetabolism in large mass in right thyroid lobe (arrows) and in metastatic ipsilateral level 2 and 3 lymph nodes (arrowhead). = clavicle, S = sternum., oronal fused 18F FDG PET/T image of abdomen shows focal hypermetabolism in liver (arrowhead) and L3 vertebral body (arrows) consistent with metastatic disease. Vertebral lesion was not seen on T alone (images not shown). urved arrow marks 18F FDG excretion into right renal pelvis. incorrect results [1]. However minor errors in SUV determination are unlikely to affect patient treatment significantly. In certain situations, it may be difficult to accurately locate an area of increased activity on PET alone due to the absence of identifiable anatomic structures, particularly in the abdomen and sometimes in the neck (Fig. 4). Investigators recognized this limitation in oncology imaging, and eyer et al. [6] at the University of Pittsburgh designed and built the first prototype PET/T scanner to be used in clinical imaging. The software used by the combined scanner precisely coregisters the PET and T images obtained during a single study on the hybrid PET/T scanner (Fig. 5). The overall combination allows focal FDG uptake on PET to be located with greater confidence because the relative PET and T weighting of the coregistered images can be altered, thus enabling FDG uptake to be precisely mapped to an anatomic structure (Fig. 5). However, the precision of coregistration is only as good as the patient s ability to remain immobile between the T and PET portions of the examination. Movement between the two examinations may result in misregistration artifact. Motion due to involuntary activity is not as much a problem in 18F FDG PET/T of the head and neck as in examinations of the chest or abdomen. dequate patient instruction and immobilization during scanning can prevent misregistration due to voluntary movements. JR:184, February

8 Kapoor et al. Downloaded from by on 12/01/17 from IP address opyright RRS. For personal use only; all rights reserved ll 18F FDG PET/T scans are obtained on a dedicated hybrid PET/T system (TI PET, Siemens Medical Solutions) and viewed after attenuation correction on a fusion workstation using the Syngo software platform (Siemens Medical Solutions). efore scanning is performed, the patient is injected IV with 370 Mq (10 mi) 18F FDG and then is instructed to lie quietly in a room to decrease muscle and vocal cord uptake. pproximately 60 min after the injection, a contrast-enhanced T scan from the skull base to iliac crests is obtained on a single-detector helical scanner (which is a component of the hybrid PET/T scanner) with a collimator width of 5.0 mm and a pitch of 1.5. PET scan is obtained immediately after the T scan without allowing the patient to move on the gantry table between the two acquisitions so that the images can be accurately coregistered. Normal Distribution of 18F FDG in the Head and Neck Numerous structures in the neck show physiologic uptake of FDG. These include muscles (tongue and paraspinal muscles, vocal cords), lymphoid tissue (mucosa-associated lymphoid tissue, palatine and lingual tonsils), brown fat, and salivary glands [9, 10] (Fig. 6). high SUV (in the malignant range) may be seen in these normal tissues as a result of physiologically increased metabolic activity (Fig. 6), and sometimes it may not be possible to distinguish benign from malignant disease on the basis of SUV alone. In such cases, the pattern of FDG uptake in the neck may be more helpful. For example, in a patient with metastasis of unknown primary cancer, asymmetry in uptake in the tonsils or tongue base may help guide biopsy (Fig. 3). Occasionally, differentiation between normal and abnormal 18F FDG uptake may be difficult on PET alone; PET/T may be valuable in such situations by accurately localizing increased 18F FDG uptake (Fig. 4). Diagnosis and Initial Staging of Head and Neck ancers with 18F FDG PET/T ccurate initial assessment of the primary site of head and neck cancers, nodal involvement, and metastasis evaluation is crucial in staging, treatment planning, and establishing the prognosis of patients with these cancers. lthough most primary malignancies of the oral cavity, larynx, and pharynx are readily accessible for clinical examination and biopsy, clinical examination often understages the extent of disease [11]. Five percent of patients with head and neck squamous cell carcinoma present with metastatic cervical nodes without an identifiable primary site at clinical examination [12, 13]. lso, evaluation of nodal status may be limited by a patient s body habitus or lack of accessibility due to the location of the node. Therefore, almost all patients with head and neck cancers need some form of cross-sectional imaging for assessment of the extent of disease. 18F FDG PET is superior to T or MRI for detecting lymph node metastasis, with sensitivity and specificity of approximately 90% and 94%, respectively, as compared with 82% and 85% for T, 80% and 79% for MRI, and 72% and 70% for sonography, respectively [14]. However, 18F FDG PET has poor spatial resolution and cannot accurately assess lymph node morphology, which is relevant for nodal staging. Number (single or multiple), distribution (ipsilateral, contralateral, or bilateral), and lymph node size (smaller than 3 cm, between 3 6 cm, and greater than 6 cm) are all important for nodal staging of head and neck cancers. lthough PET is better for the assessment of metastasis in lymph nodes that appear morphologically normal according to size criteria, T is more accurate for assessing the level and size of nodes (Fig. 7), the number of nodes in conglomerate nodal masses, and the presence of extracapsular spread factors that are important for determining the prognosis of patients [15]; macroscopic extranodal spread carries a 10 times greater risk of recurrence and reduces survival by 50% compared with nodes that have either no or only microscopic extracapsular spread. lso, intense 18F FDG uptake by the primary tumor may obscure uptake by adjacent enlarged lymph nodes, thereby resulting in false-negative results. Therefore, a combination of PET/T is likely to result in more accurate nodal staging than PET or T alone. Size and local extent of the primary tumor, which are important for staging, prognostication, and treatment planning, are more accurately assessed on T or MRI (Figs. 8 and 9). PET with 18F FDG has been shown to be able to reveal unknown primary tumors in approximately 30 50% of patients with metastatic disease to the lymph nodes in the neck who had no detectable primary tumor at clinical examination [16] (Figs. 10 and 11), whereas T and MRI in combination with endoscopy and random biopsy of likely primary sites such as tonsils, nasopharynx, and tongue base reveal the primary site in 10 20% of these patients [13]. ecause normal structures such as lymphoid tissue in the tonsils, tongue base, and nasopharynx show variable physiologic activity, they may potentially hinder detection of such unknown primaries. bnormally high or asymmetric 18F FDG uptake helps in guiding direct examination and biopsy. PET/T may also aid in the detection of a second primary tumor in patients with head and neck carcinoma who are at an increased risk for synchronous or metachronous carcinomas of the head and neck, esophagus, and lung (Fig. 12). The risk of a second primary tumor is approximately 4% per year, with 80% of the second primary lesions located in the oral cavity, 40% in the larynx or pharynx, 31% in the lungs, and 9% in the esophagus [17]. Presence of distant metastasis greatly affects the treatment (palliative vs curative) and prognosis of patients with head and neck cancers. Metastasis to the lungs, liver, and bones is likely in patients with advanced-stage and recurrent head and neck cancer [12]. PET with 18F FDG has a sensitivity and specificity of 90% and 94%, respectively, for detection of distant metastasis [18] (Figs. 12 and 13). In the presence of distant metastases, palliative therapy would be more appropriate than aggressive therapy. onclusion ccurate initial staging is critical in the treatment of patients with head and neck cancer. lthough T and MRI are superb cross-sectional imaging techniques, 18F FDG PET/T combines the excellent anatomic detail of T with metabolic activity data from 18F FDG PET in a single imaging session, thereby increasing the accuracy of initial staging in these patients. References 1. Kostakoglu L, gress H Jr., Goldsmith SJ. linical role of FDG PET in evaluation of cancer patients. RadioGraphics 2003;23: Reinhardt MJ, Kubota K, Yamada S, Iwata R, Yaegashi H. ssessment of cancer recurrence in residual tumors after fractionated radiotherapy: a comparison of fluorodeoxyglucose, L-methionine and thymidine. J Nucl Med 1997;38: Kapoor V, Mcook M, Torok FS. n introduction to PET-T imaging. RadioGraphics 2004;24: Steinert H, Hauser M, llemann F, et al. Non- 586 JR:184, February 2005

9 18F FDG PET/T of Head and Neck ancers Downloaded from by on 12/01/17 from IP address opyright RRS. For personal use only; all rights reserved small cell lung cancer: nodal staging with FDG PET versus T with correlative lymph node mapping and sampling. Radiology 1997;202: bdel-nabi H, Doerr RJ, Lamonica DM, et al. Staging of primary colorectal carcinomas with fluorine-18 fluorodeoxyglucose whole-body PET: correlation with histopathologic and T findings. Radiology 1998;206: eyer T, Townsend DW, run T, et al. combined PET/T scanner for clinical oncology. J Nucl Med 2000;41: Warburg O, Posener K, Negelein E. On the metabolism of cancer cells. iochem Z 1924;152: Wahl RL. Targeting glucose transporters for tumor imaging: sweet idea, sour result. J Nucl Med 1996;37: Fukui M, Meltzer, Snyderman, et al. ombined PET/T: physiologic/anatomic atlas of F- 18 fluorodeoxyglucose (FDG) uptake on PET imaging in the head and neck. Neurographics 2001;1:1 10. Shreve PD, nzai Y, Wahl RL. Pitfalls in oncologic diagnosis with FDG PET imaging: physiologic and benign variants. RadioGraphics 1999;19: Zbaren P, ecker M, Lang H. Pretherapeutic staging of laryngeal carcinoma: clinical findings, computed tomography and magnetic resonance imaging compared with histopathology. ancer 1996;77: Mukherji SK, Fischbein NJ, astelijns J. New imaging techniques. In: Som PM, urtin HD, eds. Head and neck imaging, 4th ed. St. Louis, MO: Mosby, 2003: Muraki S, Mancuso, Harnsberger HR. Metastatic cervical adenopathy from tumors of unknown origin: the role of T. Radiology 1984;152: dams S, aum RP, Stuckensen T, et al. Prospective comparison of 18F-FDG PET with conventional imaging modalities (T, MRI, US) in lymph node staging of head and neck cancer. Eur J Nucl Med 1998;25: Jones S, Roland NJ, Field JK, Phillips DE. The level of cervical lymph node metastases: their prognostic relevance and relationship with head and neck squamous carcinoma primary sites. lin Otolaryngol 1994;19: ssar OS, Fischbein NJ, aputo GR, et al. Metastatic head and neck cancer: role and usefulness of FDG PET in locating occult primary tumors. Radiology 1999;210: Leon X, Quer M, Diez S, Orus, Lopez-Pousa, urgues J. Second neoplasm in patients with head and neck cancer. Head Neck 1999;21: Manolidis S, Donald PJ, Volk P, Pounds TR. The use of positron emission tomography scanning in occult and recurrent head and neck cancer. cta Otolaryngol Suppl 1998;534:1 11 JR:184, February