Cancer in the head and neck region comprises a heteroge- neous group of tumors with a multitude of histologies. In this chapter we are considering tumors in the head and neck region limited to tumors arising from the mucosal lining of the aerodigestive tract and the salivary glands.
Other tumors in the head and neck region such as thyroid cancer, lymphoma, sarcomas, CNS tumors, and malignant melanoma are discussed in other chapters.
Head and neck cancer represents approximately 3% of all malignancies diagnosed annually in the United States.
More than 90% of these tumors have squamous cell pathology. Head and neck squamous cell carcinoma (HNSCC) is typically seen in males between their fifth and seventh decades of life. An increasing number of women and younger men have presented with HNSCC in recent years. There is a wide variation in the incidence of head and neck cancer among different geographic regions. In parts of central Asia, for example, head and neck cancer is the most common neoplasm (1).
The major risk factors for HNSCC are classically re- ported as prolonged tobacco and ethanol abuse. Both sub- stances are independent risk factors and, when combined, act synergistically to increase risk for the disease. Tobacco is a risk factor whether it is ignited, inhaled, or masti- cated. There is a greater risk of HNSCC of the oral cavity with masticatory tobacco use, compared to its inhaled counterpart. Other proposed risk factors are numerous and include betel nut chewing, human papilloma virus in- fection, Epstein–Barr virus (EBV) infection, gastroe- sophageal reflux disease, marijuana use, chronic and excessive use of mouthwash containing alcohol, and poor dental hygiene. Recent increase in incidence in women and younger men may be caused by to an increase in smoking among women, increased teenage smoking, in- creased use of marijuana by young people during the past three decades, or other unidentified genetic or environ- mental risks.
The geographic distribution of HNSCC is universal.
There are, however, geographic patterns that are peculiar to particular subsites of the head and neck (1). There is a
particularly high incidence of oral cavity tumors on the Indian subcontinent and adjacent regions, thought to be caused by dietary preference for highly spiced foods and the cultural acceptance of betel nut chewing. There is a high incidence of nasopharyngeal carcinoma in Southeast Asia, presumed to result in part from high rates of EBV exposure and infection.
The prognosis for most subsites and stages of HNSCC has remained unchanged over the past 40 years. Organ- sparing techniques utilizing chemotherapy and radiation have gained increased acceptance as therapeutic ap- proaches and are considered to be comparable secondary alternatives to surgery with postoperative radiotherapy for most subsites. An exception to this is carcinoma of the larynx, where an organ-sparing approach is preferred as first-line therapy at most cancer centers (2–4). Taxane de- rivatives may, in combination with platinum-based therapy, offer improvement in the organ-sparing treat- ment approach. Other treatments that have recently gained prominence are concomitant chemotherapy and radiation (chemoradiation), intraarterial chemotherapy, reirradiation, implant irradiation (brachytherapy), stereo- tactic radiosurgery, and photodynamic therapy with pho- tosensitizers. Antibody-directed therapy toward the epithelial growth factor receptor (EGFR) shows promise as an adjuvant biotherapy. Advanced reconstructive tech- niques, including microvascular free tissue reconstruc- tion, have not changed survival of patients with HNSCC, but have improved the quality of postoperative life for these patients treated by large ablative surgeries (5).
Anatomy
It is important that the interpreting physician reporting the findings of a positron emission tomography (PET) or a combined PET/computed tomography (CT) study know the complex head and neck anatomy and be familiar with the major anatomic sites and subsites. The nomenclature
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PET and PET/CT Imaging in Head and Neck Cancer
Val J. Lowe, Brendan C. Stack, Jr., and Trond V. Bogsrud
familiar to the head and neck surgeons should be used in the reports. Head and neck primary tumors are anatomi- cally divided into in four major groups or levels based on anatomic sites (5–7). Each anatomic major site has a number of subsites. The four major sites and their sub- sites are shown in Figure 8.1):
1. Nasal cavity and paranasal sinuses.
2. Lip and oral cavity including the tongue anterior to the circumvalate papillae: mucosal lip (from the vermilion boarder of the lip), buccal mucosa, upper and lower alveolar ridges, retromolar gingiva, floor of the mouth, hard palate, oral tongue (tongue anterior to the cir- cumvalate papillae).
3. Pharynx: Nasopharynx, parapharyngeal sites, orophar- ynx (soft palate including uvula, tonsils, base of tongue, pharyngeal walls), hypopharynx or laryn- gopharynx (pyriform sinus, postcricoid area, posterior hypopharyngeal wall).
4. Larynx: Supraglottic (suprahyoid epiglottis with both lingual and laryngeal epiglottic surfaces, aryepiglottic folds, arytenoid cartilages, the false vocal cords and the ventricles), glottis (the true vocal cords and the ante- rior and posterior commissures), and subglottis (from below the true vocal cords to the inferior margin of the cricoid).
The status of the regional lymph nodes in head and neck cancer has great prognostic importance and must be assessed in detail in each patient (5–7). According to the American Joint Committee on Cancer (AJCC), the Union International Contre le Cancer (UICC), and the American Academy of Otolaryngology-Head and Neck Surgery
(AAO-HNS), the lymph nodes are classified into specific groups based on anatomic location (Table 8.1, Figure 8.2) (6–8).
PET Imaging Technique in Head and Neck Cancer
PET imaging of head and neck cancer depends on the in- creased glucose metabolism of neoplasms, which was first described in the 1930s (9). Most PET imaging in head and neck cancer has been performed with
18F-2-deoxy-
D- glucose (FDG), which takes advantage of the increased anaerobic glucose metabolism of these malignancies.
Squamous cell carcinoma (SCC) primary tumors as well as metastases of the head and neck, lung, and esophagus demonstrate especially avid FDG uptake. Other PET
Figure 8.1. Anatomic sites and subsites of the head and neck. (1) Nasal cavity. (2) Oral cavity. (3a) Nasopharynx. (3b) Oropharynx. (3c) Hypopharynx (laryngopharynx). (4) Larynx.
Table 8.1. Classification of cervical lymph nodes into anatomic subsites and levels as recommended by American Joint Committee on Cancer (AJCC), the Union International Contre le Cancer (UICC), and the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS).
Level Lymph nodes Radiologic landmarks
I Submental Above hyoid bone, anterior to posterior edge of Submandibular submandibular gland, superficial to mylohyoid
muscle, between the anterior and posterior belly of the digastric muscle.
II Upper jugular Extending from the base of the skull to the inferior aspect of the hyoid bone (level II as long as you can see hyoid bone), between the posterior edge of the submandibular gland and the posterior border of sternocleidomastoid muscle.
III Midjugular Extending from just below the hyoid bone to the inferior aspect of the cricoid cartilage, between the posterior border of sternocleidomastoid muscle and the sternohyoid muscles.
IV Lower jugular Extending from below cricoid cartilage to the clavicle, between posterior border of sternocleidomastoid muscle and posterior to sternohyoid muscle.a
V Posterior triangle Extending from base of skull to clavicle, between anterior border of trapezius and posterior border of sternocleidomastoid muscle.
VI Central Extending from the hyoid bone to the suprasternal compartment notch, between the medial border of the carotid (prelaryngeal sheet/anterior border of sternohyoid muscle.
or Delphian, pretracheal and paratracheal nodes)
Supraclavi- Supraclavicular At or caudal to the clavicle, above and medial to cular the ribs lateral to the lower jugular chain.
aSternohyoid muscle origin from manubrium of sternum and medial end of clavicle and inserts at the body of the hyoid bone.
Source: Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Sixth Edition (2002), published by Springer-Verlag New York, www.springeronline.com.
tracers such as
11C-methionine,
11C-thymidine, and
18F-
L- thymidine (FLT) have also been used to evaluate head and neck neoplasms but to a lesser extent. These tracers depend on abnormalities in protein or nucleic acid syn- thesis in tumor cells (10–15).
FDG imaging is performed in the fasting state (4 h or more since last meal) to reduce blood sugar and insulin level to minimize FDG uptake in skeletal and cardiac muscle. The patients can be encouraged to have a high- protein/restricted-carbohydrate meal the evening before the study. Tube feeding is stopped 6 h and nutritional supplementation stopped 8 h before injection of FDG. In poorly controlled diabetic patients, high muscle uptake can present diagnostic problems and FDG accumulation in tumors can be decreased. Torizuka et al. (16) showed that FDG uptake of untreated primary lung tumors was significantly reduced in diabetic patients with hyper- glycemia, as compared to nondiabetic patients with nor- moglycemia. In addition, tumor/blood and tumor/muscle uptake ratios were significantly decreased. Blood glucose level should be checked before FDG injection and patients with whole blood values (plasma = whole blood × 1.12) greater than 150 to 200 dL/mg (8.3–11.1 mmol/L) should be rescheduled for imaging when their blood glucose value is under control. Diabetic patients should take their diabetic control medication and have a morning meal at least 4 h before their appointment time.
Tumor uptake of FDG continues to increase even up to 2.5 h after injection, so that standardizing the delay between injection and imaging is important. FDG emis-
sion scans should be performed at least 60 min after the intravenous administration of FDG. Improved target-to- background ratios can be obtained by waiting longer, and if patients can wait longer than 60 min without discomfort, there may be an advantage in waiting up to 90 min or more to perform the emission imaging (17–22).
Imaging should include at least the regions extending from the maxillary sinuses to the upper abdomen.
Emission images should be corrected for attenuation using measured attenuation correction when performing head and neck imaging. The acute curvatures around the mouth, nose, mandible, and neck result in severe edge ar- tifacts in non-attenuation-corrected PET images and therefore should not be used in diagnosis. Neck lymph nodes can lie near the skin surface, and edge artifacts re- sulting from noncorrected imaging can hamper their identification. The anatomic relationships of the airways and bony structures to the soft tissue can also be more re- liably assessed when an attenuation map is available for comparison to the corrected emission image. However, combined PET/CT or PET fused with diagnostic CT is optimal, and this combination results in improved specificity and is more accurate than PET alone (23).
Utilization of semiquantitative data analysis with stan- dardized uptake value (SUV) calculation may also be helpful in identifying abnormal uptake, and this can only be performed when attenuation correction is used.
Imaging of distant body regions should also be included to exclude distant metastatic disease.
Normal FDG Uptake, Variants, and Pitfalls
Interpretation of PET images of the head and neck region presents particular challenges. The region shows substan- tial variations in normal uptake that can present difficulties in the identification of pathology (Figure 8.1).
Uptake in the abundant lymphoid tissue in the pharynx, forming the Waldeyer’s ring (pharyngeal tonsil, palatine tonsils, lingual tonsillar tissue and lymphoid tissue along salpingopharyngeal folds), is easily recognized. Some asymmetry of the pharyngeal and palatine tonsils is not uncommon; however, especially when looking for a SCC with an unknown primary, an asymmetry should be noted as a possible site for the primary malignancy. A “V”- shaped high-uptake area in the floor of the mouth along the medial borders of the mandible is most likely the sub- lingual glands; however, uptake in the mylohyoid muscle is another possibility. The sublingual gland is a predomi- nant mucous gland, which may explain the consistently much higher uptake compared to the parotid (serous gland) and submandibular glands (mixed serous and mucous) (24).
Figure 8.2. Schematic diagram of the anatomic levels of cervical lymph nodes (see Table 9.2). [Adapted. Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Sixth Edition (2002) published by Springer-Verlag New York, www.springeronline.com.]
Intense uptake of the orbital muscles is common. With a high-resolution system, the individual eye muscles may be identified. On occasion, other muscle uptake can also be seen, most commonly including the sternocleidomas- toid muscles, longus capitis, and longus colli. Scalene muscle uptake is often seen after neck dissection where the sternocleidomastoid muscle has been removed.
Uptake in the intrinsic laryngeal musculature is a common finding and may be rather intense if the patient was talking during uptake of FDG. The typical finding is a symmetrical high uptake at the muscle origin and inser- tion of the arytenoid cartilage and some less-intense uptake along the course of the thyroarytenoid and vocalis muscle (Figure 8.3). Especially after unilateral surgery and radiation therapy, the cervical muscle uptake may be re- markably asymmetrical. The lower neck images some- times demonstrate uptake only at the origin of the neck muscles, which can be confused with bilateral supraclavic- ular lymph node disease. The muscle uptake is, however, usually symmetrical and linear, and palpation demon- strates no nodes of sufficient size to account the amount of uptake seen on the scan. More rarely, temporalis, ptery- goid, masseter, or other head and neck muscles accumu- late tracer, sometimes depending on specific use by the patient, so that obtaining a history of physical activity or intense chewing may be helpful. Taking steps to reduce or eliminate muscle uptake can be crucial to correct image interpretation. Ensuring that the patient is not chewing gum, chewing tobacco, reading, or talking during the
uptake phase is important. Also, some have advocated the use of a benzodiazepine drug to suppress muscle uptake.
This step appears to be effective but deserves a note of caution because head and neck cancer patients may have existing compromise of the airway. Attention to the posi- tion of the head during the uptake phase is of prime im- portance. Experimenting with chair design and pillow placement to ensure slight head flexion and complete head relaxation is necessary to avoid unnecessary muscle uptake interference. Also, with three-dimensional (3D) surface projections of PET images and careful examina- tion of all three orthogonal views, most muscle uptake can be differentiated from disease by its anatomic pattern of distribution. PET/CT or PET fused with a diagnostic CT is of great help to differentiate between physiologic muscle uptake and pathologic uptake in tumor or metastatic lymph nodes; this should not, however, replace appropri- ate patient preparation. If no combined PET/CT or a program for fusion of diagnostic CT and PET is available, CT and/or magnetic resonance imaging (MRI) images should be present for side-by-side comparison.
The cervical and upper thoracic spinal cord frequently shows mild uptake, gradually decreasing in caudal direc- tion. Brown fat uptake is typically patchy, symmetrical, and may be very intense (Figure 8.4). Brown fat uptake is commonly located in the neck, supraclavicular, suboccipi- tal, and paraspinal regions in the neck and chest and may also be located on scattered areas perivascular in the me- diastinum. Brown fat, hypermetabolic tumor, and
Figure 8.3. Transaxial fused PET/CT (right column) and PET (left column) of the neck at the level of glottis showing physiologic high uptake of the internal laryngeal muscles.
metastatic lymph nodes may coexist, and a differentiation may be difficult without PET/CT. Repeat imaging, making sure that the patient is warm and comfortable during in- jection and uptake, may be needed to resolve the issue.
We typically use warm blankets and keep uptake rooms
warm to prevent muscle uptake as much as possible (Figure 8.4). Benzodiazepine can be used as an extra measure to reduce fat uptake for repeated scans when necessary.
Degenerative joint disease in the cervical spine is very common and must not be mistaken for hypermetabolic
c
d
Figure 8.4. Brown fat uptake of a patient. (a) Coronal fused PET/CT showing extensive distribution of hyper- metabolic brown fat. (b) Coronal PET with hypermetabolic brown fat com- pared with repeat study (c) when the patient was warmed 12 h before and comfortable during injection and uptake.
(d) Left row, PET (cranial to caudal);
middle column, CT; right column, fused PET/CT.
lymph nodes (Figure 8.5). Again, PET/CT or fusion of PET and a diagnostic CT is very useful. Degenerative joint disease uptake can be bilateral and asymmetrical, and FDG uptake may be very intense,
Maxillary sinusitis is common. Increased uptake along the bony lining of the sinus is a typical finding consistent with inflammatory sinusitis (Figure 8.6). Diffuse thyroid uptake is consistent with chronic thyroiditis and may be very intense in Hashimoto’s thyroiditis. A hypermetabolic nodule in the thyroid gland as an incidental finding occurs in about 1% of oncologic patients and is associated
with malignant primary or secondary thyroid cancer in as many as 47% of the cases (25–27).
Staging Head and Neck Cancer
Accurate anatomic staging is the single most important factor in patient assessment, treatment planning, and de- termination of prognosis (5, 28, 29). Standardized disease classification facilitates the exchange of clinical informa- tion and research results among different treatment
ab
c
d
Figure 8.5. (a) Transaxial CT (top) and fused PET (bottom) show intense hyper- metabolic foci in right cervical inter- vertebral joint. A slight misalignment between PET and CT is common. (b) The bony changes corresponding to the hypermetabolic foci is seen on CT a slice lower than on the fused images (c, d).
Figure 8.6. Typical finding on FDG-PET of maxillary sinusitis (left) and recurrent maxillary squamous cell carcinoma (SCC) (on CT changes from surgery and radiation).
centers and scientists. In general, staging groups from 0 to IV are used. Carcinoma in situ is categorized as 0, whereas a patient with advanced local disease and/or with distant metastases is categorized as stage IV. Staging is based on the anatomic TNM classification. The TNM classification of a tumor describes the anatomic extent of the disease based on clinical information including imaging and biopsies if available. The TNM classification and group staging for head and neck cancers are listed in Table 8.2. When the classification is based on additional information from pathologic examination (e.g., after surgery), the prefix “p” is used (e.g., pTNM) (5, 6). The current classification and staging guidelines in use for HNSCC are defined in the 2002 manual of the American
Joint Committee on Cancer (5, 6). Staging involves an ac- curate assessment of the anatomic extent of the primary tumor (T classification), regional lymphatic metastases (N classification), and distant metastases (M classification)
Table 8.2. TNM classification and group staging for head and neck cancers.
Table 8.2.1. T classification of lip and oral carcinomas.
T1 Tumor 2 cm or less in greatest dimension
T2 Tumor more than 2 cm but not more than 4 cm in greatest dimension
T3 Tumor more than 4 cm in greatest dimension
T4 (lip) Tumor invades through cortical bone, inferior alveolar nerve, floor of mouth, or skin of face, i.e., chin or nose
T4a (oral cavity) Tumor invades adjacent structures (e.g., through cortical bone, into deep [extrinsic] muscle of tongue [genioglossus, hyoglossus, hyoglossus, palatoglossus, and styloglossus], maxillary sinus, skin of face)
T4b (oral cavity) Tumor invades masticator space, pterygoid plates, or skull base and/or encases carotid artery
Table 8.2.2. T classification of nasopharynx cancer.
T1 Tumor confined to the nasopharynx T2 Tumor extends to soft tissues
T2a Tumor extends to the oropharynx and/or nasal cavity without parapharyngeal extensiona
T2b Any tumor with parapharyngeal extensiona
T3 Tumor involves bony structures and/or paranasal sinuses T4 Tumor with intracranial extension and/or involvement of
cranial nerves, infratemporal fossa, hypopharynx, orbit, or masticator space
aParapharyngeal extension denotes posterolateral infiltration of tumor beyond the pharyngobasilar fascia.
Table 8.2.3. T classification of oropharynx cancer.
T1 Tumor 2 cm or less in greatest dimension
T2 Tumor more than 2 cm but no more than 4 cm in greatest dimension
T3 Tumor more than 4 cm in greatest dimension
T4a Tumor invades the larynx, deep/extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible
T4b Tumor invades lateral pterygoid muscle, pterygoid plates;lateral nasopharynx, or skull base or encases carotid artery
Table 8.2.4. T classification of hypopharynx cancer.
T1 Tumor limited to one subsite of hypopharynx and 2 cm or less in greatest dimension
T2 Tumor invades more than one subsite of hypopharynx or an adjacent site, or measures more than 2 cm but not more than 4 cm in greatest diameter without fixation of hemilarynx T3 Tumor more than 4 cm in greatest dimension or with fixation of
hemilarynx
T4a Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, esophagus, or central compartment soft tissuea T4b Tumor invades prevertebral fascia, encases carotid artery, or
involves mediastinal structures
aCentral compartment soft tissue includes prelaryngeal strap muscles and subcutaneous fat.
Table 8.2.5. T classification of laryngeal supraglottic cancer.
T1 Tumor limited to one subsite of supraglottic with normal vocal cord mobility
T2 Tumor invades mucosa of more than one adjacent subsite of supraglottic or glottis or region outside the supraglottic (e.g., mucus of base of tongue, vallecula, medial wall of pyriform sinus) without fixation of the larynx
T3 Tumor limited to larynx with vocal cord fixation and/or invades any of the following: postcricoid area, pre-epiglottic tissues, paraglottic space, and/or minor thyroid cartilage erosions (e.g., inner cortex)
T4a Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus)
T4b Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures
Table 8.2.6. T classification of laryngeal glottic cancer.
T1 Tumor limited to the vocal cord(s) (may involve anterior or posterior commissures) with normal mobility
T1a Tumor limited to one vocal cord T1b Tumor involves both vocal cords
T2 Tumor extends to supraglottic and/or subglottis, and/or with impaired vocal cord mobility
T3 Tumor limited to larynx with vocal cord fixation and/or invades paraglottic space, and or minor thyroid cartilage erosions (e.g., inner cortex)
T4a Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus)
T4b Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures
Table 8.2.7. T classification of laryngeal subglottic cancer.
T1 Tumor limited to the subglottis
T2 Tumor extends to vocal cord(s) with normal or impaired vocal cord mobility
T3 Tumor limited to larynx with vocal cord fixation T4a Tumor invades cricoid or thyroid cartilage and/or invades
tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus)
T4b Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures
Table 8.2.8. T classification of maxillary sinus.
T1 Tumor limited to maxillary sinus with no erosion or destruction of bone
T2 Tumor causing bone erosion or destruction including extension into the hard palate and/or middle nasal meatus, except extension to posterior wall of maxillary sinus and pterygoid plates
T3 Tumor invades any of the following: bone of the posterior wall of maxillary sinus, subcutaneous tissues, floor or medial wall of orbit, pterygoid fossa, ethmoid sinuses
T4a Tumor invades anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses
T4b Tumor invades any of the following: orbital apex, dura, brain, middle cranial fossa, cranial nerves other than V2, nasopharynx, or clivus
Table 8.2.9. T classification of nasal cavity and ethmoid sinus.
T1 Tumor restricted to any one subsite, with or without bony invasion
T2 Tumor invading two subsites in a single region or extending to involve an adjacent region within the nasoethmoidal complex, with or without bony invasion
T3 Tumor extends to invade the medial wall or floor of the orbit, maxillary sinus, palate, or cribriform plate
T4a Tumor invades any of the following: anterior orbital contents, skin of nose or cheek, minimal extension to anterior cranial fossa, pterygoid plates, sphenoid or frontal sinuses T4b Tumor invades any of the following: orbital apex, dura, brain,
middle cranial fossa, cranial nerves other than V2, nasopharynx, or clivus
Table 8.2.10. T classification of nasal cavity and ethmoid sinus.
T1 Tumor 2 cm or less in greatest dimension without extraparenchymal extension*
T2 Tumor more than 2 cm but no more than 4 cm in greatest dimensions without extraparenchymal extension*
T3 Tumor more than 4 cm and/or having extraparenchymal extension*
T4a Tumor invades skin, mandible ear canal, and/or facial nerve T4b Tumor invades skull base and/or pterygoid plates and/or
encase carotid artery
*Note: Extraparenchymal extension is clinical or macroscopic evidence of invasion of soft tissues. Microscopic evidence alone does not constitute extraparenchymal extension for classification purposes.
Table 8.2.11. The nodal classification for all head and neck cancers, except nasopharynx.
NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis
N1 Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension
N2 Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension
N2a Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension
N2b Metastasis in multiple ipsilateral lymph node, none more than 6 cm in greatest dimension
N2c Metastasis in bilateral or contralateral lymph node, none more than 6 cm in greatest dimension
N3 Metastasis in a lymph node more than 6 cm in greatest dimension
Table 8.2.12. The nodal classification of nasopharynx cancer.
NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis
N1 Unilateral metastasis in a lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa*
N2 Bilateral metastasis in lymph node(s), 6 cm or less in greatest dimension;
N3 Metastasis in a lymph node(s), greater than 6 cm and/or to supraclavicular fossa
N3a Greater than 6 cm in dimension N2b Extension to the supraclavicular fossa
*Note: Midline nodes are considered ipsilateral nodes.
Table 8.2.13. Distant metastasis (M) for all head and neck cancers.
MX Distant metastasis cannot be assessed M0 No distant metastasis
M1 Distant metastasis
Table 8.2.14. Stage grouping of all head and neck cancers, except nasopharynx.
Stage 0 Tis N0 M0
Stage I T1 N0 M0
Stage II T2 N0 M0
Stage III T3 N0 M0
T1 N1 M0
T2 N1 M0
T3 N1 M0
Stage IVA T4a N0 M0
T4a N1 M0
T1 N2 M0
T2 N2 M0
T3 N2 M0
T4a N2 M0
Stage IVB T4b Any N M0
Any T N3 M0
(Figure 8.7). For all head and neck cancers, TX is defined as primary tumor cannot be assessed; T0, no evidence of primary tumor; Tis, carcinoma in situ; MX, distant metas- tasis cannot be assessed; M0, no distant metastasis; and M1, distant metastasis. The most common sites for distant
metastasis are in the lungs, whereas bone, liver, and brain metastases occur less often. Mediastinal lymph node metastasis is classified as distant metastasis. Nodal (N) classification for all head and neck cancers is uniform except for nasopharynx cancer. The distribution and the prognostic impact of regional lymph node spread from nasopharynx cancer, particularly of the undifferentiated type, are different from those of other head and neck mucosal cancers and justify use of a different N classification. The group staging for all head and neck cancers is also uniform, again except for nasopharynx cancer: stage IVA is advanced resectable cancer, stage IVB is advanced unresectable, and stage IVC is advanced with distant metastases. The initial staging is based on all in- formation available before treatment, including physical examination, diagnostic imaging [CT, MRI, ultrasound (US), nuclear medicine procedures including PET], fine- needle aspiration (FNA) biopsy, and result of surgical ex- ploration if performed. The staging is important for selection of appropriate treatment and follow-up strategies and to facilitate the exchange of information between clini- cians and scientists. The likelihood of local and regional spread varies with the site of the primary tumor and this must be appreciated when evaluating HNSCC patients. In additional to staging, a tumor will have a histologic grade.
SCC are graded by histologic into well-differentiated (Grade I), moderately well differentiated (Grade II), or poorly differentiated to undifferentiated (Grade III) based on the amount of keratinization (5, 6).
Evaluation of the patient begins at the first consultation with a physical examination, which includes direct visual- ization of the primary tumor, either through the mouth or nose or by using outpatient endoscopy. Next, the neck is
Table 8.2.15. Stage grouping of nasopharynx cancer.
Stage 0 Tis N0 M0
Stage I T1 N0 M0
Stage IIA T2a N0 M0
Stage IIB T1 N1 M0
T2 N1 M0
T2a N1 M0
T2b N0 M0
T2b N1 M0
Stage III T1 N2 M0
T2a N2 M0
T2b N2 M0
T3 N0 M0
T3 N1 M0
T3 N2 M0
Stage IVA T4 N0 M0
T4 N1 M0
T4 N2 M0
Stage IVB Any T N3 M0
Stage IVC Any T Any N M1
Source: The data presented in Table 8.2 are used with permission of the American Joint Committee on Cancer (AJCC), Chicago, IL. From Greene FL, Page DL, Fleming ID, Fritz AG, Balch CM, Haller DG, Morrow M, editors. AJCC Cancer Staging Handbook, Sixth Edition. New York: Springer-Verlag 2002:27–87.
a b
d
c
e Figure 8.7. Eighty-five-year-old man
with stage IVC SCC left tonsillar cancer.
(a) Intense uptake in the primary tumor and in an upper posterior triangle metastatic lymph node (level V). (b) Intense uptake in the large primary tumor and in a conglomerate of upper jugular nodes metastasis (level II). (c) Intense uptake in a conglomerate of midjugular (between os hyoid and cricoid cartilage) (level III) and supraclav- icular metastatic lymph nodes (neck flexed). (d) Hypermetabolic precarinal lymph node and (e) osseous metastasis in the right iliac bone.
palpated to determine the presence of cervical lymph node enlargement. Lymph nodes less than 1 cm in diame- ter cannot be reliably appreciated on physical examina- tion. Body habitus, such as obesity or short neck, may make this assessment more difficult. Next, a histologic di- agnosis must be obtained by direct biopsy of the tumor (often by use of endoscopy under general anesthesia), by needle biopsy of a neck mass, and/or the tumor must be assessed by anatomic imaging, particularly if it is not visible, palpable, or accessible to biopsy (5).
The most commonly used imaging modality for HNSCC is CT with intravenous injection of iodinated con- trast material. MRI is being increasingly used (30). MRI is better in differentiating soft tissues, but longer imaging time results in imaging artifacts from patient motion (e.g., swallowing and breathing). Metal artifacts are a lesser problem with MRI than with CT. Lymph nodes more than 1 cm in diameter (1.5 cm for jugulodigastric nodes) or showing central necrosis are considered abnormal and suspicious for metastasis. The shortcoming to this anatomic approach to diagnosis is that it excludes the possibility of detecting early nodal metastases that have not caused enlargement of the lymph node. Ultrasound is shown to be superior to CT and MRI in evaluating cervical
lymph nodes, and US-guided fine-needle biopsy (FNAB) is shown to be superior to palpation-guided FNAB (30, 31). PET is a standard approach in many centers.
Distant metastases are unusual in a patient presenting with HNSCC, but hematogenous metastases are found in 20% to 40% during the course of the disease; this is an in- creasingly occurring phenomenon in the organ-sparing chemoradiation treatment era for HNSCC. The majority of the patients with distant metastases also have uncontrolled regional disease in the neck. The most common site for distant metastasis is the lungs, mediastinum, bone, and liver (Figure 8.7). Mediastinal lymph node metastases are considered distant metastases (5, 6). Standard assessment includes CT of the chest and abdomen.
Primary tumor at a second site, either synchronous or metachronous, is not an unusual finding in HNSCC (Figure 8.8). Synchronous tumors are defined as tumors that are diagnosed within 6 months of each other, and metachronous tumors are tumors that are diagnosed with an interval of more than 6 months. As many as 20% of pa- tients with HNSCC develop a secondary SCC malignancy (5). These lesions are usually situated in the head and neck, lung, or esophagus. The standard approach to ruling out synchronous primary tumors in HNSSC has been
a
b
c
Figure 8.8. Transaxial PET/CT (PET, left;
fused PET/CT, right) of a patient with a large pharyngeal SCC (a) shows a large, intensely hypermetabolic mass in the left soft palate with extension across midline into the right soft palate and two left and one right upper jugular (level II) metastatic lymph nodes. The tumor extends inferiorly (b) along the lateral aspect of the oropharynx, and at this level two right and one left upper jugular (level II) and one left submental (level I) metastatic lymph nodes are shown. A separate focus of hypermetabolic activity (c) is present in the left pyriform fossa with extension into the left aryepiglottic fold, representing a synchronous foci of SCC.
operative endoscopy (laryngoscopy, bronchoscopy, esophagoscopy), but improved techniques of outpatient endoscopy and CT imaging of the neck and chest have re- sulted in a decreased use of the operative approach. The greater accuracy of whole-body PET imaging has proved to be useful for detection of synchronous tumors and for surveillance for metachronous lesions.
Head and neck primary tumor location or subsite is a strong predictor for cervical metastases (Table 8.1). In many cases, failure to adequately treat the regional lym- phatics will result in regional recurrence, which is the major cause of morbidity and mortality in these patients.
Knowledge of the pattern of lymphatic metastasis for each tumor subsite is necessary to avoid undertreating HNSCC.
For example, carcinoma of the supraglottic larynx has a high probability of metastasis to bilateral neck lymph nodes, even when only unilateral lymphadenopathy is de- tected by palpation or imaging. The true vocal cords are almost devoid of lymphatic drainage, and vocal cord tumors spread to regional lymph nodes late in the course of disease (4, 6, 7). Tumors in the oral cavity have a 30%
prevalence of metastasis to regional lymph nodes at the time of presentation, but these often escape detection by palpation or CT. Nasopharyngeal tumors have a high probability of bilateral metastasis and metastasis to the posterior triangles of the neck. Laryngeal tumors, pre- sumably because of a paucity of lymphatic drainage and other anatomic barriers to tumor spread, have a lower likelihood of nodal involvement, even when presenting at an advanced local stage.
Following adequate staging of the tumor, a treatment plan is formulated. Usually, the primary tumor is surgi- cally removed, unless an organ-sparing approach has been selected. In conjunction with tumor removal, the primary site is reconstructed and the regional lymphatics are removed. If the neck is classified as N0 or N1, neck dissection and radiation are considered to be equally ef- fective for treatment. The advantage of surgical neck dis- section as treatment for the N0 neck is that a pathologic confirmation of the presence or absence of nodal metas- tases is determined. With primary irradiation of the neck, there is no pathologic diagnosis of metastatic disease. N2 disease is usually treated surgically either before or after chemoradiation. N3 disease almost always requires radical neck exploration.
The standard treatment for advanced head and neck cancer (stage III and IV) is surgery followed by postopera- tive radiation therapy (5, 32, 33), which may result in long-term morbidity and disfigurement. In an effort to di- minish morbidity, organ preservation has been achieved by means of induction chemotherapy and radiation therapy, with surgical salvage if these are unsuccessful in eradicating the tumor. Despite this approach, patient sur- vival has remained constant (3). Accordingly, disagree- ment remains over selection of advanced-stage head and neck tumors for treatment by standard surgical resection or by attempted curative chemotherapy. Chemotherapy or
radiation may be used alone to avoid the more-morbid surgical procedures such as laryngectomy, whereas partial glossectomy may be preferred to chemotherapy. A finding by PET of more-extensive disease than was suspected from the results of conventional procedures may provide a greater impetus to treat with chemotherapy rather than surgery because of its morbidity.
Primary Tumor Evaluation by PET
Evaluation of the anatomic extent of the primary tumor (T classification) using PET has been described in several pub- lished studies (34, 35). PET showed no advantage over con- ventional methods when the primary tumor was detectable by conventional techniques, so that classification of the primary tumor by PET will contribute little in most pa- tients. Conventional tumor staging, using CT imaging and physical examination with endoscopy, provides important anatomic information that is not obtainable by PET.
However, some studies have suggested that a high level of metabolic activity on FDG-PET imaging may be predictive of tumor response to treatment so that the PET result could also become a consideration in treatment selection.
Tumors having high metabolic activity might be consid- ered for more-aggressive multimodal therapy (35–38).
Diagnosis of Unknown Primary Tumor
In approximately 5% of cases, regional nodal metastasis is the presenting feature, and the primary tumor is not identified by standard techniques (8). Some of these primary tumors become apparent as the patient is followed over time, whereas others are thought to regress sponta- neously and most are never diagnosed by conventional means. The most common sites for occult primary tumor are the pyriform sinuses, the palatine tonsils, base of the tongue, and nasopharynx. The site of a lymph node metas- tasis may give a clue to where the primary tumor might be.
A metastatic node in the jugulodigastric area may indicate a primary tumor in the oropharynx, and a metastatic node in the posterior triangle may indicate a primary site in the nasopharynx. Following negative conventional evaluations, PET has identified the unknown primary tumor in 20% to 50% of cases, as reported by several groups (28, 39–47).
Regional Nodal Staging by PET
Many investigators have described the high sensitivity
and specificity of FDG-PET imaging in regional nodal
staging of head and neck cancer (34, 35, 48–56). All
studies have shown PET to be equivalent or superior to all
anatomic methods of imaging. In a study by Adams et al.,
1,400 lymph nodes were sampled in 60 patients and PET
had a 10% advantage in sensitivity and specificity over
CT, MRI, or US. The differences in accuracy between PET and anatomic imaging were found to be highly significant on statistical evaluation (48).
PET may be particularly valuable in deciding whether to perform neck dissection on patients with low-stage tumors where there is no clinical evidence of nodal spread (N0).
Myers and Wax showed that PET was more than twice as sensitive as CT for identifying regional nodal metastasis on patients with clinical N0 findings in the neck (57). When PET is added to conventional imaging, patient manage- ment is changed in 8% to 15% of the patients (58–60).
Hollenbeak et al. showed that adding a FDG-PET study in a patient classified as N0 by CT is cost effective (61).
Distant Staging by PET
Metastasis to distant regions is less common in HNSCC that in other malignant tumors, which could result from earlier detection of HNSCC due to clear-cut presenting symptoms. Because of the low prevalence of distant metastasis at initial diagnosis of HNSCC (less than 5%), PET is unlikely to identify distant disease in a clinically significant fraction of these patients.
Distant metastasis is seen more commonly in patients who have advanced-stage tumor than in patients with early-stage disease. Teknos et al. used PET to evaluate 12 patients with a new diagnosis of stage III or IV head and neck cancer (62). Two patients had true-positive mediasti- nal PET findings, with no evidence of mediastinal metas- tasis on CT. A third patient was found to have pulmonary metastasis on both CT and PET.
Whole-body PET imaging, orbits through the pelvis, is recommended as part of initial staging in all patients with head and neck cancer because such imaging may be im- portant for diagnosis of synchronous or metachronous primary tumors and could reduce the need for other addi- tional testing. Whole-body imaging may also be valuable to obtain a baseline evaluation for comparison with later scans. Subtle abnormalities resulting from chronic inflam- matory lung lesions, for example, can be documented.
Evaluation of Therapy of Head and Neck Cancer
Conventional Evaluation
Findings obtained by conventional imaging are particu- larly difficult to interpret after surgery, chemotherapy, and radiation therapy, and PET has a major potential role in evaluating tumor response to treatment. Tissue changes produced by chemotherapy or radiation, such as fibrosis, edema, and hyperemia, are frequently difficult to
differentiate from residual viable tumor by physical exami- nation or anatomic imaging. CT, MRI, and US imaging have limited ability to determine the benign or malignant nature of posttreatment changes, which include variable contrast enhancement and soft tissue distortion, that are seen following irradiation and chemotherapy. Also, changes in tumor size usually lag behind the metabolic effects of therapy, which determine tumor viability.
Because FDG-PET is a metabolic imaging method, resid- ual tumor may be diagnosed or excluded by persistence of high metabolic activity where there is no visible anatomic abnormality, or absence of high metabolic activity in the presence of persistent anatomic abnormality, respectively.
PET evaluation of nonsurgical treatment results is opti- mized when a baseline scan is available for comparison.
PET Imaging in Therapy Evaluation
FDG-PET identifies changes in tumor metabolism that occur during therapy. The posttherapy findings that are obtained by FDG-PET depend on the treatment modality used. Radiation therapy may induce an early acute inflam- matory reaction, associated with dense inflammatory infiltration and resulting increase in FDG uptake, that may be difficult to differentiate from tumor hypermetabolism (63). Highly cellular infiltrates containing large numbers of macrophages and fibroblasts, associated with high FDG activity, have been described following high-dose intracav- itary therapy of brain tumors using radioactively labeled antitumor antibodies (64). Such uptake has also been seen following external irradiation of other tumors.
Increased FDG uptake may be seen in soft tissue regions that have been recently irradiated and appears to be more intense in tissues that receive the highest radia- tion dose. On the other hand, some normal deep struc- tures may not show these radiation-related changes in metabolism (65). When such increase in FDG accumula- tion occurs in irradiated regions, it may remain apparent for as long as 12 to 16 months after treatment or more (66). The SUV of radiation-related uptake in normal tissues is generally less than the SUV values that are usually found in recurrent tumor, but overlap in FDG uptake may be seen and can lead to diagnostic confusion.
Rege et al. found no change in uptake in adenoids, lingual and palatine tonsils, parotid, submandibular, and sublin- gual glands, nasal turbinates, soft palate, and gingiva 6 weeks or more after radiation therapy when these regions were included in the radiation field (65). Increased uptake following surgery including tissue inflammation and scar- ring may last for 4 months or longer.
Following treatment by chemotherapy, FDG hyperme-
tabolism associated with inflammation does not present a
comparable problem. Decrease in tumor uptake of FDG
may be seen within days of commencing treatment, and
uptake may diminish to normal tissue levels within 1 week
(67). Lowe et al. (68) compared the accuracy of FDG-PET to needle biopsy following chemotherapy/radiation as part of organ-sparing primary treatment of HNSCC in a prospective study. They found PET sensitivity for detec- tion of residual tumor to be 90% (19/21), which was equal to the sensitivity of biopsy of the tumor region. When biopsy was repeated using FDG-PET guidance, biopsy sensitivity increased to 100%. The specificity of PET was 83% (5/6), compared to 100% for biopsy. Greven et al.
(69) compared PET to histologic diagnosis in 31 patients with HNSCC who had been treated by radiation and found PET to have 80% sensitivity and 81% specificity for detection of residual or recurrent tumor.
A positive PET has a high predictive value for recur- rent disease. If the PET scan is positive but the FNAB is negative, we recommend the biopsy be repeated with PET guidance. If the repeated FNAB is negative, de- creased FDG uptake on a follow-up scan indicates unspecific inflammation. A negative PET scan is most likely predictive of a good treatment response. In a prospective study, Yao et al. studied 41 patients with ad- vanced regional head and neck cancer treated with radi- ation therapy or chemoradiation (70). Treatment response was evaluated on FDG-PET and CT. Twelve of the patients had persistent lymphadenopathy on CT, and they all underwent either neck dissection or ultra- sound-guided FNAB. Four of the 12 were found to have viable residual tumor. The finding of residual tumor did not correlate with the size of the involved lymph nodes on neither the preradiation nor the postradiation CT.
The pathology correlated strongly, however, with the postradiation PET study. Patients with a SUV
maxless than 3.0 on postradiation PET were all free from residual disease. They conclude that a negative postradiation therapy FDG-PET is very predictive of negative pathol- ogy in neck dissection or FNAB, even with large residual lymphadenopathy. In a nicely performed study, Goerres et al. (71) calculated disease probability based on data from their own institution and performed a systematic review of available data in the literature up to October 2001 on the accuracy of FDG-PET in primary staging and follow-up of head and neck cancer. They conclude that the main advantage of PET is the ability to reliably rule out the presence of disease in both primary staging and restaging. Rogers et al. (72) conducted a prospective study of 12 patients with stage III and IV cancer. FDG- PET was performed before and 1 month after radiation therapy. All patients underwent planned neck dissec- tion. The presence of a positive PET 1 month after radia- tion therapy accurately indicated the presence of residual disease. However, in 6 of the 7 patients with negative PET, the pathology was positive. In 4 of the 6 patients with positive histology, there was significant necrosis and no comment could be made regarding the viability of the tissue. Further, the resolution of their camera was 8 mm and not quite optimal.
Assessment of Recurrent Head and Neck Cancer
Clinical Considerations and Conventional Evaluation
All HNSCC patients are at high risk for tumor recurrence and second primary tumor in the aerodigestive tract. All the cells of the mucosal lining of the upper aerodigestive tract have been exposed to the same carcinogenic agents, with consequently increased incidence of malignancy at multiple sites. The probability of tumor recurrence is related to specific tumor subsite and to the stage of the tumor at presentation, as already discussed. The patho- logic features of the primary tumor that correlate with in- creased incidence of recurrence include nerve invasion, extracapsular spread in lymph nodes, and positive surgi- cal margins. Persistence of smoking and alcohol con- sumption are ongoing risk factors for development of a second primary tumor.
Most tumor recurrences are diagnosed within the first 24 months following primary therapy for HNSCC. When local recurrences are detected early, they can often be treated by reexcision. Further surgical resection will further compromise any posttreatment dysfunction of speech, voice, swallowing, or airway and will have a nega- tive impact on the patient’s quality of life. Local and re- gional recurrences may occur following surgery, irradiation, or both. Direct carotid artery involvement by tumor may occur and can result in stroke or death from acute arterial hemorrhage. Treatment for local and re- gional tumor recurrence can include reoperation or reir- radiation (external beam or implant) with curative intent, chemotherapy with palliative intent, or supportive mea- sures only.
HNSCC patients require long-term surveillance for re- currence or second primary tumor and can by deemed
“cured” only after 5 years of disease-free follow-up.
Methods of surveillance can include primary physical examination or CT or MR imaging. Indirect or direct en- doscopy is used when physical examination findings or the patient’s symptoms arouse suspicion for recurrent or second primary tumor. FDG-PET has proved to be a powerful posttreatment surveillance tool and is shown to detect tumor at an earlier stage than by other methods.
Anatomic imaging by CT or MRI usually shows post-
treatment abnormalities, and change from previous
imaging findings is the most useful means of detecting re-
current tumor. Chong and Fan compared MRI and CT for
identifying recurrent nasopharyngeal cancer and showed
that both modalities had a sensitivity of approximately
50%, with substantial interobserver variation in image in-
terpretation (k = 0.563) (33).
PET in Detection of Locoregional Recurrence
The superiority of PET to anatomic imaging modalities for identifying local and regional recurrence of head and neck cancer after therapy has been demonstrated in a number of published evaluations (33, 35, 52, 73–80).
Perlow et al. (81) showed, in a small series of patients with advanced HNSCC evaluated for locoregional and/or distant metastases, that FDG-PET found unsuspected re- currences in half their patients. Shu-Hang et al. (82) showed that FDG-PET added significant information to MRI findings in 18 of 37 patients with MRI findings ques- tionable for tumor recurrence. Kunkel el al. (83) studied 97 patients with previously resected HNSCC and found PET to be highly valuable for diagnosing recurrence in a postoperative setting.
Anzai et al. (73) used receiver operating characteristic (ROC) analysis to compare PET and CT/MRI in patients presenting with symptoms suggesting recurrence and no obvious tumor masses. Clearly higher sensitivity and specificity of PET were demonstrated, accompanied by a major difference in area under the ROC curve. When Fischbein et al. (78) used PET in routine surveillance of patients who had completed treatment for head and neck cancer, they found that nearly twice as many recurrences were detected by PET as by regular physical examination and routine CT imaging.
As expected, most additional recurrences that were de- tected by PET only were small, at times requiring repeated attempts at biopsy for confirmation. If an initial biopsy at the site of a PET abnormality is not positive, repeat biopsy or close follow-up should be undertaken. Surgical explo-
ration should be considered with a clear-cut positive PET result because such results are not commonly incorrect.
Currently instrumentation is lacking to help guide sur- geons in the pursuit of these lesions. New device develop- ment may help with this scenario in the future (84).
PET in Detection of Distant Recurrence
Distant recurrences are more common in patients with locally recurrent disease than are distant metastases at initial staging. The lungs are the most common site of distant recurrence but the liver or skeleton may also be involved (5, 85). Before embarking on therapy of locally recurrent disease, whole-body FDG-PET imaging should be performed to exclude distant recurrence so as to avoid the morbidity of attempted curative surgery or radiation in the presence of noncurable distant tumor.
PET and Salivary Glands
About 70% of all salivary neoplasms arise in the parotid gland and about 75% of are benign (24). The most common parotid tumor is pleomorphic adenoma (benign mixed tumor). Other benign parotid tumors are monomorphic adenomas and Warthin’s tumor. Cancer of the salivary glands is relatively rare, accounting for less than 1% of all cancers in the United States.
Mucoepidermoid carcinoma and adenoid cystic carci- noma are the most common. About 50% of the sub- mandibular tumors and almost all the sublingual tumors are malignant. Spread to regional lymph nodes is less
a b
Figure 8.9. Grade 2 (of 4) adenocarci- noma possibly arising in a pleomorphic adenoma left parotid gland in 85-year- old woman with 10-year history of left fascial nerve palsy.
common than for head and neck SCC. Distant spread is most common to the lungs.
Only a few groups have studied the use of
18F-FDG-PET in salivary gland cancers (85–91). Keyes et al. (86) studied 26 patients with parotid masses, finding false-positive scan for malignancy in 8 of 26 (31%), and concluded that FDG-PET was not useful in classifying parotid tumors as benign or malignant. Okamura et al. (88) studied 28 pa- tients with parotid masses. High accumulation of FDG was found in all 5 carcinomas, in all Warthin’s tumors, and in 8 of 12 pleomorphic adenomas, with mean SUV 5.92, 7.03, and 4.07, respectively. Five inflammatory lesions demonstrated only low accumulation of FDG.
Because FDG concentrates in pleomorphic adenoma, the most common tumor in salivary glands, as well as in benign Warthin’s tumor, it is not expected that PET will be useful in differentiation between benign and primary or secondary malignancy in the parotid gland. In fact, a hypermetabolic tumor in the parotid gland is more likely to be benign than malignant (Figure 8.9).
The incidence of lymph node metastases is less common than from HNSCC. Lymphatic spread tends to be orderly, first to intraglandular nodes, followed by peri- parotid and submandibular, then upper and midjugular nodes. Occasionally retropharyngeal nodes are involved, while bilateral spread is rare. Apparently no one has studied the use of PET for nodal staging, but we would expect FDG-PET to be useful for this purpose. We also expect PET to be useful for follow-up and restaging to dif- ferentiate between residual or recurrent tumor from post- treatment fibrosis.
Conclusion
PET imaging can improve the management of head and neck cancer. PET is highly accurate for nodal staging of the head and neck. TNM classification and staging of HNSCC by FDG-PET imaging may lead to more-appropri- ate patient treatment. Patients with more-extensive lo- coregional spread than is demonstrated by anatomic imaging may benefit from bilateral rather than unilateral neck dissection. Earlier detection of recurrence could provide a means of improving survival in recurrent HNSCC. Numerous comparisons of metabolic and anatomic imaging in diagnosis of recurrent tumor have shown higher sensitivity, specificity, and accuracy by PET compared to other imaging modalities. A negative PET scan excludes residual or recurrent disease with high cer- tainty. FDG-PET is especially useful after initial treatment to differentiate residual or recurrent tumor from scar after surgery and postradiation and postchemotherapy changes. PET identifies unknown primary tumor in about 30% of cases. Diagnosis of unknown primary tumors of the head and neck may permit more-localized radiation therapy than irradiation with ports from the maxillary
sinuses to the lower neck, which is commonly undertaken without a primary diagnosis. Occasionally, unnecessary surgery of the head and neck or conjoint head and neck and thoracic procedures with curative intent might be avoided in patients who are found to have distant metas- tasis by PET.
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