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Combined PET-CT in the Head and Neck

Part 2. Diagnostic Uses and Pitfalls of Oncologic Imaging¹

¹ From the Department of Radiology, Allegheny General Hospital, 320 E North Ave, Pittsburgh, PA 15212 (M.B.F.) and the Departments of Radiology (T.M.B., D.W.T., C.C.M.), Otolaryngology (C.H.S., J.J.J., E.N.M.), Psychiatry (C.C.M.), and Neurology (C.C.M.), University of Pittsburgh, Pa. Presented as an education exhibit at the 2001 RSNA Annual Meeting. Received June 28, 2004; revision requested July 22 and received March 11, 2005; accepted March 14. T.M.B. is a consultant for Petnet Pharmaceuticals; D.W.T. is a consultant for CPS Innovations; all remaining authors have no financial relationships to disclose. Address correspondence to M.B.F. (e-mail: mfukui{at}wpahs.org).

	Abstract

Top Abstract Introduction PET-CT Technique Diagnostic Uses: Indications for... Pitfalls: Limitations of PET-CT Conclusions References

 
Positron emission tomography (PET) with 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG) is effective for monitoring head and neck cancer. However, lack of anatomic landmarks, variable physiologic FDG uptake, and asymmetric FDG distribution in the neck can confound image interpretation. This is particularly true in the treated neck, where distortion of normal tissue planes makes detection of early disease recurrence difficult with conventional computed tomography (CT) and magnetic resonance imaging. Combined PET-CT helps prevent the misinterpretation of FDG PET findings in patients with head and neck cancer. Superior localization of FDG uptake with this technique can improve diagnostic accuracy and help avoid interpretative pitfalls. In the future, development of tumor-specific ligands will enhance the usefulness of PET-CT in the detection of initial tumors and tumor recurrence, in the evaluation of tumors with low FDG avidity, and in treatment targeting. Furthermore, improved scanner resolution will help address the limitations of PET-CT with respect to small lesions and may make this modality more valuable in initial tumor staging.

© RSNA, 2005

	Introduction

Top Abstract Introduction PET-CT Technique Diagnostic Uses: Indications for... Pitfalls: Limitations of PET-CT Conclusions References

 
Positron emission tomography (PET) provides a unique opportunity to examine a variety of physiologic functions in vivo and thus provides information that is complementary to that obtained with anatomic imaging techniques such as computed tomography (CT) or magnetic resonance (MR) imaging. A highly sensitive tool for noninvasive imaging of the physiologic features of tissue, PET can be used to measure blood flow and to evaluate metabolic processing and receptor-mediated function. The overwhelming majority of clinical PET studies are performed with 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG).

FDG PET is an effective means of detecting head and neck cancer. PET has both greater sensitivity (86%–100%) and greater specificity (69%–87%) than CT (67%–82% and 25%–56%, respectively) for the detection of both primary tumors and lymph node metastases (1,2); however, limited anatomic localization and variable physiologic uptake reduce the effectiveness of PET in the head and neck region (3–6). Nearby anatomic structures, nonspecific FDG uptake by tissues, and limited spatial resolution make it difficult to localize areas of uptake to the tumor site on a PET scan. In addition, inflammation of head and neck tissues due to mucosal ulceration, associated infection, and treatment-related effects may result in nonspecific FDG uptake.

Although the combination of separately acquired CT and PET scans using retrospective or prospective registration methods (7) is more accurate than CT alone (8), this approach is limited by patient movement and by difficulty in exactly correlating points on CT and PET scans. Computer algorithms for coregistering anatomic and functional images, although successful with anatomically fixed organs such as the brain (9), are less so in the more mobile head and neck, whose position can change between scans with changes in patient position; therefore, the two sets of images cannot be precisely aligned with linear transformation. A stereotactic system could be used for scanning the head and neck to ensure use of the same reference system for the PET and CT scans. Alternatively, an immobilization system could be used to ensure stable positioning for separately acquired PET and CT scans; however, this approach would be cumbersome, in addition to requiring prospective implementation. The most effective solution to the problem of coregistration is to acquire both functional and anatomic images on the same scanner without moving the patient from the scanning table (ie, during a single imaging session). Early experience with scanning suggests that combined PET-CT is superior to PET and CT performed separately in monitoring therapy (10). Minimizing complications of radiation therapy requires that tumor be distinguished from surrounding normal structures, which can be accomplished only with the anatomic detail provided by CT. The coregistration of FDG PET and CT scans on a single device offers the potential for improved detection and localization of head and neck cancer with one imaging tool.

In this article, we review PET-CT technique in our study of over 800 patients with head and neck cancer. We also discuss indications for PET-CT in this patient population, including detection of recurrent thyroid carcinoma or cranial base neoplasm, directing biopsy, detection of the unknown primary tumor site, staging of head and neck cancer, and tumor surveillance. In addition, we discuss various limitations of PET-CT relating to physiologic FDG uptake, inadequate scanner resolution, recent surgery or radiation therapy–chemotherapy, inflammatory tissue, and low FDG avidity, and outline strategies for avoiding misdiagnosis due to these limitations.

	PET-CT Technique

Top Abstract Introduction PET-CT Technique Diagnostic Uses: Indications for... Pitfalls: Limitations of PET-CT Conclusions References

 
Combined PET-CT was performed on three tomographs: (a) a prototype device consisting of an ECAT ART PET scanner (CTI, Knoxville, Tenn) and a Somatom AR.SP CT scanner (Siemens Medical Systems, Iselin, NJ) (11), (b) a commercial device consisting of an ECAT HR+ PET scanner (CPS Innovations, Knoxville, Tenn) and a single-section CT scanner (Siemens Emotion), and (c) a commercial device with a lutetium oxyorthosilicate–based PET scanner (CTI) and a dual-section CT scanner (Siemens Emotion).

PET-CT was performed approximately 1 hour following the intravenous injection of 6–15 mCi (222–555 MBq) of FDG, with acquisition of helical CT data (pitch, 1.1–1.6) immediately preceding acquisition of three-dimensional emission data (5–10 minutes per bed position, two to five bed positions per patient). CT was performed with dynamic injection of 90 mL of intravenous contrast material (ioversol) (Optiray; Mallinckrodt, St Louis, Mo) unless there was a contraindication. The PET scans were corrected for attenuation with coefficients obtained by scaling the CT numbers from the CT scans to the PET energy level (511 kV) (12). The helical CT scans were reconstructed into 512 x 512 images with a section thickness to match those of the PET scans (2.4–3.4 mm).

Images were evaluated by at least one neuroradiologist and one nuclear medicine physician with experience in PET scan interpretation.

	Diagnostic Uses: Indications for PET-CT

Top Abstract Introduction PET-CT Technique Diagnostic Uses: Indications for... Pitfalls: Limitations of PET-CT Conclusions References

 
In our experience, the most powerful application of PET-CT has been the detection of residual or recurrent head and neck neoplasm after treatment. Posttreatment effects make it difficult to distinguish normal posttherapy tissue changes from tumor recurrence clinically, radiologically, and histologically (13,14). Neck dissection and flap reconstruction distort the normal neck anatomy and make detection of recurrent neoplasm challenging on the basis of structural changes alone. Radiation therapy can further complicate imaging by making tissue planes indistinct and by causing edema that may produce an increase in tissue volume. Serial imaging with CT and MR imaging is the mainstay for monitoring patients with head and neck tumors. Stability of a lesion over several months suggests scar, whereas interval growth indicates residual or recurrent neoplasm; however, potential treatment time may have been lost, and the stage of cancer may progress. Indeed, the main criterion for tumor recurrence at conventional CT or MR imaging—tumor growth over time—may occur as a normal postirradiation effect (14). Biopsy of residual or recurrent neoplasm may be impeded by inaccessibility and by potential morbidity in irradiated tissue. Aggressive biopsy of radiation-injured soft tissues may lead to frank necrosis and result in increased morbidity but yield a poor return in terms of detection of recurrent neoplasm (15).

PET has proved to be a useful adjunct in detecting tumor and differentiating recurrent tumor from posttherapy tissue necrosis (16). Diminished FDG uptake appears to coincide with a decline in the number of viable tumor cells (17).

In the treated neck, we have been able to detect recurrent tumor earlier and with greater confidence than we would have with CT alone (Figs 1–3). An initial series of 47 patients evaluated for recurrent head and neck neoplasm with PET-CT at our institution were reviewed. Of these 47 patients, 25 underwent biopsy of lesions detected at PET-CT that proved to be recurrent neoplasm. Biopsy demonstrated recurrent squamous cell carcinoma in 18 patients. A variety of other cell types were identified in the remaining seven cases, including adenocarcinoma, basal cell carcinoma, osteosarcoma, and lymphoma. The sensitivity and specificity of PET-CT for detecting recurrent head and neck neoplasm in this initial series were 95% and 60%, respectively. These findings are similar to those seen in detecting recurrent neoplasm with PET alone. Wong et al (18) reviewed a series of 143 patients with treated squamous cell carcinoma of the head and neck and reported a sensitivity and specificity of 96% and 72%, respectively, for FDG PET in the detection of recurrent neoplasm. In the future, PET-CT evaluation of larger series of patients with recurrent head and neck carcinoma may demonstrate an increase in specificity for the detection of tumor recurrence.

View larger version (87K): [in this window] [in a new window] [Download PPT slide]   Figure 1a.  Recurrent tumor. (a) Fused PET-CT scan shows a squamous cell carcinoma of the tonsil (arrow). The patient underwent partial mandibulectomy. (b) CT scan obtained 4 months later fails to demonstrate recurrent disease at the posterior flap margin (arrow), as did physical examination. (c) Follow-up PET-CT scan shows a small (<1-cm) focus of increased FDG uptake (standardized uptake value [SUV] = 2.5) (arrow). Subsequent surgery helped confirm tumor recurrence at the superficial posterior aspect of the muscle flap.

View larger version (99K): [in this window] [in a new window] [Download PPT slide]   Figure 1b.  Recurrent tumor. (a) Fused PET-CT scan shows a squamous cell carcinoma of the tonsil (arrow). The patient underwent partial mandibulectomy. (b) CT scan obtained 4 months later fails to demonstrate recurrent disease at the posterior flap margin (arrow), as did physical examination. (c) Follow-up PET-CT scan shows a small (<1-cm) focus of increased FDG uptake (standardized uptake value [SUV] = 2.5) (arrow). Subsequent surgery helped confirm tumor recurrence at the superficial posterior aspect of the muscle flap.

View larger version (56K): [in this window] [in a new window] [Download PPT slide]   Figure 1c.  Recurrent tumor. (a) Fused PET-CT scan shows a squamous cell carcinoma of the tonsil (arrow). The patient underwent partial mandibulectomy. (b) CT scan obtained 4 months later fails to demonstrate recurrent disease at the posterior flap margin (arrow), as did physical examination. (c) Follow-up PET-CT scan shows a small (<1-cm) focus of increased FDG uptake (standardized uptake value [SUV] = 2.5) (arrow). Subsequent surgery helped confirm tumor recurrence at the superficial posterior aspect of the muscle flap.

View larger version (104K): [in this window] [in a new window] [Download PPT slide]   Figure 2a.  Recurrent tumor in a 61-year-old patient with a history of squamous cell carcinoma of the right side of the tongue base. The patient had undergone extensive resection of the primary tumor. CT and PET-CT were performed to investigate the cause of recurrent pain. (a) CT scan fails to demonstrate recurrent neoplasm (arrow). (b) PET-CT scan shows focal intense FDG uptake in the supraglottic larynx (arrow), a finding that proved to be recurrent neoplasm.

View larger version (65K): [in this window] [in a new window] [Download PPT slide]   Figure 2b.  Recurrent tumor in a 61-year-old patient with a history of squamous cell carcinoma of the right side of the tongue base. The patient had undergone extensive resection of the primary tumor. CT and PET-CT were performed to investigate the cause of recurrent pain. (a) CT scan fails to demonstrate recurrent neoplasm (arrow). (b) PET-CT scan shows focal intense FDG uptake in the supraglottic larynx (arrow), a finding that proved to be recurrent neoplasm.

View larger version (102K): [in this window] [in a new window] [Download PPT slide]   Figure 3a.  Unsuspected residual tumor in a 72-year-old patient with a history of nasal adenocarcinoma that had invaded the orbit. The patient had undergone left maxillectomy, orbital exenteration, and left ethmoidectomy with flap reconstruction 6 weeks earlier. (a) CT scan demonstrates soft tissue along the posterior flap margin (arrow), a finding that was suspicious for neoplasm. (b) PET-CT scan demonstrates intense FDG uptake localized to the lateral flap border (arrow), a finding that proved to be residual neoplasm at histologic analysis. (c) Follow-up PET-CT scan obtained after resection of the residual neoplasm shows no disease (arrow).

View larger version (76K): [in this window] [in a new window] [Download PPT slide]   Figure 3b.  Unsuspected residual tumor in a 72-year-old patient with a history of nasal adenocarcinoma that had invaded the orbit. The patient had undergone left maxillectomy, orbital exenteration, and left ethmoidectomy with flap reconstruction 6 weeks earlier. (a) CT scan demonstrates soft tissue along the posterior flap margin (arrow), a finding that was suspicious for neoplasm. (b) PET-CT scan demonstrates intense FDG uptake localized to the lateral flap border (arrow), a finding that proved to be residual neoplasm at histologic analysis. (c) Follow-up PET-CT scan obtained after resection of the residual neoplasm shows no disease (arrow).

View larger version (72K): [in this window] [in a new window] [Download PPT slide]   Figure 3c.  Unsuspected residual tumor in a 72-year-old patient with a history of nasal adenocarcinoma that had invaded the orbit. The patient had undergone left maxillectomy, orbital exenteration, and left ethmoidectomy with flap reconstruction 6 weeks earlier. (a) CT scan demonstrates soft tissue along the posterior flap margin (arrow), a finding that was suspicious for neoplasm. (b) PET-CT scan demonstrates intense FDG uptake localized to the lateral flap border (arrow), a finding that proved to be residual neoplasm at histologic analysis. (c) Follow-up PET-CT scan obtained after resection of the residual neoplasm shows no disease (arrow).

An initial series of eight patients with thyroid carcinoma underwent PET-CT (22). Half of these cases (n = 4) demonstrated recurrent neoplasm at PET-CT, with initial histologic findings of papillary carcinoma in three cases and medullary carcinoma in one case. Eight lesions in three cases were sampled, with 75% of lesions demonstrating recurrent neoplasm (Figs 4, 5) (22).

View larger version (126K): [in this window] [in a new window] [Download PPT slide]   Figure 4a.  Recurrent papillary carcinoma of the thyroid gland. The patient had a rising thyroglobulin level but a negative 131I scan. (a) CT scan shows a paratracheal nodule (arrow) that had not been discovered at two previous surgeries, likely because of distorted anatomy and scar from the original thyroidectomy. (b) PET-CT scan demonstrates increased FDG uptake in the thyroidectomy bed (arrow) and provides the additional data needed to justify and guide a third surgical procedure, which helped confirm recurrent neoplasm.

View larger version (129K): [in this window] [in a new window] [Download PPT slide]   Figure 4b.  Recurrent papillary carcinoma of the thyroid gland. The patient had a rising thyroglobulin level but a negative 131I scan. (a) CT scan shows a paratracheal nodule (arrow) that had not been discovered at two previous surgeries, likely because of distorted anatomy and scar from the original thyroidectomy. (b) PET-CT scan demonstrates increased FDG uptake in the thyroidectomy bed (arrow) and provides the additional data needed to justify and guide a third surgical procedure, which helped confirm recurrent neoplasm.

View larger version (115K): [in this window] [in a new window] [Download PPT slide]   Figure 5a.  Recurrent thyroid papillary carcinoma in a 28-year-old patient with a rising thyroglobulin level but a negative 131I scan. CT (a) and fused PET-CT (b) scans show minimal asymmetric FDG uptake in the right side of the neck (arrow), a finding that represents a normal-sized level II lymph node. Recurrent papillary carcinoma was confirmed at histologic analysis.

View larger version (84K): [in this window] [in a new window] [Download PPT slide]   Figure 5b.  Recurrent thyroid papillary carcinoma in a 28-year-old patient with a rising thyroglobulin level but a negative 131I scan. CT (a) and fused PET-CT (b) scans show minimal asymmetric FDG uptake in the right side of the neck (arrow), a finding that represents a normal-sized level II lymph node. Recurrent papillary carcinoma was confirmed at histologic analysis.

Detection of Recurrent Cranial Base Neoplasm
Recurrent skull base neoplasm is notoriously difficult to detect with anatomic imaging techniques owing to distortion of anatomy caused by flap reconstruction and irradiation. Use of structural imaging (CT and MR imaging) alone typically requires serial scans to document tumor growth and may potentially result in lost treatment time. PET-CT may help detect these recurrences in a single imaging session (Fig 6) (24). Successful treatment of skull base neoplasm is predicated on precisely localizing tumor and differentiating it from scar. Combined radiation therapy and surgical treatment for skull base cancer results in soft-tissue changes (bone or cartilaginous necrosis, edema, desmoplastic changes) that distort the normal anatomy. These changes most frequently manifest in the 1st year after completion of adjuvant therapy, the same time period during which tumor is most likely to recur (25). Biopsy of recurrent or residual skull base neoplasm is impeded by inaccessibility at surgery and by potential morbidity.

View larger version (95K): [in this window] [in a new window] [Download PPT slide]   Figure 6a.  Recurrent skull base tumor in a 79-year-old man with a history of inverting papilloma complicated by sphenoid sinus carcinoma, which had previously been resected. Follow-up CT showed soft tissue in the right sphenoid sinus and an adjacent discontinuity in the lateral sphenoid sinus wall that was interpreted as either a surgical defect or neoplastic erosion. (a, b) Initial PET (a) and PET-CT (b) scans show focal FDG uptake localized to the soft-tissue lesion (arrow). The patient refused to undergo biopsy. (c, d) PET (c) and PET-CT (d) scans obtained 3 months later show increased FDG uptake in the lesion (arrow), a finding that supported the diagnosis of recurrent squamous cell carcinoma.

View larger version (105K): [in this window] [in a new window] [Download PPT slide]   Figure 6b.  Recurrent skull base tumor in a 79-year-old man with a history of inverting papilloma complicated by sphenoid sinus carcinoma, which had previously been resected. Follow-up CT showed soft tissue in the right sphenoid sinus and an adjacent discontinuity in the lateral sphenoid sinus wall that was interpreted as either a surgical defect or neoplastic erosion. (a, b) Initial PET (a) and PET-CT (b) scans show focal FDG uptake localized to the soft-tissue lesion (arrow). The patient refused to undergo biopsy. (c, d) PET (c) and PET-CT (d) scans obtained 3 months later show increased FDG uptake in the lesion (arrow), a finding that supported the diagnosis of recurrent squamous cell carcinoma.

View larger version (102K): [in this window] [in a new window] [Download PPT slide]   Figure 6c.  Recurrent skull base tumor in a 79-year-old man with a history of inverting papilloma complicated by sphenoid sinus carcinoma, which had previously been resected. Follow-up CT showed soft tissue in the right sphenoid sinus and an adjacent discontinuity in the lateral sphenoid sinus wall that was interpreted as either a surgical defect or neoplastic erosion. (a, b) Initial PET (a) and PET-CT (b) scans show focal FDG uptake localized to the soft-tissue lesion (arrow). The patient refused to undergo biopsy. (c, d) PET (c) and PET-CT (d) scans obtained 3 months later show increased FDG uptake in the lesion (arrow), a finding that supported the diagnosis of recurrent squamous cell carcinoma.

View larger version (86K): [in this window] [in a new window] [Download PPT slide]   Figure 6d.  Recurrent skull base tumor in a 79-year-old man with a history of inverting papilloma complicated by sphenoid sinus carcinoma, which had previously been resected. Follow-up CT showed soft tissue in the right sphenoid sinus and an adjacent discontinuity in the lateral sphenoid sinus wall that was interpreted as either a surgical defect or neoplastic erosion. (a, b) Initial PET (a) and PET-CT (b) scans show focal FDG uptake localized to the soft-tissue lesion (arrow). The patient refused to undergo biopsy. (c, d) PET (c) and PET-CT (d) scans obtained 3 months later show increased FDG uptake in the lesion (arrow), a finding that supported the diagnosis of recurrent squamous cell carcinoma.

View larger version (72K): [in this window] [in a new window] [Download PPT slide]   Figure 7a.  Squamous cell carcinoma in a patient with a known right-sided level II lymph node. Primary site of neoplasm was unknown. Neoplasm was not identified in five tissue samples obtained at direct laryngoscopy and directed biopsies of the tongue base, tonsils, and nasopharynx. PET (a) and PET-CT (b) scans show an area of intense FDG uptake (SUV = 8) in the right tonsil (arrow). The next day, the patient again underwent direct laryngoscopy and multiple biopsies of the right side of the tongue base; analysis of six additional samples showed squamous cell carcinoma.

View larger version (61K): [in this window] [in a new window] [Download PPT slide]   Figure 7b.  Squamous cell carcinoma in a patient with a known right-sided level II lymph node. Primary site of neoplasm was unknown. Neoplasm was not identified in five tissue samples obtained at direct laryngoscopy and directed biopsies of the tongue base, tonsils, and nasopharynx. PET (a) and PET-CT (b) scans show an area of intense FDG uptake (SUV = 8) in the right tonsil (arrow). The next day, the patient again underwent direct laryngoscopy and multiple biopsies of the right side of the tongue base; analysis of six additional samples showed squamous cell carcinoma.

Cervical metastasis is a common manifestation of occult carcinoma. Previous studies have demonstrated a sensitivity of 30%–47% for FDG PET alone in detecting the undiscovered head and neck primary tumor (33–35). Although FDG uptake in primary neoplasms is usually greater than that observed in even the most metabolically active normal structures (3), overlap between tumor and physiologic uptake proved to limit sensitivity in our experience. Currently, this overlap is likely an important limitation of FDG PET in localizing the occult head and neck primary neoplasm (Fig 8) (36).

View larger version (95K): [in this window] [in a new window] [Download PPT slide]   Figure 8a.  Occult carcinoma. (a) PET-CT scan shows intense FDG uptake in a right-sided level II lymph node (arrow) that proved to be squamous cell carcinoma at pathologic analysis. FDG uptake in the tongue base was symmetric. Direct la-ryngoscopy and directed biopsies failed to reveal the primary site of neoplasm. (b) PET-CT scan obtained at the level of the tonsils also shows symmetric FDG uptake (arrow). Because PET-CT also failed to demonstrate the primary site of neoplasm, bilateral tonsillectomies were performed. Histologic examination showed hyperplasia in the left tonsil and squamous cell carcinoma in the right tonsil.

View larger version (106K): [in this window] [in a new window] [Download PPT slide]   Figure 8b.  Occult carcinoma. (a) PET-CT scan shows intense FDG uptake in a right-sided level II lymph node (arrow) that proved to be squamous cell carcinoma at pathologic analysis. FDG uptake in the tongue base was symmetric. Direct la-ryngoscopy and directed biopsies failed to reveal the primary site of neoplasm. (b) PET-CT scan obtained at the level of the tonsils also shows symmetric FDG uptake (arrow). Because PET-CT also failed to demonstrate the primary site of neoplasm, bilateral tonsillectomies were performed. Histologic examination showed hyperplasia in the left tonsil and squamous cell carcinoma in the right tonsil.

where ROI = region of interest, ROI counts are in megabacquerels per milliliter, injected dose is in megabacquerels, and body weight is in grams.

Typically, a lesion with an SUV greater than 2.5–3.0 is considered suspicious for malignancy (18,38). However, these values may vary considerably depending on the clinical scenario; inflammatory lesions may also demonstrate high SUVs in the range associated with malignant lesions.

In the evaluation of lesions less than 1 cm in size, PET sensitivity may be reduced; as a result, SUVs in the typically benign range may indicate malignancy. This reduced sensitivity results from partial volume averaging of the metabolic activity of a small lesion with that of the normal surrounding tissue, a phenomenon that is especially relevant in the search for lymph node metastases (Fig 9). However, PET-CT may increase confidence in determining the extent of the primary lesion or in identifying recurrent carcinoma at the primary site. In certain cases, PET-CT may provide information that permits more conservative surgery than would be anticipated on the basis of CT findings alone (Fig 10 ). Detection of distant metastases at presentation may be challenging at conventional CT and MR imaging (Fig 11). PET-CT also aids in the detection of a second primary lung tumor, which is why we advocate chest scanning as a routine procedure (Fig 12).  

View larger version (126K): [in this window] [in a new window] [Download PPT slide]   Figure 9a.  Lymph node metastases in a 23-year-old patient with squamous cell carcinoma of the left ethmoid sinus. The patient had undergone two previous surgeries. (a–c) CT (a), PET (b), and PET-CT (c) scans obtained 10 months after presentation show local recurrence in the naso-pharynx (arrow). (d–i) CT scans (d, f, g, i; f and i are magnified views) and PET scans (e, h) show bilateral focal FDG uptake in small (<1-cm) cervical lymph nodes (arrow). These findings prompted resection of the local recurrence as well as bilateral modified neck dissections, the results of which confirmed recurrent neoplasm in both lymph nodes.

View larger version (93K): [in this window] [in a new window] [Download PPT slide]   Figure 9b.  Lymph node metastases in a 23-year-old patient with squamous cell carcinoma of the left ethmoid sinus. The patient had undergone two previous surgeries. (a–c) CT (a), PET (b), and PET-CT (c) scans obtained 10 months after presentation show local recurrence in the naso-pharynx (arrow). (d–i) CT scans (d, f, g, i; f and i are magnified views) and PET scans (e, h) show bilateral focal FDG uptake in small (<1-cm) cervical lymph nodes (arrow). These findings prompted resection of the local recurrence as well as bilateral modified neck dissections, the results of which confirmed recurrent neoplasm in both lymph nodes.

View larger version (115K): [in this window] [in a new window] [Download PPT slide]   Figure 9c.  Lymph node metastases in a 23-year-old patient with squamous cell carcinoma of the left ethmoid sinus. The patient had undergone two previous surgeries. (a–c) CT (a), PET (b), and PET-CT (c) scans obtained 10 months after presentation show local recurrence in the naso-pharynx (arrow). (d–i) CT scans (d, f, g, i; f and i are magnified views) and PET scans (e, h) show bilateral focal FDG uptake in small (<1-cm) cervical lymph nodes (arrow). These findings prompted resection of the local recurrence as well as bilateral modified neck dissections, the results of which confirmed recurrent neoplasm in both lymph nodes.

View larger version (143K): [in this window] [in a new window] [Download PPT slide]   Figure 9d.  Lymph node metastases in a 23-year-old patient with squamous cell carcinoma of the left ethmoid sinus. The patient had undergone two previous surgeries. (a–c) CT (a), PET (b), and PET-CT (c) scans obtained 10 months after presentation show local recurrence in the naso-pharynx (arrow). (d–i) CT scans (d, f, g, i; f and i are magnified views) and PET scans (e, h) show bilateral focal FDG uptake in small (<1-cm) cervical lymph nodes (arrow). These findings prompted resection of the local recurrence as well as bilateral modified neck dissections, the results of which confirmed recurrent neoplasm in both lymph nodes.

View larger version (120K): [in this window] [in a new window] [Download PPT slide]   Figure 9e.  Lymph node metastases in a 23-year-old patient with squamous cell carcinoma of the left ethmoid sinus. The patient had undergone two previous surgeries. (a–c) CT (a), PET (b), and PET-CT (c) scans obtained 10 months after presentation show local recurrence in the naso-pharynx (arrow). (d–i) CT scans (d, f, g, i; f and i are magnified views) and PET scans (e, h) show bilateral focal FDG uptake in small (<1-cm) cervical lymph nodes (arrow). These findings prompted resection of the local recurrence as well as bilateral modified neck dissections, the results of which confirmed recurrent neoplasm in both lymph nodes.

View larger version (140K): [in this window] [in a new window] [Download PPT slide]   Figure 9f.  Lymph node metastases in a 23-year-old patient with squamous cell carcinoma of the left ethmoid sinus. The patient had undergone two previous surgeries. (a–c) CT (a), PET (b), and PET-CT (c) scans obtained 10 months after presentation show local recurrence in the naso-pharynx (arrow). (d–i) CT scans (d, f, g, i; f and i are magnified views) and PET scans (e, h) show bilateral focal FDG uptake in small (<1-cm) cervical lymph nodes (arrow). These findings prompted resection of the local recurrence as well as bilateral modified neck dissections, the results of which confirmed recurrent neoplasm in both lymph nodes.

View larger version (148K): [in this window] [in a new window] [Download PPT slide]   Figure 9g.  Lymph node metastases in a 23-year-old patient with squamous cell carcinoma of the left ethmoid sinus. The patient had undergone two previous surgeries. (a–c) CT (a), PET (b), and PET-CT (c) scans obtained 10 months after presentation show local recurrence in the naso-pharynx (arrow). (d–i) CT scans (d, f, g, i; f and i are magnified views) and PET scans (e, h) show bilateral focal FDG uptake in small (<1-cm) cervical lymph nodes (arrow). These findings prompted resection of the local recurrence as well as bilateral modified neck dissections, the results of which confirmed recurrent neoplasm in both lymph nodes.

View larger version (97K): [in this window] [in a new window] [Download PPT slide]   Figure 9h.  Lymph node metastases in a 23-year-old patient with squamous cell carcinoma of the left ethmoid sinus. The patient had undergone two previous surgeries. (a–c) CT (a), PET (b), and PET-CT (c) scans obtained 10 months after presentation show local recurrence in the naso-pharynx (arrow). (d–i) CT scans (d, f, g, i; f and i are magnified views) and PET scans (e, h) show bilateral focal FDG uptake in small (<1-cm) cervical lymph nodes (arrow). These findings prompted resection of the local recurrence as well as bilateral modified neck dissections, the results of which confirmed recurrent neoplasm in both lymph nodes.

View larger version (124K): [in this window] [in a new window] [Download PPT slide]   Figure 9i.  Lymph node metastases in a 23-year-old patient with squamous cell carcinoma of the left ethmoid sinus. The patient had undergone two previous surgeries. (a–c) CT (a), PET (b), and PET-CT (c) scans obtained 10 months after presentation show local recurrence in the naso-pharynx (arrow). (d–i) CT scans (d, f, g, i; f and i are magnified views) and PET scans (e, h) show bilateral focal FDG uptake in small (<1-cm) cervical lymph nodes (arrow). These findings prompted resection of the local recurrence as well as bilateral modified neck dissections, the results of which confirmed recurrent neoplasm in both lymph nodes.

View larger version (85K): [in this window] [in a new window] [Download PPT slide]   Figure 10a.  Tumor recurrence in a 50-year-old patient with a history of squamous cell carcinoma of the tongue base. The patient had undergone chemotherapy and radiation therapy in Germany 2 years earlier. MR imaging performed there demonstrated extensive tumor involvement of the tongue base and larynx. PET-CT scans show tumor recurrence in the tongue base (arrow in a) but sparing of the supraglottic larynx (arrow in b), involvement of which had been suspected at CT. The PET-CT findings allowed the patient to undergo more conservative surgery than would have been indicated by the CT data alone.

View larger version (71K): [in this window] [in a new window] [Download PPT slide]   Figure 10b.  Tumor recurrence in a 50-year-old patient with a history of squamous cell carcinoma of the tongue base. The patient had undergone chemotherapy and radiation therapy in Germany 2 years earlier. MR imaging performed there demonstrated extensive tumor involvement of the tongue base and larynx. PET-CT scans show tumor recurrence in the tongue base (arrow in a) but sparing of the supraglottic larynx (arrow in b), involvement of which had been suspected at CT. The PET-CT findings allowed the patient to undergo more conservative surgery than would have been indicated by the CT data alone.

View larger version (80K): [in this window] [in a new window] [Download PPT slide]   Figure 11a.  Distant metastasis in a 61-year-old patient with recently diagnosed squamous cell carcinoma of the right side of the oropharynx. The patient had undergone CT, which showed no evidence of distant metastasis. (a) CT scan shows no lesion in the sternum (arrow). (b) PET-CT scan shows a small focus of FDG uptake localized to the sternum (arrow), a finding that is consistent with metastasis. PET-CT also showed intense FDG uptake at the primary site.

View larger version (93K): [in this window] [in a new window] [Download PPT slide]   Figure 11b.  Distant metastasis in a 61-year-old patient with recently diagnosed squamous cell carcinoma of the right side of the oropharynx. The patient had undergone CT, which showed no evidence of distant metastasis. (a) CT scan shows no lesion in the sternum (arrow). (b) PET-CT scan shows a small focus of FDG uptake localized to the sternum (arrow), a finding that is consistent with metastasis. PET-CT also showed intense FDG uptake at the primary site.

View larger version (85K): [in this window] [in a new window] [Download PPT slide]   Figure 12a.  Second primary lung tumor in a patient who presented with throat pain. The patient had undergone chemotherapy and radiation therapy for squamous cell carcinoma of the oropharynx 6 years earlier. (a) PET-CT scan demonstrates recurrent neoplasm in the left retromolar trigone (arrow). (b) CT scan shows stranding in the lung apices (arrow), a finding that was interpreted as radiation-induced change. (c) PET-CT scan demonstrates intense FDG uptake in the right lung apex (arrow), a finding that proved to be a second primary adenocarcinoma.

View larger version (135K): [in this window] [in a new window] [Download PPT slide]   Figure 12b.  Second primary lung tumor in a patient who presented with throat pain. The patient had undergone chemotherapy and radiation therapy for squamous cell carcinoma of the oropharynx 6 years earlier. (a) PET-CT scan demonstrates recurrent neoplasm in the left retromolar trigone (arrow). (b) CT scan shows stranding in the lung apices (arrow), a finding that was interpreted as radiation-induced change. (c) PET-CT scan demonstrates intense FDG uptake in the right lung apex (arrow), a finding that proved to be a second primary adenocarcinoma.

View larger version (102K): [in this window] [in a new window] [Download PPT slide]   Figure 12c.  Second primary lung tumor in a patient who presented with throat pain. The patient had undergone chemotherapy and radiation therapy for squamous cell carcinoma of the oropharynx 6 years earlier. (a) PET-CT scan demonstrates recurrent neoplasm in the left retromolar trigone (arrow). (b) CT scan shows stranding in the lung apices (arrow), a finding that was interpreted as radiation-induced change. (c) PET-CT scan demonstrates intense FDG uptake in the right lung apex (arrow), a finding that proved to be a second primary adenocarcinoma.

Further study will be required to determine the usefulness of PET-CT for tumor surveillance. The theory that a decrease in metabolic activity immediately after treatment may herald a response has been controversial. Such a finding is largely dependent on the interval between treatment and imaging: Imaging performed 1 month after treatment may be unreliable in terms of evaluating tumor response, whereas imaging performed 4 months after treatment may provide prognostic information (Fig 13) (41). In addition, a lack of reduction in metabolic activity may signal the need to change treatment or to opt for a more aggressive therapy (Fig 14).

View larger version (73K): [in this window] [in a new window] [Download PPT slide]   Figure 13a.  Recurrent neoplasm in a 67-year-old patient with progressive dyspnea in whom squamous cell carcinoma of the tongue base had been diagnosed. (a) Initial PET-CT scan shows a large focus of intense FDG uptake in the tongue base (arrow) and uptake in bilateral level II lymph nodes. The patient subsequently underwent chemotherapy and radiation therapy. (b) PET-CT scan shows a decrease in FDG uptake in the tongue base (arrow) and resolution of the nodal uptake. (c) PET-CT scan reveals new FDG uptake in the vocal cords and sclerosis of the left side of the thyroid cartilage (arrow). These findings were interpreted as representing inflammation. Direct laryngoscopy was performed and showed radiation-induced change in the true vocal cords. (d) Follow-up PET-CT scan shows increased FDG uptake in the thyroid cartilage (arrow), a finding that represents recurrent neoplasm in proximity to the vocal cords.

View larger version (73K): [in this window] [in a new window] [Download PPT slide]   Figure 13b.  Recurrent neoplasm in a 67-year-old patient with progressive dyspnea in whom squamous cell carcinoma of the tongue base had been diagnosed. (a) Initial PET-CT scan shows a large focus of intense FDG uptake in the tongue base (arrow) and uptake in bilateral level II lymph nodes. The patient subsequently underwent chemotherapy and radiation therapy. (b) PET-CT scan shows a decrease in FDG uptake in the tongue base (arrow) and resolution of the nodal uptake. (c) PET-CT scan reveals new FDG uptake in the vocal cords and sclerosis of the left side of the thyroid cartilage (arrow). These findings were interpreted as representing inflammation. Direct laryngoscopy was performed and showed radiation-induced change in the true vocal cords. (d) Follow-up PET-CT scan shows increased FDG uptake in the thyroid cartilage (arrow), a finding that represents recurrent neoplasm in proximity to the vocal cords.

View larger version (76K): [in this window] [in a new window] [Download PPT slide]   Figure 13c.  Recurrent neoplasm in a 67-year-old patient with progressive dyspnea in whom squamous cell carcinoma of the tongue base had been diagnosed. (a) Initial PET-CT scan shows a large focus of intense FDG uptake in the tongue base (arrow) and uptake in bilateral level II lymph nodes. The patient subsequently underwent chemotherapy and radiation therapy. (b) PET-CT scan shows a decrease in FDG uptake in the tongue base (arrow) and resolution of the nodal uptake. (c) PET-CT scan reveals new FDG uptake in the vocal cords and sclerosis of the left side of the thyroid cartilage (arrow). These findings were interpreted as representing inflammation. Direct laryngoscopy was performed and showed radiation-induced change in the true vocal cords. (d) Follow-up PET-CT scan shows increased FDG uptake in the thyroid cartilage (arrow), a finding that represents recurrent neoplasm in proximity to the vocal cords.

View larger version (65K): [in this window] [in a new window] [Download PPT slide]   Figure 13d.  Recurrent neoplasm in a 67-year-old patient with progressive dyspnea in whom squamous cell carcinoma of the tongue base had been diagnosed. (a) Initial PET-CT scan shows a large focus of intense FDG uptake in the tongue base (arrow) and uptake in bilateral level II lymph nodes. The patient subsequently underwent chemotherapy and radiation therapy. (b) PET-CT scan shows a decrease in FDG uptake in the tongue base (arrow) and resolution of the nodal uptake. (c) PET-CT scan reveals new FDG uptake in the vocal cords and sclerosis of the left side of the thyroid cartilage (arrow). These findings were interpreted as representing inflammation. Direct laryngoscopy was performed and showed radiation-induced change in the true vocal cords. (d) Follow-up PET-CT scan shows increased FDG uptake in the thyroid cartilage (arrow), a finding that represents recurrent neoplasm in proximity to the vocal cords.

View larger version (67K): [in this window] [in a new window] [Download PPT slide]   Figure 14a.  Squamous cell carcinoma of the tongue in a 60-year-old patient who had undergone chemotherapy and radiation therapy 2 years earlier. (a, b) PET-CT scans show faint FDG uptake in the left side of the tongue base (primary site) and in a left-sided level II lymph node (long arrow), as well as intense physiologic uptake in the genioglossus muscle (short arrow). The patient subsequently underwent gene therapy. (c, d) PET-CT scans obtained 3 months later show disease progression, with increased FDG uptake in the left side of the tongue base and in the lymph node (arrow).

View larger version (70K): [in this window] [in a new window] [Download PPT slide]   Figure 14b.  Squamous cell carcinoma of the tongue in a 60-year-old patient who had undergone chemotherapy and radiation therapy 2 years earlier. (a, b) PET-CT scans show faint FDG uptake in the left side of the tongue base (primary site) and in a left-sided level II lymph node (long arrow), as well as intense physiologic uptake in the genioglossus muscle (short arrow). The patient subsequently underwent gene therapy. (c, d) PET-CT scans obtained 3 months later show disease progression, with increased FDG uptake in the left side of the tongue base and in the lymph node (arrow).

View larger version (72K): [in this window] [in a new window] [Download PPT slide]   Figure 14c.  Squamous cell carcinoma of the tongue in a 60-year-old patient who had undergone chemotherapy and radiation therapy 2 years earlier. (a, b) PET-CT scans show faint FDG uptake in the left side of the tongue base (primary site) and in a left-sided level II lymph node (long arrow), as well as intense physiologic uptake in the genioglossus muscle (short arrow). The patient subsequently underwent gene therapy. (c, d) PET-CT scans obtained 3 months later show disease progression, with increased FDG uptake in the left side of the tongue base and in the lymph node (arrow).

View larger version (77K): [in this window] [in a new window] [Download PPT slide]   Figure 14d.  Squamous cell carcinoma of the tongue in a 60-year-old patient who had undergone chemotherapy and radiation therapy 2 years earlier. (a, b) PET-CT scans show faint FDG uptake in the left side of the tongue base (primary site) and in a left-sided level II lymph node (long arrow), as well as intense physiologic uptake in the genioglossus muscle (short arrow). The patient subsequently underwent gene therapy. (c, d) PET-CT scans obtained 3 months later show disease progression, with increased FDG uptake in the left side of the tongue base and in the lymph node (arrow).

	Pitfalls: Limitations of PET-CT

Top Abstract Introduction PET-CT Technique Diagnostic Uses: Indications for... Pitfalls: Limitations of PET-CT Conclusions References

Localization of a lesion either within or in proximity to an anatomic structure with inherently high FDG uptake such as the brain or tonsils may make it difficult to distinguish pathologic from physiologic metabolic activity (Figs 6, 8, 15–17).

View larger version (106K): [in this window] [in a new window] [Download PPT slide]   Figure 15a.  Nasopharyngeal carcinoma in a 62-year-old patient. (a) Coronal PET scan shows intense FDG uptake (arrow) in proximity to the brain. (b) Axial fused PET-CT scan helps localize the FDG uptake to extensive neoplastic erosion of the sphenoid bone (arrow) rather than the brain.

View larger version (90K): [in this window] [in a new window] [Download PPT slide]   Figure 15b.  Nasopharyngeal carcinoma in a 62-year-old patient. (a) Coronal PET scan shows intense FDG uptake (arrow) in proximity to the brain. (b) Axial fused PET-CT scan helps localize the FDG uptake to extensive neoplastic erosion of the sphenoid bone (arrow) rather than the brain.