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Nuclear Medicine |
1 Departments of Radiology (O.S.A., N.J.F., G.R.C., D.C.P., W.P.D., R.A.H.)
2 Otolaryngology (M.J.K., M.I.S.), University of California Medical Center, 505 Parnassus Ave, San Francisco, CA 94143.
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Abstract |
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 TOP Abstract IntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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MATERIALS AND METHODS: Seventeen patients with metastatic cervical adenopathy of unknown primary origin were referred for FDG PET of the head and neck. All patients had undergone correlative anatomic imaging within 1 month of FDG PET. Surgical, clinical, and histopathologic findings were used to assess the performance of FDG PET.
RESULTS: Increased apical lung uptake at FDG PET led to a biopsy-proved diagnosis of primary lung cancer in two patients. Of the remaining 15 patients, 10 had a focus of increased activity; directed biopsy of these sites led to confirmation of a primary carcinoma in seven patients. Correlative anatomic imaging failed to demonstrate the primary sites of disease in two of these seven patients. None of the five patients with negative FDG PET studies have manifested evidence of a primary site of disease during follow-up of 8–42 months (mean, 29 months).
CONCLUSION: FDG PET allows effective localization of the unknown primary site of origin in metastatic head and neck cancer and can contribute substantially to patient care.
Index terms: Fluorine • Head and neck neoplasms, diagnosis, 20.373 • Head and neck neoplasms, emission CT (ECT), 20.12163 • Head and neck neoplasms, secondary, 20.375
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Introduction |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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An exploitable characteristic of head and neck neoplasms is their increased glycolytic rate, a feature that makes these neoplasms ideal candidates for metabolic imaging. The most common tracer used in this type of imaging is the positron emitter 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG). This glucose analogue has a metabolic profile that includes uptake paralleling the glycolytic rate of metabolically active cells, from which the tracer is then unable to escape (5,6). Because FDG uptake reflects cellular metabolism, infection, inflammation, or a neoplasm can result in focal accumulation of the tracer. A high target-to-background ratio of FDG uptake in primary head and neck tumors has been well documented (6–8). FDG positron emission tomography (PET) of the head and neck has been shown to supplement clinical examination and anatomic imaging in nodal staging, evaluation for disease recurrence, and monitoring of therapeutic response (7–10). However, to our knowledge there have been few dedicated studies of the role of FDG PET in the subset of head and neck cancer patients with metastatic cervical adenopathy of unknown primary origin (11). Therefore, we performed a study to evaluate the usefulness of FDG PET in locating the primary tumor in such patients.
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MATERIALS AND METHODS |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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PET images were obtained with a scanner (HR Exact; Siemens Medical Systems, Iselin, NJ) with an in-plane resolution of 3.5 mm full width half maximum in the center of the field of view. All patients fasted for at least 4 hours before scanning. Immediately after injection of approximately 10 mCi (370 MBq) of FDG, transmission scanning with three germanium-68/gallium-68 rotating rod sources was performed for attenuation correction at the first of two bed positions. Emission scanning at the first bed position followed, and the cycle was repeated for the second bed position; two series of 47 attenuation-corrected emission images with coverage from the skull base to the thoracic inlet were thus generated. The transmission and emission series required 20 and 40 minutes to complete, respectively. The matrix size was 128 x 128 with a 30-cm field of view, and the nominal section thickness was 3 mm.
Scatter, decay, and arc correction were performed with ECAT 7.0 software (Siemens), and images were reconstructed by means of filtered back projection with use of a Hanning filter with a z cutoff of 0.2. Images were viewed on a workstation (IPX; Sun Microsystems, Mountain View, Calif) that permits simultaneous viewing in all three planes with easy cross-referencing between planes. PET images were evaluated visually at the time of study alongside correlative anatomic imaging studies by experienced nuclear medicine physicians (G.R.C., D.C.P., R.A.H.), each of whom had over 4 years of experience in interpreting FDG PET studies. Clinical and histopathologic findings, which included results of biopsy of suspicious lesions, were used to assess the performance of FDG PET.
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RESULTS |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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In the remaining 15 patients, histopathologic analysis of cervical nodes revealed squamous carcinoma in 14 patients and adenocarcinoma in one patient. Primary sites were subsequently identified in seven of these 15 patients. In the remaining eight patients, no primary site has been identified by any means. Follow-up for these 15 patients ranged from 8 to 42 months (mean, 29 months). The clinical, imaging, and histopathologic findings in these patients are summarized in the Table.
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Although PET allowed correct detection of eight primary sites in seven patients, concurrent imaging with MR or CT allowed detection of five of the eight biopsy-proved primary sites (Fig 1). A biopsy-proved primary tonsillar carcinoma was not apparent at CT in one patient (Fig 2), and a primary base-of-tongue carcinoma was not apparent at CT in another. This second patient had an unsuspected concurrent primary carcinoma of the esophagus, which was demonstrated with FDG PET (Fig 3). The base-of-tongue carcinoma in this patient as well as a primary base-of-tongue carcinoma in another patient were not visualized with direct laryngoscopy and endoscopy performed after PET. Focal FDG uptake in the base of the tongue was used to guide biopsy in these two patients, which led to the diagnosis of primary base-of-tongue carcinoma. The primary tonsillar carcinoma that was not apparent at CT had not been visualized at direct laryngoscopy performed 3 weeks before PET. Surgical reexamination of this patient with PET guidance led to a positive diagnosis.
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MR imaging and CT allowed correct detection of primary sites in five of the 15 patients (33%), whereas use of FDG PET increased the number of patients with established primary sites to seven (47%).
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DISCUSSION |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Our findings must be interpreted in light of the relatively small number of patients included in the study. However, the detection with FDG PET of two primary carcinomas that were not seen at clinical examination or anatomic imaging suggests that FDG PET is useful in patients with head and neck cancer of unknown primary origin. Furthermore, FDG PET allowed identification of two primary sites in one patient; one of these tumors (a concurrent esophageal carcinoma) was unsuspected before performance of FDG PET. MR imaging and CT enabled location of a primary site in five patients (33%), whereas use of FDG PET increased the number of patients with a located primary site to seven (47%). The larger yield with FDG PET than with the conventional modalities can be explained by the difference in the imaging strategies used. In the head and neck, diagnosis of primary cancer with CT or MR imaging requires detection of a mass or an area of gross change in attenuation or signal intensity; these findings may not accompany all tumors with the potential to metastasize. An advantage of FDG PET is the ability to demonstrate metabolically active small, superficial, and/or submucosal lesions that are potentially "invisible" at clinical examination and conventional imaging. The primary lesions that were overlooked with conventional imaging in this study were small and were situated in the tonsil and the base of the tongue, areas where subtle structural abnormalities can be difficult to detect.
Two of the three false-positive FDG PET studies were proved with biopsy to be due to inflammation, a process involving increased cellular metabolism and thereby increased FDG uptake. Malignant and benign sources of increased FDG uptake can be indistinguishable; however, this fact should not dissuade biopsy of suspicious foci of uptake on FDG PET studies of the head and neck. Given the accessibility and minimal risk of biopsy of putative primary sites in the head and neck and the importance of establishing a definite diagnosis, a small number of false-positive results is acceptable because the goal is to locate as many primary sites as possible.
During the period of treatment and follow-up subsequent to FDG PET (mean, 29 months), no additional primary lesions have been identified in the 15 patients; therefore, eight patients (53%) continue to have a diagnosis of head and neck cancer of unknown primary origin. This percentage of persistently occult primary tumors is in agreement with the results of previous studies (18,19). There are several possible explanations for the failure of primary lesions to become apparent. First, there is no way to be certain that the primary site is in the head and neck; in our study, two of the 17 patients were found to have primary apical lung carcinoma with FDG PET. This site of origin should be considered in all patients with cervical nodal metastases of occult origin, especially if the affected nodes are low in the neck. Furthermore, some primary neoplasms may spontaneously involute (20) and some may be eradicated by radiation therapy (21), which was administered in seven of the eight patients in our study who never demonstrated evidence of a primary tumor.
The findings in this group of patients suggest that, if FDG PET does not demonstrate a primary site, none is likely to be found at subsequent imaging, clinical examination, or biopsy of clinically suspicious areas. Recently, Braams et al (11) reported the results of FDG PET performed with a detector that has a resolution of 6 mm full width half maximum. Among 13 patients with metastatic cervical adenopathy of unknown origin, four of five biopsy-proved primary sites were demonstrated with FDG PET. Mukherji et al (18) studied 18 patients with FDG single photon emission CT for the same indication. Using biopsy-proved primary sites as the standard of reference and a single photon emission CT system with a resolution of 1.7 cm, they achieved a sensitivity of 82% with two false-negative FDG studies. The higher photon sensitivity inherent in PET coupled with the high resolution of our system provide a substantial technical edge in detection of small foci of uptake and may explain the fact that there were no false-negative FDG PET results in our study. The potential of FDG PET to demonstrate small primary lesions that might otherwise escape detection was revealed in the study by Braams et al (11), in which a base-of-tongue carcinoma 3 mm in diameter was detected with FDG PET but not with any other modality, including endoscopy. FDG PET demonstrated a similar potential in our study by allowing identification of a 4-mm-diameter base-of-tongue lesion that was inapparent at clinical examination, anatomic imaging, and endoscopy.
In conclusion, our study demonstrates the ability of FDG PET to supplement clinical examination and anatomic imaging in patients with metastatic cervical adenopathy of unknown primary origin. The use of FDG PET increased the number of patients with established primary sites to 47% from the 33% identified with anatomic imaging alone. In addition, FDG PET was used to guide successful endoscopic biopsy in three patients. No patient with a negative FDG PET study subsequently demonstrated evidence of a primary site of disease. The results in this relatively small group of patients suggest that FDG PET is useful in locating the primary tumor in patients with metastatic head and neck cancer of unknown primary origin and has the potential to contribute substantially to patient care.
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Footnotes |
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From the 1997 RSNA scientific assembly.
Abbreviation: FDG = 2-[fluorine-18]fluoro-2-deoxy-D-glucose
Author contributions: Guarantor of integrity of entire study, O.S.A.; study concepts, O.S.A., N.J.F., G.R.C., W.P.D., R.A.H., M.J.K., M.I.S., D.C.P.; study design, O.S.A., N.J.F., R.A.H.; definition of intellectual content, O.S.A., N.J.F., M.J.K., W.P.D., R.A.H.; literature research, O.S.A., N.J.F.; clinical studies, O.S.A., N.J.F., D.C.P., G.R.C., R.A.H., W.P.D., M.I.S., M.J.K.; data acquisition, O.S.A., N.J.F.; data analysis, O.S.A.; statistical analysis, O.S.A.; manuscript preparation, O.S.A.; manuscript editing, O.S.A., N.J.F., G.R.C., W.P.D., R.A.H., M.J.K., M.I.S., D.C.P.; manuscript review, O.S.A., N.J.F., G.R.C., W.P.D., D.C.P., M.J.K., M.I.S., R.A.H.
Received March 2, 1998;
revision requested May 5, 1998; revision received June 8, 1998;
accepted August 24, 1998.
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References |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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