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Recurrent Laryngeal Nerve Palsy in Patients with Lung Cancer: Detection with PET-CT Image Fusion—Report of Six Cases¹

¹ From the Division of Nuclear Medicine, Department of Medical Radiology, University Hospital of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland. Received July 23, 2001; revision requested September 6; revision received November 13; accepted December 12. E.M.K. supported by the Swiss Federal Commission for Scholarships for Foreign Students. Address correspondence to H.C.S. (e-mail: hans.steinert@dmr.usz.ch).

	ABSTRACT

TOP ABSTRACT INTRODUCTION Materials and Methods Findings Discussion REFERENCES

 
Positron emission tomography (PET) with fluorodeoxyglucose (FDG) was performed for preoperative staging of lung cancer. In six of 184 patients, there was an intense FDG accumulation in the lower anterior neck. Fusion of PET and computed tomographic images revealed that the focal FDG uptake was localized in the internal laryngeal muscles. This finding was a result of compensatory laryngeal muscle activation caused by contralateral recurrent laryngeal nerve palsy due to direct nerve invasion by lung cancer of the left mediastinum or lung apices. The knowledge of this pitfall is important to avoid false-positive PET results.

© RSNA, 2002

Index terms: Computed tomography (CT), 27.12112, 27.12115 • Data fusion • Image fusion • Larynx, abnormalities, 271.829 • Lung neoplasms, 60.321 • Positron emission tomography (PET), 27.12163, 27.12166

	INTRODUCTION

TOP ABSTRACT INTRODUCTION Materials and Methods Findings Discussion REFERENCES

 
Accurate tumor staging is essential for choosing the appropriate treatment strategy for cancer in general and for lung cancer in particular. In non–small cell lung cancer, the treatment regimen depends on preoperative staging. Curable surgical resection is possible for early stages (stage IIIA or less or stage T3N2M0 or less) of non–small cell lung cancer. If contralateral mediastinal lymph node involvement (N3) or extrathoracic metastases (M1) exists, surgery is generally not indicated. Recently, it has been shown that whole-body positron emission tomography (PET) with fluorodeoxyglucose (FDG) is a sensitive method for detecting metastases in patients with lung cancer (1–4). A drawback of FDG PET imaging is that FDG uptake is not specific to malignant tissue. Tissues such as myocardium, intestine, and skeletal muscle also show FDG accumulation after dynamic or static exercise (5–8). For PET scan interpretation, it is important to be aware of normal variants, artifacts, and causes of false-positive results to avoid misinterpretation. The purpose of our study was to determine a pattern of focal FDG accumulation in the lower anterior neck, which is occasionally seen in patients with lung cancer.

	Materials and Methods

TOP ABSTRACT INTRODUCTION Materials and Methods Findings Discussion REFERENCES

 
The study was approved by the local ethics committee. All patients signed a consent form after the procedure was explained to them.

Between July 2000 and June 2001, whole-body FDG PET was performed in 184 patients for preoperative staging of lung cancer. In six patients (four men, two women; age range, 31–76 years; mean age, 64 years), a focal FDG accumulation was observed in the lower anterior neck just lateral to the midline. In all patients, exact localization of the primary tumor was defined. Fusion of PET and computed tomographic (CT) images was available in four patients. Three experienced nuclear medicine physicians (E.M.K., G.W.G., H.C.S.) compared the findings with those of clinical history, routine clinical laboratory tests, physical examination of the neck, and laryngoscopy to obtain the definitive diagnoses.

To suppress myocardial glucose utilization, patients were asked to fast for at least 4 hours before undergoing FDG PET examination. No patients had history of diabetes. After arriving at the PET center, the patients were placed on a stretcher and asked to relax. Then they received an intravenous injection of 300–400 MBq of FDG and rested for 40–50 minutes for the organ uptake of FDG. FDG was produced in house by using a 17.8-MeV cyclotron (PET Trace 2000; GE Medical Systems, Uppsala, Sweden) and an automated FDG synthesis module (PET Tracer Synthesizer; Nuclear Interface, Münster, Germany) with well-known techniques (9). Before PET scanning, patients were encouraged to void to minimize activity in the bladder owing to renal excretion of FDG. Then, the patients were transferred to the PET table. At 50–60 minutes after FDG injection, static whole-body PET scanning was performed and covered the patient from the pelvic floor to the head. Transmission scans were acquired in all patients.

During the study, two imaging techniques were applied. Until February 2001, FDG PET scanning was performed by using a 14.6-cm axial field of view PET scanner (Advance NXi; GE Medical Systems, Milwaukee, Wis). PET scans were obtained with a 4-minute acquisition time at every table position, which typically required six to seven bed positions to cover the entire field of view. After emission scanning, transmission scanning was started by using rotating germanium 68 pin sources. Transmission scanning was performed from the head to the pelvic floor, with a 2-minute acquisition time at every table position. Image data sets were reconstructed iteratively with segmented attenuation correction.

After PET scanning and on the basis of clinical information, patients were examined with concomitant CT to evaluate a prototype configuration of an integrated PET-CT system for image coregistration and CT-based transmission correction. The spiral CT scanner (HiSpeed CT/I; GE Medical Systems, Milwaukee) was separated by approximately 10 m from the PET scanner. Data were acquired with 140 kV, 80 mA, tube rotation time of 1.0 second, pitch of 1.7, and 5-mm section thickness. Potential misalignment of the PET-CT image coregistration was controlled by placing the patient on a vacuum mattress (Vac Fix; Sirad SA, Le Locle, Switzerland), which when evacuated fits itself to the body contours, assuming castlike properties. This procedure limited patient motion throughout both studies. Repositioning of patients was performed with a laser system (HiSpeed CT/I; GE Medical Systems, Milwaukee) integrated in the CT scanner. Image fusion was performed with special software (PMOD; available at: www.pmod.com), which allowed coregistration of the two image sets with a simple rigid transformation based on anatomic landmarks (10). Optimum coregistration between the two studies was interactively achieved by experienced users (E.M.K., G.W.G). Two patients with an intense FDG uptake in the lower anterior neck were examined with this technique.

Starting in March 2001, all image data acquisitions were performed with a combined in-line PET-CT device (Discovery LS; GE Medical Systems, Milwaukee), which consists of PET and multisection helical CT (LightSpeed Plus; GE Medical Systems, Milwaukee) scanners, which are integrated into this dedicated system. The axes of both systems are mechanically aligned so that a simple translation of the patient table by approximately 60 cm between CT and PET data acquisitions moves the patient from the CT to the PET gantry. The resulting PET and CT images are coregistered with the hardware to an accuracy of approximately 1 mm, if the patient does not move between both examinations.

Data acquisition in the combined system was as follows: At 45–55 minutes after FDG injection, multidetector CT scanning was performed from the head to the pelvic floor (scanning length, 86.7 cm) with 140 kV, 80 mA, tube rotation time of 0.5 second, pitch of 6, and 5-mm section thickness, which was matched to PET section thickness. Immediately after CT scanning, a PET emission scan was obtained that covered the identical transverse field of view. Acquisition time was 4 minutes at each table position. The PET and CT data sets were acquired at two independent computer consoles that were connected by an interface to transfer CT data to the PET scanner. PET image data sets were reconstructed iteratively by using CT data for attenuation correction, and coregistered images were displayed with software (eNTEGRA; GE Medical Systems, Milwaukee). Two patients with an intense FDG uptake in the lower anterior neck were examined with this technique.

	Findings

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Findings in the six patients showed a focal FDG accumulation in the lower anterior neck just right of the midline. In four patients, the primary tumor was located in the left lung and reached to the aortopulmonary window, whereas the remaining two patients had left-sided Pancoast tumors (Table). In four patients, fusion of PET and CT images was performed. The coregistered PET-CT fusion images demonstrated that the focal FDG uptake was localized in the right internal laryngeal muscles (Figs 1, 2). In our department, two PET scanners were installed: a combined PET-CT scanner and a conventional PET scanner. In two patients with an intense FDG uptake in the lower anterior neck, only conventional PET scanning was performed; therefore, image fusion was not available. However, on the basis of the information obtained in the four cases with PET-CT fusion images, there is no doubt that the two patients who underwent only PET showed the same phenomenon.

View larger version (65K): [in this window] [in a new window] [Download PPT slide]   Figure 1a. (a) Coronal FDG and coregistered (b) coronal and (c) transverse PET-CT fusion images show intense FDG uptake in the left Pancoast tumor (arrow) and in the right intrinsic laryngeal muscles (arrowhead).

View larger version (89K): [in this window] [in a new window] [Download PPT slide]   Figure 1b. (a) Coronal FDG and coregistered (b) coronal and (c) transverse PET-CT fusion images show intense FDG uptake in the left Pancoast tumor (arrow) and in the right intrinsic laryngeal muscles (arrowhead).

View larger version (172K): [in this window] [in a new window] [Download PPT slide]   Figure 1c. (a) Coronal FDG and coregistered (b) coronal and (c) transverse PET-CT fusion images show intense FDG uptake in the left Pancoast tumor (arrow) and in the right intrinsic laryngeal muscles (arrowhead).

View larger version (95K): [in this window] [in a new window] [Download PPT slide]   Figure 2a. (a) Coronal FDG PET and (b) coregistered transverse PET-CT fusion image of the neck shows increased FDG uptake in the right intrinsic laryngeal muscles (arrowhead). (c) Coronal (left) CT, (middle) FDG PET, and (right) PET-CT fusion images show the primary lung tumor (arrows) in the aortopulmonary window.

View larger version (128K): [in this window] [in a new window] [Download PPT slide]   Figure 2b. (a) Coronal FDG PET and (b) coregistered transverse PET-CT fusion image of the neck shows increased FDG uptake in the right intrinsic laryngeal muscles (arrowhead). (c) Coronal (left) CT, (middle) FDG PET, and (right) PET-CT fusion images show the primary lung tumor (arrows) in the aortopulmonary window.

View larger version (76K): [in this window] [in a new window] [Download PPT slide]   Figure 2c. (a) Coronal FDG PET and (b) coregistered transverse PET-CT fusion image of the neck shows increased FDG uptake in the right intrinsic laryngeal muscles (arrowhead). (c) Coronal (left) CT, (middle) FDG PET, and (right) PET-CT fusion images show the primary lung tumor (arrows) in the aortopulmonary window.

PET-CT findings were suggestive of a recurrent left-sided nerve palsy, with a compensatory laryngeal muscle activation on the right side. However, a focal active inflammatory process or a secondary tumor of the vocal cord could potentially also exhibit the same findings. As part of a diagnostic bronchoscopic procedure or with direct laryngoscopy, the vocal cords were evaluated for motility or morphologic changes in all six patients. A typical finding of left recurrent laryngeal nerve palsy (fixed ipsilateral vocal fold in the left paramedian position) was reported in all six patients, with normal laryngeal nerve function on the right side. Because of these findings, laryngeal inflammatory foci or other morphologic changes of the vocal cords could be excluded, and biopsies were not required. After surgical treatment of the primary lung tumors, clinical follow-up in all six patients was performed between 6 and 12 months. The areas of increased FDG uptake in the neck remained free of malignant involvement.

	Discussion

TOP ABSTRACT INTRODUCTION Materials and Methods Findings Discussion REFERENCES

 
Whole-body FDG PET is a sensitive imaging modality for staging of lung cancer. However, the anatomic localization of lesions detected at PET is poor and in many cases, direct comparison of PET and CT images is necessary for an adequate localization of lesions. For PET images of lesions smaller than 1 cm, definitive localization may become difficult or even impossible. In this study, the anatomic location of the focal FDG accumulation in the lower anterior neck could not be determined adequately with PET images alone. The findings could have been misinterpreted as a small scalene lymph node metastasis of lung cancer. With the coregistered PET-CT fusion images, the focal FDG uptake was reliably localized in the small internal laryngeal muscles. In all six patients with intense FDG accumulation in the one-sided internal laryngeal muscles, contralateral laryngeal nerve palsy was confirmed. Five patients showed evidence of abnormal phonation. In one patient, laryngeal nerve palsy was not suspected prior to the PET examination. This patient was talking normally without any evidence of abnormal phonation.

The glucose analogue FDG is well known to accumulate in benign and malignant tissues with increased glucose consumption. In skeletal muscle, the amount of glucose taken up is directly proportional to the degree of muscle work (11). Therefore, increased FDG uptake, mainly in the sternocleidomastoid muscles and muscles of the shoulder girdle, can be seen in tense and anxious patients. The injection of diazepam has been suggested by some authors (12) to avoid masking potential sites of disease in this situation. Usually, patients are instructed to relax and not move during the FDG uptake to avoid increased FDG accumulation in the muscles. In our institution, patients with head and neck cancers are instructed not to speak or chew after FDG injection and for the whole length of the examination to avoid increased FDG uptake in the muscles of mastication, the mouth, and the larynx (13).

The position and shape of the laryngeal vocal folds are controlled by a group of muscles that control their different positions during speech and relaxation. In laryngeal nerve palsy, the vocal fold is fixed in a paramedian position on the affected side, resulting in an abnormal gap due to the unopposed medializing pull of the intact cricothyroid muscle, which is innervated by the superior laryngeal nerve (14,15). As a compensatory step during phonation, the vocal process of the normal vocal fold moves medially in an attempt to contact the vocal process of the paralyzed muscle (16). The compensatory movement causes an increased workload of the right vocal fold muscle group, and it must be assumed that this consequently leads to increased local glucose consumption. While no FDG activity is observed in the denervated group, increased FDG uptake may become visible in the contralateral laryngeal muscles in patients with laryngeal nerve palsy, owing to direct nerve infiltration by a central lung cancer on the left side or at the apex of the lung (ie, in the anatomic course of the recurrent laryngeal nerve) (17).

The combination of a left mediastinal mass reaching the aortopulmonary window and a lung tumor located in the left apex with a concomitant right-sided increased uptake in laryngeal muscles is, therefore, a finding that can be seen in patients with recurrent left-sided laryngeal nerve palsy. In patients with right-sided recurrent laryngeal nerve palsy caused by nerve invasion of the right upper pulmonary lesions, it seems possible that a compensatory activation of the left laryngeal muscles might be detected. In our series, the FDG uptake in the intrinsic laryngeal muscles could be related to the short communication time between patients and the nursing staff after FDG injection, but it may also represent a compensatory chronic work overload on these muscles. During this early phase, high blood concentration of the tracer will allow the metabolically active right-sided laryngeal muscles to accumulate sufficient amounts of FDG so that focal uptake is detectable. This pattern may mimic a tumorlike lesion, which may result in a false-positive diagnosis of the FDG accumulation in cancer patients.

In our study, all patients had lung cancer. The finding described here could potentially also be seen in patients after one-sided resection of the vocal fold due to cancer or other causes of unilateral laryngeal nerve palsy.

We conclude that knowledge of this nonmalignant finding is important to avoid false-positive PET results. Fusion of PET-CT images is a promising tool for the anatomic localization of lesions detected on the PET scans.

	ACKNOWLEDGMENTS

 
The authors thank Thomas Berthold, Conny Britt, Michelle Farrell, Merill Griff, and Lucia Meier for their technical support.

	FOOTNOTES

 
Abbreviation: FDG = fluorodeoxyglucose

Author contributions: Guarantor of integrity of entire study, H.C.S.; study concepts, G.W.G., H.C.S.; study design, H.C.S.; literature research, E.M.K.; clinical studies, E.M.K., G.W.G., H.C.S.; data acquisition, C.B.; data analysis/interpretation, E.M.K., G.W.G., H.C.S.; manuscript preparation, E.M.K., G.W.G.; manuscript definition of intellectual content, H.C.S.; manuscript editing, all authors; manuscript revision/review, G.K.v.S., H.C.S.; manuscript final version approval, all authors.

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This Article Abstract Figures Only Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kamel, E. M. Articles by Steinert, H. C. Search for Related Content PubMed PubMed Citation Articles by Kamel, E. M. Articles by Steinert, H. C.