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Journal of Clinical Oncology, Vol 23, No 30 (October 20), 2005: pp. 7740-7742 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.02.1972
Modern Treatment of Lung CancerCASE 3. Non-Metastatic Bilateral F-18 Fluorodeoxyglucose Avid Adrenal Glands in Non–Small-Cell Lung CancerBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA A 49-year-old male smoker presented with 6 months of dry cough and 1 week of hemoptysis. His medical history did not include adrenal disorders or use of corticosteroids. Physical examination demonstrated decreased breath sounds and ronchi in the right upper lobe. He had clubbing in his upper extremity digits. A computed tomography (CT) scan of the chest demonstrated a 5.8 x 5.8-cm mass within the medial right upper lobe, and a 1-cm right hilar node (Fig 1A). CT scans of the head, abdomen, and pelvis were unremarkable. A bronchoscopic fine-needle aspiration of the mass was positive for non–small-cell carcinoma. Mediastinoscopy showed no malignancy. A position emission tomography (PET) scan with PET/CT fusion images (Fig 1A) showed intense F-18 fluorodeoxyglucose (FDG) uptake within the right lung, corresponding to the CT mass with a measured standardized uptake value (SUV) of 21. In addition, there was increased FDG uptake within both the left and right adrenal glands (Fig 1A), with SUV of 6.1 and 4.7, respectively. The CT images of both adrenal glands appeared normal without any masses (Fig 2). A left adrenal fine-needle aspiration was nondiagnostic. Basal serum cortisol and adrenocorticotropic hormone were within normal limits, and a cosytropin stimulation test was normal. A 24-hour urine cortisol level and dexamethasone suppression test were normal. He was seen in consultation by endocrinology, and it was felt that this evaluation adequately excluded adrenal functional abnormalities. Chemotherapy with carboplatin 6 area under the curve and docetaxel 75 mg/m2 for two cycles was initiated. A repeat PET/CT fusion scan revealed marked improvement in the size of the right upper lobe tumor, now measuring 1.7 x 2.7 cm, and the FDG avidity had decreased to an SUV of 2.6 (Fig 1B). Both adrenal glands continued to show unchanged FDG uptake (Fig 1B). The neoadjuvant chemotherapy was followed by 6 weeks of concurrent chemoradiotherapy, with weekly carboplatin and docetaxel. Follow-up PET/CT showed a slight decrease in size and FDG uptake of the right upper lobe tumor. However the FDG uptake in adrenal glands was essentially unchanged. A second left adrenal fine-needle aspiration was nondiagnostic. The patient went on to have a right upper lobectomy for a presumed locally advanced non–small-cell lung cancer (NSCLC). The final pathology showed only small foci of residual large-cell carcinoma surrounded by scar tissue in the lung parenchyma. There was no lymph node involvement. A repeat PET/CT done 3 months after the surgical resection (and 8 months from diagnosis) continued to show unchanged FDG uptake of adrenal glands (Fig 1C). At his most recent follow-up, there is no evidence of recurrent disease (Fig 1C).
A substantial percentage of patients with newly diagnosed NSCLC have distant metastases at diagnosis.1 The most common metastatic sites include brain, bone, liver, and adrenal glands in order of prevalence.2 Metastases to the adrenal glands can be found in more than 30% of end-stage NSCLC patients at autopsy.3 In newly diagnosed cases of localized NSCLC, less than 5% of patients have adrenal metastases.2 Interestingly, in an unselected series of 330 patients with NSCLC, approximately 10% had evidence of unilateral or bilateral adrenal masses by conventional CT imaging,4 but more than two thirds of the lesions were not metastases.4 In another series of 246 patients with otherwise operable NSCLC, 5% had a unilateral adrenal mass, of which only 40% were found to be metastases, as proven by biopsy or cytology.5 Both authors point to the fact that the presence of an isolated adrenal mass should not preclude potentially curative surgery until a pathologic specimen confirms metastases.4,5 Magnetic resonance imaging can better visualize adrenal masses in patients with NSCLC; however, there is considerable signal intensity overlap between benign and malignant lesions leading to a significant number of false-positive results.6 The role of FDG PET to differentiate benign from malignant adrenal abnormalities in NSCLC has been studied.7-10 In 27 patients with NSCLC and adrenal masses on CT imaging, PET with FDG had a sensitivity of 100% and a specificity of 80% in identifying malignant disease using biopsy as the reference standard.8 In another series of 139 patients in which 15 had adrenal abnormalities by CT scans, PET was 100% accurate in identifying the six proven adrenal metastases.9 There were no false-positive results.9 In the largest cohort to date, 113 adrenal masses were evaluated (19 were bilateral), and the sensitivity, specificity, and accuracy of FDG PET for detecting metastatic disease were 93%, 90%, and 92%, respectively.10 False-positive results were due to either adenomas or pheochromocytomas.10 Adrenal lesions were considered benign in the absence of a biopsy if there was no radiographic change in serial CT images, despite effective chemotherapeutic treatment for the primary tumor or if the images remained stable for 4 to 6 months.5,7-10 Little is known about the characteristics of normal adrenal glands by FDG PET/CT; however, a small study of 20 patients demonstrated that there is a wide range of FDG uptake (SUV ranging from 0.95 to 2.46), and a single case in their cohort had significant bilateral adrenal uptake in the absence of adrenal pathology by CT scan or laboratory values.11 Our case illustrates that although FDG PET/CT is a highly accurate, sensitive, and specific method of identifying metastatic disease in adrenal glands of patients with NSCLC,8-10 false-positive results may incorrectly stage an individual patient. The nonmalignant nature of adrenal FDG uptake in NSCLC should be considered when: (1) the FDG uptake is not associated with an identifiable abnormality in the CT scan image, and (2) there is no change in the pattern of adrenal uptake with chemotherapy that causes a response in the primary lesion. Further studies of FDG PET/CT in NSCLC will hopefully define patterns of benign FDG adrenal uptake and permit appropriate staging of patients with otherwise localized malignancy amenable to curative interventions. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest.
Acknowledgment We thank Robert L. Thurer, MD, and Stuart M. Berman, MD, for their guidance and contribution to the patient's care. REFERENCES
1. Jemal A, Tiwari RC, Murray T, et al: Cancer statistics, 2004. CA Cancer J Clin 54:8-29, 2004
2. Quint LE, Tummala S, Brisson LJ, et al: Distribution of distant metastases from newly diagnosed non-small cell lung cancer. Ann Thorac Surg 62:246-250, 1996 3. Abrahams HL, Spiro R, Goldstein N: Metastases in carcinoma: Analysis of 1000 autopsied cases. Cancer 3:74-85, 1950[CrossRef][Medline]
4. Oliver TW, Bernardino ME, Miller JI, et al: Isolated adrenal masses in non-small cell bronchogenic carcinoma. Radiology 153:217-218, 1984 5. Ettinghausen SE, Burt ME: Prospective evaluation of unilateral adrenal masses in patients with operable non-small-cell lung cancer. J Clin Oncol 9:1462-1466, 1991[Abstract]
6. Burt M, Heelan RT, Coit D, et al: Prospective evaluation of unilateral adrenal masses in patients with operable non-small-cell lung cancer: Impact of magnetic resonance imaging. J Thorac Cardiovasc Surg 107:584-588, 1994
7. Schrevens L, Lorent N, Dooms C, et al: The role of PET scan in diagnosis, staging and management of non-small cell lung cancer. Oncologist 9:633-643, 2004
8. Erasmus JJ, Patz EF, McAdams HP, et al: Evaluation of adrenal masses in patients with bronchogenic carcinoma using 18F-fluorodeoxyglucose positron emission tomography. AJR Am J Roentgenol 168:1357-1360, 1997
9. Marom EM, McAdams HP, Erasmus JJ, et al: Staging non-small cell lung cancer with whole-body PET. Radiology 212:803-809, 1999
10. Kumar R, Xiu Y, Yu JQ, et al: 18F-FDG PET in evaluation of adrenal lesions of patients with lung cancer. J Nucl Med 45:2058-2062, 2004
11. Bagheri B, Maurer AH, Cone L, et al: Characterization of the normal adrenal gland with F-FDG PET/CT. J Nucl Med 45:1340-1343, 2004
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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