British Journal of Radiology (2007) 80, e67-e71
© 2007 British Institute of Radiology
doi: 10.1259/bjr/33076108
Impact of [18F]-fluorodeoxyglucose ([18F]-FDG) imaging in sarcoidosis: unsuspected neurosarcoidosis discovered by [18F]-FDG PET and early metabolic response to corticosteroid therapy
N Aide, MD
1
M Benayoun, MD
1
K Kerrou, MD
1
A Khalil, MD
2
J Cadranel, MD, PhD
3 and
J N Talbot, MD, PhD
1
1 Hôpitaux de Paris PET centre, Departments of 2 Radiology and 3 Pneumology, Hôpital Tenon AP-HP et Université Pierre et Marie Curie, Paris, France
Correspondence: Nicolas Aide, Department of Nuclear Medicine, Centre François Baclesse, Avenue du general Harris, 14000 Caen, France. E-mail: n.aide{at}baclesse.fr
 |
Abstract
|
|---|
A 46-year-old woman, with biopsy proven pulmonary sarcoidosis, was referred for an [18F]-FDG PET/CT scan that depicted multivisceral involvement and an unusual [18F]-FDG focus located in the pituitary fossa consistent with pituitary sarcoidosis. This was confirmed by decreased antidiuretic hormone blood levels and contrast-enhanced CT scan. This unsuspected neurosarcoidosis prompted corticosteroid therapy. A [18F]-FDG-PET/CT examination performed 10 weeks after initiation of treatment revealed complete recovery. It is suggested that the skull base should be included in the PET scanning of patients with sarcoidosis. [18F]-FDG imaging may be useful in the early evaluation of response to treatment.
|
Introduction
|
|---|
Among organs commonly involved in sarcoidosis, the nervous system is affected in 5–15% of cases [1]. The ability to identify this patient population is important since cerebral sarcoidosis should require systemic corticosteroid therapy [2].
"Whole body" positron emission tomography (PET) imaging with [18F]-FDG has been recognized as an efficient modality in the management of oncology patients. This imaging tool can also be used in evaluating the extent of inflammatory diseases, such as sarcoidosis, in which [18F]-FDG is known to be actively taken up [3].
To the best of our knowledge, we report the first case of unsuspected cerebral sarcoidosis to be diagnosed by [18F]-FDG PET/CT. The present case also illustrates the usefulness of [18F]-FDG to show an early response to systemic corticosteroid therapy in comparison with CT.
|
Case report
|
|---|
A 46-year-old woman, with biopsy proven pulmonary sarcoidosis was referred for a whole body [18F]-FDG PET/CT in order to evaluate the extent of her disease.
The PET study showed bilateral multiple hypermetabolic foci involving mediastinal and pulmonary hilar nodes, subdiaphragmatic nodes (Figure 1a
) and the axial skeleton (Figure 1b). Moreover, our attention was drawn to an unusual focus of [18F]-FDG uptake in the midpart of the skull base (Figure 1b) which corresponded to the posterior part of the pituitary fossa, as observed on the PET/CT fusion images (Figure 2).
View larger version (105K):
[in this window]
[in a new window]
|
Figure 1. (a) [18F]-FDG PET maximum intensity projection view shows thoracic (mediastinal hilar, head arrow) and subdiaphragmatic nodal involvement (hepatic hilar and left groin nodes, black arrows). (b) Sagittal slice shows bony lesions (dotted arrow), involving mostly the axial skeleton and an unusual [18F]-FDG uptake in the middle part of the skull base (white arrow). (c) Brain contrast-enhanced multidetector row CT scan shows an abnormal contrast enhancement of the leptomeninges close to the clivus (sagittal slice), as well as (e) an enlargement of the pituitary gland (12 mm on the coronal slice). (d) The bone window showed an osteolysis of the clivus. This feature was consistent with the diagnosis of neurosarcoidosis.
|
|
View larger version (89K):
[in this window]
[in a new window]
|
Figure 2. Transverse, sagittal and coronal PET slices, displayed side by side on the CT part of the PET/CT examination, show a moderate [18F]-FDG focus located in the posterior part of the pituitary fossa.
|
|
To be sure that this finding was not a variant of the normal brain biodistribution of [18F]-FDG, we examined retrospectively the [18F]-FDG PET/CT appearance of the corresponding area in 15 female patients in the 40–50 year age group. These "control" patients did not present with any neurological symptoms and no focus of [18F]-FDG uptake was found in the pituitary area (data not shown).
This [18F]-FDG focus located in the pituitary fossa prompted investigations of the hypothalamic–pituitary axis, including hormonal dosages and a brain CT scan. MRI of the brain would have been undertaken were it not for the fact that the patient suffered from acute claustrophobia.
A brain CT scan was performed and revealed thickening and contrast enhancement of the skull base leptomeninges, enlargement of the pituitary gland and lytic involvement of the clivus (Figure 1c–e
). This appearance was consistent with basal meningeal and pituitary sarcoidosis.
Antidiuretic hormone blood levels were decreased (1.3 pg ml–1, normal range: 3–6 pg ml–1). There was no other biological anomaly of hypothalamopituitary axis function.
This observation resulted in a change in the patient's management by formally indicating a corticosteroid treatment.
Follow up imaging studies were performed in accordance with guidelines on the treatment of sarcoidosis [2], and also because there was a need for therapy follow up, in the intention to reduce corticosteroid doses, as the patient complained of side effects.
A second PET study performed 10 weeks after the beginning of oral corticosteroid therapy showed that the [18F]-FDG foci had disappeared (Figure 3a and b). A brain CT scan revealed resolution of leptomeningeal enhancement over the clivus and normalization of the size of the pituitary gland (Figures 3d and e). Interestingly, the CT part of the PET/CT examination still showed enlarged mediastinal nodes and osteoblastic bony lesions (Figure 3c).
View larger version (98K):
[in this window]
[in a new window]
|
Figure 3. A second[18F]-FDG PET [(a) maximum intensity projection (MIP); and (b) whole body sagittal slice] performed after 10 weeks of corticosteroid therapy shows complete disappearance of the pathological [18F]-FDG foci depicted on the first PET scan. (c) The CT part of the PET/CT examination still shows osteoblastic lesions. (d) Contrast-enhanced multidetector row CT scan performed after 10 weeks of treatment with oral corticosteroids shows resolution of leptomeningeal enhancement over the clivus (sagittal slice) and (e) normalization of the appearance of the pituitary gland (coronal slice), as compared with Figure 1.
|
|
|
Discussion
|
|---|
Sarcoidosis is a multisystemic inflammatory disease which involves the central nervous system in up to 25% of those patients studied at autopsy. However, only 5–10% of these patients experience clinical symptoms [4]. The most frequently involved areas are the skull base meninges and the pituitary gland [5].
[18F]-FDG is a radiotracer that is widely used for the management of cancer patients, but is not specific for malignant tumours, since it is actively taken up in inflammatory processes, such as the epitheloid granulomas of sarcoidosis. Thus, [18F]-FDG imaging can be used to evaluate the extent of the disease in patients with known or suspected sarcoidosis and to target an optimal site for biopsy [3]. In this case report, multivisceral and bony involvement were depicted with this single imaging modality and either the mediastinal nodes or the left inguinal lymph node (Figure 1a) could have been readily accessible for biopsy.
However, the brain is not systematically included in whole body [18F]-FDG PET imaging, as reported in the Material and methods section of articles in which previous generations of "whole body" PET devices have been used, either dealing with oncology [6–8] or inflammatory diseases [9, 10]. Indeed, the main drawback of [18F]-FDG imaging in detecting central nervous system lesions is its high physiological uptake in the brain, which thus minimizes the lesion/brain ratio. As such, [18F]-FDG PET is considered to be of little interest in the above settings and more often the brain is not included in the so-called "whole body" PET images. Therefore, subclinical skull base involvement can be missed.
Nonetheless, no elevated [18F]-FDG uptake was seen in the pituitary area in any of the 15 female patients from the same age group. These results are in accordance with a previous study on pituitary microadenomas, where no false positive cases were noted in 20 healthy control subjects [11]. Thus, detection of an abnormal [18F]-FDG uptake seems possible in the region of the pituitary fossa: a structure which is commonly involved in cases of neurosarcoidosis. The attitude in our institution, since a PET/CT machine has been in use, is to include the brain in the PET scanning session. This rapid machine with LSO crystals allows a larger volume to be explored (without increasing the acquisition time) and yields high-resolution images when compared with our former PET machine equipped with NaI crystals.
CT performed for attenuation correction and localization purposes enhances the effective dose above the typical value of 7 mSv for [18F]-FDG PET, even though the CT acquisition parameters are set to low values (120 kV, 30–60 mAs in our centre). The effective dose for a [18F]-FDG PET/CT examination is lower than that delivered either by gallium-67 citrate scintigraphy or by whole body contrast-enhanced CT. Hence, in a recent study that compared several PET/CT protocols used in four hospitals [12], the effective dose of PET, low dose CT and diagnostic CT, respectively, ranged from 5.7 mSv to 7 mSv, from 1.3 mSv to 4.5 mSv and from 14.1 mSv to 18.6 mSv. Thus, the effective dose of a whole body PET/CT examination with low dose CT ranged from 8 mSv to 11.5 mSv. This is far lower than the irradiation dose induced by a gallium-67 citrate examination (18.5 mSv for the average recommended injected activity in an adult [13]), which is the current standard in nuclear medicine for imaging sarcoidosis.
[18F]-FDG brain parenchymal avid uptake or focal brain hypometabolism in neurosarcoidosis lesions has been demonstrated in symptomatic patients [14, 15]. However, to the best of our knowledge, this is the first case of unsuspected subclinical neurosarcoidosis as revealed by [18F]-FDG PET/CT. Moreover, it is noteworthy that this finding resulted in a change in patient management, since it prompted an immediate corticosteroid therapy, instead of the "wait and see" attitude initially planned. While the symptoms that necessitate corticosteroid therapy remain controversial, systemic therapy is indeed clearly indicated for neurological disease [2, 16, 17].
The second PET examination performed after 10 weeks of corticosteroid therapy showed a complete metabolic recovery, whereas conventional imaging still showed persistent abnormalities. Indeed, PET imaging may be employed to assess metabolic disturbances and their response to treatment, at a time when morphological changes are not detectable on conventional imaging techniques. [18F]-FDG imaging has indeed demonstrated efficacy for monitoring therapeutic response in a wide range of cancers [18]. In the light of the present case, one might assume that [18F]-FDG PET could be useful to predict therapy response early in the course of therapy of inflammatory diseases such as sarcoidosis.
In conclusion, we suggest that nuclear physicians should include at least the skull base in "whole body" scanning when patients undergo [18F]-FDG PET for staging of a known, or suspected, visceral sarcoidosis. Future studies with a larger number of patients are required to assess the diagnostic performance of [18F]-FDG PET in this setting and its ability to predict early response to systemic treatment.
|
Acknowledgments
|
|---|
Dr Alan R Young and Mrs Heather Costil are thanked for manuscript editing.
Received for publication October 12, 2005.
Revision received December 22, 2005.
Accepted for publication April 3, 2006.
|
References
|
|---|
- Hoitsma E, Faber CG, Drent M, Sharma OP. Neurosarcoidosis: a clinical dilemma. Lancet Neurol 2004;3:397–407.[CrossRef][Medline]
- Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med 1999;160:736–55.[Free Full Text]
- Zhuang H, Alavi A. 18-fluorodeoxyglucose positron emission tomographic imaging in the detection and monitoring of infection and inflammation. Semin Nucl Med 2002;32:47–59.[CrossRef][Medline]
- Christoforidis GA, Spickler EM, Recio MV, Mehta BM. MR of CNS sarcoidosis: correlation of imaging features to clinical symptoms and response to treatment. AJNR Am J Neuroradiol 1999;20:655–69.[Abstract/Free Full Text]
- Sato N, Sze G, Kim JH. Cystic pituitary mass in neurosarcoidosis. AJNR Am J Neuroradiol 1997;18:1182–5.[Abstract]
- Eubank WB, Mankoff DA, Takasugi J, Vesselle H, Eary JF, Shanley TJ, et al. 18fluorodeoxyglucose positron emission tomography to detect mediastinal or internal mammary metastases in breast cancer. J Clin Oncol 2001;19:3516–23.[Abstract/Free Full Text]
- Kalff V, Hicks RJ, Ware RE, Hogg A, Binns D, McKenzie AF. The clinical impact of (18)F-FDG PET in patients with suspected or confirmed recurrence of colorectal cancer: a prospective study. J Nucl Med 2002;43:492–9.[Abstract/Free Full Text]
- Pitman AG, Hicks RJ, Binns DS, Ware RE, Kalff V, McKenzie AF, et al. Performance of sodium iodide based (18)F-fluorodeoxyglucose positron emission tomography in the characterization of indeterminate pulmonary nodules or masses. Br J Radiol 2002;75:114–21.[Abstract/Free Full Text]
- Aberg C, Ponzo F, Raphael B, Amorosi E, Moran V, Kramer E. FDG positron emission tomography of bone involvement in sarcoidosis. AJR Am J Roentgenol 2004;182:975–7.[Free Full Text]
- Hendrickx BW, van Herpen CM, Bonenkamp JJ, Bulten J, Oyen WJ. Positive positron emission tomography scan in sarcoidosis and two challenging cases of metastatic cancer: Case 1. Mediastinal sarcoidosis in a melanoma patient treated with interferon. J Clin Oncol 2005;23:8906–7.[Free Full Text]
- De Souza B, Brunetti A, Fulham MJ, Brooks RA, DeMichele D, Cook P, et al. Pituitary microadenomas: a PET study. Radiology 1990;177:39–44.[Abstract/Free Full Text]
- Brix G, Lechel U, Glatting G, Ziegler SI, Munzing W, Muller SP, et al. Radiation exposure of patients undergoing whole-body dual-modality 18F-FDG PET/CT examinations. J Nucl Med 2005;46:608–13.[Abstract/Free Full Text]
- Radiation dose to patients from radiopharmaceuticals (addendum 2 to ICRP publication 53). Ann ICRP 1998;28:1–126.[Medline]
- Sponsler JL, Werz MA, Maciunas R, Cohen M. Neurosarcoidosis presenting with simple partial seizures and solitary enhancing mass: case reports and review of the literature. Epilepsy Behav 2005;6:623–30.[CrossRef][Medline]
- Dubey N, Miletich RS, Wasay M, Mechtler LL, Bakshi R. Role of fluorodeoxyglucose positron emission tomography in the diagnosis of neurosarcoidosis. J Neurol Sci 2002;205:77–81.[CrossRef][Medline]
- Sharma OP. Neurosarcoidosis: a personal perspective based on the study of 37 patients. Chest 1997;112:220–8.[CrossRef][Medline]
- White ES, Lynch JP, 3rd. Sarcoidosis involving multiple systems: diagnostic and therapeutic challenges. Chest 2001;119:1593–7.[CrossRef][Medline]
- Avril NE, Weber WA. Monitoring response to treatment in patients utilizing PET. Radiol Clin North Am 2005;43:189–204.[CrossRef][Medline]
Top
Abstract
Introduction
