Bronchogenic Carcinoid Tumours That Are 18F-Fluorodeoxyglucose Avid

European Journal of Cardio-Thoracic Surgery 45 (2014) 527–530 ORIGINAL ARTICLE doi:10.1093/ejcts/ezt436 Advance Access publication 18 September 2013

Bronchogenic carcinoid tumours that are 18F-fluorodeoxyglucose avid on positron emission tomography

Ben M. Hunt, Matthew P. Horton and Eric Vallières*

Swedish Medical Center and Cancer Institute, Seattle, WA, USA

* Corresponding author. 1101 Madison Street, Seattle, WA 98104, USA. Tel: +1-206-2156800; fax: +1-206-2156801; e-mail: [email protected] (E. Vallières).

Received 8 April 2013; received in revised form 6 June 2013; accepted 25 June 2013 Downloaded from https://academic.oup.com/ejcts/article/45/3/527/440512 by guest on 28 September 2021 Abstract OBJECTIVES: Bronchogenic carcinoid tumours are widely cited as non-fluorodeoxyglucose (FDG) avid. However, three case reports of FDG- avid bronchogenic carcinoid tumours have been published, leading to speculation as to which clinicopathological factors may be associated with increased activity on FDG-positron emission tomography. We reviewed a series of cases from our institution and compared them with the available reports in the literature, to attempt to identify the factors associated with FDG avidity in bronchogenic carcinoids. METHODS: We performed a single-institution retrospective review. RESULTS: One patient was identified at our institution who had a typical carcinoid tumour with a standardized uptake value (SUV) of 26, onco- cytic features on histology and positive staining for glucose transporter 1 (GLUT1). Three additional patients were identified in the literature with typical bronchogenic carcinoids with SUVs of 39, 38 and 33. Two of these tumours stained positive for GLUT1, and the remaining patient was not tested. Two of these patients had oncocytic features on histology, and results on the remaining patient are not reported. Additionally, 4 patients at our institution were identified with bronchogenic carcinoids with average SUV of 2.6. All were GLUT1 negative, and none had oncocytic features. In the reported literature, excluding the four most FDG-avid tumours described above, atypical carcinoids had a higher mean SUV than typical carcinoids (5.7 vs 3.4, P = 0.02), but size was not correlated with SUV (r =0.7,P =0.3). CONCLUSIONS: FDG uptake is commonly associated with worse prognosis in malignancy; however, bronchogenic carcinoids, particularly oncocytic typical carcinoids, are a possible source of extremely high SUVs on FDG-PET. Keywords: Bronchogenic carcinoid • FDG-PET • Oncocytic • GLUT1

pathological glucose transporter 1 (GLUT1) data were available. A

INTRODUCTION THORACIC PubMed search for bronchogenic carcinoids with reported stan- Increased glucose metabolism as measured by 18F- dardized uptake value (SUV) values on FDG-PET was conducted. fluorodeoxyglucose (FDG) positron emission tomography (PET) is Search terms were ‘carcinoid’ combined with ‘FDG’, ‘fluorodeoxy- used to stage a wide variety of malignancies, including lung cancer glucose’, ‘PET’ and/or ‘Positron Emission Tomography.’ Abstracts [1]. The high metabolic activity of malignant tissue is theorized to and manuscripts were reviewed for bronchogenic carcinoids, and result in rapid uptake of FDG, which is a radioactive glucose ana- bibliographies were reviewed for additional relevant papers. logue that can be imaged with PET. Initial reports suggested that Group means were compared with the Student’s t-test. A linear re- FDG-PET has a low sensitivity for bronchogenic carcinoids [2, 3]. gression analysis was used to correlate SUV with tumour size. All More recently, it has been recognized that FDG uptake in broncho- statistical tests were performed with the R software genic carcinoids is variable [4]. Despite several reports that broncho- (www.r-project.org). genic carcinoids can be FDG-avid, they are still commonly cited as negative on FDG-PET in major textbooks [1]. The aims of this study are to raise awareness that bronchogenic carcinoids can be RESULTS FDG-avid and to determine the clinical significance of FDG-avidity in this group of tumours. A 58-year old male ex-smoker presented with a round, smooth, well-demarcated 2 cm left lower lobe lung nodule. FDG-PET was obtained to further characterize the lesion, and the SUV was mark- MATERIALS AND METHODS edly elevated at 26 (Fig. 1). There were no other areas of abnormal tracer uptake concerning for metastasis. A transbronchial biopsy A single-institution retrospective review was performed in patients was performed, which showed a typical carcinoid with oncocytic with bronchogenic carcinoids in whom preoperative FDG-PET and histology. A lung-sparing anatomical resection (superior

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Figure 1: (A) Computed tomography (CT) and (B) PET-CT images of a FDG-avid (SUV = 26) typical bronchogenic carcinoid. segmentectomy) was performed. Final pathological stage was T1aN0M0R0. The tumour was a 2.1 cm typical carcinoid tumour with appropriate strong reactivity with chromogranin and synap- tophysin by immunohistochemistry and oncocytic features on histology (Fig. 2A). A GLUT1 stain was diffusely positive (Fig. 2B). The patient is asymptomatic with no evidence of recurrence on repeat imaging 7 years later. Four additional patients with carcinoid tumours who had undergone FDG-PET were identified from our institution, all with moderately elevated FDG-avidity (average SUV 2.6), and the resected specimens were stained for GLUT1. All were negative. The specimens were also re-examined for histological evidence of oncocytic features, and none were present (Fig. 2C). All these tumours displayed appropriate strong reactivity with chromogra- nin and synaptophysin by immunohistochemistry.

Figure 2: (A) Oncocytic typical carcinoid (SUV = 26), (B) same tumour stained for GLUT1 and (C) typical carcinoid without oncocytic features, with negative DISCUSSION GLUT1 staining (SUV = 2.6).

An influential early series of patients with bronchogenic carcinoid FDG-avid tumours are typical carcinoids. The long-term follow-up reported low FDG avidity (average SUV 2.4) and a high rate of is available on 2 of the patients, and both had a favourable negative FDG-PET scans: 86% (6/7) of patients had SUV below 2.5 outcome [5 and the current report]. [2]. Low FDG uptake in carcinoids was confirmed by other authors Excluding the four cases of extremely FDG-avid bronchogenic [3], and carcinoids became well-known as a common cause of carcinoids from the dataset, the pooled available literature de- false-negative FDG-PET scans [1]. More recently, however, three scribing patients with carcinoid tumours in whom FDG-PET results cases of extremely FDG-avid bronchogenic carcinoids with SUVs were reported supports the view that atypical carcinoids are more of 39 [5], 38 [6] and 32.9 [7] have been reported in the literature, FDG-avid than typical carcinoids (Table 1). Mean SUVs were and the patient who prompted this series is the fourth (SUV = 26). higher in the atypical group (5.7 vs 3.4, P = 0.02). There was no cor- Three of these four tumours stained positive for GLUT1 (the fourth relation between tumour size and SUV (r = 0.7 and 0.3). Not was not stained), and three tumours have the oncocytic histotype enough data on clinical outcomes were available to make compar- (unspecified in the fourth tumour). All four of the extremely isons between outcome and SUV in the literature. B.M. Hunt et al. / European Journal of Cardio-Thoracic Surgery 529

Table 1: Reported SUVs on FDG-PET of bronchogenic carcinoid tumours and their associated characteristics

Study Number of patients SUV Typical/atypical Oncocytic GLUT1 Size (cm)

Erasmus et al.[2] 5 2.8 T 3.1 Erasmus et al.[2] 1 2.3 A 2.1 Abe et al.[20] 1 Negative T 1.5 Kadowaki et al. [5] 1 39 T Y Y 3.0 Krüger et al. [14] 12 3.2 T 2.3 Krüger et al. [14] 1 9.0 A 3.0 Chong et al.[4] 2 3.3 T 3.7 Chong et al.[4] 5 4.3 A 3.6 Suemitsu et al.[7] 1 32.9 T Y 3.2 Kaira et al.[19] 6 5 T/1A 1/6 positive et al Wartski .[12] 1 4.9 T N Downloaded from https://academic.oup.com/ejcts/article/45/3/527/440512 by guest on 28 September 2021 Wartski et al.[12] 1 6.0 A N 1.0 Marom et al.[9] 6 5 positive, 1 negative Belhocine et al.[8] 2 Positive T Belhocine et al.[8] 1 Positive A Kayani et al.[15] 12 5.2 T 2.9 Kayani et al.[15] 2 13.1 A Daniels et al.[13] 8 Positive T 1.7 Daniels et al.[13] 3 Negative T 1.7 Daniels et al.[13] 4 Positive A 3.3 Daniels et al.[13] 1 Negative A 1.3 Eren et al.[21] 1 2.5 T N 0.6 Cheng et al.[22] 1 3.3 T N 1.7 Turan et al.[6] 1 38 T Y 2.8 Jindal et al.[11] 6 Negative T Jindal et al.[11] 7 2.9 T Jindal et al.[11] 7 8.4 A Prieto-Tenreiro et al. [18] 1 Positive A 1.1 Jindal et al. [23] 1 3.1 T Tani et al. [24] 1 Negative T N 1.7 Avram et al. [25] 1 Negative T 3.0 Shin et al. [17] 1 1.6 T 1.3 Nguyen and Ram [16] 1 Intensely positive A 1.5 Jain et al. [10] 1 Intensely positive T 2.8 Rege et al.[3] 1 Negative T Current series 1 26.0 T Y Y 2.1 Current series 4 2.6 T N N 2.9 THORACIC

Various predictors of FDG activity in bronchogenic carcinoids Bronchogenic carcinoids have a wide range of FDG-avidity. have been suggested. Atypical carcinoids might be more metabol- Based on published studies reviewed here, typical carcinoids often ically active and therefore more FDG-avid than typical carcinoids have lower SUVs than atypical carcinoids, and a mild elevation in [4, 11–18], as we found to be the case in this review. An association SUV in a tumour that otherwise appears to be a bronchogenic car- has been suggested between FDG-avidity and tumour size [2, 4, cinoid should raise the suspicion of an atypical carcinoid. 13], but this hypothesis was not supported by the current analysis. Markedly elevated SUVs (20s–30s), on the other hand, appear to Lesions that are metastatic might have higher FDG-avidity [7], but be associated with the oncocytic histotype of typical carcinoid data on metastasis were not available in this study. Expression of tumour and positive staining with GLUT1, but not with a poor the GLUT1 glucose transport protein might predict glucose uptake prognosis. and, therefore, FDG avidity [5, 7, 19]. This was found to be the case in at least three of the four most FDG-avid carcinoids in the litera- CONCLUSIONS ture. However, several cases of less extremely FDG-avid broncho- genic carcinoids (SUVs 4.9 and 6.0) have stained negative for High FDG uptake is commonly associated with more aggressive GLUT1 expression [12]. malignancies, but it is important to remember that some indolent We found extremely high levels of FDG uptake on PET in carcin- tumours (e.g. typical carcinoids) can also be very FDG-avid. oid tumours with the oncocytic histotype. Since an oncocytic ap- Oncocytic typical carcinoids should be kept in mind as a possible pearance on histology is due to an abundance of mitochondria in source of extremely high SUVs on FDG-PET. the cytoplasm, and mitochondria are a main site of glucose me- tabolism, it is not surprising that these tumours have increased glucose uptake resulting in increased FDG avidity. High SUVs on Funding FDG-PET have also been reported in oncocytic tumours of the pancreas, an oncocytic Schneiderian papilloma, and an oncocytic The authors acknowledge the support of the Ryan Hill Foundation tumour of the parotid. and the Foundation for Surgical Fellowships. 530 B.M. Hunt et al. / European Journal of Cardio-Thoracic Surgery

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