Combination of 18 F-FDG and 68 Ga-DOTATOC PET-CT to differentiate endobronchial carcinoids and inflammatory myofibroblastic tumorsT Jindal1, A Kumar1, R Dutta1, R Kumar2
1 Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, India
2 Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0022-3859.58932
Source of Support: None, Conflict of Interest: None
Bronchial masses in young patients are a diagnostic challenge as the signs and symptoms are overlapping. Conventional radiological investigations reveal a mass but are not diagnostic and biopsy remains the only means of preoperative diagnosis. Functional imaging is now emerging as an important tool in the evaluation of these patients and may have a potential to suggest a possible diagnosis. A combination of 18 F-FDG PET-CT and 68 Ga-DOTATOC PET-CT scan is one such example, which revealed contrasting findings in two patients that are being presented here.
Keywords: Bronchial carcinoid, inflammatory myofibroblastic tumor, positron emission tomography-computed tomography
Bronchial masses pose a diagnostic dilemma especially in young patients. Most of these patients present with nonspecific symptoms such as cough, wheeze, hemoptysis, and recurrent chest infections. The differential diagnoses can vary from an infection to an inflammatory myofibroblastic tumor to a pulmonary carcinoid. Radiological investigations such as chest radiographs, computed tomography (CT) and magnetic resonance imaging (MRI) demonstrate the tumor and its extent but there are no specific signs for making a definitive diagnosis. , Bronchial biopsy remains the 'gold standard' for establishing diagnosis.
Recently, positron emission tomography (PET) has been increasingly employed in the management of various cancers.  Fluorodeoxyglucose (FDG) is the most commonly used radiotracer for PET/PET-CT scan. The scan shows an increased uptake in lung cancer and inflammatory/infective lung masses. , However, 18 F-FDG-PET has limited role in typical pulmonary neuroendocrine tumors due to their low glucose metabolizing activity.  In such patients, somatostatin receptor analog radiotracer 68 Ga-DOTATOC (68 Gallium 1, 4, 7, 10-Tetraazacyclododecane-N I , N II , N III , N IIII ,- tetra acetic acid (D)-Phel 1 -Tyr 3 -octreotide) is reported to be helpful.  Thus, a combination of 18 F-FDG PET-CT and 68 Ga-DOTATOC PET-CT scan may help in suggesting a possible diagnosis in patients with bronchial mass. We present the first experience with the use of such a combination in two young patients with bronchial masses.
A 19-year old male presented with history of cough and hemoptysis for 2 years. CT scan revealed a well circumscribed, enhancing mass with central lucency in the right lower lobe of the lung measuring 69 x 56 x 56 mm. Bronchoscopic examination revealed a vascular mass occluding the right main bronchus, which bled profusely on touch as well as at attempted biopsy, so it was abandoned. On the basis of clinical history and imaging features, a provisional diagnosis of bronchial carcinoid was made. The patient underwent 68 Ga-DOTATOC PET-CT scan to confirm neuroendocrine tumor. However, there was no significant radiotracer uptake, questioning the diagnosis of carcinoid [Figure 1] upper panel. Therefore, 18 F-FDG PET-CT scan was performed which demonstrated an intense uptake in the mass (SUVmax 12) [Figure 1] lower panel. At surgery, there was a tumor in the lower lobe bronchus extending up to the proximal right main bronchus with significant extra-bronchial component making lobectomy or sleeve resection impossible. Right pneumonectomy was performed. Histopathology revealed an inflammatory myofibroblastic tumor of lung.
A 16-year-old female presented with cough, chest pain and dyspnoea for one year. Her systemic examination revealed absence of breath sounds on the left side. Chest X-ray revealed an collapse of the left lung. CT scan revealed a mass in the left main bronchus with collapse of lung and parenchymal destruction. At bronchoscopy, a vascular mass was seen filling the left main bronchus, which bled profusely on touch. The bronchoscopic biopsy was inconclusive. On the basis of history, imaging features and bronchoscopy finding, a carcinoid tumor was suspected. We performed 68 Ga-DOTATOC PET-CT scan, which revealed high tracer uptake (SUVmax 58) [Figure 2] upper panel. As a part of the present protocol in our hospital to evaluate all such patients with a combination of 68 Ga-DOTATOC as well as 18 F-FDG PET-CT scan, she underwent 18 F-FDG PET-CT scan which revealed mild uptake in the tumor (SUVmax 3.1) [Figure 2] lower panel. At surgery, the tumor was completely occluding the left main bronchus. The lung parenchyma looked grossly abnormal and fibrosed, hence left pneumonectomy was performed. Histopathology revealed features of typical bronchial carcinoid.
The myofibroblastic tumors and carcinoids can present as bronchial masses with similar symptoms. , Conventional imaging modalities such as CT scan and MRI demonstrate a space occupying lesion but do not provide additional information that could make more specific diagnosis possible. , Tumor markers have been described for carcinoids but suffer from lower sensitivity and cannot localize the site of the tumor. 
In this report, we describe the 'flip-flop phenomenon' between 18 F-FDG PET-CT and 68 Ga-DOTATOC PET-CT scan observed in two young patients. Inflammatory myofibroblastic tumors are associated with intense inflammation, which results in preferential FDG uptake.  On the other hand, typical carcinoid tumors are well differentiated and exhibit low proliferative activity, thereby showing poor FDG concentration.  However, most of the neuroendocrine tumors including carcinoids exhibit somatostatin receptors especially subtype 2 and 5.  Somatostatin receptor scintigraphy using 111 In-pentetreotide had shown good results in the management of neuroendocrine tumors. However, it has low spatial resolution and therefore low sensitivity in case of small tumors.  Recently, 68 Ga-DOTATOC, a novel somatostatin receptor analogue has been used with PET-CT. This provides high-resolution images with ability to detect even small tumors.
A positive 68 Ga-DOTATOC PET-CT confirms the presence of somatostatin receptors on the tumour surface and therefore the neuroendocrine nature. On the contrary, a negative 68 Ga-DOTATOC scan with an increased FDG uptake may open a wider range of differential diagnosis including inflammatory myofibrobalstic tumour, low-differentiation grade NET, lung cancer, etc.
Case-1 underwent a 68 Ga-DOTATOC PET-CT scan based on clinical diagnosis of carcinoid tumour, which showed minimal uptake, much less than that usually observed in carcinoid tumors. However, 18 F-FDG PET-CT scan showed intense uptake in this tumour. On the basis of 18 F-FDG PET-CT and 68 Ga-DOTATOC PET-CT findings, the lung mass was thought to be either a poorly differentiated neuroendocrine tumor which does not express somatostatin receptors or a tumor associated with poor differentiation or intense inflammation such as an inflammatory myofibroblastic tumor. At histopathology, it turned out to be an inflammatory myofibroblastic tumor. Case-2 had similar clinical presentation as case-1. 18 F-FDG PET-CT revealed a mild uptake in left bronchial mass, while 68 Ga-DOTATOC PET-CT scan showed a high radiotracer uptake. On the basis of 18 F-FDG PET-CT and 68 Ga-DOTATOC PET-CT findings, the mass was diagnosed as bronchial carcinoid, which was confirmed on histopathology.
This initial experience of 'flip-flop phenomenon' on a combination of 18 F-FDG PET-CT and 68 Ga-DOTATOC PET-CT scan in these two patients encourages us to suggest further evaluation of such a combination of functional radiology to establish its exact role in the workup of young patients with endobronchial masses.
[Figure 1], [Figure 2]