18FDG Uptake in Sinonasal Inverted Papilloma Detected by Positron Emission Tomography/Computed Tomography

Inverted papilloma (IP) is a benign but locally aggressive sinonasal tumour. Aggressive surgical treatment has thus been traditionally recommended because of the risk of transformation in squamous carcinoma. CT and MRI are used to evaluate bone destruction and soft-tissue extension before surgery but may be ineffective to differentiate an inverted papilloma from squamous cell carcinoma. In recent years, F-18 Fluorodeoxyglucose positron emission tomography (18FDG-PET) is widely used as diffuse imaging procedure for diagnosis and followup of malignancy affecting the head and neck district. To evaluate the utility of 18FDG-PET/CT in the diagnosis of patients with suspicious lesions for IP, twelve patients with suspicious sinonasal inverted papilloma were selected for this study. 18FDG-PET/CT imaging was performed, and standard uptake value (SUV) was calculated for each patient. SUVmax⁡ was considered as the maximum value measured in the visualized lesions. Seven of the twelve cases exhibited uptake of 18FFDG with an SUVmax⁡ ranging from 1 to 8.1. Histopathologic diagnosis after surgery confirmed the diagnosis of IP in five cases; all these cases had an SUVmax > 3. The five cases, which exhibited absence of 18FDG uptake, had a histological diagnosis of absence of IP.


Introduction
Inverted papilloma (IP) is a benign but locally aggressive sinonasal tumour that origins from the ectodermal epithelium of the nose and paranasal sinuses. Its endophytic growth results in erosion of surrounding stroma and bone. The inverted papilloma is a rare disease accounting from 0.5 to 4% of all nasal tumours [1], but its significance is related to the tendency to recur after removal. Recurrence of IP following surgery is correlated to several factors including tumor location, extent, and methods of removal, but the most important determinant of recurrence is the completeness of resection.
Aggressive surgical treatment has thus been traditionally recommended [2] because the risk of transformation in squamous carcinoma is estimated as 5-15% of cases [3].
These evidences support the use of diagnostic imaging, although the clinical evaluation is the main step in the evaluation of patients with IP. In particular CT and MRI are used to evaluate bone destruction and soft-tissue extension before surgery, but it may be ineffective to differentiate an inverted papilloma from squamous cell carcinoma [4,5].
In recent years, F-18 Fluorodeoxyglucose positron emission tomography ( 18 FDG-PET) is widely used as diffuse imaging procedure for diagnosis and follow up of malignancy affecting the head and neck district [6].
In a previous study on patients with suspicious recurrence of IP we reported the ability of 18 FDG-PET to detect the recurrence of IP in patients that presented a 18 FDG-PET uptake in their lesion [7].
The purpose of this study was to evaluate the utility of 18 FDG-PET/CT in the diagnosis of patients with suspicious lesions for IP.  All patients included in the study provided informed consent to perform a 18 FDG-PET/CT before surgery instead of standard computed tomography. The study was approved by the institutional review board of the "Magna Graecia" University of Catanzaro. Whole-body CT was performed without the administration of intravenous or oral contrast. In this study, our series of patients 18 FDG-PET/CT scan has been acquired by using a low-dose CT. In particular this technical approach warrants an acceptable dosimetric impact for the patient because the emission PET scan gives an effective radiation dose of 6-7 mSv irrespective of the length of acquisition.

Measurements of
Statistical analysis has been made using MedCalc software version 9.0. An independent t-test was used to compare SUV max between groups, test was 2-tailed, and P < 0.05 was considered significant.

Patients.
Eleven patients were male and one female, and their average age was 58.5 years (range, 35-73 years). They presented mainly unilateral nasal obstruction, facial pain, and rhinorrea. On physical examination using nasal endoscopy, a unilateral similpolypoid neoformation was observed in the nasal cavity in all the patients.
These patients were assessed using 18 FDG/PET before surgical treatment. Ten of the twelve patients underwent surgical excision via functional endoscopic sinus surgery, and two patients underwent endoscopic-assisted surgery. From each patient surgical specimens were taken from the different involved localizations and separately submitted to histological examination. Seven of the Twelve (58.3%) patients exhibited 18 FDG uptake. These patients showed an 18 FDG uptake with a SUV max that ranged from 1 to 8.1, with a maximum SUV of 8.1 detected in a case with a histological diagnosis of recurrent IP associated with SCC.

Measurements of
The histological diagnosis was inverted papilloma in 5 of the 12 patients examined, while 7 were negative for IP. All patients (100%) with histological diagnosis of inverted papilloma showed 18 FDG uptake on FDG-PET/CT images; in this group the mean SUV max value was of 5.88 ± 1.3 (range 4.5-8.1). Of the seven patients with negative diagnosis for IP, five (71.4%) showed no signs of the 18 FDG uptake on FDG-PET/CT; in this group the mean SUV max was of 0.55 ± 1.0 (range 0-2.9).
The difference in the values of SUV max between patients with diagnosis of IP and negative for IP was statistically significant (P = 0.0001). Comparing FDG-PET/CT findings with histological diagnosis, FDG-PET/CT revealed a sensitivity and specify of 100%, considering a SUV max of <3.0 as a criterion for negative finding. Furthermore we noted that the cases with SUV max < 3 showed diffuse 18 FDG uptake (Figure 1), while well-defined areas of 18 FDG uptake ( Figure 2) could be observed in the cases with SUV max > 3.

Discussion
The literature on the diagnostic role of 18 FDG-PET/CT in sinonasal IP remains scarce [8][9][10][11][12] and includes mostly case reports [8,9]. In all reported cases, the 18 FDG SUV max values for benign IPs were lower than those detected for IP with coexistent SCC. Ninomiya et al. [11] made a comparative study using C-choline and 18 FDG PET on 22 patients with different pathological diagnosis of the nasal cavity and paranasal sinuses. This study include 5 cases of inverted papilloma with SUV max ranging from 2.30 to 5.20. In another original study Shojaku et al. [12] report five untreated patients with histological diagnosis of IP, made by biopsy in two different institutions, in which they perform a 18 FDG-PET before surgical treatment. They found a SUV max ranging from 4.9 to 7.3 in 3 patients with IP and 8.9 to 20.9 in two patients with IP and SCC. In this our study, if we considered a cut-off of SUV max of >3.0, 18 FDG-PET/CT was able to make diagnosis of IP with a sensitivity and specify of 100%. Lesions with a negative or diffuse 18 FDG uptake with SUV max less than 3 should be considered negative for IP. A SUV max of <3.0 as a criterion for negative findings on FDG-PET has already been used by Yao et al. [13] in order to detect metastatic lymph nodes in head and neck tumors, reaching a sensitivity and negative predictive value of 100%.
In light of these data, we believe that with further investigations the range and the cut-off SUV max for the diagnosis of IP could be assessed.
PET/CT seems to be a useful diagnostic tool providing a definition of the location of IP and of the extent of disease, with the advantage (compared with CT alone and MRI) of integrating morphological and metabolic data in one single session [14]. We believe that the standardization of the range of SUV max in each institution is of key importance in order to determine the reliability of PET/CT for the diagnosis of IP.
Our study had some limitations, which included the small size of the series and the lack of comparison with MRI findings.