N. Fakhry

18F-FDG Avidity of Pheochromocytomas and Paragangliomas: A New Molecular Imaging Signature?

Our objective was to evaluate 18F-FDG PET uptake in patients with nonmetastatic and metastatic chromaffin-derived tumors. Methods: Twenty-eight consecutive unrelated patients with chromaffin tumors, including 9 patients with genetically determined disease, were studied. A combination of preoperative imaging work-up, surgical findings, and pathologic analyses was used to classify the patients into 2 groups: those with nonmetastatic disease (presumed benign, n = 18) and those with metastatic tumors (n = 10). 18F-FDG PET was performed in all cases. Visual and quantitative analyses were individually graded for each tumor. Somatic mutations of the succinate dehydrogenase subunits B and D and Von-Hippel Lindau genes were also evaluated in 6 benign sporadic tumor samples. Results: All but 2 patients showed significantly increased 18F-FDG uptake on visual analysis. The maximum standardized uptake value (SUVmax) ranged from 1.9 to 42 (mean ± SD, 8.2 ± 9.7; median, 4.6) in nonmetastatic tumors and 2.3 to 29.3 (mean ± SD, 9.7 ± 8.4; median, 7.4) in metastatic tumors. No statistical difference was observed between the groups (P = 0.44), but succinate dehydrogenase–related tumors were notable in being the most 18F-FDG–avid tumors (SUVmax, 42, 29.3, 21, 17, and 5.3). Succinate dehydrogenase and Von-Hippel Lindau–related tumors had a significantly higher SUVmax than did neurofibromatosis type 1 and multiple endocrine neoplasia type 2A syndrome–related tumors (P = 0.02). 18F-FDG PET was superior to 131I-metaiodobenzylguanidine in all metastatic patients but one. By contrast, 18F-FDG PET underestimated the extent of the disease, compared with 6-18F-fluorodopa PET, in 5 patients with metastatic pheochromocytoma. However, succinate dehydrogenase mutations (germline and somatic) and functional dedifferentiation do not adequately explain 18F-FDG uptake since most tumors were highly avid for 18F-FDG. Conclusion: 18F-FDG PET positivity is almost a constant feature of pheochromocytomas and paragangliomas. It may be considered a molecular signature of such tumors, although which aspect of the plethora of molecular changes associated with dedifferentiation, germline genetic defects, or the adaptive response to hypoxia is responsible for this characteristic requires further elucidation.

Functional characterization of nonmetastatic paraganglioma and pheochromocytoma by (18) F-FDOPA PET: focus on missed lesions.

To evaluate the clinical value of 18F‐fluorodihydroxyphenylalanine (18F‐FDOPA) PET in relation to tumour localization and the patients genetic status in a large series of pheochromocytoma/paraganglioma (PHEO/PGL) patients and to discuss in detail false‐negative results.

Comparison of [111In]pentetreotide‐SPECT and [18F]FDOPA‐PET in the localization of extra‐adrenal paragangliomas: the case for a patient‐tailored use of nuclear imaging modalities

Aims and methods  The aim of this prospective study was to compare the diagnostic value of [18F]FDOPA‐PET and [111In]pentetreotide‐SPECT somatostatin receptor scintigraphy (SRS) in patients with nonmetastatic extra‐adrenal paragangliomas (PGLs). Twenty‐five consecutive unrelated patients who were known or suspected of having nonmetastatic extra‐adrenal PGLs were prospectively evaluated with SRS and [18F]FDOPA‐PET. 131I‐MIBG and [18F]FDG‐PET were added to the work‐up in patients with a personal or familial history of PGL, predisposing mutations, abdominal PGLs, metanephrine hypersecretion and abdominal foci on SRS and/or [18F]FDOPA‐PET.

Fine-needle aspiration cytology in the management of parotid masses: Evaluation of 249 patients

INTRODUCTION The role of fine-needle aspiration cytology (FNAC) in the management of parotid tumours is still the subject of controversy. The purpose of this study was to determine the diagnostic value of FNAC in our institution in order to define its place in the diagnostic strategy. PATIENTS AND METHODS This retrospective study was based on 249 patients who had undergone preoperative FNAC before being operated in our institution between 2001 and 2008. All examinations were performed and interpreted by the same experienced pathologist. RESULTS Among the 249 patients included in this study, 187 (75%) had a benign tumour and 62 (25%) had a malignant tumour. No complications of FNAC were observed. Cytological findings were non-contributory in 47 patients (18%). The sensitivity of FNAC for the diagnosis of malignancy was 80% with a specificity of 89.5%. Among the 11 false-negative results, lymphomas and low-grade mucoepidermoid carcinomas were the most common histological types. Among the 16 false-positive results, Warthins tumours, pleomorphic adenomas and lymphoepithelial lesions were the most common histological types. Accurate histological classification of the tumour was reported in 79.5% of cases (86% for benign tumours and 44% for malignant tumours). CONCLUSION FNAC is a reliable examination providing important information to the surgeon in the preoperative diagnostic assessment.

Sinonasal mucosal melanomas: the prognostic value of tumor classifications.

The purpose of this study was to assess the prognostic value of the 3 staging systems found in the literature for sinonasal mucosal melanomas tumors: the Ballantyne staging system modified by Prasad (Ballantyne/Prasad staging system), the American Joint Committee on Cancer (AJCC) TNM classification for mucosal melanomas (mmTNM), and the 2009 AJCC TNM classification for carcinomas of the nasal cavity and sinuses (carTNM).

Sinonasal squamous cell carcinomas: clinical outcomes and predictive factors.

This was a retrospective study of 33 patients treated for sinonasal squamous cell carcinoma between 1995 and 2008. Epidemiological, clinical, histological, and therapeutic aspects of this series of patients were analysed, and their impacts on overall survival and disease-free survival established using the Kaplan-Meier method. A search for prognostic factors was made using a log-rank test. There were 27 men. The average age at diagnosis was 64.7 years. Tobacco-smoking was found to be a risk factor in 24 patients (72.7%). The median follow-up was 66 months (range 0-99 months). Tumours were classified as T1 in 18.3%, T2 in 27.3%, T3 in 6%, and T4 in 48.5% of cases. Disease-free survival rates at 1 and 5 years were 58.5% and 46.1%, respectively, and overall survival rates were 70.3% and 40%, respectively. Overall survival was correlated to tumour status (TNM, American Joint Committee on Cancer) (P = 0.010) and involvement of key structures (skull base, dura mater, brain, orbit, cavernous sinus, infratemporal fossa, skin) (P = 0.049). Surgery followed by radiotherapy improved overall survival (P = 0.005) and disease-free survival (P = 0.028) when compared to other treatment modalities. When compared to surgery alone, it improved disease-free survival (P = 0.049) regardless of tumour stage.

Prognostic value of the status of resection margins after endoscopic laser cordectomy for T1a glottic carcinoma.

OBJECTIVES The small size of endoscopic laser cordectomy (ELC) specimens frequently leads the histopathologist to assess excision margins as pathologic. The present study sought to assess the prognostic value of margin status in terms of overall and of recurrence-free survival in a population of T1a glottic carcinoma operated on by ELC. MATERIAL AND METHODS Sixty-four records of T1a squamous-cell carcinoma treated between 1996 and 2006 were retrospectively analyzed. Overall and recurrence-free survival for the group with negative margins (group 1) and with positive margins (group 2) were analyzed following Kaplan-Meier. The influence of resection margin histologic status was assessed on Log Rank test. RESULTS Six female and 58 male patients were included. Forty (62.5%) had negative margins (group 1) and 24 (37.5%) positive margins (group 2). Overall five-year survival was 97% (95% in group 1 and 100% in group 2). Five-year recurrence-free survival was 94% (91.7% in group 1 and 95% in group 2). There was no significant difference in overall or recurrence-free survival according to resection margin histologic status. CONCLUSIONS The present results show that margins considered positive after laser resection do not significantly impact carcinologic course, while still requiring close surveillance. The most generally recommended attitude is control endoscopy with biopsy at 10 weeks.

18F-FDG PET/CT as a predictor of hereditary head and neck paragangliomas

Hereditary head and neck paragangliomas (HNPGLs) account for at least 35% of all HNPGLs, most commonly due to germline mutations in SDHx susceptibility genes. Several studies about sympathetic paragangliomas have shown that 18F‐FDG PET/CT was not only able to detect and localize tumours, but also to characterize tumours (18F‐FDG uptake being linked to SDHx mutations). However, the data concerning 18F‐FDG uptake specifically in HNPGLs have not been addressed. The aim of this study was to evaluate the relationship between 18F‐FDG uptake and the SDHx mutation status in HNPGL patients.

Fine needle aspiration cytology and frozen section in the diagnosis of malignant parotid tumours.

The aim of this study was to determine the value of fine needle aspiration cytology (FNAC) and frozen section (FS) in the diagnosis of malignant parotid tumours. One hundred and thirty-eight patients who underwent FNAC and FS of a parotid tumour between 2006 and 2011 were analyzed retrospectively. The sensitivity, specificity, and positive and negative predictive values of FNAC and FS were determined using final histological diagnosis as the gold standard. Of the 138 tumours assessed in our study, 30 were malignant and 108 benign. For FNAC, the sensitivity was 73%, specificity 87%, positive predictive value 61%, and negative predictive value 90%. For FS, the sensitivity was 80%, specificity 98%, positive predictive value 92%, and negative predictive value 94%. Four false-negative results by FNAC were corrected by FS, and surgery was completed. Two false-positive results were identified by both FNAC and FS. FNAC is an important examination that provides valuable information for the preoperative diagnostic work-up and alerts the surgeon to the possible presence of malignancy. However, FNAC cannot be used alone, and FS has a very important place in the intraoperative management of parotid tumours.

Magnetic resonance spectroscopy of paragangliomas: new insights into in vivo metabolomics

Paragangliomas (PGLs) can be associated with mutations in genes of the tricarboxylic acid (TCA) cycle. Succinate dehydrogenase (SDHx) mutations are the prime examples of genetically determined TCA cycle defects with accumulation of succinate. Succinate, which acts as an oncometabolite, can be detected by ex vivo metabolomics approaches. The aim of this study was to evaluate the potential role of proton magnetic resonance (MR) spectroscopy ((1)H-MRS) for identifying SDHx-related PGLs in vivo and noninvasively. Eight patients were prospectively evaluated with single voxel (1)H-MRS. MR spectra from eight tumors (four SDHx-related PGLs, two sporadic PGLs, one cervical schwannoma, and one cervical neurofibroma) were acquired and interpreted qualitatively. Compared to other tumors, a succinate resonance peak was detected only in SDHx-related tumor patients. Spectra quality was considered good in three cases, medium in two cases, poor in two cases, and uninterpretable in the latter case. Smaller lesions had lower spectra quality compared to larger lesions. Jugular PGLs also exhibited a poorer spectra quality compared to other locations. (1)H-MRS has always been challenging in terms of its technical requisites. This is even more true for the evaluation of head and neck tumors. However, (1)H-MRS might be added to the classical MR sequences for metabolomic characterization of PGLs. In vivo detection of succinate might guide genetic testing, characterize SDHx variants of unknown significance (in the absence of available tumor sample), and even optimize a selection of appropriate therapies.