Head and neck paragangliomas: molecular imaging and genetics

Introduction and Aim: Head and neck paragangliomas (HNP), are usually slowly growing, biochemically silent, benign tumors derived from parasympathetic ganglia. However, screening for genetic alterations is mandatory nowadays because HNP can be part of paraganglioma syndrome, due to mutations in SDHB, SDHC and SDHD genes, associated with tumors arising in adrenal gland, orthosympatetic para aortic and retroperitoneal paraganglia. Aim of the study was to correlate an uptake ratio of 111In pentetreotide with genetic testing in 14 cases of HNP. Material and Methods: Charts of 14 consecutive patients [3 males (21.5%), 11 females (78.5%), median age 59 years, range 26 76] who underwent 111In pentetreotide scintigraphy from 2005 to 2007 were reviewed. SPET and whole body 111In pentetreotide scintigraphy (mean dose of 150 MBq) at 5 and 24 hours after injection, were performed in all patients. As concerns semiquantitative indexes, a ratio was obtained comparing counts/pixel derived from a VOI in the tumour area with mirrored VOI in the contralateral site (or non affected areas if bilateral HNP). Mutation of genes encoding for succinate dehydrogenase subunit B(SDHB), C(SDHC), D(SDHD) have been studied by direct sequencing of all exons and intronic flanking regions in all patients. Multiple ligation dependent probe amplification method (MLPA P226 kit, MRC Holland) was used to assess gross deletions. RET and VHL mutations were also analyzed in all patients. Results: Two groups of patients were identified: group A (6 patients, 11 lesions) with positive genetic testing† † group B (8 patients, 8 lesions) with negative genetic testing. Identified mutations were SDHD c.341 G>C p.Y114C substitution (5 patients) and SDHC c.439 C>G p.Q147X substitution (1 patient). All but one patient in both groups (histologically confirmed) presented high radiopharmaceutical uptake (group A mean ratio=14.78±20, group B mean ratio=12.57±9.18). Mann Whitney U Test demonstrated no statistically significant difference between uptake in the two groups (p=0.184). Interestingly in group A 5 of 6 patients presented bilateral uptake while in group B none. Conclusions: HNP, in the majority of cases (16 of 19), presented high uptake of 111In pentetreotide. Mutations in genes encoding for succinate dehydrogenase subunit do not affect radiopharmaceutical uptake suggesting that the high content of somatostatin receptors is independent from this genetic background. Data suggest that patients presenting genes mutation are often affected by multiple lesions and therefore SPET and whole body scan should be analyzed carefully to assess spread of disease. On the other hand, when multiple sites of uptake are present, patient should be referred to geneticist.