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Paragangliomas (PGLs) are neuroendocrine tum-ors that arise embryologically from the neural crest. Sympathetic PGLs can be located in the thoracic-abdominal region while parasympathetic PGLs are mainly situated in the head and neck region. Most PGLs are sporadic, but in 30% of cases they are hereditary (associated with mutations of SDHB, SDHC, SDHD, SDHAF2, SDHA, TMEM, MAX, and VHL); they can be classified into 4 different paraganglioma syndromes: PGL1, PGL2, PGL3, and PGL4. Surgery is the treatment of choice for both sympathetic and parasympathetic PGLs. Other types of treatment include medical agents (such as gemcitabine, cisplatin, or sunitinib) and radiotherapy (external-beam radiotherapy or stereotactic surgery). Surgery and radiotherapy, however, can cause important side effects such as vascular complications and peripheral nerve damage (hypoglossal, recurrent laryngeal, glossopharyngeal, and vagus). Another possible treatment option is the use of peptide receptor radionuclide therapy (PRRT), including PRRT with 177Lu-DOTATATE. We studied 4 patients with hereditary nonmetastatic paraganglioma syndrome type 1 (PGL1), with progressive disease, in whom surgical excision was not possible. They were treated with 177Lu-DOTATATE (3-5 cycles) and all had a partial response (PR) or a stable disease (SD) to the treatment. In conclusion, a good alternative treatment when surgical or radiation therapy are contraindicated could be radiometabolic therapy with 177Lu-DOTATATE.

Carotid body paragangliomas (PGLs) are highly vascularized lesions that arise from the paraganglia located at the carotid bifurcation.To evaluate the usefulness of gray-scale ultrasound (US) and color Doppler ultrasound (CDUS) in the detection and follow-up of carotid PGLs of the neck.The authors retrospectively reviewed US and CDUS examinations of the neck performed in 40 patients with PGL syndrome type 1 and single or bilateral neck PGLs confirmed by CT or MRI; the patients had a total of 60 PGLs of the neck. US and CDUS outcome was compared to the outcome of second-line imaging techniques such as magnetic resonance imaging (MRI) or computed tomography (CT). The following findings were considered: presence/absence of focal lesions at US imaging and difference in maximum diameter of the lesion measured at US and MRI/CT. Results were compared using the Student's t-test.Of the 60 PGLs of the neck only 5 (8.3%) were not visualized at US or CDUS examination. The difference in maximum diameter of these lesions measured at CT/MRI and US/CDUS ranged between -5 mm and +16 mm (mean difference 2.2 ± 6.0). This difference was statistically significant (p = 0.008).US and CDUS are useful methods for identifying carotid PGLs also measuring less than 10 mm in diameter. However, diagnostic accuracy of US and CDUS is reduced in the measurement of the exact dimensions of the lesions.I paragangliomi (PGLs) carotidei sono lesioni altamente vascolarizzate che originano dai paragangli localizzati a livello della biforcazione carotidea.Valutare l’utilità dell’ecografia (US) e dell’Eco color Doppler (USD) del collo nella diagnosi e nel follow-up dei PGLs carotidei.Abbiamo visionato retrospettivamente tutte le US e gli USD del collo, eseguiti nell’Ospedale Santa Chiara di Trento tra il 2007 e il 2011, di soggetti affetti da sindrome paraganglioma di tipo 1 con sicuri paragangliomi del collo singoli o bilaterali. Abbiamo quindi confrontato i risultati con quelli di metodiche di imaging di secondo livello, Risonanza Magnetica (RM) o Tomografia Computerizzata (TC). Sono stati calcolati i casi discordanti in termini di presenza/assenza della lesione focale alle immagini ecografiche e in termini di differenze del diametro maggiore rilevate tra le due metodiche.Sono stati revisionati i dati di imaging (US e/o USD, RM o TC) eseguiti tra il 2007 e il 2011 di 40 pazienti aventi 60 sicuri paragangliomi del collo. Di questi solo 5/60 (8,3%) non sono stati visualizzati mediante US e/o USD. La differenza nella misura del diametro maggiore di tali lesioni rilevate dalle due tecniche di imaging, è risultata compresa tra -5 e +16 mm (media di 2,2 ± 6,0). Tale differenza è risultata statisticamente significativa (L’US e l’USD del collo risultano metodiche di imaging utili nell’identificazione dei PGL carotidei anche in caso di dimensioni inferiori al centimetro. La loro accuratezza diagnostica si riduce se consideriamo le misure esatte delle lesioni.

The aim of this pictorial essay is to illustrate the morphological [computed tomography (CT) and magnetic resonance imaging (MRI)], vascular (angiography) and functional (nuclear medicine) features of paragangliomas, uncommon lesions of the head and neck region and even more of the thorax, abdomen and pelvis, arising in an endemic area in northern Italy. These hypervascular, well-circumscribed masses usually have innocuous clinical manifestations as slowly enlarging soft-tissue lesions; however, more rarely, they can cause cranial-nerve palsy, particularly lesions arising near the skull base, or symptoms related to their secreting activity. Most paragangliomas are benign and their prognosis is directly related to the location of the tumour: those arising at the carotid body have the best outcome, whereas those located at the skull base have a less favourable prognosis. Angiography is required preoperatively in larger paragangliomas for surgical planning (vascular mapping) and, rarely, for preoperative embolisation. Morphological and functional imaging is also mandatory for surgical and/or radiometabolic treatment planning and follow-up.

BackgroundGermline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene and the p27KIP1 encoding gene CDKN1B have been associated with two well-defined hereditary conditions, familial isolated pituitary adenoma (FIPA) and multiple endocrine neoplasia type 4 (MEN4). Somatotropinomas are present in most AIP mutated FIPA kindreds, as well as in two-thirds of MEN4 patients who carry pituitary tumors.MethodsGermline DNA samples of 131 Italian sporadic acromegalic patients including 38 individuals with multiple tumors, and of six FIPA families (four homogeneous for prolactinomas and two heterogeneous with prolactin/nonfunctioning pituitary adenomas) were collected in a multicentric collaborative study. The prevalence of AIP and CDKN1B gene point mutations and copy number variations were evaluated.ResultsTwo novel (IVS3+1G>A and c.871G>A) and one previously described (c.911G>A) AIP mutations were detected in four apparently sporadic cases (3.1%) with relatively high age at diagnosis (49±18, range 30–67). No mutations/rearrangements were detected in FIPA families. The highly conserved c.871G>A substitution was detected in a patient who also carried a MEN1 mutation suggesting that she is a double heterozygote. The possible pathogenic effect on AIP splicing of the silent substitution c.144G>A found in another patient was ruled out using a minigene-based approach. CDKN1B mutations/rearrangements were neither identified in patients with multiple neoplasia nor in FIPA families.ConclusionAIP is mutated in about 3% of apparently sporadic acromegalic patients. The relatively high age at diagnosis, as well as its sporadic presentation, suggests that these patients are carriers of mutations with reduced pathogenicity. p27KIP1 is unlikely to represent the common unifying nonendocrine etiology for acromegaly and cancer.