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.

The precise diagnosis of thyroid neoplasias will guide surgical management. Primary thyroid paraganglioma has been rarely reported. Data on prevalence, immunohistochemistry (IHC), and molecular genetics in a systematic series of such patients are pending. We performed a multinational population-based study on thyroid paraganglioma and analyzed prevalence,

Background: Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene and the p27 KIP1 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. Methods: Germline 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. Results: Two novel (IVS3C1GOA and c.871GOA) and one previously described (c.911GOA) AIP mutations were detected in four apparently sporadic cases (3.1%) with relatively high age at diagnosis (49G18, range 30-67). No mutations/rearrangements were detected in FIPA families. The highly conserved c.871GOA 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.144GOA 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. Conclusion: AIP 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. p27 KIP1 is unlikely to represent the common unifying nonendocrine etiology for acromegaly and cancer.

A combination of particular demographic, geographical, and historical conditions has resulted in the oldest and largest SDHD founder effect so far characterized and has transformed a rare disease into an endemic disease with major public health implications.

KEYWORDSCarotid body paraganglioma; Carotid-body tumor; Ultrasound; Color Doppler ultrasound.Abstract Introduction: Carotid body paragangliomas (PGLs) are highly vascularized lesions that arise from the paraganglia located at the carotid bifurcation. Purpose: 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. Materials and methods: 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. Results: 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 À5 mm and þ16 mm (mean difference 2.2 AE 6.0). This difference was statistically significant (p Z 0.008). Conclusions: 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.Sommario Introduzione: I paragangliomi (PGLs) carotidei sono lesioni altamente vascolarizzate che originano dai paragangli localizzati a livello della biforcazione carotidea. Scopo: Valutare l'utilità dell'ecografia (US) e dell'Eco color Doppler (USD) del collo nella diagnosi e nel follow-up dei PGLs carotidei. Materiali e metodi: 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. Risultati: 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 þ16 mm (media di 2,2 AE 6,0). Tale differenza è risultata statisticamente significativa (p Z 0,008) (test-Student). Conclusioni: L'US e l'USD del collo risultano metodiche di imaging utili nell'...