Paraganglioma of the carotid body: treatment strategy and SDH-gene mutations.

OBJECTIVES: The aim of the present study was to review treatment results in patients with paraganglioma (PGL) of the neck presenting as carotid body tumour, long-term follow-up and relevance of genetic testing for succinate dehydrogenase (SDH)-gene mutations. DESIGN: Retrospective analysis of prospectively collected data and prospective genetic analysis. MATERIALS AND METHODS: Over a 25-year period (1987-2011) 50 patients were operated for 63 PGLs of the neck. Pre-, intra- and postoperative findings were analysed. Sanger sequencing was performed for genetic testing of SDH-gene mutations (SDH B, SDHC and SDHD). RESULTS: Fifty patients underwent resection of 63 PGLs (62 benign, one malignant) without mortality. Eight patients underwent preoperative embolisation. Vascular surgical procedures were required in 15 operations (15/63 = 23.8%). Nerve lesions occurred after 13 operations (13/63 = 20.6%) and were associated with large tumours. A total of 44 patients are alive after a mean follow-up of 9.8 years. In 40 patients 17 SDH-gene mutations were detected (17/40 = 42.5%): 14 SDHD mutations, two SDHB mutations and one rare SDHC mutation. CONCLUSION: Surgery for PGL is recommended. All PGL patients should be screened for SDH mutations because it impacts the individual follow-up strategy. Whereas all PGL patients require annual ultrasound control, mutation carriers and family members with proven mutations should in addition be regularly examined by magnetic resonance imaging (MRI) of head, neck, thorax, abdomen and pelvis.

[Hereditary gastric cancer]. / Hereditäres Magenkarzinom.

Hereditary diffuse gastric cancer is an autosomal dominant cancer syndrome with approximately 70%-80% penetrance. The cumulative lifetime risk of clinically detected gastric cancer is 63%-83% for women and 40%-67% for men. The average age at diagnosis is 40 years. Approximately 25%-40% of patients carry a germline mutation of the CDH1 gene. This gene encodes the transmembrane protein E-cadherin which plays a central role in cell adhesion and signal transduction. Classified according to Laurén, patients develop multifocal diffuse signet-ring cell carcinoma and, in late stages, linitis plastica. In the foveolar neck region, the site of gastric stem cells, in situ signet-ring cell carcinoma has been identified as a precursor lesion of invasive cancer. Therein, pagetoid spread of tumour cells below the preserved epithelium within the basal membrane represents the characteristic morphology. PAS staining may facilitate detection of tiny lesions.The present article provides detailed information on this cancer syndrome from the point of view of the pathologist as well as the human geneticist, focussing on the multidisciplinary management of affected patients.