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BackgroundMedullary thyroid cancer (MTC) comprises only 4% of all thyroid cancers and originates from the parafollicular C-cells. HIF-1α expression has been implied as an indicator of worse prognosis in various solid tumors. However, whether expression of HIF-1α is a prognosticator in MTC remained unclear. Our aim was to evaluate the prognostic value of HIF-1α in patients with MTC.MethodsAll patients with MTC who were operated on between 1988 and 2014 in five tertiary referral centers in The Netherlands were included. A tissue microarray was constructed in which 111 primary tumors could be analyzed for expression of HIF-1α, CAIX, Glut-1, VEGF and CD31 and correlated with clinicopathologic variables and survival.ResultsThe mean age of patients was 46.3 years (SD 15.6), 59 (53.2%) were male. Of the 111 primary tumors, 49 (44.1%) were HIF-1α negative and 62 (55.9%) were HIF-1α positive. Positive HIF-1α expression was an independent negative indicator for progression free survival (PFS) in multivariate cox regression analysis (HR 3.1; 95% CI 1.3 – 7.3). Five-years survival decreased from 94.0% to 65.9% for the HIF-1α positive group (p=0.007). Even within the group of patients with TNM-stage IV disease, HIF-1α positivity was associated with a worse prognosis, shown by a decrease in 5-years survival of 88.0% to 49.3% (p=0.020).ConclusionExpression of HIF-1α is strongly correlated with adverse prognosis of MTC. This could open up new ways for targeted systemic therapy of MTC.

Routine follow-up FNA in patients whose initial FNA is benign has a low diagnostic upgrading value and is relatively costly. In patients whose initial FNA is benign, we recommend the FNA be repeated only if clinically suspicious signs or complaints develop.

Three patients presented some decades after severe traumatic injury with atypical bowel symptoms which were caused by a giant myelolipoma of the adrenal gland. The aetiology of this rare, benign and generally asymptomatic tumour is virtually unknown at present and several hypotheses have been devised. This report describes a possible association between high-energy trauma and the development of giant myelolipomas, further contributing to the hypothesis that severe systemic stress could be an aetiological factor in the development of an adrenal myelolipoma.