Endocrine Abstracts

Objectives: Medullary thyroid carcinoma (MTC) is a rare neoplasm that occurs in sporadic (75%) (sMTC) or familial (25%) (fMTC) form, the latter caused by germinal mutations of the RET gene. In fMTC, cases can be distinguished into index cases, the first case who were diagnosed in a specific family, then apparently sporadic at the time of surgery, and gene carriers identified through RET screening starting from the index case. The aim of this study was to evaluate potential differences in clinical presentation and outcome between patients with sMTC and index cases of fMTC.

Methods: We performed a retrospective observational study through a prospectively collected database of 671 sMTC and 116 fMTC index case patients followed at the Unit of Endocrinology of the University Hospital of Pisa from 2000 to 2021.

Results: At diagnosis, patients with fMTC were younger than sMTC (median age 44 vs. 55 years, P < 0.001), without difference in gender (males 39% vs. 44%, P = 0.3). Median tumor dimension did not differ between fMTC and sMTC (1.2 vs. 1.4 cm, P = 0.3). Conversely, fMTC patients showed higher prevalence of aggressive histologic features compared to sMTC, such as minimal extrathyroidal extension (37.3% vs. 19.1%, P < 0.001), tumor with T stage > 2 (21.6% vs. 13%, P = 0.03), lymph node metastases (59% vs. 43%, P = 0.002) mainly in the central compartment (59% vs. 39%, P = 0.005). However, no difference in rate of distant metastases (11.8% vs 8.9%, P = 0.37) and stage IV disease (27.5% vs 28.9%, P= 0.82) were highlighted between fMTC and sMTC. After a median follow-up of 10 years in fMTC and 6.8 years in sMTC, at last follow up excellent response was lower in fMTC than sMTC (33.9% vs 54.2%, P < 0.001).

Conclusions: In our series, index cases of fMTC and patients with sMTC showed a different clinical presentation being more aggressive in fMTC. This evidence is reflected also in the clinical outcome at last follow-up characterized by lower rate of excellent response in fMTC. Therefore, the possibility of having fMTC in relatively young patients with an aggressive MTC and apparently negative familial history should not be overlooked.