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. 2022 Sep;77(3):527-537.
doi: 10.1007/s12020-022-03099-4. Epub 2022 Jun 13.

Thymic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1

Iina Yliaska  1 , Heikki Tokola  2 , Tapani Ebeling  3 , Outi Kuismin  4 , Olavi Ukkola  3 , Minna L Koivikko  3 , Timo Lesonen  5 , Jussi Rimpiläinen  6 , Tuuli Felin  7 , Eeva Ryhänen  8 , Saara Metso  7 , Camilla Schalin-Jäntti  8 , Pasi Salmela  3
Affiliations

Thymic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1

Iina Yliaska et al. Endocrine. 2022 Sep.

Abstract

Objective: MEN1 is associated with an increased risk of developing tumors in different endocrine organs. Neuroendocrine tumors of the thymus (TNETs) are very rare but often have an aggressive nature. We evaluated patients with MEN1 and TNET in three university hospitals in Finland.

Design/methods: We evaluated patient records of 183 MEN1-patients from three university hospitals between the years 1985-2019 with TNETs. Thymus tumor specimens were classified according to the new WHO 2021 classification of TNET. We collected data on treatments and outcomes of these patients.

Results: There were six patients (3.3%) with MEN1 and TNET. Five of them had the same common gene mutation occurring in Finland. They originated from common ancestors encompassing two pairs of brothers from sequential generations. The mean age at presentation of TNET was 44.7 ± 11.9 years. TNET was classified as atypical carcinoid (AC) in five out of six patients. One patient had a largely necrotic main tumor with very few mitoses and another nodule with 25 mitoses per 2 mm2, qualifying for the 2021 WHO diagnosis of large cell neuroendocrine carcinoma (LCNEC). In our patients, the 5-year survival of the TNET patients was 62.5% and 10-year survival 31.3%.

Conclusion: In this study, TNETs were observed in one large MEN1 founder pedigree, where an anticipation-like earlier disease onset was observed in the most recent generation. TNET in MEN1 patients is an aggressive disease. The prognosis can be better by systematic screening. We also show that LCNEC can be associated with TNET in MEN1 patients.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Family tree of a large pedigree of a founder mutation of MEN1 in Northern Finland. TNET-patients and their ancestors shown only
Fig. 2
Fig. 2
Large cell neuroendocrine carcinoma of patient #4. A–D, low-power magnification showing organoid architecture and large necrosis on bottom left. Hematoxylin and eosin A, cytokeratin B, synaptophysin C and Chromogranin A D. Original magnifications A–D: 100×. E solid growth with the number of mitotic figures (arrowheads) exceeding 10 mitoses per 2 mm2, thereby fulfilling the 2015 WHO criteria of LCNEC. Ki-67 staining in the insert on top right (hematoxylin and eosin; original magnifications: 630×)
Fig. 3
Fig. 3
Kaplan–Meier curve showing overall survival of the MEN1 patients with TNET
See this image and copyright information in PMC

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