Thymic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1

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.

Neuroendocrine tumor of thymus with ectopic production of adrenocorticotropic hormone in a 13-year-old child. Case report, 5-year follow-up

“…В настоящее время идут клинические исследования препаратов в качестве 2-й линии терапии при прогрессировании после ХТ. Эверолимус продемонстрировал обнадеживающие результаты как в рандомизированных клинических исследованиях, так и в отдельных сообщениях с клиническими случаями [14][15][16], сейчас обсуждается в качестве кандидата для 1-й линии терапии пациентов с НЭО тимуса. Ингибиторы ангиогенеза, такие как сунитиниб и пазопаниб, привели к контролю заболевания в контексте НЭО в 85% случаев с достижением выживаемости без прогрессирования в 10 мес [17,18].…”

Hereditary Syndromes Associated with Pancreatic and Lung Neuroendocrine Tumors

“…TNETs are rare neoplasms that are often sporadic, but nearly 25% of TNETs can be associated with MEN1 [ 87 ]. Their prevalence is 2–8% among patients with MEN1 [ 7 ].…”

“…TNETs can be functioning, leading to Cushing’s syndrome due to hypersecretion of Adrenocorticotropic Hormone (ACTH). The 5-year survival of the TNET patients is approximately 62.5% and the 10-year survival is 31.3% [ 87 , 88 ].…”

“…TNETs often follow an aggressive course and contribute significantly to the morbidity and mortality in MEN1 patients [ 10 ]. Resectability is the key factor in prognosis [ 87 ]. Prophylactic thymectomy during initial parathyroidectomy in MEN1, as well as prophylactic thymectomy in young MEN1 mutation carriers with a family history of TNET, has been suggested to reduce the risk [ 7 , 10 ].…”

“…Median sternotomy and thoracotomy with thymus resection and lymph node dissection for TNETs is recommended [ 10 ]. Specific guidelines for MEN1-related TNETs are not available, but a similar approach to AC is usually employed in the presence of metastatic disease [ 10 , 87 ]. European Society for Medical Oncology (ESMO) guidelines suggest that in patients with slowly progressing advanced Somatostatin Receptor Imaging (SRI)-positive TNET, SSAs along with locoregional therapy, including surgery, are advised as the first line of treatment [ 10 ].…”