Standard biochemical and radiological methods were used in screening and follow-up protocols were based on current guidelines. All patients with TNETs had their follow-up at the Endocrine unit at the Oulu University Hospital. TNET was diagnosed according to histopathological examination of tumor tissue. Patients with MEN1 were collected from patient files from the years 1985 to 2019 from three university hospitals in Finland. Here, we describe the clinical characteristics, family history and underlying mutations, diagnostic work-up, histopathological characteristics, treatments and outcome of MEN1 patients with TNETs. As published data is scarce, we searched for MEN1 patients characterized by TNETs within a large cohort of Finnish patients. There are no randomized clinical trials and no definitive guidelines on the screening, diagnosing and treatment of TNETs in patients with MEN1. There are recent large series of patients on the outcome of TNET, but these studies do not contain data on the natural course of TNET in MEN1 patients, in whom only small studies with a low number of patients are available. Due to only a few reported studies it is still uncertain whether this classification is prognostic for TNET. In the most recent 2021 World Health Organization (WHO) classification of thymic tumors, TNETs are classified into low-grade typical carcinoids (TC), intermediate-grade atypical carcinoids (ACs), and two high-grade malignancies, large cell neuroendocrine carcinomas (LCNEC) and small cell carcinomas (SCC), similarly to the classification of broncho-pulmonary neuroendocrine neoplasms (bpNEN). TNETs are often aggressive and are an important cause of morbidity and mortality among MEN1 patients. These tumors can be sporadic, but nearly 25% of TNETs are associated with MEN1. TNETs are very rare neoplasms accounting for only 0.4% of all neuroendocrine tumors and 5% of all anterior mediastinal neoplasms, and their age-adjusted incidence rate in the USA is 0.18 per one million persons. In addition, also other tumors such as thymic neuroendocrine tumors (TNET) associate with MEN1. The classical manifestations of the syndrome are primary hyperparathyroidism (PHPT), pituitary adenomas, and pancreatic (PNET) and duodenal (DNET) neuroendocrine tumors. Multiple endocrine neoplasia type 1 (MEN1) is an inherited autosomal dominant tumor-predisposing syndrome caused by inactivating mutations of the MEN1 gene, which is located on chromosome 11q13 and encodes the 610 amino acid protein menin. We also show that LCNEC can be associated with TNET in MEN1 patients. The prognosis can be better by systematic screening. TNET in MEN1 patients is an aggressive disease. 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. In our patients, the 5-year survival of the TNET patients was 62.5% and 10-year survival 31.3%. One patient had a largely necrotic main tumor with very few mitoses and another nodule with 25 mitoses per 2 mm 2, qualifying for the 2021 WHO diagnosis of large cell neuroendocrine carcinoma (LCNEC). TNET was classified as atypical carcinoid (AC) in five out of six patients. The mean age at presentation of TNET was 44.7 ± 11.9 years. They originated from common ancestors encompassing two pairs of brothers from sequential generations. Five of them had the same common gene mutation occurring in Finland. There were six patients (3.3%) with MEN1 and TNET. We collected data on treatments and outcomes of these patients. Thymus tumor specimens were classified according to the new WHO 2021 classification of TNET. We evaluated patient records of 183 MEN1-patients from three university hospitals between the years 1985–2019 with TNETs. We evaluated patients with MEN1 and TNET in three university hospitals in Finland. Neuroendocrine tumors of the thymus (TNETs) are very rare but often have an aggressive nature. MEN1 is associated with an increased risk of developing tumors in different endocrine organs.
0 Comments
Leave a Reply. |