Thymic Neuroendocrine Carcinoma (Carcinoid) in Multiple Endocrine Neoplasia Type 1 Syndrome: The Italian Series

Abstract

Neuroendocrine tumors may occur in the setting of multiple endocrine neoplasia type 1 (MEN1) syndrome. Among these, a probably underestimated prevalence of well differentiated neuroendocrine thymic carcinoma (carcinoid), a neoplasm characterized by very aggressive behavior, has been described. We report characterization of the seven Italian cases in which this association occurred among a series of 221 MEN1 patients (41 sporadic and 180 familial cases; prevalence, 3.1%). All of the patients were male, and six of seven (85%) were heavy smokers. No associated hormonal hypersecretion was detected. The first diagnosis was between the second and fifth decades. Familial clusters were present in three of seven (42.8%). No genotype-phenotype correlation was found. All seven cases were associated with hyperparathyroidism. In one patient, prophylactic thymectomy revealed a small nodular lesion suggestive of a thymic carcinoid, providing evidence that preventive thymectomy might prevent additional growth of an occult thymic carcinoid. These findings confirm that thymic carcinoids are associated with a very high lethality, with a near-total prevalence in smoker males. Therefore, prophylactic thymectomy should be considered at neck surgery for primary hyperparathyroidism in MEN1 male patients, especially for smokers, and, due to the frequent familial clusters distribution of this pathology, in subjects with affected relatives presenting this feature. Thus, we recommend screening every patient affected with a neuroendocrine thymic neoplasm for MEN1 syndrome.

Gender-related differences in MEN1 lesion occurrence and diagnosis: a cohort study of 734 cases from the Groupe d'étude des Tumeurs Endocrines

“…We demonstrated the greater lifetime likelihood of developing ZES/gastrinomas in men and of developing pituitary tumors in women. In contrast, both genders have a similar and very high probability of developing pHPT whereas, as expected, th-NET occurred mostly in men (7)(8)(9)(10). Furthermore, the diagnosis of MEN1 tended to be delayed in women, especially when pituitary tumors, and to some extent duodeno-pancreatic tumors, were the first lesions to occur in the course of the disease.…”

“…These large cohorts comprised more than 200 MEN1 patients. period of MEN1 diagnosis), and in Germany (nZ306: 1980-2006 period of MEN1 diagnosis) (9,12,26,27). The multicenter aspect of this study reduces the risk of bias encountered in single-center cohorts, which may select patients through a specific aspect of the disease such as the age of the patient, or the organ involved (duodeno-pancreas, pituitary, parathyroid glands, etc.).…”

“…MEN1 disease is usually described as an autosomal dominant cancer syndrome with very high penetrance and a similar distribution in men and women (6). Nevertheless, studies focusing on MEN1-related th-NET, largely confined to men, show the importance of gender in at least this type of lesion (7)(8)(9)(10). There are large variations between studies in the sex ratio, depending on the center, the population size, and the type of lesion studied.…”

Unraveling the intrafamilial correlations and heritability of tumor types in MEN1: a Groupe d'étude des Tumeurs Endocrines study

“…This strategy is well known for thNETs because thNET clusters were evidenced early. The right imaging tool to detect this tumor is still debated because yearly CT scans of the chest could be harmful, but it is known and accepted that we must pay particular attention to the relatives of patients with thNETs (11,12,14,15). Pituitary adenomas and adrenal tumors are underdiagnosed tumor types in MEN1.…”

“…Gender is recurrently shown to modify tumor development in patients, notably for pituitary or thNETs (8,11,12,13). Additionally, several families from various ethnic origins are reported to present recurrent thNETs (11,14,15). Nevertheless no direct genotype-phenotype correlation in MEN1 disease regarding the tumor types has ever been found (16,17,18).…”