Clinical Features, Management, and Molecular Characteristics of Familial Small Bowel Neuroendocrine Tumors

Abstract

Small bowel neuroendocrine tumors are rare tumors with an increasing incidence over the last several decades. Early detection remains challenging because patients commonly develop symptoms late in the disease course, often after the tumors have metastasized. Although these tumors were thought to arise from sporadic genetic mutations, large epidemiological studies strongly support genetic predisposition and increased risk of disease in affected families. Recent studies of familial small bowel neuroendocrine tumors have identified several novel genetic mutations. Screening for familial small bowel neuroendocrine tumors can lead to earlier diagnosis and improved patient outcomes. This review aims to summarize the current knowledge of molecular changes seen in familial small bowel neuroendocrine tumors, identify clinical features specific to familial disease, and provide strategies for screening and treatment.

Neuroendocrine neoplasms in the context of inherited tumor syndromes: a reappraisal focused on targeted therapies

“…The disease course initially is paucisymptomatic with the onset of abdominal pain, intestinal obstruction, or carcinoid syndrome usually at advanced stages. Compared to the sporadic counterparts, familial SI-NETs often present an earlier age at diagnosis and occur more frequently as multiple synchronous primary tumors with most lesions located in the ileum and secondly in the jejunum [128,131]. Familial SI-NETs seem to be more often associated with distant metastasis and carcinoid syndrome than the sporadic ones [129].…”

“…Familial small-intestine neuroendocrine tumors (SI-NETs) represent a relatively new inherited disorder, defined as at least two cases in first-degree relatives not associated with other genetic syndromes [128]. Hereditary SI-NETs are rare with an estimated prevalence among all SI-NETs of 2.6-3.7% [129].…”

“…Hereditary SI-NETs are rare with an estimated prevalence among all SI-NETs of 2.6-3.7% [129]. Epidemiological evidence in European and US families suggest an autosomal dominant inheritance with incomplete penetrance (Table 1) [128]. However, underlying molecular pathogenesis still remains unclear.…”

“…In the setting of a locoregional disease, surgical resection of the primary tumor with extensive lymph-node dissection represents the only curative approach [132,133]. When metastatic disease occurs, primary tumor(s) resection should be considered, since it appears associated with better survival outcomes [128,133,134]. In case of unreseactable metastatic SI-NET, several target therapies may be evaluated [128,[135][136][137].…”

“…When metastatic disease occurs, primary tumor(s) resection should be considered, since it appears associated with better survival outcomes [128,133,134]. In case of unreseactable metastatic SI-NET, several target therapies may be evaluated [128,[135][136][137]. SSAs represent so far the first-line systemic therapy, which leads to a major control of carcinoid syndrome and to tumor growth inhibition [34,128,134].…”