Neuroendocrine tumors of the gallbladder (Review)

Abstract

A gallbladder neuroendocrine neoplasm (GB-NEN) is a unique heterogeneous neoplasm, originating from neuroendocrine cells and able to secrete peptides as its neurotransmitter. Among all the neuroendocrine tumors (NETs), the GB-NEN prevalence is 0.5%, which accounts for ~2.1% of all gallbladder tumors. The current study aimed to present an up-to-date review of the clinical features, diagnosis and treatment of NETs of the gallbladder. A systematic literature search was performed in order to identify all relevant studies published. Thus far, the etiology and pathogenesis of GB-NEN remains unclear. Moreover, an ambiguous clinical manifestation exists as observed during laboratory examinations. As GB-NEN is a rare gallbladder lesion and is seldom seen in clinical practice, there is a limited availability of review reports, and it is therefore often considered only as a case study. It is difficult to distinguish GB-NEN from other gallbladder diseases using imaging diagnostic techniques. Although chemotherapy treatment provides prolonged progression-free survival, surgery is considered the best option. Thus, to overcome the inherent risks or shortfalls of traditional surgery; early detection, diagnosis and treatment of GB-NEN are required to improve patient longevity.

Outcomes of metastatic neuroendocrine carcinoma of the gallbladder

“…The liver was the most common site of metastasis for these cancers, followed by abdominal and retroperitoneal lymph nodes [8,11,13]. This distribution of metastasis was also seen in our study, with liver as the most common site of metastasis.…”

“…A large proportion of these cases (90%) were not staged at diagnosis [7]. Neuroendocrine tumour of gallbladder accounts for less than 0.5% of all malignant tumours of gallbladder [8]. It is usually classified into four major categories based on tumour grade and mitotic index: well-differentiated neuroendocrine tumour (typical carcinoid), well-differentiated NEC (atypical carcinoid), poorly differentiated NEC (small or large cell) types and mixed exocrine-endocrine carcinomas.…”

A metastatic neuroendocrine small cell carcinoma of the gall bladder: case report and a comprehensive review of the literatures

“…As there are no neuroectodermal cells in the GB mucosa, few investigators postulated that SCC arises from epithelial metaplasia secondary to cholelithiasis and chronic cholecystitis. Novel research methods in the pathogenesis demonstrate the role of epidermal growth factor receptor, protein kinase B, a target protein of rapamycin, and extracellular signals that regulate kinase expression (3). The details regarding published case reports and case series of metastatic SCC-GB are tabulated.…”

“…These are usually large tumour with extensive necrosis, have diffuse growth pattern that mostly involves the submucosa. Poorly differentiated NETs grow in sheets and cords and have cells with irregular nuclei, inconspicuous nucleoli, cytoplasmic neurosecretory granules along with high mitotic index (3,6). SCC typically express neuronspecific enolase (NSE), while some express synaptophysin, chromogranin, cytokeratin, and Leu-7 (7).…”

Neuroendocrine neoplasms of the biliary tree, liver and pancreas: a pathological approach

“…Overall, these neoplasms represent 0.2 to 2% of all NENs, and around 2% of all primary malignancies arising in EHBD and GB 3 , 4 . Gallbladder NENs most commonly arise in women (M:F ratio = 1:4), whereas only a slight female prevalence (M:F ratio = 2:3) is seen in patients with NENs of EHBD 3 .…”