High neuroendocrine component is a factor for poor prognosis in gastrointestinal high-grade malignant mixed adenoneuroendocrine neoplasms

Chen, Ming-Huang; Kuo, Ying‐Ju; Yeh, Yi‐Chen; Lin, Ying‐Chu; Tzeng, Cheng‐Hwai; Liu, Chia Jen; Chang, Peter Mu‐Hsin; Chen, Ming‐Han; Jeng, Yung‐Ming; Chao, Yee

doi:10.1016/j.jcma.2015.04.002

Cited by 28 publications

(38 citation statements)

References 16 publications

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“…Nevertheless, metachronous metastases are rarely biopsied, and nuclear medicine tools cannot help distinguishing between adenocarcinoma and PDNEC because, for example, both components display 18 FDG positron-emitting tomography positivity, and negative somatostatin receptor scintigraphy due to lack of somatostatin receptors expression [83] . The cell type present in tumour emboli on resected primary tumours may be similar to that found in lymph node and distant metastases; thus, its analysis could be an alternative to metastasis biopsy [22] .…”

Section: Management Of Minenmentioning

confidence: 93%

“…Highgrade MiNEN generally combine a non-neuroendocrine carcinoma (usually adenocarcinoma, but possibly squamous-cell carcinoma or acinar-cell carcinoma in the pancreas as mentioned above) or an adenoma (villous or tubulo-villous) with a PDNEC component, which is generally more aggressive [20][21][22][23][24] . The prognosis of intermediate-grade MiNEN is generally determined by the non-neuroendocrine component rather than the G1 or G2 NET component.…”

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confidence: 99%

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Digestive System Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms

Cros²,

et al. 2017

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Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) are a heterogeneous subgroup of rare neoplasms that represent about a third of all poorly differentiated neuroendocrine carcinomas (PDNEC). MiNEN combine a neuroendocrine component, usually a PDNEC, and a non-neuroendocrine component, generally an adenocarcinoma, both accounting for at least 30% of the neoplasm. MiNEN are classified as high-, intermediate-, or low-grade malignancies depending on the metastatic potential of the tumour components. High-grade malignant component should be considered even if it represents <30% of the tumour. The prognosis of MiNEN is generally intermediate between those of the two “pure” components composing it. The aim of this comprehensive review of the literature is to suggest a standardized management of MiNEN. An increasing body of evidence suggests that PDNEC components share molecular abnormalities with their adenocarcinoma counterparts, but also display additional alterations. This advocates for a common origin, and that the presence of a PDNEC component in an adenocarcinoma could indicate a turning point in carcinogenesis.

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Section: Management Of Minenmentioning

confidence: 93%

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confidence: 99%

Digestive System Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms

Cros²,

et al. 2017

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“…14,15 Some authors have suggested that the prognosis of digestive MANECs is determined by the most aggressive histologic component. 1,15 Chen et al 30 recently demonstrated that a high volume of high-grade NET (.50% of the total tumoral volume) is an independent predictor of poor prognosis in digestive MANECs. Expression of CD117 detected by immunohistochemistry correlates with a worse prognosis in colorectal MANECs, but it is uncertain whether this is true for biliary MANECs.…”

Section: Immunohistochemical and Ultrastructuralmentioning

confidence: 99%

“…20,25 However, information on follow-up is limited to 11 cases, many of which report follow-up intervals of 12 months or less. 19,20,24,25,27,28,30 Kim et al 31 found that prognosis of biliary MANECs is very poor and comparable with pure NET grade 3, with a disease-free survival of 5.3 months, overall survival of 12.2 months, and 0 of 7 patients alive after 2 years.…”

Section: Immunohistochemical and Ultrastructuralmentioning

confidence: 99%

Primary Biliary Mixed Adenoneuroendocrine Carcinoma (MANEC): A Short Review

Acosta

Wiley²

2016

Archives of Pathology &Amp; Laboratory Medicine

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Mixed adenoneuroendocrine carcinomas (MANECs) are composite neoplasms with areas of adenocarcinoma or squamous cell carcinoma intermingled with neuroendocrine carcinoma or neuroendocrine tumor, each composing at least 30% of the neoplasm. MANECs are very infrequent overall, and they are more commonly diagnosed in the appendix, colon, and stomach. Biliary MANECs are particularly rare, and their histogenesis is debated because neuroendocrine cells are seldom identified in the normal biliary tract. They can show one of the 3 different architectural patterns described in Lewin's original classification: collision tumors, combined lesions, or amphicrine neoplasms. The neuroendocrine component is usually of a high grade, with small or large cell cytomorphology, whereas the adenocarcinoma component is either an intestinal or biliary type. Clinical presentation is characterized by locally advanced disease at the time of initial diagnosis. Recent studies suggest that treatment should be guided by the most aggressive histologic component.

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“…3,6 These characteristics make mixed adenoneuroendocrine carcinomas diagnostically challenging, as only appropriate immunohistochemical screening for neuroendocrine differentiation may reveal the tumor's dual nature. 3 Clinically, colorectal mixed adenoneuroendocrine carcinomas are usually aggressive neoplasms, [7][8][9] with a clinical need for intensified treatment strategies. However, even if the dual nature of these tumors is fully recognized, there exists no unifying concept of how to treat colorectal mixed adenoneuroendocrine carcinoma patients.…”

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Colorectal mixed adenoneuroendocrine carcinomas and neuroendocrine carcinomas are genetically closely related to colorectal adenocarcinomas

et al. 2017

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Colorectal mixed adenoneuroendocrine carcinomas are rare and clinically aggressive neoplasms with considerable morphological heterogeneity. Data on their genomic characteristics and molecular associations to either conventional colorectal adenocarcinomas or poorly differentiated neuroendocrine neoplasms is still scarce, hampering optimized patient treatment and care. Tissue from 19 colorectal mixed adenoneuroendocrine carcinomas and eight colorectal poorly differentiated neuroendocrine neoplasms (neuroendocrine carcinomas) was microdissected and subjected to next-generation sequencing using a colorectal adenocarcinoma-specific panel comprising 196 amplicons covering 32 genes linked to colorectal adenocarcinoma, and poorly differentiated neuroendocrine neoplasm tumorigenesis. Mixed adenoneuroendocrine carcinomas were also examined for microsatellite instability and MLH-1 promoter methylation status. In three mixed adenoneuroendocrine carcinomas, exocrine and endocrine components were analyzed separately. Genetic testing of colorectal mixed adenoneuroendocrine carcinomas identified 43 somatic mutations clustering in 13/32 genes. Sixteen (84%) tumors harbored at least one somatic mutation, two tumors (11%) displayed high microsatellite instability. Compared with colorectal adenocarcinomas, mixed adenoneuroendocrine carcinomas were more frequently BRAF (37%; P=0.006), and less frequently KRAS (21%; P=0.043) and APC (16%; P=0.001) mutated. Point mutations in neuroendocrine neoplasm-related genes like RB1 or RET were not detected, but one tumor harbored a heterozygous RB1 deletion. Separately analyzed adenocarcinoma and neuroendocrine carcinoma components revealed a shared mutational trunk of driver genes involved in colorectal adenocarcinoma carcinogenesis. Colorectal neuroendocrine carcinomas were similar in their mutation profile to colorectal adenocarcinomas, but compared with mixed adenoneuroendocrine carcinomas, had a higher rate of APC mutations (P=0.027). Our data indicate that colorectal mixed adenoneuroendocrine carcinomas and neuroendocrine carcinomas are genetically closely related to colorectal adenocarcinomas, suggesting that the cells giving rise to these tumors primarily have an intestinal coinage. The identification of BRAF mutations and the frequently present KRAS wild-type status principally render some mixed adenoneuroendocrine carcinomas eligible to targeted treatment strategies used for colorectal adenocarcinomas.

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High neuroendocrine component is a factor for poor prognosis in gastrointestinal high-grade malignant mixed adenoneuroendocrine neoplasms

Abstract: The predominant tumor component in primary tumors was a prognostic factor and could predict tumor emboli and liver metastases pathology in high-grade malignant MANECs.

Cited by 28 publications

References 16 publications

Digestive System Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms

Digestive System Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms

Primary Biliary Mixed Adenoneuroendocrine Carcinoma (MANEC): A Short Review

Colorectal mixed adenoneuroendocrine carcinomas and neuroendocrine carcinomas are genetically closely related to colorectal adenocarcinomas

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