Mixed Neuroendocrine Non-Neuroendocrine Neoplasms of the Gastrointestinal Tract: A Case Series

Abstract

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) refer to heterogenous rare neoplasms constituted of at least a neuroendocrine population—either well-differentiated, or more frequently poorly differentiated—and a non-neuroendocrine population, both accounting for at least 30% of the whole tumor mass. Several studies recently focused on the key genetic and epigenetic changes underlying MiNENs to better understand how they develop, and explore biological similarities among the two components and their pure counterparts. However, their molecular landscape still remains poorly understood. NGS may represent a useful tool to study this orphan disease by detecting the main genetic alterations and possible therapeutic targets. NGS analysis on tissue and/or blood samples through the Foundation One (F1) platform was performed on consecutive samples collected from four patients diagnosed with MiNENs of the gastroenteric tract. Several genetic alterations were shared among samples from the same patients, thus suggesting a common origin between them, although morphology sometimes changed at histopathological evaluation. Common molecular alterations among samples from different patients that had not been previously described to our knowledge were also detected. Finally, it is of the utmost importance to clarify if the maintenance of the 30% cut-off is still essential in defining MiNENs and really manages to include all of the mixed neoplasms.

Case report: Coexistence of sigmoid tumor with unusual pathological features and multiple colorectal neuroendocrine tumors with lymph node metastases

“…When dual differentiation was present within the same cell, it can be defined as amphicrine. While the exact pathogenesis of these neoplasms is still a topic of open debate, the tumorigenesis of different types may be distinct ( 8 – 10 ). The first hypothesis about the mechanism of tumorigenesis is that the epithelial and endocrine components descend from different precursor cells independently and grow into the same space by chance.…”

Diagnostic value of liquid biopsy in the era of precision medicine: 10 years of clinical evidence in cancer

“…The liquid biopsy is a minimally invasive and repeatable assay that can be used during longitudinal monitoring, making this test feasible for different aims, including screening. The ctDNA is the most investigated and used biomarker of the liquid biopsy in clinical practice applications [202][203][204]. It offers a snapshot of the genomic cancer profile, giving a real, instantaneous, and complete picture of the inter and intra-tumor heterogeneity [43,[202][203][204][205].…”

“…The ctDNA is the most investigated and used biomarker of the liquid biopsy in clinical practice applications [202][203][204]. It offers a snapshot of the genomic cancer profile, giving a real, instantaneous, and complete picture of the inter and intra-tumor heterogeneity [43,[202][203][204][205].…”

“…There are many clinical applications of ctDNA liquid biopsy, some of which are widely applied and approved in clinical practice, others are under investigation and for all of them many works and clinical trials have been conducted and others are still in progress [202][203][204][206][207][208][209][210]. Some clinical applications of the liquid biopsy are depicted in Figure 2, like the identification of cancer biomarkers and the detection of therapeutic targets for treatment selection [211], the real-time monitoring of therapeutic efficacy and response [212], the disease progression assessment and the identification of resistance mechanisms [213,214], the early detection of cancer and the MRD assessment [58,215], and the cancer screening [90,216,217].…”

Molecular factors, diagnosis and management of gastrointestinal tract neuroendocrine tumors: An update

“…Mixed neuroendocrine neoplasms (MiNEN), neuroendocrine and nonneuroendocrine, are very rare, but with increasing incidence, heterogeneous lesions found in the GI tract, which were previously known as mixed adeno-neuroendocrine carcinomas, present a diagnostic and therapeutic challenge. Their histopathologic differentiation is mainly poor and less commonly well, which determines their biological behavior[ 9 - 12 ]. Neuroendocrine carcinoma (NEC) with poor differentiation represents a more aggressive sub-group located mainly (over one-third) in the GI tract that requires careful assessment for surgical therapeutic excision[ 13 ].…”