Classification of neuroendocrine neoplasms: lights and shadows

Rosa, Stefano La; Uccella, Silvia

doi:10.1007/s11154-020-09612-2

Cited by 45 publications

(37 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In presence of such morphology, the immunoreactivity for general neuroendocrine markers (preferentially chromogranin A, and when chromogranin A is negative, diffuse positivity for synaptophysin and INSM1) is diagnostic for LCNEC. Positivity alone for synaptophysin or non-specific markers (e.g., CD56, CD57, and NSE) should be used to make the diagnosis of LCNEC, even when dealing with a indefinitely poorly differentiated morphology [15,16].…”

Section: Discussionmentioning

confidence: 99%

Mixed Neuroendocrine/Non-neuroendocrine Neoplasm (MiNEN) of the Ovary Arising from Endometriosis: Molecular Pathology Analysis in Support of a Pathogenetic Paradigm

Maragliano

Libera

Carnevali³

et al. 2021

Endocr Pathol

Self Cite

View full text Add to dashboard Cite

Primary ovarian neuroendocrine neoplasms (Ov-NENs) are infrequent and mainly represented by well-differentiated forms (neuroendocrine tumors — NETs — or carcinoids). Poorly differentiated neuroendocrine carcinomas (Ov-NECs) are exceedingly rare and only few cases have been reported in the literature. A subset of Ov-NECs are admixed with non-neuroendocrine carcinomas, as it occurs in other female genital organs, as well (mostly endometrium and uterine cervix), and may be assimilated to mixed neuroendocrine/non-neuroendocrine neoplasms (MiNENs) described in digestive and extra-digestive sites. Here, we present a case of large cell Ov-NEC admixed with an endometrioid carcinoma of the ovary, arising in the context of ovarian endometriosis, associated with a uterine endometrial atypical hyperplasia (EAH). We performed targeted next-generation sequencing analysis, along with a comprehensive immunohistochemical study and FISH analysis for TP53 locus, separately on the four morphologically distinct lesions (Ov-NEC, endometrioid carcinoma, endometriosis, and EAH). The results of our study identified molecular alterations of cancer-related genes (PIK3CA, CTNNB1, TP53, RB1, ARID1A, and p16), which were present with an increasing gradient from preneoplastic lesions to malignant proliferations, both neuroendocrine and non-neuroendocrine components. In conclusion, our findings underscored that the two neoplastic components of this Ov-MiNEN share a substantially identical molecular profile and they progress from a preexisting ovarian endometriotic lesion, in a patient with a coexisting preneoplastic proliferation of the endometrium, genotypically and phenotypically related to the ovarian neoplasm. Moreover, this study supports the inclusion of MiNEN in the spectrum ovarian and, possibly, of all gynecological NENs, among which they are currently not classified.

show abstract

Section: Discussionmentioning

confidence: 99%

Mixed Neuroendocrine/Non-neuroendocrine Neoplasm (MiNEN) of the Ovary Arising from Endometriosis: Molecular Pathology Analysis in Support of a Pathogenetic Paradigm

Maragliano

Libera

Carnevali³

et al. 2021

Endocr Pathol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors originating from neuroendocrine cells dispersed in different organs (1)(2)(3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Role of FGF System in Neuroendocrine Neoplasms: Potential Therapeutic Applications

et al. 2021

View full text Add to dashboard Cite

Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors originating from neuroendocrine cells dispersed in different organs. Receptor tyrosine kinases are a subclass of tyrosine kinases with a relevant role in several cellular processes including proliferation, differentiation, motility and metabolism. Dysregulation of these receptors is involved in neoplastic development and progression for several tumors, including NENs. In this review, we provide an overview concerning the role of the fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) system in the development and progression of NENs, the occurrence of fibrotic complications and the onset of drug-resistance. Although no specific FGFR kinase inhibitors have been evaluated in NENs, several clinical trials on multitarget tyrosine kinase inhibitors, acting also on FGF system, showed promising anti-tumor activity with an acceptable and manageable safety profile in patients with advanced NENs. Future studies will need to confirm these issues, particularly with the development of new tyrosine kinase inhibitors highly selective for FGFR.

show abstract

“…On the other hand, poorly differentiated neuroendocrine carcinomas (NECs) show atypia, solid growth patterns with either small or large cells with necrosis and high proliferation indexes (G3). This classification system applies to all gastroenteropancreatic NENs while lung NENs still use a classification specific for the thoracic site [ 5 , 6 , 7 ]: typical (low-grade) and atypical (intermediate-grade) carcinoids and high-grade large-cell neuroendocrine carcinomas and small-cell lung cancer (SCLC). The differential diagnosis of site of origin in metastatic, well-differentiated NETs may be possible using a variety of immunohistochemical markers, while these are rarely helpful in identifying origin in poorly differentiated NECs’ metastases [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Insights into Mechanisms of Tumorigenesis in Neuroendocrine Neoplasms

Pastorino

Grillo

Albertelli

et al. 2021

IJMS

View full text Add to dashboard Cite

Genomic studies have identified some of the most relevant genetic players in Neuroendocrine Neoplasm (NEN) tumorigenesis. However, we are still far from being able to draw a model that encompasses their heterogeneity, elucidates the different biological effects consequent to the identified molecular events, or incorporates extensive knowledge of molecular biomarkers and therapeutic targets. Here, we reviewed recent insights in NEN tumorigenesis from selected basic research studies on animal models, highlighting novel players in the intergenic cooperation and peculiar mechanisms including splicing dysregulation, chromatin stability, or cell dedifferentiation. Furthermore, models of tumorigenesis based on composite interactions other than a linear progression of events are proposed, exemplified by the involvement in NEN tumorigenesis of genes regulating complex functions, such as MEN1 or DAXX. Although limited by interspecies differences, animal models have proved helpful for the more in-depth study of every facet of tumorigenesis, showing that the identification of driver mutations is only one of the many necessary steps and that other mechanisms are worth investigating.

show abstract

Classification of neuroendocrine neoplasms: lights and shadows

Cited by 45 publications

References 76 publications

Mixed Neuroendocrine/Non-neuroendocrine Neoplasm (MiNEN) of the Ovary Arising from Endometriosis: Molecular Pathology Analysis in Support of a Pathogenetic Paradigm

Mixed Neuroendocrine/Non-neuroendocrine Neoplasm (MiNEN) of the Ovary Arising from Endometriosis: Molecular Pathology Analysis in Support of a Pathogenetic Paradigm

Role of FGF System in Neuroendocrine Neoplasms: Potential Therapeutic Applications

Insights into Mechanisms of Tumorigenesis in Neuroendocrine Neoplasms

Contact Info

Product

Resources

About