AJMP2503 - CME/CMLE - Histopathologic and genetic distinction of well-differentiated grade 3 neuroendocrinemtumor versus poorly-differentiated neuroendocrine carcinoma in high-grade neuroendocrine neoplasms-Histopathologic and genetic distinction of well-differentiated grade 3 neuroendocrinemtumor versus poorly-differentiated neuroendocrine carcinoma in high-grade neuroendocrine neoplasms

Histopathologic and genetic distinction of well-differentiated grade 3 neuroendocrinemtumor versus poorly-differentiated neuroendocrine carcinoma in high-grade neuroendocrine neoplasms

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This review article examines the distinction between well-differentiated grade 3 neuroendocrine tumors (G3-NETs) and poorly-differentiated neuroendocrine carcinomas (NECs), focusing on histopathological and genetic characteristics. Recognizing the 2022 WHO classification, the article discusses how G3-NETs and NECs have identical proliferation indices, creating diagnostic challenges due to overlapping features. However, accurate differentiation is crucial as the two types have different prognoses and chemotherapy responses.<br /><br />Histopathologically, G3-NETs exhibit features like monotonous round nuclei and organoid patterns, while NECs display poorly-differentiated nuclear features without neuroendocrine morphology. NECs are further subdivided into small cell and large cell types based on morphological characteristics. Distinguishing the two relies significantly on morphology, although additional immunohistochemistry markers such as TP53, RB, and somatostatin receptors (SSTRs) help improve diagnostic accuracy.<br /><br />Genetically, G3-NETs and NECs exhibit distinct mutation profiles. For example, G3-NETs show mutations in genes like ATRX and DAXX, whereas NECs are characterized by frequent TP53 and RB1 mutations. The article suggests that a diagnostic gene panel could enhance classification precision by exploiting these differences.<br /><br />Furthermore, it addresses the therapy variations in these tumors, noting that G3-NETs respond better to treatments similar to lower-grade NETs, whereas NECs generally require intensive chemotherapy.<br /><br />Overall, this comprehensive review provides pathologists a framework for differentiating these tumors, emphasizing the necessity of precise immunohistochemical and genetic testing to facilitate accurate diagnoses and, consequently, more effective patient management.

Keywords

G3-NETs

NECs

2022 WHO classification

histopathology

genetic characteristics

immunohistochemistry

TP53

RB1

mutation profiles

chemotherapy response