Open issues on G3 neuroendocrine neoplasms: back to the future

Introduction: Extrapulmonary small-cell cancer (EPSCC) is a relatively rare malignancy. The management of EPSCC is usually extrapolated from small-cell lung cancer (SCLC). In spite of the morphological similarity of the 2 malignancies, there are many differences in clinical features, prognosis, and recommendations of treatment of these disorders. The data on the correlation of clinical-pathological characteristics of EPSCC and treatment results is scarce. Materials and Methods: This retrospective analysis of 41 consecutively treated patients diagnosed with EPSCC in 2015–2018 was performed in a tertiary medical center. The correlation between the clinical and pathological characteristics and the treatment outcome (response rate, disease-free interval, and overall medial survival) was done using the standard statistics, Kaplan-Meier method, and multivariate analyses. The stratification was done on the stage of the disease, Ki-67 proliferative index, the location of the tumor, and smoking. Results: Forty-one patients were included with a median age of 66.3 years. The most common primary site was the gastrointestinal tract (28, 68.3%) including the pancreas. The most common distant metastasis site was the liver (23, 56.1%). Only 2 patients (4.9%) had brain metastases. Unlike in SCLC, most patients did not have any history of smoking (23, 56.1%). Nineteen patients with metastatic disease received systemic treatment, mostly cisplatin-based chemotherapy, with a response rate of 57.9%. The results of treatment were significantly better in patients with disseminated EPSCC with Ki-67 <55%, while its role in limited disease was nonsignificant. Discussion: The results of our study show the unique entity of EPSCC. The rarity of brain metastases proves that prophylactic brain irradiation should not be recommended in practice. The provocative idea of prophylactic liver irradiation in limited-stage EPSCC of gastrointestinal origin can be evaluated in future studies. The predictive role of Ki-67 is important in metastatic EPSCC. There is probably no role of smoking in developing EPSCC.

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“…Zatelli et al [11] and Fazio and Milione [12] suggested a new classification of HG NETs, based on Ki-67 index more or less than 55%.…”

Section: Introductionmentioning

confidence: 99%

Extrapulmonary Small Cell Cancer: A New Insight into a Rare Disease

et al. 2021

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“…The latest group of NENs includes very heterogeneous neoplasms. Within the same histological grade, morphological features characterising these tumours are not uniform in all sites (Zatelli et al 2018). Thus, the WHO classification of 2019 distinguishes between well-differentiated G3 NETs with a mitotic count >20/2 mm 2 and/or a Ki-67 >20% and poorly differentiated NECs also with a mitotic count >20/2 mm 2 and/or a Ki-67 >20% (Nagtegaal et al 2020).…”

Section: Pathologymentioning

confidence: 99%

Changing biological behaviour of NETs during the evolution of the disease: progress on progression

Alexandraki

Spyroglou

Kykalos

et al. 2021

Endocrine-Related Cancer

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Following improvements in the management and outcome of neuroendocrine neoplasms (NENs) in recent years, we see a subset, particularly of pancreatic NENs, which become more aggressive during the course of the disease. This is reflected by an increase in the Ki-67 labelling index, as a marker of proliferation, which may lead on occasion to an increase in grading, but generally does not appear to be correlated with histologically confirmed de-differentiation. A systematic review of the literature was performed in PubMed, Cochrane Library, and Embase until May 2020 to identify cases that have behaved in such a manner. We screened 244 articles: only 7 studies included cases in their cohort, or in a subset of the cohort studied, with a proven increase in the Ki-67 during follow-up through additional biopsy. In addition to these studies, we have also tried to identify possible pathophysiological mechanisms implicated in advanced NENs, although currently no studies appear to have addressed the mechanisms implicated in the switch to a more aggressive biological phenotype over the course of the disease. Such progression of the disease course may demand a change in management. Summarising the evidence overall, we suggest that future studies should concentrate on changes in molecular pathways during disease progression with sequential biopsies in order to shed light on the mechanisms that render a neoplasm more aggressive than its initial phenotype or genotype.

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“…In der ENETS Consensus Guideline Update für das Management von Patienten mit funktionellen panNET und nichtfunktionellen panNET wird die PRRT bei fortgeschrittenen NET und Versagen einer medikamentösen Therapie empfohlen [25] Circa 5 % der NEN zeigen eine G3-Differenzierung mit einem OS von 41 bis 55 Monaten [94]. Bei lokalisiertem oder regional begrenztem GEP-NET G3 und NEC wird ein operatives Vorgehen angestrebt, ggf.…”

Section: Knochenmarkreserve Des Patienten Ausreichend Hoch Seinunclassified

Gastroenteropankreatische neuroendokrine Neoplasien – Heterogenität, Management und Perspektiven der Versorgung und Forschung

Luley

Gebauer

et al. 2020

Internist

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Medizin aktuell Tab. 1 Einteilung der GEP-NEN laut WHO-Klassifikation. (Lloyd et al. [57], Nagtegaal et al. [70]) NET NEC MiNEN G1 G2 G3 Anteil Ki67-positiver Tumorzellen (%) <3 3-20 >20 Variabel Variabel Mitosen/10 HPF <2 2-20 >20 Variabel Variabel NET-Morphologie Erhalten Erhalten Erhalten Fehlt Erhalten oder fehlend GEP-NEN gastroenteropankreatische neuroendokrine Neoplasien, HPF "high-power field" (Hauptgesichtsfeld), MiNEN "mixed neuroendocrine-nonneuroendocrine neoplasm" (gemischte neuroendokrine/nichtneuroendokrine Neoplasien), NEC neuroendokrine Karzinome, NET neuroendokrine Tumoren, WHO World Health Organization

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Open issues on G3 neuroendocrine neoplasms: back to the future

Cited by 16 publications

References 60 publications

Extrapulmonary Small Cell Cancer: A New Insight into a Rare Disease

Extrapulmonary Small Cell Cancer: A New Insight into a Rare Disease

Changing biological behaviour of NETs during the evolution of the disease: progress on progression

Gastroenteropankreatische neuroendokrine Neoplasien – Heterogenität, Management und Perspektiven der Versorgung und Forschung

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