scholarly journals Neuroendocrine Carcinomas of the Digestive Tract: What Is New?

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3766
Author(s):  
Anna Pellat ◽  
Anne Ségolène Cottereau ◽  
Benoit Terris ◽  
Romain Coriat
Keyword(s):  
Peptide Receptor Radionuclide Therapy ◽  
Large Cell ◽  
Current Data ◽  
World Health ◽  
High Grade ◽  
Ki 67 ◽  
Lung Cancers ◽  
Platinum Based Chemotherapy ◽  
Line Setting ◽  
Neuroendocrine Carcinomas

Neuroendocrine carcinomas (NEC) are rare tumors with a rising incidence. They show poorly differentiated morphology with a high proliferation rate (Ki-67 index). They frequently arise in the lung (small and large-cell lung cancer) but rarely from the gastrointestinal tract. Due to their rarity, very little is known about digestive NEC and few studies have been conducted. Therefore, most of therapeutic recommendations are issued from work on small-cell lung cancers (SCLC). Recent improvement in pathology and imaging has allowed for better detection and classification of high-grade NEN. The 2019 World Health Organization (WHO) classification has described a new entity of well-differentiated grade 3 neuroendocrine tumors (NET G-3), with better prognosis, that should be managed separately from NEC. NEC are aggressive neoplasms often diagnosed at a metastatic state. In the localized setting, surgery can be performed in selected patients followed by adjuvant platinum-based chemotherapy. Concurrent chemoradiotherapy is also an option for NEC of the lung, rectum, and esophagus. In metastatic NEC, chemotherapy is administered with a classic combination of platinum salts and etoposide in the first-line setting. Peptide receptor radionuclide therapy (PRRT) has shown positive results in high-grade NEN populations and immunotherapy trials are still ongoing. Available therapies have improved the overall survival of NEC but there is still an urgent need for improvement. This narrative review sums up the current data on digestive NEC while exploring future directions for their management.

scholarly journals mASH1 is Highly Specific for Neuroendocrine Carcinomas: An Immunohistochemical Evaluation on Normal and Various Neoplastic Tissues

2016 ◽  
Vol 141 (2) ◽  
pp. 288-292 ◽  
Author(s):  
David Altree-Tacha ◽  
Jillian Tyrrell ◽  
Faqian Li
Keyword(s):  
Cell Layer ◽  
Granular Cell ◽  
Large Cell ◽  
Nuclear Staining ◽  
High Grade ◽  
Lung Cancers ◽  
Normal Tissues ◽  
Specificity And Sensitivity ◽  
Neuroendocrine Carcinomas ◽  
Neoplastic Tissues

Context.—High-grade neuroendocrine carcinomas and carcinoids can arise in different sites such as lung, gastrointestinal tract, prostate, and skin. Classic neuroendocrine markers such as CD56, synaptophysin, and chromogranin cannot distinguish carcinoids from high-grade neuroendocrine carcinomas. Recently, mouse monoclonal mASH1 has been shown to help discriminate carcinoids from high-grade neuroendocrine carcinomas in various neoplastic sites. To date, there have been no comprehensive immunohistochemistry studies with mASH1 on nonneuroendocrine neoplasms. Objective.—To evaluate the specificity and sensitivity of mASH1 in various normal and neoplastic tissues, including lung cancers. Design.—Formalin-fixed, paraffin-embedded tissue microarrays consisting of normal tissues and various neoplastic tissues were immunohistochemically evaluated with mASH1. Results.—In normal tissues (n = 30), mASH1 (nuclear staining) was sparsely expressed in the molecular cell layer, white matter, and granular cell layer of cerebellum; C cells in thyroid; and epithelial cells in thymus. In lung cancers, mASH1 stained 1.1% (1 of 93) of adenocarcinomas, 0.9% (1 of 111) of squamous cell carcinomas, 0% (0 of 30) of large cell carcinomas, 66.7% (6 of 9) of large cell neuroendocrine carcinomas, and 82.5% (94 of 114) of small cell carcinomas. In various other neoplastic tissues (n = 1114), mASH1 was expressed in thyroid medullary carcinomas, thymic carcinomas, and brain cancers; mASH1 was also expressed in a very low percentage of breast carcinomas, ovarian cancers, and pancreatic neuroendocrine tumors. All typical carcinoids of various sites were negative (0 of 11), however, in lung atypical carcinoids, mASH1 was expressed in 42.9% (9 of 21). Conclusions.—Although not organ specific, mASH1 is highly specific for high-grade neuroendocrine carcinomas versus carcinoids and other nonneuroendocrine neoplasms.

scholarly journals Esophageal neuroendocrine carcinoma presenting as a rare cause of dysphagia

2018 ◽  
Vol 5 (2) ◽  
pp. 1
Author(s):  
Sylvester Luu ◽  
Brian C. Benson ◽  
Kelly A. Haeusler ◽  
Robert O. Brady ◽  
Katherine M. Cebe ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Neuroendocrine Carcinoma ◽  
Poor Prognosis ◽  
Gastroesophageal Junction ◽  
Prior History ◽  
High Grade ◽  
Active Smoking ◽  
Platinum Based Chemotherapy ◽  
History Of ◽  
Neuroendocrine Carcinomas

A 60-year-old male with prior history of laryngeal carcinoma and active smoking presented with six months of solid food dysphagia. Endoscopy showed a large, friable gastroesophageal junction mass. Biopsies revealed a high-grade, poorlydifferentiated neuroendocrine carcinoma. He was subsequently started on platinum based chemotherapy and radiation therapy and his tumor decreased dramatically in size. This case is unique as neuroendocrine carcinomas (NECs) are rarely found in the esophagus and usually have a poor prognosis at time of diagnosis.

Challenges in Ki‐67 assessments in pulmonary large‐cell neuroendocrine carcinomas*

2020 ◽  
Author(s):  
Ann E Walts ◽  
James M Mirocha ◽  
Alberto M Marchevsky
Keyword(s):  
Large Cell ◽  
Ki 67 ◽  
Neuroendocrine Carcinomas

Outcomes of peptide receptor radionuclide therapy (PRRT) in metastatic grade 3 neuroendocrine tumors (NETs).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15694-e15694
Author(s):  
Mei Sim Lung ◽  
Michael Hofman ◽  
Grace Kong ◽  
Sue-Ping Thang ◽  
Michael Michael ◽  
...  
Keyword(s):  
Treatment Option ◽  
Treatment Options ◽  
Somatostatin Receptor ◽  
Peptide Receptor Radionuclide Therapy ◽  
Receptor Expression ◽  
Unknown Primary ◽  
Receptor Imaging ◽  
Ki 67 ◽  
Prior Chemotherapy ◽  
Platinum Based Chemotherapy

e15694 Background:Grade 3 (G3) NETs have a poor prognosis and limited treatment options (usually chemotherapy). PRRT is a potential treatment option if all sites of disease demonstrate high uptake on somatostatin-receptor imaging (SSRI). We retrospectively evaluated the efficacy of PRRT in G3 NETs. Methods: We reviewed records of patients with metastatic G3 NETs (Ki-67 > 20%) who received PRRT at our institution. Patients were treated with up to 5 cycles of PRRT, predominantly 177Lu-DOTA-octreotate. Further maintenance PRRT was administered upon progression if deemed suitable on SSRI. Radio-sensitizing chemotherapy was administered unless contra-indicated. Kaplan-Meier estimate was used to determine median overall survival (OS) and median time to new treatment/death (TNTD) defined from start of PRRT. Subgroup-analysis was performed for patients with Ki67 < 55% and ≥55%. Results: 26 patients with metastatic G3 NET received PRRT; 22 combined with chemotherapy (capecitabine/temozolomide (n = 12), 5-fluorouracil or capecitabine (n = 8), other (n = 2)). 58% were male. The median age was 62 (range 16-78 years). 61% had pancreatic NET, 19% small bowel, 8% lung, 8% unknown primary, 4% rectal. 77% had received at least one line of prior chemotherapy. 54% received prior platinum-based chemotherapy. Median follow-up was 33 months (range 8-83 months). Patients received a median of 4 cycles of PRRT (range 1-15). The estimated median OS from start of PRRT was 18 months: for Ki-67 < 55% (n = 21), 20 months; and Ki-67≥ 55% (n = 5), 9 months. The estimated median TNTD was 12 months: for Ki-67 < 55%, 16 months; and Ki-67≥55%, 4 months. 31% of patients were alive without a change in treatment modality following PRRT. Conclusions: In thispoor prognosis G3 NET cohort of whom 77% had received prior chemotherapy, a median OS of 18 months from start of PRRT is encouraging and warrants further study. PRRT is a promising treatment option for patients with G3 NET with high somatostatin-receptor expression selected by SSRI.

NRG1 fusion-positive lung cancers: Clinicopathologic profile and treatment outcomes from a global multicenter registry.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9081-9081 ◽  
Author(s):  
Michaël Duruisseaux ◽  
Stephen V. Liu ◽  
Ji-Youn Han ◽  
Valerie Gounant ◽  
Jin-Yuan Shih ◽  
...  
Keyword(s):  
Single Agent ◽  
Treatment Strategies ◽  
Stage Iv ◽  
Large Cell ◽  
Disease Stage ◽  
Lung Cancers ◽  
Best Response ◽  
Pathologic Features ◽  
Platinum Based Chemotherapy ◽  
Stage Iv Disease

9081 Background: NRG1 fusions are potentially actionable driver events enriched in NSCLCs, particularly invasive mucinous adenocarcinomas (IMAs). These fusions activate HER3/HER2, supporting the therapeutic use of HER3 and/or HER2 inhibitors, but optimal treatment strategies remain unclear. Methods: A global, multicenter network of thoracic oncologists (6 countries, 13 institutions) identified patients with pathologically confirmed NRG1 fusion-positive NSCLCs. Anonymized clinical/pathologic features and clinical outcomes were collected retrospectively. Best response to systemic therapy was determined (RECIST v1.1). PFS was calculated (Kaplan-Meier). Results: 80 NRG1 fusion-positive NSCLCs were identified. RNA-based sequencing identified 66% (n = 53/80), DNA-based sequencing 18% (n = 14/80), and FISH 16% (n = 13/80) of cases. The most common upstream partners were CD74 (45%), SLC3A2 (31%), and SDC (9%). Most patients were female (64%) and never smokers (58%). Histology was adenocarcinoma in 95% (IMA, 91%), squamous 4%, large cell neuroendocrine 1%. At diagnosis, most patients had non-metastatic disease (stage: I 33%, II 27%, III 18%, IV 22%). The lifetime frequency of brain metastases was 15%. 12 patients received the HER2 inhibitor afatinib for stage IV disease. PD was the best response in 55% (n = 6/11) of evaluable patients with 18% PR (n = 2/11) and SD 18% (n = 2/11); median PFS was 3.5 months (range 0.6-16.5 months). 19 patients received platinum-based chemotherapy; most patients had SD as their best response (47%, n = 8); PD 41% (n = 7), PR 12% (n = 2). PD-L1 was negative in the majority of tumors (79%, n = 26/33) and none had high PD-L1 expression (range 0-20%). No responses to single-agent anti-PD-1/L1 therapy were observed (PD n = 5/6, SD n = 1/6: nivolumab/atezolizumab). No responses to chemoimmunotherapy (carboplatin, pemetrexed, pembrolizumab) were observed (SD n = 4/5, PD n = 1/5). Conclusions: RNA-based testing is an important component of NRG1 fusion detection. Novel targeted therapeutic approaches are needed as overall outcomes with afatinib are poor. NRG1 fusion-positive NSCLCs do not highly express PD-L1 and outcomes with immunotherapy ± chemotherapy are poor.

Ki-67 index of 55% distinguishes two groups of bronchopulmonary pure and composite large cell neuroendocrine carcinomas with distinct prognosis

2020 ◽  
Author(s):  
Massimo Milione ◽  
Patrick Maisonneuve ◽  
Federica Grillo ◽  
Alessandro Mangogna ◽  
Giovanni Centonze ◽  
...  
Keyword(s):  
Large Cell ◽  
Ki 67 ◽  
Neuroendocrine Carcinomas

Comparative Outcomes in Patients With Small- and Large-Cell Neuroendocrine Carcinoma (NEC) and Mixed Neuroendocrine-Non-Neuroendocrine Neoplasm (MiNEN) of the Stomach

2020 ◽  
pp. 000313482095000
Author(s):  
Nam Young Choi ◽  
Byung-Sik Kim ◽  
Sung Tae Oh ◽  
Jeong Hwan Yook ◽  
Beom Su Kim
Keyword(s):  
Clinical Outcomes ◽  
Disease Free Survival ◽  
Large Cell ◽  
Small Cell ◽  
Neuroendocrine Neoplasm ◽  
Neuroendocrine Neoplasms ◽  
High Grade ◽  
Intermediate Grade ◽  
Free Survival ◽  
Neuroendocrine Carcinomas

Background Gastric neuroendocrine carcinomas (NECs), consisting of both large- and small-cell NECs, and mixed adenoneuroendocrine carcinomas (MANECs), including mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs), are a group of high-grade malignancies. Few studies to date have reported clinical outcomes, including prognosis, in patients with these tumors. This study therefore evaluated the clinicopathologic outcomes and prognosis in patients with NECs and MANECs. Methods This study included 36 patients diagnosed with gastric NECs, including 23 with large-cell and 13 with small-cell NECs, and 85 with MiNENs, including 70 with high-grade and 15 with intermediate-grade MiNENs. Clinical outcomes, including overall survival (OS) and disease-free survival (DFS), were assessed. Results DFS was significantly poorer in patients with NEC than in patients with intermediate-grade MiNEN ( P < .05), whereas both OS and DFS were similar in patients with NEC and high-grade MiNEN ( P > .05). Patients with large-cell NEC were more likely to undergo aggressive surgery than patients with high-grade MiNEN ( P < .05). Lymphovascular invasion was more frequent and DFS poorer in patients with large-cell than small-cell NECs ( P < .05 each). Conclusion DFS is significantly poorer in patients with NEC than in patients with intermediate-grade MiNEN and significantly lower in patients with large-cell than small-cell NECs.

Correlation of Ki-67 and p53 With the New World Health Organization/International Society of Urological Pathology Classification System for Urothelial Neoplasia

2001 ◽  
Vol 125 (5) ◽  
pp. 646-651 ◽  
Author(s):  
Stephen J. Cina ◽  
Kristen J. Lancaster-Weiss ◽  
Kristen Lecksell ◽  
Jonathan I. Epstein
Keyword(s):  
Papillary Carcinoma ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Ki 67 ◽  
Papillary Lesions ◽  
Flat Lesions ◽  
Papillary Hyperplasia ◽  
Health Organization ◽  
Papillary Neoplasm

Abstract Objective.—The present study examines p53 and Ki-67 staining patterns of the diagnostic entities included within the new World Health Organization/International Society of Urological Pathology (WHO/ISUP) classification of urothelial neoplasms. Design.—We retrospectively studied 151 bladder biopsies from 81 patients with the following neoplasms: normal urothelium (n = 34 biopsies); low-grade intraurothelial neoplasia (LGIUN; n = 19); high-grade intraurothelial neoplasia (HGIUN; n = 20); papillary hyperplasia (n = 4); papilloma (n = 3); papillary neoplasm of low malignant potential (LMP; n = 12); low-grade papillary carcinoma (n = 28); and high-grade papillary carcinoma (n = 31). Sections were labeled immunohistochemically with antibodies to p53 and Ki-67 (MIB-1). Two hundred cells from each lesion were visually counted, and the percentage of positive cells was tabulated without knowledge of the WHO/ISUP diagnosis. Results.—In flat lesions, p53 positivity was of limited diagnostic utility; the marker was present in 6 of 34 benign biopsies, 6 of 19 LGIUNs, and 10 of 20 HGIUNs. In one case in which HGIUN was present elsewhere in the bladder, 29% of the benign urothelial cells were p53 positive. In papillary lesions, p53 positivity was not seen in 4 of 4 cases of papillary hyperplasia, 3 of 3 papillomas, and 8 of 12 LMP tumors. In contrast, p53 was detected in 18 of 28 low-grade and 26 of 31 high-grade papillary urothelial carcinomas. A p53 labeling index (LI) greater than 30% was only seen in HGIUNs and high-grade papillary carcinomas. In flat lesions, an increased Ki-67 LI separated out benign urothelium (mean LI, 0.62%) from dysplasia (mean LI, 3.3%) and HGIUN (mean LI, 11.6%). In papillary lesions, Ki-67 positivity was as follows: papillary hyperplasia (mean LI, 1.1%); papilloma (mean LI, 4.3%); LMP tumors (mean LI, 2.5%), low-grade papillary carcinoma (mean LI, 7.3%); and high-grade carcinoma (mean LI, 15.7%). A Ki-67 LI greater than 10% was seen only in low- and high-grade papillary carcinomas, HGIUN, and single cases of LGIUN and papillary neoplasm of LMP. Conclusions.—An increased proliferative index as demonstrated by immunohistochemical staining for Ki-67 (MIB-1) is most often seen in papillary carcinoma and HGIUN. Marked p53 positivity is also characteristic of carcinoma but may be seen in benign-appearing urothelium, suggesting a “field effect” with occult molecular aberration.

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