scholarly journals Ki67 proliferative index of the neuroendocrine component drives MANEC prognosis

2018 ◽  
Vol 25 (5) ◽  
pp. 583-593 ◽  
Author(s):  
Massimo Milione ◽  
Patrick Maisonneuve ◽  
Alessio Pellegrinelli ◽  
Federica Grillo ◽  
Luca Albarello ◽  
...  
Keyword(s):  
Digestive System ◽  
Multivariable Analysis ◽  
Prognostic Index ◽  
Primary Site ◽  
Beta Catenin ◽  
Ki67 Index ◽  
Risk Of Death ◽  
Poorly Differentiated Neuroendocrine Carcinoma ◽  
Pathologic Features ◽  
Poorly Differentiated

Mixed adenoneuroendocrine carcinomas (MANECs) are composed of a poorly differentiated neuroendocrine carcinoma (NEC) and a non-neuroendocrine (non-NEC) neoplastic epithelial component, each representing at least 30% of the tumor. At present, prognostic factors for MANECs remain largely unexplored. We investigated the clinical-pathologic features of a large multicenter series of digestive system MANECs. Surgical specimens of 200 MANEC candidates were centrally reviewed; diagnosis was confirmed in 160 cases. While morphology, proliferation (mitotic count (MC), Ki67 index) and immunophenotype (p53, SSTR2a, beta-Catenin, Bcl-2, p16, Rb1, ALDH, mismatch repair proteins and CD117) were investigated separately in both components, genomic (TP53,KRAS,BRAF) alterations were searched for on the entire tumor. Data were correlated with overall survival (OS). MANEC sites were: 92 colorectal, 44 gastroesophageal and 24 pancreatobiliary. Median OS was 13.2 months. After adjustment for primary site, Ki67 index of the NEC component (but not of the non-NEC component) was the most powerful prognostic marker. At multivariable analysis, patients with Ki67 ≥ 55% had an 8-fold risk of death (hazard ratio (HR) 7.83; 95% confidence interval (CI) 4.17–14.7;P < 0.0001) and a median OS of 12.2 months compared to those with Ki67 < 55% (median OS 40.5 months). MC (HR 1.51; 95% CI 1.03–2.20,P = 0.04) was a weaker prognostic index. Colorectal primary site (HR 1.60; 95% CI 1.11–2.32;P = 0.01) was significantly associated with poorer survival. No single immunomarker, in either component, was statistically significant. This retrospective analysis of a large series of digestive system MANECs, showed that the NEC component, particularly its Ki67 index, was the main prognostic driver.

Multicenter retrospective analysis of systemic chemotherapy in poorly differentiated neuroendocrine carcinoma of the digestive system.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 274-274 ◽  
Author(s):  
Tomohiro Yamaguchi ◽  
Nozomu Machida ◽  
Akiyoshi Kasuga ◽  
Hideaki Takahashi ◽  
Kentaro Sudo ◽  
...  
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Digestive System ◽  
Systemic Chemotherapy ◽  
Small Cell Lung Carcinoma ◽  
Outcome Data ◽  
Small Cell ◽  
Standard Regimen ◽  
Cell Lung Carcinoma ◽  
Poorly Differentiated Neuroendocrine Carcinoma ◽  
Poorly Differentiated

274 Background: Poorly differentiated neuroendocrine carcinoma (PDNEC) is a rare and aggressive disease. No standard regimen has yet been established for advanced PDNEC, although regimens for small-cell lung carcinoma such as irinotecan + cisplatin (IP) or etoposide + cisplatin (EP), are usually adopted. The aim of this study was to investigate the outcomes according to the patient’s characteristics and treatment regimens for patients with PDNEC of the digestive system. Methods: Data was collected from the medical records of patients at 23 hospitals. The selection criteria were as follows: 1) histologically proven PDNEC, small cell carcinoma, mixed endocrine-exocrine carcinoma with a PDNEC component, or histologically proven neuroendocrine tumor with rapidly progressive clinical course; 2) primary tumor arising from the gastrointestinal tract (GI) or the hepato-biliary-pancreatic system (HBP); and 3) inoperable or recurrent disease treated with systemic chemotherapy between April 2000 and March 2011. Results: There were 258 patients (pts). The median age was 62.5 years (range, 26-81); male/female, 182/76 pts; the primary site was the esophagus/stomach/small bowel/colorectum/hepato-biliary system/pancreas in 85/70/6/31/31/35 pts. According to these primary sites, the median overall survival period (mOS) was 13.4/13.3/29.7/7.6/7.9/8.5 months, respectively. The most commonly used regimen was IP (160 pts, 62%), followed by EP (46 pts, 18%). For the patients treated with IP/EP, the response rates (RR) were 50%/27%, the progression free survival periods (mPFS) were 5.2/4.0 months, and mOS were 13.0/7.3 months. The subgroup outcome data for patients with HBP or GI cancers are shown in Table. A multivariate analysis demonstrated that a primary HBP cancer (HR=1.96, p=0.002), and a poor PS (HR=2.33, p=0.01) were independent unfavorable prognostic factors. Conclusions: PDNEC of the HBP has a poorer prognosis than GI. IP was the most commonly selected treatment regimen, and seemed to have a favorable treatment outcome. [Table: see text]

Multicenter retrospective analysis of systemic chemotherapy for advanced poorly differentiated neuroendocrine carcinoma of the digestive system.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4046-4046
Author(s):  
Nozomu Machida ◽  
Tomohiro Yamaguchi ◽  
Akiyoshi Kasuga ◽  
Hideaki Takahashi ◽  
Kentaro Sudo ◽  
...  
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Digestive System ◽  
Systemic Chemotherapy ◽  
Small Cell Lung Carcinoma ◽  
Performance Status ◽  
Small Cell ◽  
Standard Regimen ◽  
Cell Lung Carcinoma ◽  
Poorly Differentiated Neuroendocrine Carcinoma ◽  
Poorly Differentiated

4046 Background: No standard regimen is yet established for advanced poorly differentiated neuroendocrine carcinoma (PDNEC) although regimens for small-cell lung carcinoma are usually adopted such as irinotecan + cisplatin (IP) or etoposide + cisplatin (EP). Our aim was to respectively investigate outcomes for advanced PDNEC of the digestive system according to patient characteristics and regimens. Methods: Data was collected from patient medical records at 23 hospitals in Japan. The selection criteria were as follows: 1) histologically proven PDNEC, small cell carcinoma, mixed endocrine-exocrine carcinoma with a PDNEC component, or histologically proven neuroendocrine tumor with rapidly progressive clinical course; 2) primary tumor arising from the gastrointestinal tract (GI) or the hepato-biliary-pancreatic system (HBP); and 3) inoperable or recurrent disease treated with systemic chemotherapy (Cx) between April 2000 and March 2011. Results: This study included 258 patients (males/females, 182/76) with median age of 62.5 years. Primary sites were esophagus/stomach/small bowel/colorectum/hepato-biliary system/pancreas in 85/70/6/31/31/35 patients (pts). According to the primary sites, the median overall survival period (mOS) was 13.4/13.3/29.7/7.6/7.9/8.5 months, and that of GI/HBP was 13.0/7.9 months, respectively. Most common regimen was IP (160 pts, 62%), followed by EP (46 pts, 18%). For IP/EP patients, response rates (RR) were 50%/27%, the median progression free survival periods (mPFS) were 5.2/4.0 months. Second line Cx was performed for 88 pts (55%)/28 pts (61%) and mOS from first line Cx were 13.0/7.3 months in IP/EP groups. Multivariate analysis demonstrated that a primary site of HBP (HR=1.96, p=0.003) and performance status of 2 and more (HR=2.32, p=0.01) were independent unfavorable prognostic factors of PDNEC patients treated with systemic Cx, while the hazard ratio comparing IP with EP was 0.79 (p=0.305). Conclusions: PDNEC of HBP had poorer prognosis than GI. IP was the most common treatment regimen and seemed to show better treatment outcomes than EP.

scholarly journals Extranodal NHL- A retrospective review of clinico-pathologic features and outcome and comparison with nodal NHL. Single institution experience years: 1988–2004

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17542-17542
Author(s):  
A. Lal ◽  
S. Adil ◽  
N. Masood
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Early Stage ◽  
Univariate Analysis ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Primary Site ◽  
Stage I ◽  
Pathologic Features ◽  
Significant Difference

17542 Background: Non-Hodgkin’s lymphoma (NHL) arising in an extra nodal (EN) site is not uncommon and its natural history and treatment is clearly characterized in the literature. Data on EN-NHL and comparison with N-NHL with relation to survival and prognostic factors is scarce in our part of the world. The primary objective of this study was to analyze the anatomic distribution, clinical features and outcome of DLBCL patients according to the primary site with applicability of International Prognostic Index (IPI). Methods: From 1988 to 2004, 557 patients were analyzed for the clinico-pathologic characteristics, treatment outcome and prognostic factors affecting overall survival. Results: Median age was 48.7 ± 15.3 years ; the M: F ratio was 2:1. The distribution according to the primary site was: lymph node, 322 cases (58%) of these 145 cases (44%) stage IV, 76 cases (23%) Stage III, 60 cases (18%) stage II and 47 cases(15%) stage I ; and EN sites, 235 (42%), including GIT (44%) followed by upper aerodigestive tract (19%), bones (08%), spine (05%), and 3% each as breast, CNS, testis,lungs. The median survival rate was 4.8 and 6.3 years in NL and ENL respectively vary according to primary site/stage of the lymphoma. In the univariate analysis age less than 60 years, early stage I-II, extra nodal involvement primarily gastric or bone, 0–1 extra nodal site, 0–1 PS, lack of B symptoms, normal LDH level has been associated with good prognosis. In the multivariate analysis age, PS, stage and level of LDH were the main variables to predict OS; no nodal or extranodal site maintained their prognostic value. Conclusion: Our data correspond with series from west increasing incidence extranodal lymphoma due to improved diagnostic techniques and superior results with chemotherapy by preserving the organ. Few patients with bowel obstruction or cord compression lymphoma required surgery for diagnosis or relief of symptoms. There is significant difference from western data in histologies DLBC-NHL is the most common histologies in our study. Overall survival patients with EN-NHL were similar to nodal NH-Lymphoma but largely depended on IPI. No significant financial relationships to disclose.

Phase II Trial of Paclitaxel, Carboplatin, and Etoposide in Advanced Poorly Differentiated Neuroendocrine Carcinoma: A Minnie Pearl Cancer Research Network Study

2006 ◽  
Vol 24 (22) ◽  
pp. 3548-3554 ◽  
Author(s):  
John D. Hainsworth ◽  
David R. Spigel ◽  
Sharlene Litchy ◽  
F. Anthony Greco
Keyword(s):  
Phase Ii ◽  
Neuroendocrine Carcinoma ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Small Cell ◽  
Primary Site ◽  
Unknown Primary ◽  
Small Cell Lung ◽  
Poorly Differentiated Neuroendocrine Carcinoma ◽  
Poorly Differentiated

Purpose To evaluate the efficacy of chemotherapy with paclitaxel, carboplatin, and etoposide in advanced adult poorly differentiated neuroendocrine carcinomas. Patients and Methods Patients eligible for this multicenter, phase II trial had metastatic poorly differentiated neuroendocrine carcinoma and had received no previous treatment. Patients with a variety of known primary sites (excepting small-cell lung cancer) and patients with unknown primary site were eligible. Patients received four courses of chemotherapy with paclitaxel, carboplatin, and etoposide, administered at 3-week intervals. After completing four courses of treatment, patients with objective response or stable disease received three courses (24 weeks) of weekly paclitaxel. Results Seventy-eight patients were treated; 62% had unknown primary site. Forty-one patients (53%) had major responses (complete response rate, 15%), and five patients remain disease free from 18 to 66 months after therapy. Response rates were similar regardless of histology (small-cell v poorly differentiated carcinoma) or primary site. The median, 2-year, and 3-year survivals for the entire group were 14.5 months, 33%, and 24%, respectively. Myelosuppression was the major toxicity, as has been reported previously with this regimen. Conclusion This prospective phase II trial provides additional evidence that this family of relatively uncommon carcinomas is initially chemosensitive, with a high overall response rate to combination chemotherapy and a minority of complete responses. The three-drug regimen evaluated in this trial is moderately toxic, and has no obvious efficacy advantages when compared with standard platinum/etoposide regimens. Treatment for advanced poorly differentiated neuroendocrine carcinoma should parallel treatments used for small-cell lung cancer.

Clinico-pathologic Features of Esophageal Poorly Differentiated Neuroendocrine Carcinomas, a Case Series and Review of Literature

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S64-S64
Author(s):  
I Perveze ◽  
D Rao
Keyword(s):  
Metastatic Disease ◽  
Correct Diagnosis ◽  
Case Series ◽  
Disease Process ◽  
Malignant Neoplasm ◽  
Distal Esophagus ◽  
Poorly Differentiated Neuroendocrine Carcinoma ◽  
Pathologic Features ◽  
Poorly Differentiated ◽  
Neuroendocrine Carcinomas

Abstract Introduction/Objective Esophageal neuroendocrine carcinomas (NECs) constitute an extremely rare and distinct group of neoplasms. The clinico-pathologic characteristics are poorly understood and differ starkly from high grade well differentiated neuroendocrine tumors. Only one case series describing clinico-pathologic features of NECs has been described in recent literature. Methods We describe a case series of three patients highlighting the typical presentation, diagnostic techniques and pathologic attributes for this rare disease process. Results All three patients were middle age to elderly with two males (ages 58 and 83) and one female (age 72). The typical presentation was dysphagia (2/3, 66%) followed by severe GERD (1/3, 33%). Typical locations were distal esophagus (2/3, 66%) and gastro-esophageal junction (1/3, 33%). Computed tomography showed bulky masses in all patients (3/3, 100%) with median size of 5.6 cm. PET imaging showed metastatic disease (mediastinal or epigastric lymphadenopathy and lung metastasis) in 2/3, 66% of the patients. All the patients were found to have necrotic masses on EGD with biopsy showing poorly differentiated neuroendocrine carcinoma in all (3/3, 100%). Immuno- histochemical stains revealed Synaptophysin positivity in 3/3, 100%, Chromogranin in 1/3, 33% and CD56 in 1/3, 33% of the patients. Patients with metastatic disease at presentation (2/3, 66%) opted for palliative care while the patient without any evidence of metastasis (1/3, 33%) underwent surgical resection followed by chemotherapy. Conclusion ENCs are an exceedingly rare group of malignant neoplasm with variable presentations posing a diagnostic challenge for the clinician and pathologist alike. Most patients tend to be elderly with advanced disease at presentation and guarded prognosis. This case series underscores the importance of including this entity among the differential diagnosis for poorly differentiated carcinomas of the distal esophagus. IHC with positive neuroendocrine markers particularly Synaptophysin helps make the correct diagnosis when combined with typical morphology.

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