RESUMEN
The WHO 2010 classification divides gastrointestinal neuroendocrine neoplasms (GI-NENs) into neuroendocrine tumor (NET) G1, NET G2, neuroendocrine carcinoma (NEC) and mixed adenoendocrine carcinoma (MANEC) groups. A total of 136 cases of GI-NENs diagnosed at our hospitals as gastrointestinal carcinoids, endocrine cell carcinomas and NENs over the last 11 years, using the WHO 2010 classification were assessed. Among the 136 cases, 88.2% (120/136) were classified into the NET group (NET G1/G2) and 11.8% (16/136) were classified into the NEC group (NEC/MANEC). The incidences of lymphatic and venous invasions were higher in the NEC group compared with in the NET group (P<0.0001 and P=0.0021, respectively). The immunohistochemical staining of cluster of differentiation 73 (CD73) was evaluated in GI-NENs. CD73 is a potentially useful molecule in tumor immunity. In general, CD73 on the tumor cell membrane converts adenosine monophosphate to adenosine, which restrains the production of interferon-γ and cytocidal activity. Although the association between stem cells of pancreatic NENs and CD73 has been reported, few studies have reported on CD73 expression in GI-NENs. Immunohistochemical CD73 expression on the cytomembrane of neuroendocrine cells was detected in 27.2% (37/136) of the GI-NENs. The positive ratio of CD73 was significantly higher in the NEC group compared with in the NET group (P=0.0015). CD73 is also considered as a potential biomarker of anti-programmed death-1 (PD-1) therapy. The expression of programmed death-ligand 1 (PD-L1) on the cytomembrane of GI-NENs was assessed. The positive ratio of PD-L1 was higher in the NEC group compared with in the NET group (P=0.0011). Furthermore, CD73 expression status was significantly correlated with PD-L1 expression (P<0.0001). These results indicate that CD73 may be an interesting candidate for a biomarker for certain prognostic factors and therapeutics concerning PD-1 therapy.
RESUMEN
BACKGROUND: A novel morphological classification using resected specimens predicted malignant potential and prognosis in patients with pancreatic neuroendocrine tumors (P-NETs). The aim of this study was to examine the predictive ability of morphological diagnoses made using non-invasive multi-detector computed tomography (MDCT) in P-NETs. METHODS: Between 2002 and 2015, 154 patients were diagnosed with P-NETs at the Tokyo Medical and Dental University, and 82 patients who underwent surgical treatment were enrolled. The primary tumors were classified by MDCT into three types: Type I, simple nodular tumor; Type II, simple nodular tumor with extra-nodular growth; and Type III, confluent multinodular tumor. Patients were stratified by 15 clinical specialists according to classification and without any other clinical or pathological information. Clinicopathological features and patient survival were reviewed retrospectively. RESULTS: The mean observation time was 1004 days. Forty-six, 22, and 14 patients had Type I, II, and III tumors, respectively. Morphological classification was significantly correlated with advanced features such as tumor size, Ki-67 index, and synchronous liver metastasis (p < 0.001 for all). There were significant differences between all three tumor types as judged by ENETS TNM classification (p < 0.001), AJCC TNM classification (p = 0.046), WHO 2004 classification (p < 0.001), and WHO 2010 classification (p < 0.001). Five-year progression-free survival (PFS) rates for patients with Type I, II, and III tumors were 97, 43, and 31%, respectively (I vs. II, p < 0.001; I vs. III, p < 0.001; II vs. III, p = 0.017). Multivariate analysis revealed Type II/III tumors and synchronous liver metastasis to be independent risk factors for poor PFS. CONCLUSION: A novel simple morphological classification system would predict Type II and III tumors that may have higher malignant potential than Type I tumors.
Asunto(s)
Tomografía Computarizada Multidetector/métodos , Tumores Neuroendocrinos/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Tumores Neuroendocrinos/clasificación , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/clasificación , Neoplasias Pancreáticas/patología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Adulto JovenRESUMEN
A 68-year-old man was referred to our hospital because of left upper quadrant pain. Contrast enhanced computed tomography showed a low density mass with delayed contrast effects as well as para-aortic node swelling with homogenous contrast effects. Histological examination of specimens obtained by endoscopic ultrasound fine needle aspiration revealed a pancreatic neuroendocrine tumor (NET) G2, according to the World Health Organization 2010 classification, and lymph node metastasis. Distal pancreatectomy and lymph node dissection were performed. On histological examination, the tumor showed well-differentiated morphology with an organoid pattern. The Ki67 labeling index was 21.6 %, and the mitotic count was 25/10 high power fields. As mentioned above, we made a final diagnosis of the lesion as "NET G3," because the tumor presented with well-differentiated morphology. Chemotherapy with Everolimus was administered. Liver metastasis occurred 11 months after the first operation, and a partial hepatectomy was performed. Histological findings were similar to those of the first operation. Herein we present a case of pancreatic well-differentiated neuroendocrine tumor with a high proliferative rate referred to as "NET G3," and review the relevant literature.
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Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/patología , Anciano , Proliferación Celular , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Hepatectomía , Humanos , Antígeno Ki-67/análisis , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Índice Mitótico , Tumores Neuroendocrinos/secundario , Tumores Neuroendocrinos/cirugía , Pancreatectomía , Neoplasias Pancreáticas/cirugíaRESUMEN
OBJECTIVE: To assess the prognostic value in Chinese patients of two new systems, the World Health Organization (WHO)-2010 and the American Joint Committee on Cancer and the Union for International Cancer Control (AJCC/UICC) systems, for the classification of gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). METHODS: One hundred and three patients with GEP-NEN treated at the First Affiliated Hospital of Nanjing Medical University from January 2003 to December 2011 were included in the study. All patients were diagnosed pathologically and had complete follow-up data. Univariate and multivariate analyses of their clinicopathological characteristics were performed. RESULTS: The 5-year survival rates were 95%, 74%, 24% and 15% based on the AJCC/UICC stages I to IV, and 92%, 62% and 29% according to WHO-2010 grades 1 to 3, respectively, in patients with GEP-NEN. A higher mortality was observed in patients with AJCC/UICC stage III and IV tumors compared with those at stage I-II, and patients with stage II compared with those with stage I, whereas there was no difference in survival between stage IV and III patients. Based on the WHO-2010 grading classification, patients with grade 3 tumors had the lowest survival rate than those with grade 1 and 2 tumors, followed by patients with grade 2 tumors. CONCLUSION: The WHO-2010 and AJCC/UICC staging systems can effectively evaluate the prognosis of patients with GEP-NEN, although the latter might not accurately discriminate the prognosis of patients with local metastasis from those having distant metastasis.
Asunto(s)
Neoplasias Gastrointestinales/clasificación , Tumores Neuroendocrinos/clasificación , Adolescente , Adulto , Anciano , Pueblo Asiatico , Femenino , Estudios de Seguimiento , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/patología , Humanos , Estimación de Kaplan-Meier , Masculino , Oncología Médica/organización & administración , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Tumores Neuroendocrinos/mortalidad , Tumores Neuroendocrinos/patología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Organización Mundial de la Salud , Adulto JovenRESUMEN
BACKGROUND: It is difficult to predict the malignant potential of pancreatic neuroendocrine tumors (PNETs) precisely. This study investigated the validity of a new grading system adopted by the World Health Organization 2010 classification to determine risk factors for recurrence of PNETs. METHODS: Data of 70 patients with PNETs who underwent curative resection were retrospectively examined by uni- and multivariate analyses. Histopathological findings were re-reviewed by experienced pathologists. NET G1 was defined as mitotic count <2 per 10 high power fields (HPF) and/or ≤2% Ki67 index, and NET G2 as 2-20 mitosis per 10 HPF and/or 3-20% Ki67 index. RESULTS: There were 58 patients with NET G1 and 12 with NET G2. Incidence of recurrence was 11.4%. Univariate analysis demonstrated significant risk factors for recurrence including NET G2 of histological grade (P = 0.0089), male gender (P = 0.0333), tumor size ≥ 20 mm (P = 0.0117), lymph node metastasis (P = 0.0004), liver metastasis (P < 0.0001), lymphatic invasion (P = 0.046), and neural invasion (P = 0.0002). By multivariate analysis, histological grade (hazard ratio; 59.76, P = 0.0022) and neural invasion (hazard ratio; 147.49, P = 0.0016) were significantly associated with recurrence of PNETs. CONCLUSIONS: This study confirmed the prognostic relevance of the new grading classification and that evaluation of perineural invasion and histological grade should be considered as prognostic predictors in well-differentiated PNETs (NET G1 and G2).