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Introduction Bronchopulmonary (BP) neuroendocrine tumors (NETs; typical carcinoids and atypical carcinoids (TCs and ACs)) account for 20–25% of NETs and 1–2% of lung malignancies ( Öberg et al. 2012 , Filosso et al. 2018 , Baudin et al
Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California, USA
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Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA
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Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California, USA
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Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA
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Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California, USA
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site after the gastrointestinal tract ( Modlin et al. 2003 ). Lung NETs have a wide spectrum of clinical behavior and a unique pathologic classification as either typical carcinoids (grade 1) or atypical carcinoids (grade 2) ( Travis et al. 2015
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choice for low-to-intermediate grade (i.e. typical carcinoids (TCs) or atypical carcinoids (ACs)) and localized tumors, while in HG and/or disseminated lesions chemotherapy is generally preferred ( Pelosi et al . 2006 , Garcia-Yuste et al . 2008
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Institute of Anatomic Pathology, Service of Biometry and Clinical Epidemiology, Service of Pathology, Thoracic Unit, Medical Oncology Unit, Unit of Pathological Anatomy, Medical Oncology Unit of Respiratory Tract and Sarcomas, Division of Thoracic Surgery, Department of Thoracic Surgery, Division of Pathology, Division of Thoracic Surgery, Division of Pathology and Laboratory Medicine, Department of Biomedical and Clinical Sciences ‘Luigi Sacco’, Università Cattolica del Sacro Cuore – Policlinico A. Gemelli, Rome, Italy
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, typical carcinoid; AC, atypical carcinoid; LCNEC, large-cell neuroendocrine carcinoma; SCLC, small-cell lung carcinoma; RL, right lung; LL, left lung; T, tumor definition according to the American Joint Cancer Committee 2010 ( Edge et al . 2010 ); N
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ABSTRACT
Typical and atypical carcinoids are neuroendocrine epithelial lung tumours which are difficult to distinguish. Confusion has been introduced by designating atypical carcinoids as well differentiated neuroendocrine carcinomas and including some tumours which are large cell neuroendocrine carcinomas.
We therefore investigated 32 typical and 23 atypical carcinoids of the lung, and 9 combined forms of atypical carcinoid and small cell carcinoma. The following parameters were each independently correlated in a multivariate analysis with 10-year survival data: nuclear and nucleolar polymorphism, mitotic counts, vascular invasion, lymph node metastasis, structural pattern, location of the tumours, immunohistochemistry, age and sex of the patients.
Typical carcinoids were characterized by an absence of vascular invasion and lymph node metastases, and a mean mitotic rate of 0.75/10 high power fields (HPFs), while atypical carcinoids were characterized by vascular invasion and/or metastases, a mean mitotic rate of 4.25/10 HPFs and nuclear pleomorphism. Combined forms of atypical carcinoid and small cell carcinoma were characterized by vascular invasion, metastases and a mean mitotic rate of 20.7/10 HPFs. Vascular invasion, lymph node metastases, mitotic counts and nuclear pleomorphism significantly correlated with 10-year survival data, whereas location, size and structural pattern of the tumour, age and sex did not correlate with survival. All tumours were positive for cytokeratins and at least two out of three general neuroendocrine markers. However, positive reactivity for different peptides, hormones, and neurotransmitters did not correlate with one of the structural subtypes of carcinoid or with patient survival.
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Section of Endocrinology, Laboratorio in Rete del Tecnopolo ‘Tecnologie delle Terapie Avanzate’ (LTTA), Department of Cardiological, Department of Morphology, Department of Medical Sciences, University of Ferrara, Via Savonarola 9, 44121 Ferrara, Italy
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Section of Endocrinology, Laboratorio in Rete del Tecnopolo ‘Tecnologie delle Terapie Avanzate’ (LTTA), Department of Cardiological, Department of Morphology, Department of Medical Sciences, University of Ferrara, Via Savonarola 9, 44121 Ferrara, Italy
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Section of Endocrinology, Laboratorio in Rete del Tecnopolo ‘Tecnologie delle Terapie Avanzate’ (LTTA), Department of Cardiological, Department of Morphology, Department of Medical Sciences, University of Ferrara, Via Savonarola 9, 44121 Ferrara, Italy
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and immunohistochemical diagnosis of TBCs, according to the WHO classification ( Travis & Brambilla 2004 ; Table 1 ). Table 1 Clinical characteristics of BC patients Patient no. Sex Age Side Diameter (cm) Histology TNM 1 M 38 dx 1.7 Typical carcinoid
Università Cattolica del Sacro Cuore, Rome, Italy
ENETS Center of Excellence, Neuroendocrine Tumour (NET) Center, Rome, Italy
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ENETS Center of Excellence, Neuroendocrine Tumour (NET) Center, Rome, Italy
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any, mitotic activity and intense expression of the general neuroendocrine markers chromogranin A and synaptophysin. (A) Lung typical carcinoid; (B) pheochromocytoma; (C) insulinoma. (D, E and F) NEC displays a solid structure with abundant and
Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
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National Hospital Organization, Sendai Medical Center, Sendai, Japan
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Member of the German Cancer Consortium (DKTK)
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. 2017 ). The study has been approved by the ethics committees of all participating institutions. Table 1 Clinicopathological characteristics of 225 patients with neuroendocrine tumors of the lung. N (%) Typical carcinoid N
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clarification of criteria for atypical carcinoid and its separation from typical carcinoid . American Journal of Surgical Pathology 22 934 – 944 doi:10.1097/00000478-199808000-00003 . Walch AK Zitzelsberger HF Aubele MM Mattis AE Bauchinger M
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MiNEN c a Not included in criteria; b Amount of the non-NEN components is not defined; c Each component accounts for at least 30% of total tumor cell population. TC, typical carcinoid; AC, atypical carcinoid; LCNEC, large cell