Neuroendocrine tumors of lung

Abstract

Lung neuroendocrine tumors are a rare group of lung tumors that undergo neuroendocrine differentiation and progress slowly. The origin and development of these tumors are controversial. It is believed that these tumors originate from Kulchitzky cells (or enterochromaffin cells) normally found in bronchial mucosa. Approximately 20-25% of all invasive lung malignancies are neuroendocrine tumors. Neuroendocrine tumors develop from endocrine cells, which were first described as carcinoid tumors by Siegfried Oberndorfer in 1904. These tumors also have neuron-like characteristics, hence they are called neuroendocrine tumors. However, 60% of these tumors are functionally active (they produce hormones). According to the World Health Organization (WHO) 2015 classification, they are divided into three main categories: Carcinoid tumors (typical (TC) / atypical (AC)), Large cell neuroendocrine carcinomas (LCNEC), Small cell carcinomas (SCLC). Neuroendocrine tumors account for less than 2% of all lung malignancies in adults. Lung NETs typically occur in the second decade of life. Atypical neuroendocrine tumors are less common than typical neuroendocrine tumors and have a slower doubling time. The etiology of lung NETs is unknown. Smoking is considered a risk factor. It has been reported that smoking rates are higher in atypical tumors. Rarely, they have been shown to be associated with multiple endocrine neoplasia type 1 (MEN1). Histologically, lung neuroendocrine tumors have different structures. Typical neuroendocrine tumors, which have low metastatic potential, low grade (well-differentiated), and slow growth, can be found. Small cell lung cancer (SCLC) and large cell NECs grow and spread rapidly. The behavior of atypical neuroendocrine tumors is intermediate between typical neuroendocrine tumors and SCLC. Unlike gastrointestinal neuroendocrine tumors, the terms \"typical\" and \"atypical\" are used to describe low and intermediate grade tumors occurring in the lung. Well-differentiated neuroendocrine tumors are called low-grade (typical carcinoid), and poorly differentiated neuroendocrine tumors are referred to as intermediate-grade (atypical carcinoid). Typical low-grade neuroendocrine tumors consist of regular round or oval cells with dispersed chromatin and small nucleoli. They have a polygonal cell structure. There is no low mitosis or necrosis. Low-grade neuroendocrine tumors located in the periphery of the lung have a distinct cell growth pattern. They are accompanied by neuroendocrine cell hyperplasia (DIPNECH) and/or tumorlets (neuroendocrine cell clusters smaller than 5 mm in diameter) in the adjacent lung tissue. In the histology of intermediate-grade atypical neuroendocrine tumors, 2-10 mitoses are observed. Cytological atypia is characteristic. Metastases to hilar or mediastinal lymph nodes are more common in intermediate-grade tumors, and recurrence rates are higher. Immunohistochemically, the release of cytoplasmic chemicals such as synaptophysin, neuron-specific enolase, and chromogranin can identify neuroendocrine differentiation. Thyroid transcription factor 1 (TTF1) is positive in 50% of lung neuroendocrine tumors.