Pulmonary neuroendocrine tumor

Last updated September 12, 2019

Pulmonary neuroendocrine tumors are neuroendocrine tumors localized to the lung: bronchus or pulmonary parenchyma.

Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. Many are benign, while some are malignant. They most commonly occur in the intestine, where they are often called carcinoid tumors, but they are also found in the pancreas, lung and the rest of the body.

The lungs are the primary organs of the respiratory system in humans and many other animals including a few fish and some snails. In mammals and most other vertebrates, two lungs are located near the backbone on either side of the heart. Their function in the respiratory system is to extract oxygen from the atmosphere and transfer it into the bloodstream, and to release carbon dioxide from the bloodstream into the atmosphere, in a process of gas exchange. Respiration is driven by different muscular systems in different species. Mammals, reptiles and birds use their different muscles to support and foster breathing. In early tetrapods, air was driven into the lungs by the pharyngeal muscles via buccal pumping, a mechanism still seen in amphibians. In humans, the main muscle of respiration that drives breathing is the diaphragm. The lungs also provide airflow that makes vocal sounds including human speech possible.

A bronchus is a passage of airway in the respiratory system that conducts air into the lungs. The first bronchi to branch from the trachea are the right main bronchus and the left main bronchus. These are the widest and enter the lungs at each hilum, where they branch into narrower secondary bronchi or lobar bronchi, and these branch into narrower tertiary bronchi or segmental bronchi. Further divisions of the segmental bronchi are known as 4th order, 5th order, and 6th order segmental bronchi, or grouped together as subsegmental bronchi. The bronchi when too narrow to be supported by cartilage are known as bronchioles. No gas exchange takes place in the bronchi.

Pulmonary neuroendocrine tumors include a spectrum of tumors from the low-grade typical pulmonary carcinoid tumor and intermediate-grade atypical pulmonary carcinoid tumor to the high-grade pulmonary large cell neuroendocrine carcinoma (LCNEC) and pulmonary small cell carcinoma (SCLC), with significant clinical, epidemiologic and genetic differences.^[1]

Types

Pulmonary neuroendocrine tumor are classified according to tumoral grade:

Low grade pulmonary neuroendocrine tumor: Typical pulmonary carcinoid tumour (TC; low-grade);
Intermediate-grade pulmonary neuroendocrine tumor: Atypical pulmonary carcinoid tumour (AC; intermediate-grade)
High-grade pulmonary neuroendocrine tumor
- Small cell lung cancer (SCLC)
- Large cell neuroendocrine carcinoma (LCNEC of the lung)

Typical pulmonary carcinoid tumour is a subtype of pulmonary carcinoid tumour. It is an uncommon low-grade malignant lung mass that is most often in the central airways of the lung.

Atypical pulmonary carcinoid tumour is a subtype of pulmonary carcinoid tumor. It is an uncommon low-grade malignant lung mass that is most often in the central airways of the lung. It is also known as "atypical lung carcinoid tumour", " atypical lung carcinoid" or "moderately differentiated neuroendocrine carcinoma".

Low-grade nodular neuroendocrine proliferations ≥ 0.5 cm are classified as carcinoid tumors and smaller ones are called pulmonary tumorlets.

When neuroendocrine cell hyperplasia and tumorlets are extensive, they represent the rare preinvasive lesion for carcinoids known as "diffuse idiopathic pulmonary neuroendocrine cell hyperplasia".

Both LCNEC and SCLC can demonstrate histologic heterogeneity with other major histologic types of lung carcinoma, such as pulmonary adenocarcinoma or pulmonary squamous cell carcinoma, but is not characteristic of TC or AC.

Risk factor

Multiple endocrine neoplasia type I (MEN1)can be found in carcinoid tumor patients, but not those with LCNEC and SCLC.

Genetics

Genetic changes are very high in SCLC and LCNEC, but usually low for TC, intermediate for AC.

Diagnosis

The diagnosis of SCLC, TC and AC can be made by light microscopy without the need for special tests in most cases, but for LCNEC it is required to demonstrate NE differentiation by immunohistochemistry or electron microscopy.

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Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a diffuse parenchymal lung disease which often presents with symptoms of cough and shortness of breath. The pathological definition published by the World Health Organization is “a generalized proliferation of scattered single cells, small nodules, or linear proliferations of pulmonary neuroendocrine (PNE) cells that may be confined to the bronchial and bronchiolar epithelium.” The true prevalence of this disease is not known. To date, just under 200 cases have been reported in the literature. However, with an increase in recognition of this disease by radiologists and pulmonologists, the number of cases has been increasing. DIPNECH predominantly affects middle-aged women with slowly progressive lung obstruction. DIPNECH is usually discovered in one of two ways: 1) as an unexpected finding following a lung surgery; or 2) by evaluation of a patient in a pulmonary clinic with longstanding, unexplained symptoms.

References

↑ Travis, W. D. (2010). "Advances in neuroendocrine lung tumors". Annals of Oncology. 21 Suppl 7: vii65–71. doi:10.1093/annonc/mdq380. PMID 20943645.

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[1] Travis, W. D. (2010). "Advances in neuroendocrine lung tumors". Annals of Oncology. 21 Suppl 7: vii65–71. doi:10.1093/annonc/mdq380. PMID 20943645.