Epidemiological analysis of lung and mediastinal neuroendocrine neoplasms in Japan based on the national database

Abstract

Background

Neuroendocrine neoplasms (NENs) are rare and can originate from any body part. However, there are only few epidemiological studies, especially on lung and mediastinal NENs. This study investigated the epidemiological trends and differences between lung and mediastinal NENs in Japan.

Methods

Patients with lung and mediastinal NENs were identified in a national hospital-based cancer registry between 2009 and 2015 in Japan. NENs were subclassified into neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). NECs were further subdivided into large neuroendocrine carcinomas (LCNECs) and small cell carcinomas (SCCs). We examined the patient characteristics: sex, age, histology, year of diagnosis, diagnostic opportunity, and initial treatment.

Results

We identified 48,433 patients with 47,888 lung (98.9%) and 545 mediastinal (1.1%) NENs. The commonest subtype of lung NENs was SCCs (87%), followed by LCNECs (10%) and NETs (3%). In the mediastinum, SCCs were also the commonest (48%), followed by NETs (38%) and LCNECs (14%). The number of lung NEN annually increased; however, that of mediastinal NENs did not change over time. The mean age of patients with lung NETs was lower than that of patients with lung LCNECs and SCCs (NETs, 62 ± 14 years; LCNECs, 70 ± 9 years; SCCs, 71 ± 9 years; p < .001). The lung and mediastinal NENs were mainly detected based on symptoms, except for lung NETs. Surgical intervention, including multimodal therapy, was performed for 89.3% of lung NETs (surgery alone: 83.6%), while only 15.6% of lung NECs were treated with surgery. For the mediastinum, 75.9% of NETs were treated with surgery, with 27.1% of cases treated with surgery plus multimodal therapy. Surgery was performed more frequently for mediastinal NECs (37%) than for lung NECs (15.6%).

Conclusions

This study highlights differences in trends of lung and mediastinal NENs. This study’s findings support the importance of epidemiological evaluations based on the primary sites and histological subtypes.

Highlights

• • The most frequent subtype of lung and mediastinal NENs was small cell carcinomas.
• • A continuous increase was observed in the number of lung NENs, but that of mediastinal NENs did not significantly change.
• • Lung and mediastinal NENs were mainly detected based on symptoms except for lung NETs.
• • Surgical intervention was performed more frequently for mediastinal NECs than lung (lung: 15.6%, mediastinum: 37%)
  

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  Introduction

  Neuroendocrine neoplasms (NENs) arise from neuroendocrine cells and can develop in any body organ. The incidence of NENs increased to 6.98/100,000 in 2012 according to data from all the sites of the Surveillance, Epidemiology, and End Results (SEER) registry [1] . The highest prevalence of NENs was observed in the rectum, followed by the lungs, with an annual incidence of 1.49 per 100,000. In 2018, the World Health Organization (WHO) and the International Agency for Research on Cancer proposed to unify the nomenclature of NENs ariging from different organ systems; typical and atypical carcinoids are well-differentiated neoplasms corresponding to neuroendocrine tumors (NETs), while large-cell neuroendocrine carcinomas (LCNECs) and small cell carcinomas (SCCs) are poorly differentiated neoplasms corresponding to neuroendocrine carcinomas (NECs) [2] . However, the clinical features, diagnostic criteria, and terms of NENs vary according to the primary site [3] . For example, the current WHO classification of digestive NENs has divided them into NETs (G1-G3) and NECs, based on the morphological differentiation, mitosis, and Ki67 proliferation index [4] . Meanwhile, the diagnostic criteria for lung NENs has been the morphological findings, presence of necrosis, not being included Ki67 proliferation index [5] . The term carcinoid is still widely accepted for the lungs, instead of NETs. Therefore, site-specific analyses for NENs are needed to evaluate their etiology and features.

  In addition, the classification, diagnosis and nomenclature of mediastinal NENs, including thymic NENs follow those of lung NENs. Mediastinal NENs were initially classified as thymic carcinomas, but were allocated to a new category of thymic tumors in the 2015 WHO classification. They are classified into four entities under two histopathological subtypes. Compared with lung NENs, mediastinal NENs are very rare, with an annual incidence of only 0.02 per 100,000 [6] , accounting for 2–5% of all anterior mediastinal neoplasms [7] . Therefore, little is known about the epidemiological features of mediastinal NENs, and the difference between lung and mediastinal NENs among thoracic physicians and surgeons, who mainly involve with these diseases, despite the similar classifications and diagnostic criteria. Furthermore, Japanese epidemiological studies of NENs concern mainly digestive NENs 8910 .

  In this study, we evaluated the demographic data of patients with lung and mediastinal NENs from a national hospital-based cancer registry (HBCR) to elucidate the epidemiological trends and differences in Japan.

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