Characteristics of 252 patients with bronchopulmonary neuroendocrine tumours treated at the Copenhagen NET Centre of Excellence
Introduction
Bronchopulmonary neuroendocrine tumours (BP-NETs) represent a group of rare neoplasms with increasing incidence. [[1], [2], [3], [4]] In the 2015 WHO classification the group included low-grade typical carcinoid (TC), intermediate-grade atypical carcinoid (AC), high-grade large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) [5]. TC includes tumours with a mitotic count of <2/2mm2 and no necrosis, AC a mitotic count of 2–10/2 mm2 and/or tumour necrosis and LCNEC and SCLC a mitotic count >10/2mm2 and abundant necrosis. The SCLC comprises 15% of all lung malignancies, but will not be further addressed in this paper. LCNEC represents 3% whereas bronchopulmonary carcinoids (TC and AC) represent 1%–2% of all new lung cancers. The diagnostic work-up of these tumours has evolved over the past decades with analysis of histological differentiation and new improved methods such as immune staining for neuroendocrine features as diagnostic corner stones [6]. The gold standard of treatment for localized TC and AC is surgical resection, whereas the treatment regimen in advanced disease still remains a field of controversy. Management and treatment of LCNEC is also associated with controversy, which is probably partly due to the heterogeneity of the disease, but the majority of studies have shown that the treatment of LCNEC with chemotherapy mimicking SCLC treatment regime is associated with better survival than treatments used in non-small cell lung cancer [[7], [8], [9]]. The highest mortality is found in high-grade tumours, however advanced disease in low-grade tumours similarly is associated with poor prognosis. Few studies have compared lung carcinoids and LCNEC despite their common histological neuroendocrine features. This study aims to illustrate the similarities and differences amongst TC, AC and LCNEC through a comprehensive evaluation of diagnostic procedures, prognostic factors and overall survival in 252 patients from a single institution.
Section snippets
Patient cohort and preoperative work-up
The study included all patients with TC, AC and LCNEC referred to and treated at the departments of thoracic surgery, oncology, endocrinology and gastrointestinal surgery at the Neuroendocrine Tumour (NET) Centre of Excellence at Rigshospitalet, University of Copenhagen through collection of data from November 2008 to December 2016. All patients with neuroendocrine tumours as well as all patients in need of thoracic surgery from Eastern Denmark (population 2.4 mill.) are referred to and treated
Results
Demographic and clinical features are listed in Table 1. From the prospective NET database we consecutively included 252 patients: 162 patients with TC, 29 patients with AC and 61 patients with LCNEC. The median follow-up time was 48 months (42–54 months) calculated according to the reverse Kaplan Meier method [16]. Median age at diagnosis was 69 (19–89) years. Median age was higher in AC and LCNEC compared to TC (p = 0.046). Gender distribution varied amongst the subtypes with TC and AC
Discussion
In this study of 252 patients the distribution of tumour subtype consisted of 64% with TC, 12% AC and 24% LCNEC. This correlates well with prior studies describing a 10:1 relationship between frequencies of TC and AC and the fact that TC represent approximately 70–80% of neuroendocrine lung tumours [17]. TC presented with centrally located tumours in 58% of patients whereas both AC and LCNEC presented with peripherally located tumours in the majority of patients, 52% and 64% respectively. This
Conclusion
To our knowledge this study is the largest study to analyse and compare diagnostic and prognostic factors in a group of 252 BP-NET patients treated at a single institution.
Our study supports the assumption that the Ki67 index may play an important role as both a diagnostic as well as a prognostic marker together with the mitotic count and amount of necrosis in BP-NETs. Our study suggests that the WHO classification regarding Ki67 in TC tumours may be changed to include proliferation index up to
Conflict of interest
No author of this work had any conflicts of interest. Co-author R.H. Petersen has received speeker fees from Medtronic.
Funding
Danish Cancer Society, Denmark.
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Long-term outcomes after video-assisted thoracoscopic surgery in pulmonary large-cell neuroendocrine carcinoma
2022, Surgical OncologyCitation Excerpt :Pathology staging was performed according to the AJCC Cancer Staging Manual (7th edition) [22]. The Ki-67 index was determined as previously described [23]. Following definitive diagnosis, postoperative treatment for all patients was discussed at the Neuroendocrine Tumor Board at Rigshospitalet.
Multiple endocrine neoplasia type 1 (MEN-1) and neuroendocrine neoplasms (NENs)
2022, Seminars in Cancer BiologyCitation Excerpt :Bronchopulmonary NENs usually present in the fifth to sixth decade of life (median age at presentation 64 years) [325], while age at diagnosis of MEN-1/bronchopulmonary NENs is 42–49 years [350–354], with the youngest described cases being in their early 20 s [350,354]. The initially reported female predominance has not been confirmed by later studies [348,351,352,355–357]. Unlike thymic NENs, bronchopulmonary NENs have not been associated with increased mortality in MEN-1 patients (only 0–2.3 % of MEN-1 deaths directly related with MEN-1/bronchopulmonary NENs) [350,351,354].
Somatostatin Receptor Imaging PET in Neuroendocrine Neoplasm
2021, PET ClinicsLung and thymic carcinoids: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up<sup>☆</sup>
2021, Annals of OncologyCitation Excerpt :Frozen sections of bronchial and vascular margins are recommended to rule out tumour involvement of resection margins, a condition that consequently imposes a greater pulmonary resection. Systematic lymph node dissection is recommended as lymph node metastases may be observed in up to 27% of TCs and in up to 47% of ACs, and lymph node resection influences the prognosis and the modality of follow-up5,45,48,49,56 [IV, B]. R0 resection is achieved in >85% of cases.7,10
Pulmonary large cell neuroendocrine carcinoma (LCNEC) with confirmed liver metastases negative on <sup>18</sup>F-FDG and <sup>68</sup>Ga-DOTATATE PET
2020, Radiology Case ReportsCitation Excerpt :While no or minimal uptake of 68Ga-DOTATATE is expected in intermediate and high-grade NENs, due to their lack of differentiation and lost SSTR expression, FDG negativity is not. De- or undifferentiated NENs, being characterized by a high proliferation rate and thus high glucose consumption, are 18F-FDG-avid [4,5]. Grondahl et al. showed in a study comprising of 252 bronchopulmonary NENs that all LCNEC showed FDG uptake as compared to 93% of TC and 96% of AC.