Abstract
Typical (TCs) and atypical carcinoids (ACs) are defined based on morphological criteria, and no grading system is currently accepted to further stratify these entities. The 2015 WHO classification restricts the Ki-67 role to biopsy or cytology samples, rather than for prognostic prediction. We aimed to investigate whether values and patterns of Ki-67 alone would allow for a clinically meaningful stratification of lung carcinoids, regardless of histological typing. Ki-67 proliferation index and pattern (homogeneous versus heterogeneous expression) were assessed in a cohort of 171 TCs and 68 ACs. Cases were subdivided into three Ki-67 ranges (<4/4–9/≥10%). Correlations with clinicopathological data, univariate and multivariate survival analyses were performed. The majority of cases (61.5%) belonged to the <4% Ki-67 range; 25.1 and 13.4% had a proliferation index of 4–9% and ≥10%, respectively. The <4% Ki-67 subgroup was significantly enriched for TCs (83%, p < 0.0001); ACs were more frequent in the subgroup showing Ki-67 ≥ 10% (75%, p < 0.0001). A heterogeneous Ki-67 pattern was preferentially seen in carcinoids with a Ki-67 ≥10% (38%, p < 0.02). Mean Ki-67 values ≥4 and ≥10% identified categories of poor prognosis both in terms of disease-free and overall survival (p = 0.003 and <0.0001). At multivariate analysis, the two thresholds did not retain statistical significance; however, a Ki-67 ≥ 10% identified a subgroup of dismal prognosis even within ACs (p = 0.03) at univariate analysis. Here, we describe a subgroup of lung carcinoids showing brisk proliferation activity within the necrosis and/or mitotic count-based categories. These patients were associated with specific clinicopathological characteristics, to some extent regardless of histological subtyping.
Highlights
Carcinoid tumours of the lung are rare primary lesions accounting for 0.2% to 2% of resected lung cancers
Results homogeneous Ki-67 labelling pattern was a significant feature of the low (
Vascular invasion and pleural involvement were relatively more represented in the carcinoid subgroup with Ki-67 ≥ 10%, and the differences among subgroups were statistically significant (p = 0.001, Table 1)
Summary
Carcinoid tumours of the lung are rare primary lesions accounting for 0.2% (atypical carcinoids, AC) to 2% (typical carcinoids, TC) of resected lung cancers. According to the 2015 WHO classification [1], they make up the morphologically defined group of neuroendocrine tumour (NETs) based upon cytological traits, mitotic count and necrosis. Virchows Arch (2017) 471:713–720 outcomes, which are currently best stratified according to the 2015 WHO classification and 8th edition TNM staging [1]. Surgery is the best treatment modality choice for both TCs and ACs [2], with TCs usually exhibiting long life expectancy with 5- and 10-year survival rate by far over 90% [3]. ACs exhibit a more aggressive clinical course and a 5-year survival rate ranging from 56 to 87%, which is lower in node positive patients, suggesting that this subgroup could benefit from some adjuvant treatment [4,5,6,7,8]
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