Jens C. Rueckert

OBJECTIVES Thymic epithelial tumours (TETs) are relatively rare indolent malignancies in the mediastinum. Lymph node metastasis (LNM) is an important prognostic indicator for TETs; however, the pattern of LNM involved in TETs has yet to be elucidated. METHODS Patients diagnosed with histologically confirmed thymoma (A–B3), thymic carcinomas and thymic neuroendocrine tumours, between 1988 and 2016 were identified from the Surveillance, Epidemiology, and End Results database. Univariable and multivariable logistic regression analyses were applied to identify the predictors for LNM. The predictive nomogram was built from the independent risk factors and measured using the concordance statistic. RESULTS The overall proportion of TETs with LNM was 18.5% (200/1048). The rate of LNM in thymoma, thymic carcinomas and thymic neuroendocrine tumours was 6.8% (42/622), 30.2% (100/331) and 61.1% (58/95), respectively. According to the logistic regression analysis, histology type and T stage were independent factors correlated with LNM. A predictive nomogram model was developed with a concordance statistic of 0.807 (95% confidence interval: 0.773–0.841), which was significantly better than the T stage (P < 0.001) while had limited benefit to the histology type (P = 0.047). The calibration curve for the nomogram comparing the predicted and actual probabilities after bias correction showed good agreement. CONCLUSIONS Nodal involvement was not uncommon in TETs. Main factors related to LNM in TETs were histology type and T stage. The probability of LNM could be well calculated using the predictive model.

Lung carcinoid tumors, also referred to as pulmonary neuroendocrine tumors or lung carcinoids, are rare neoplasms of the lung with a more favorable prognosis than other subtypes of lung cancer. Still, some patients suffer from relapsed disease and metastatic spread. Several recent single‐cell studies have provided detailed insights into the cellular heterogeneity of more common lung cancers, such as adeno‐ and squamous cell carcinoma. However, the characteristics of lung carcinoids on the single‐cell level are yet completely unknown. To study the cellular composition and single‐cell gene expression profiles in lung carcinoids, we applied single‐cell RNA sequencing to three lung carcinoid tumor samples and normal lung tissue. The single‐cell transcriptomes of carcinoid tumor cells reflected intertumoral heterogeneity associated with clinicopathological features, such as tumor necrosis and proliferation index. The immune microenvironment was specifically enriched in noninflammatory monocyte‐derived myeloid cells. Tumor‐associated endothelial cells were characterized by distinct gene expression profiles. A spectrum of vascular smooth muscle cells and pericytes predominated the stromal microenvironment. We found a small proportion of myofibroblasts exhibiting features reminiscent of cancer‐associated fibroblasts. Stromal and immune cells exhibited potential paracrine interactions which may shape the microenvironment via NOTCH, VEGF, TGFβ and JAK/STAT signaling. Moreover, single‐cell gene signatures of pericytes and myofibroblasts demonstrated prognostic value in bulk gene expression data. Here, we provide first comprehensive insights into the cellular composition and single‐cell gene expression profiles in lung carcinoids, demonstrating the noninflammatory and vessel‐rich nature of their tumor microenvironment, and outlining relevant intercellular interactions which could serve as future therapeutic targets.