The WHO Histological classification of Lung Tumours, published in 1967, has been revised. The main features are as follows: Squamous cell carcinoma (epidermoid carcinoma) has the same definition as in the original version, i.e., the identification of keratin and/or intercellular bridges by light microscopy. Three degrees of histological differentiation are described. Dysplasia and carcinoma in situ are discussed. Small cell carcinoma is divided into oat-cell carcinoma, an intermediate cell type and a category for oat-cell carcinomas combined with other major types. Adenocarcinoma includes the acinar, papillary and bronchiolo-alveolar forms and the solid carcinomas with mucus formation (previously part of the large cell carcinoma group). Mesothelial tumours are divided into fibrous, epithelial and biphasic subtypes. A number of less common tumours and tumour-like lesions are defined.

Histological Typing of Lung Tumours

Clinicopathological features and prognostic analysis of 247 small cell lung cancer with limited-stage after surgery.

YAP1 protein expression has variant prognostic significance in small cell lung cancer (SCLC) stratified by histological subtypes.

Delta-like protein 3 (DLL3) is a protein of the Notch pathway, and it is a potential therapeutic target for high-grade lung neuroendocrine tumors (NETs), i.e., small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). However, DLL3 prevalence in lung NETs and its association with clinicopathological characteristics and prognosis remained unclear. We analyzed the immunohistochemical expression of DLL3 and its prognostic role in a consecutive series of 155 surgically resected lung NETs, including typical carcinoid (TC), atypical carcinoid (AC), LCNEC, and SCLC patients. The DLL3 expression was categorized as high (>50% positive tumor cells) or low (<50%). In addition, tumors were categorized by H-score (i.e., percentage of positive cells by staining intensity, ≥150 vs. <150). DLL3 staining was positive in 99/155 (64%) samples, and high DLL3 expression was frequently observed in high-grade tumors. In detail, 46.9% and 75% of SCLC and 48.8% and 53.7% of LCNEC specimens showed a high DLL3 expression by using H-score and percentage of positive tumor cells, respectively. Regarding low-grade NETs, only 4.9% and 12.2% TCs and 19.5% and 24.4% ACs had high DLL3 expression considering H-score and percentage of positive tumor cells, respectively. High DLL3 expression was associated with advanced American Joint Committee on Cancer (AJCC) stage, peripheral location, and chromogranin A expression in high-grade tumors (p < 0.05). In low-grade NETs, high DLL3 expression was associated with female sex, peripheral location, a higher number of mitoses, higher Ki-67 index, presence of necrosis, and pleural infiltration (p < 0.05). No association was observed between high DLL3 expression and overall survival (OS) and disease-free survival (DFS) in high-grade NETs, whereas high DLL3 expression was associated with lower DFS in ACs (p = 0.01). In conclusion, our study demonstrated a high prevalence of DLL3 expression in high-grade lung NET patients and its association with aggressive clinicopathological features. These findings confirm that DLL3 could represent a useful biomarker for target therapy in high-grade tumors. Our results also suggest that the DLL3 expression could identify a subset of AC tumors with more aggressive behavior, thus providing the basis for new therapeutic options in this group of patients.

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Prevalence of Delta-Like Protein 3 in a Consecutive Series of Surgically Resected Lung Neuroendocrine Neoplasms.

Small cell lung cancer (SCLC) is the most malignant and common form of neuroendocrine lung cancer with pure (P‐SCLC) and combined subtypes (C‐SCLC). However, little is known about the differences between these two groups and in this study we aimed to provide a more comprehensive insight into SCLC.

Different clinical characteristics and survival between surgically resected pure and combined small cell lung cancer

Background Histologically, SCLC are classified as pure (P-SCLC) and combined subtypes (C-SCLC). Currently, few studies compare the clinicopathological characteristics and explore the treatment strategies applied to them. Methods Between July 2005 and April 2016, the clinical records of 297 postoperative patients with pathologically confirmed SCLC were retrospectively analyzed. Kaplan-Meier method and Cox regression model were separately used for stratified univariate and multivariate survival analysis. Results A total of 46 cases (15.5%) of C-SCLCs and 251 cases (85.5%) of pure SCLCs (P-SCLCs) were included in this study. The average age of C-SCLCs was a little higher than that of P-SCLCs (59.65 ± 8.72 vs. 56.56 ± 10.12; P = 0.053). More patients had a history of smoking in C-SCLC (78.3% vs. 63.3%; P = 0.074). The five-year overall survival (OS) rate for P-SCLCs and C-SCLCs was 65.1% and 56.7%, respectively (P = 0.683). For P-SCLC, stage and an intervention of prophylactic cranial irradiation (PCI) were independent factors that affected OS. In C-SCLCs cases, performing sublobectomy was an independent risk factor for poor prognosis. Conclusions We identified no significant difference in clinical characteristics and outcome between C-SCLCs and P-SCLCs. However, the factors affecting the prognosis of the two subtypes were slightly inconsistent. For C-SCLCs, the extent of resection had a greater impact on survival, and lobectomy combined with systemic lymph node dissection should therefore be performed as extensively as possible. In addition, PCI was beneficial in improving the SCLC OS rate. Key points This study demonstrated the prognosis of C-SCLCs did not significantly differ from that of P-SCLCs, but was more susceptible to the extent of resection. Patients with C-SCLC who underwent limited resection had a significantly increased risk of shorter OS. This study highlighted the importance of performing lobectomy for resectable C-SCLC patients. This study also proved the benefit of PCI in improving the OS rate for both P-SCLC and C-SCLC patients.

Comparative study of clinicopathological characteristics and prognosis between combined and pure small cell lung cancer (SCLC) after surgical resection.

ARID1A is a key component of the SWI/SNF chromatin remodeling complexes which is important for the maintaining of biological processes of cells. Recent studies had uncovered the potential role of ARID1A alterations or expression loss in the therapeutic sensitivity of cancers, but the studies in this field requires to be further summarized and discussed. Therefore, we proposed a series of mechanisms related to the resistance to EGFR-TKIs induced by ARID1A alterations or expression loss and the potential therapeutic strategies to overcome the resistance based on published studies. It suggested that ARID1A alterations or expression loss might be the regulators in PI3K/Akt, JAK/STAT and NF-κB signaling pathways which are strongly associated with the resistance to EGFR-TKIs in NSCLC patients harboring sensitive EGFR mutations. Besides, ARID1A alterations or expression loss could lead to the resistance to EGFR-TKIs via a variety of processes during the tumorigenesis and development of cancers, including epithelial to mesenchymal transition, angiogenesis and the inhibition of apoptosis. Based on the potential mechanisms related to ARID1A, we summarized that the small molecular inhibitors targeting ARID1A or PI3K/Akt pathway, the anti-angiogenic therapy and immune checkpoint inhibitors could be used for the supplementary treatment for EGFR-TKIs among NSCLC patients harboring the concomitant alterations of sensitive EGFR mutations and ARID1A.

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F. Teng

Papers

Comparative study of clinicopathological characteristics and prognosis between combined and pure small cell lung cancer (SCLC) after surgical resection.

Clinicopathological features and prognostic analysis of 247 small cell lung cancer with limited-stage after surgery.

ARID1A serves as a receivable biomarker for the resistance to EGFR-TKIs in non-small cell lung cancer.