Cytological features of stromal spindle cells and their prognostic significance in lung adenocarcinoma

Cancer-associated fibroblasts (CAFs) in the tumour microenvironment play a key role in tumour development, proliferation, invasion, and metastasis. The cytological features of spindle cells including CAFs-defined as stromal spindle cells (SSCs) adjacent to cancer cells-are frequently encountered in pulmonary adenocarcinomas. This study aimed to investigate the association between the presence of SSCs in cytological specimens and the clinicopathological features.We evaluated 211 patients with pulmonary adenocarcinoma who underwent surgical resection. All participants had cytological specimens corresponding to the histological specimens available for review.Of the 211 cases examined, 89 were SSC-positive (SSC+ ) and 122 were SSC-negative (SSC- ). SSC+ cases were more frequently associated with higher pathological stage (P < 0.001), lymph node metastasis (P = 0.002), anaplastic lymphoma kinase (ALK) gene rearrangement (P = 0.04), high tumour grade (P < 0.001), solid and micropapillary predominant pattern (P = 0.02), and lymphatic vessel (P = 0.003), blood vessel (P < 0.001), and pleural invasion (P = 0.03) as compared to SSC- cases. Patients with SSC+ adenocarcinoma had a significantly shorter recurrence-free survival than those with SSC- adenocarcinoma (P = 0.009). Cytologically, necrotic background (P = 0.002), mucinous cancer cells (P = 0.02), pleomorphic cells (P < 0.001), and mutual cell inclusions (P = 0.01) were observed more frequently in SSC+ adenocarcinomas.The presence of SSCs could be an important cytological feature for predicting poor prognosis in lung adenocarcinomas.