Abstract

Introduction. Lung squamous cell carcinoma (LUSCC) lacks consistent morphological criteria for tumour grading. Tumour budding (TB), defined as isolated cells or clusters of fewer than 4 cells at the invasive front, is prognostic in several carcinomas but remains insufficiently validated in LUSCC.

Objective. To assess histopathological features of aggressiveness (including TB) in resected LUSCC as prognostic parameters and grading factors.

Methods. We retrospectively analysed 296 LUSCC cases (2010-2021, University of Turin). Clinical data were collected and slides were reviewed for subtype, nuclear features, mitotic count, infiltration pattern, TB, spread through air spaces (STAS), desmoplasia, pleural/vascular/perineural invasion, and tumour-infiltrating lymphocytes. Associations with recurrence-free and overall survival were tested.

Results. High TB (≥ 5 buds) correlated with pleural invasion and advanced T stage and was significantly associated with shorter recurrence-free (HR 1.84, p = 0.008) and overall survival (HR 1.73, p = 0.003), independently of stage. Nuclear enlargement and necrosis also predicted worse outcomes, while surgery had an overall protective impact.

Conclusion. TB, necrosis, and nuclear size are independent predictors of outcome in LUSCC. Their inclusion in pathology reports may improve grading, refine prognosis, and guide management.

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Authors

Giorgia Andrea Impalà - Department of Medical Sciences, City of Health and Sciences, University of Turin, Turin, Italy https://orcid.org/0009-0005-3868-5062

Alessandra Pittaro - Pathology Unit, City of Health and Sciences hospital, Turin, Italy.

Francesco Guerrera - Thoracic Surgery Unit, City of Health and Sciences hospital, Turin, Italy Department of Surgical Sciences, City of Health and Sciences hospital, University of Turin, Turin, Italy

Simona Sobrero - Thoracic Surgery Unit, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.

Giuseppe Bogina - Pathology Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella, Verona, Italy.

Giulia Orlando - Department of Oncology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Turin, Italy.

Vanessa Zambelli - Department of Oncology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Turin, Italy.

Francesca Napoli - Department of Oncology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Turin, Italy.

Francesco Leo - Department of Oncology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Turin, Italy.

Enrico Ruffini - Department of Surgical Sciences, City of Health and Sciences hospital, University of Turin, Turin, Italy.

Marco Volante - Department of Oncology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Turin, Italy.

Mauro Papotti - Pathology Unit, City of Health and Sciences hospital, Turin, Italy. Department of Oncology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Turin, Italy.

Luisella Righi - Department of Oncology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Turin, Italy.

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Copyright (c) 2026 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology

How to Cite
Impalà, G. A., Pittaro, A., Guerrera, F., Sobrero, S., Bogina, G., Orlando, G., Zambelli, V., Napoli, F., Leo, F., Ruffini, E., Volante, M., Papotti, M., & Righi, L. (2026). Analysis of histological parameters of aggressiveness in resected lung squamous cell carcinoma. Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology, 118(1). https://doi.org/10.32074/1591-951X-1726
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