Iranian Journal of Pathology

Prognostic Impact of CD8+ and CD4+ Tumor-Infiltrating Lymphocytes and Perineural/Vascular Invasion in Laryngeal Squamous Cell Carcinoma

Articles in Press

Document Type : Original Research

Authors

Maryam Lotfi 1
Mina Majdi 1
Parin Tanzifi 2
Tahereh Yousefi 1
Elham Nazar 3
Aysan Nozheh 4

1 Department of Pathology, Amir-Alam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Pathology, Douglass Hanly Moir Pathology, New South Wales, Australia

3 Department of Pathology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran

4 Department of Pathology, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran

10.30699/ijp.2026.2066899.3493
Abstract
Background & Objective: Squamous cell carcinoma (SCC) is characterized by infiltration of CD4+ and CD8+ T lymphocytes, which represent an early host immune response against malignant cells. This immune response may inhibit tumor progression and suppress malignancy. This study aimed to evaluate the density of CD4+ and CD8+ lymphocytes and their ratio within tumor nests and surrounding stroma in conventional laryngeal SCC. It also examined associations with prognostic factors such as regional lymph node metastasis, tumor histologic differentiation, vascular invasion, and perineural invasion.
Methods: This retrospective study analyzed 54 laryngeal SCC samples from patients who underwent total laryngectomy and cervical lymph node dissection without prior neoadjuvant chemoradiation therapy. Immunohistochemistry was used to assess CD4+ and CD8+ T lymphocytes in tumor nests and surrounding stroma. Statistical analyses evaluated correlations between lymphocyte infiltration and prognostic factors, including lymph node metastasis, histologic differentiation, vascular invasion, and perineural invasion.
Results: A significant association was found between high intratumoral CD8+ T lymphocyte density and a lower incidence of vascular and perineural invasion (mean, 10.9 cells/HPF vs 4.5 cells/HPF; p = 0.03). No significant correlations were observed between lymphocyte density and lymph node metastasis or tumor histologic differentiation.
Conclusion: High intratumoral CD8+ T-cell infiltration correlates with reduced vascular and perineural invasion in laryngeal SCC, suggesting a protective role in limiting tumor invasiveness. These findings highlight the prognostic significance of CD8+ T lymphocytes and warrant further research into immune mechanisms affecting SCC progression and patient outcomes.

Keywords

Laryngeal squamous cell carcinoma, CD4+, CD8+, T lymphocytes, lymph node metastasis, histologic grading

Subjects

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Iranian Journal of Pathology

Articles in Press, Accepted Manuscript
Available Online from 20 February 2026

  • Receive Date 24 July 2025
  • Revise Date 07 November 2025
  • Accept Date 03 February 2026

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