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Nathalie Audet, MD, CM, FRCSC; Nigel J. Beasley, MBBS, FRCS; Christina MacMillan, MD, FRCPC; David G. Jackson, PhD; Patrick J. Gullane, MB, FRCS; Suzanne Kamel-Reid, PhD

Arch Otolaryngol Head Neck Surg. 2005;131:1065-1070.

Objective  To examine the relationship between intratumoral lymphatic vessel density and clinical and pathological variables in patients with head and neck squamous cell carcinoma.

Design  Archived paraffin-embedded biopsy specimens were sectioned and stained with hematoxylin-eosin and anti–LYVE-1 antibody, a highly specific marker for lymphatic endothelium. Tumor grade, infiltrating margin, inflammatory infiltrate, and percentage of tumor necrosis were noted and lymphatic vessel density measured using Chalkley point counting.

Setting  Tertiary care center at a university hospital.

Patients  A total of 168 previously untreated patients with advanced squamous cell carcinoma (73, larynx; 62, oropharynx; and 33, hypopharynx) treated with primary radiation (with or without planned neck dissection) and salvage surgery from 1992 to 1999.

Interventions  Measurement of intratumoral lymphatic vessel density in pretreatment tissue biopsy specimen.

Main Outcome Measures  Disease-free and disease-specific survival, tumor occurrence, and nodal status.

Results  In patients with laryngeal carcinoma there was a significant relationship between the presence of intratumoral lymphatics and nodal metastases at presentation (P = .02) and poorly differentiated tumor grade (P = .02). Patients with high lymphatic vessel density also had a significantly worse disease-specific survival (P = .03). However, this difference was not significant with multivariate analysis. No significant relationship existed between the presence of intratumoral lymphatics and any of the clinical or pathological variables in oropharyngeal and hypopharyngeal carcinoma.

Conclusions  In this patient sample, the development of intratumoral lymphatics in laryngeal carcinoma, but not in oropharyngeal or hypopharyngeal carcinoma, is associated with a spread of the tumor to regional lymph nodes. Detecting tumor lymphatic vessel proliferation is another step in the understanding of tumor biology, and the targeting of lymphatic growth may be of potential therapeutic benefit in selected patients with head and neck squamous cell carcinoma.

Author Affiliations: Departments of Otolaryngology, Wharton Head and Neck Centre (Drs Audet, Gullane, and Kamel-Reid), and Pathology (Dr Kamel-Reid), Princess Margaret Hospital, University of Toronto, Toronto, Ontario; Department of Otolaryngology–Head and Neck Surgery, Queen Medical Centre, Nottingham, England (Dr Beasley); Department of Pathology, Mount Sinai Hospital, University of Toronto (Dr MacMillan); and Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, England (Dr Jackson).

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