Pathologic effects of external-beam irradiation on human vocal folds.
OBJECTIVE
We sought to better characterize pathologic changes that occur in the human vocal fold after radiotherapy for head and neck cancer.


METHODS
In a blinded, controlled study of archived tissue, we evaluated postirradiation salvage laryngectomy vocal fold tissue without evidence of malignant disease. Clinical and demographic patient data were collected. In a blinded fashion, irradiated tissue was compared to nonirradiated, benign control tissue. Histomorphometric analysis was used to assess muscle and collagen organization, superficial lamina propria (SLP) and vocal ligament thickness, vocalis muscle fiber area, collagen content, and hyaluronic acid content. Immunohistochemical analysis was used to assess the content of type I collagen, type IV collagen, vimentin, fibronectin, alpha-smooth muscle actin, matrix metalloproteinase 9, and laminin.


RESULTS
Twenty irradiated vocal folds were evaluated and compared to control specimens. Collagen and muscle disorganization was noted in the irradiated specimens. The SLP and vocal ligament thicknesses and the mean muscle fiber diameters did not differ significantly. The SLP fibronectin and the vocalis muscle and SLP collagen content were significantly increased in the irradiated vocal folds, and the SLP collagen content increased significantly with time between irradiation and resection. The laminin content of irradiated vocalis muscles was significantly decreased.


CONCLUSIONS
Radiotherapy results in significant vocal fold tissue changes. Having more precisely defined these changes, we plan continued investigation seeking targeted preventive and therapeutic interventions for improved vocal quality following radiotherapy.
Department of Otolaryngology-Head and Neck Surgery, Emory University School of Medicine, Atlanta, Georgia, USA.
Eric E
EE
Berg
Vasantha
V
Kolachala
Ryan C
RC
Branski
Susan
S
Muller
Michael M
MM
Johns
D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000532:radiotherapy*; D007825:Laryngectomy; D008297:Male; D008875:Middle Aged; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D016879:Salvage Therapy; D014827:Vocal Cords / Q000473:pathology* / Q000528:radiation effects* / Q000601:surgery