title: Chemoradiation-induced cell loss in human submandibular glands.
abstract: OBJECTIVE
  Chemoradiation-induced xerostomia affects approximately 40,000 head and neck cancer patients annually in the United States. No human histopathologic or immunohistochemical data exist that characterize chemoradiation-related salivary gland damage. The objective of this study was to describe the histopathologic and immunohistochemical features of the non-acute phase of human submandibular gland damage after chemoradiation therapy.
  
  
  METHODS
  Pathologic materials were retrieved from patients who had undergone neck dissection after protocol-driven chemoradiotherapy for stage IV head and neck cancer at a tertiary head and neck cancer institute. Histologic and immunohistochemical analyses were performed on representative sections of chemoradiated submandibular glands, and findings were compared to age- and sex-matched, untreated control glands.
  
  
  RESULTS
  Forty patients were identified who had undergone neck dissection an average of 11 weeks after treatment with induction chemotherapy and chemoradiation therapy for non-oral head and neck cancer. In the chemoradiated glands, light microscopic findings included pronounced acinar cell loss with accompanying ductal metaplasia and ductal proliferation and increased fibrosis, chronic inflammation, nuclear atypia, and cytoplasmic vacuolization when compared with controls. Microvascular density was marginally affected by chemoradiation; cytokeratin staining showed preservation of ductal epithelium when compared to controls.
  
  
  CONCLUSIONS
  Nonacute changes seen in human submandibular glands after chemoradiation therapy are compared to those seen in previously described irradiated animal and human models. Primary dysfunction in humans appears to be related to a reduction in function and number of submandibular gland acinar cells. The ductal system appears to be preserved after chemoradiation therapy. Implications for management of xerostomia are discussed.
authors.affiliation: Department of Otolaryngology--Head and Neck Surgery, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina 27157, USA. csulliva@wfubmc.edu
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Sullivan
authors.forename: Robert I
authors.initials: RI
authors.lastname: Haddad
authors.forename: Roy B
authors.initials: RB
authors.lastname: Tishler
authors.forename: Anand
authors.initials: A
authors.lastname: Mahadevan
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Krane
mesh_terms: D000368:Aged; D003131:Combined Modality Therapy; D005260:Female; D005355:Fibrosis / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D008297:Male; D008875:Middle Aged; D037981:Neck Dissection; D013363:Submandibular Gland / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D014987:Xerostomia / Q000209:etiology