Proteomic analysis of saliva from patients with oral chronic graft-versus-host disease.

Chronic graft-versus-host disease (cGVHD) is an immune-mediated disorder and is the major long-term complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The oral mucosa, including the salivary glands, is affected in the majority of patients with cGVHD; however, at present there is only a limited understanding of disease pathobiology. In this study, we performed a quantitative proteomic analysis of saliva pooled from patients with and without oral cGVHD-cGVHD(+) and cGVHD(-), respectively-using isobaric tags for relative and absolute quantification labeling, followed by tandem mass spectrometry. Among 249 salivary proteins identified by tandem mass spectrometry, 82 exhibited altered expression in the oral cGVHD(+) group compared with the cGVHD(-) group. Many of the identified proteins function in innate or acquired immunity, or are associated with tissue maintenance functions, such as proteolysis or the cytoskeleton. Using ELISA immunoassays, we further confirmed that 2 of these proteins, IL-1 receptor antagonist and cystatin B, showed decreased expression in patients with active oral cGVHD (P < .003). Receiver operating curve characteristic analysis revealed that these 2 markers were able to distinguish oral cGVHD with a sensitivity of 85% and specificity of 60%, and showed slightly better discrimination in newly diagnosed patients evaluated within 12 months of allo-HSCT (sensitivity, 92%; specificity 73%). In addition to identifying novel potential salivary cGVHD biomarkers, our study demonstrates that there is coordinated regulation of protein families involved in inflammation, antimicrobial defense, and tissue protection in oral cGVHD that also may reflect changes in salivary gland function and damage to the oral mucosa.

Reliability of histologic diagnosis of clinically normal intraoral tissue adjacent to clinically suspicious lesions in former upper aerodigestive tract cancer patients.

Oral lesion biopsies often include adjacent clinically normal tissue to assess lesion spread, but the reliability of adjacent tissue histologic diagnoses has not been reported. Sixty-seven patients presenting with subsequent suspicious intraoral lesions underwent tissue staining with tolonium chloride. Biopsies of unstained tissue adjacent to suspicious lesions were reviewed by independent pathologists. The weighted kappa (kappa(w)) for histologic classification was 0.75 (95% confidence interval [CI] 0.64, 0.86) and was lower for: inflamed specimens [kappa(w)=-0.13 (95% CI -0.30, 0.05)] versus noninflamed specimens [kappa(w)=0.81 (95% CI 0.69, 0.92)], wedge biopsies [kappa(w)=0.58 (95% CI 0.37, 0.79)] versus punch biopsies [kappa(w)=0.90 (95% CI 0.83, 0.97)], and current smokers [w=0.59 (95% CI 0.32, 0.86)] versus past and never smokers [kappa(w)=0.82 (95% CI 0.72, 0.91)]. Histologic diagnosis of subsets of clinically normal oral specimens adjacent to suspicious tissue has low reliability. Molecular techniques may improve diagnoses in these subsets.

Intraoral melanoma: long-term follow-up and implication for dental clinicians. A case report and literature review.

Primary intraoral melanoma is a rare neoplasm with a poor prognosis, accounting for 1% to 8% of all melanoma in Europe and the United States. The incidence (12%) and 5-year survival rate (17.4%) are higher in Japan. We report a case of oral lentiginous melanoma in a Japanese-American man who survived disease-free for more than 5 years after surgery, radiation therapy, and chemotherapy but developed chronic mucositis of the palate under the denture in the primary radiated field. This lesion responded to antifungal therapy. Subsequent multiple biopsies ruled out the recurrence of melanoma but demonstrated prolonged melanocytic hyperplasia and focal epithelial atypia. We reviewed clinical differences in oral melanoma reported in the United States and Japanese literature, and describe the wide variety of oral clinical features of postoperative radiation and chemotherapy, as well as the oral tissue changes caused by denture-induced mucositis and candidiasis in such patients. Dental clinicians should conduct a thorough head, neck, and oral follow-up with increased vigilance in patients with a history of prior cancer.

Proliferative verrucous leukoplakia and its progression to oral carcinoma: report of three cases.

Proliferative verrucous leukoplakia (PVL) is a distinct clinical form of oral leukoplakia defined by its progressive clinical course, changing clinical and histopathologic features, and potential to develop into cancer. PVL behaves in a more aggressive and relentless manner than the more innocuous white oral lesions that it can resemble clinically. We present three cases of PVL that progressed to carcinoma and discuss the histopathologic findings that may either hinder or assist in the diagnosis.

Interobserver reliability in the histopathologic diagnosis of oral pre-malignant and malignant lesions.

BACKGROUND: The histologic classification of pre-cancerous and cancerous oral lesions has generally shown poor agreement between pathologists, but lesion and patient characteristics that may affect diagnostic reliability have not been explored. METHODS: Eighty-seven clinically suspicious oral lesions biopsied from 81 patients with previous upper aerodigestive tract cancer were independently classified by their local pathologist and a central pathology committee. Interobserver reliability between the local pathologist and the central pathology committee was measured with weighted kappa (kappa w) statistics and corresponding 95% confidence intervals (CI). RESULT: The kappa w for pathologic diagnosis was 0.59 (95% CI: 0.45, 0.72), and was higher for lesions without inflammation (0.67 (95% CI: 0.53, 0.80) than inflamed lesions (-0.10 (95% CI: -0.27, 0.07)). Greatest agreement was seen for lesions located in the buccal mucosa/vestibule (kappa w = 0.68 (95% CI: 0.46, 0.91)) and tongue (kappa w = 0.62 (95% CI: 0.40, 0.84)). Least agreement was found for lip/labial mucosa lesions (kappa w = -0.04 (95% CI: -0.34, 0.27)). Punch biopsies (kappa w = 0.67 (95% CI: 0.54, 0.80)) had greater interobserver reliability than wedge biopsies (kappa w = 0.38 (95% CI: 0.12, 0.64)). CONCLUSIONS: These data suggest that the presence of inflammation, lesion site, and biopsy technique modifies the reliability of oral lesion histologic diagnoses.