Oral and ophthalmic pathology of graft versus host disease in man: Predictive value of the lip biopsy

Abstract

Previous histologic studies of human chronic graft versus host disease after bone marrow transplantation have demonstrated stomatitis and sialadenitis. We studied these histologic findings to develop criteria that would provide a relatively high specificity and predictive value for chronic oral graft versus host disease and to evaluate the chronological sequence of oral and lacrimal graft versus host disease. The study sample consisted of 115 lip biopsy specimens from 84 patients, lacrimal tissue from 22 autopsies, and minor salivary glands from 31 autopsies from patients with and without graft versus host disease. We utilized two thresholds for grading histologic findings in lip and lacrimal tissue. Grade 1 signified lymphocytic inflammation of the oral mucosa or about the ducts in the lacrimal and salivary glands. Grade 2 signified inflammation with epithelial cell necrosis of the mucosal surface or ducts. Both grades were strongly associated with the development of graft versus host disease. Grade 1 criteria were 80 to 86 per cent sensitive and 50 to 56 per cent specific. Grade 2 criteria were 50 to 72 per cent sensitive and 68 to 77 per cent specific. In grade 2 lesions in both lip and lacrimal glands there was a statistically significant association with both acute and chronic graft versus host disease, whereas a history of total body irradiation showed no statistically significant association with these lesions. Sequential analysis of chronic graft versus host disease in 19 patients with multiple lip samples showed that the initial glandular lesions were centered primarily about the ductal epithelium with lymphocytic infiltration followed by destruction, interstitial myxoid degeneration, and fibrous involution of the lobules. Our data strongly support the hypothesis that a Sjögren-like lesion involving primarily the oral mucosa and lacrimal and salivary duct epithelium is directly attributable to human graft versus host disease rather than to a nonimmunologic side effect of chemoradiotherapy or infection.