Significance of mucosal vs salivary gland changes in lip biopsies in the diagnosis of chronic graft-vs-host disease

Lip biopsy is frequently utilized to diagnose and stage chronic graft-vs-host disease (cGVHD). However, the significance of mucosal (MU) vs salivary gland (SG) involvement as well as the minimal histologic changes necessary for diagnosis remain unclear. We evaluated 68 lip and oral mucosa biopsy specimens using published diagnostic criteria. Thirty-four specimens contained both MU and SG tissue. Both MU and SG were definitely involved in 30 patients while apparent false-negatives for MU of 20% (2/10) and SG of 11% (1/9) were observed. No clinical differences were noted among the patients with both MU-alone-, or SG-alone-positive biopsy specimens. Patients with no evidence of cGVHD in either MU or SG showed significantly less other organ involvement than patients with positive evidence. Patients with minimal MU changes (rare dyskeratotic cells) were clinically indistiguishable from negative patients in terms of other organ involvement. However, 50% of the biopsy specimens with minimal MU involvement in which SG were present had definite GVHD in the SG. These data indicate that lip biopsy specimens must include both MU and SG tissue to rule out oral GVHD. Minimal MU changes are insufficient to diagnose oral cGVHD, although they do warrant close follow-up and a second biopsy if SG tissue is not present in the specimen.