Diagnostic and distinctive features of oral GVHD. Chronic GVHD may be clinically diagnosed by the presence of lichen planus–like hyperkeratosis on the oral mucosa in a patient who has undergone stem cell transplantation. (a) Chronic GVHD may present as white reticulate, hyperkeratotic plaques on the buccal mucosa. (b) Erythema, hyperkeratotic plaques, and pseudomembranous ulceration may be observed in chronic GVHD. Acute GVHD may have a similar ulcerated presentation with mild erythema and without hyperkeratotic plaques. (c) Mucocutaneous candidiasis, presenting here as white plaques on the posterior soft palate and anterior pillar of fauces (arrows) and yellow-coated tongue, can mimic acute or chronic GVHD but is generally accompanied by a burning sensation relieved with topical and systemic antifungal therapy

Oral ulcerations in post-transplant patients. Ulcerations may occur at any site on the oral mucosa, including the roof of the mouth, buccal mucosa, tongue, gingiva, vestibules, and lips. Establishing a clear diagnosis is critical for successful treatment. Ulcers may result from GVHD, viral infection, systemic medications or other causes. (a) Acute GVHD may present as mucositis involving any site on the oral mucosa (Photo courtesy of Robert Range, DDS). (b, c) Pseudomembranous ulcerations in chronic GVHD occur in many forms, and may eventually lose their pseudomembranous covering. Common sites include the base of the ventral tongue and the buccal mucosa. (d) Chronic GVHD may present on the cutaneous lip as wide, irregularly shaped ulcers in the setting of white lacy lesions, chapping, or generalized superficial hyperkeratosis of the cutaneous lip. (e) Ulcerations on the cutaneous lip may also be caused by viruses, including herpes simplex virus (HSV). HSV presents as clustered vesicles that, when unroofed, leave punched-out ulcerations. (f) Sirolimus, and less frequently other mTOR inhibitors, may induce isolated painful oral ulcerations, mucositis, or stomatitis. These findings typically occur in the setting of supratherapeutic serum drug levels and resolve with adjustment of drug dose. Palliative care may be required to help reduce oral pain until resolution of the ulcers

Palatal changes in oral chronic GVHD. Alterations in the palatal mucosa may be seen in chronic GVHD. (a) Palatal hyperkeratosis, erythema, and ulceration may be present on the hard palate and soft palate in chronic GVHD. (b) The presence of mucoceles is a distinctive, but not diagnostic, sign of oral chronic GVHD. Mucoceles occur when the ductal openings of the minor salivary glands are blocked, either with foreign material or because of lymphocytic infiltrate in the underlying skin or salivary glands. These are most commonly seen on the lower labial mucosa and at the junction between the hard and soft palate. Though typically painless, mucoceles may be bothersome and slow to resolve. (c) Milder changes involving the palate, such as a mottled red and white discoloration, may also be seen in chronic GVHD

Tongue changes in post-transplant patients. The tongue is a sensitive indicator of changes in the post-transplant period. In the setting of long-standing xerostomia or prolonged oral chronic GVHD, the tongue may lose its filiform and fungiform papillae, resulting in smooth appearance of the dorsal tongue. (a) When xerostomia is induced by chronic GVHD, associated white hyperkeratotic plaques may also be seen on the dorsal surface. (b) Hyperkeratotic plaques on the dorsal tongue may also be patchy and intermixed with patches of atrophy and erythema. (c) Chronic GVHD may induce isolated or multiple tufted, hyperkeratotic papules and plaques on the dorsal tongue, which require careful monitoring and evaluation with diagnostic biopsy to assess for human papillomavirus (HPV) or secondary malignancy

Genital GVHD. Chronic GVHD of the genitals may manifest as erythema, white plaques, erosions, fissures, ulcerations, or significant scarring resulting in loss of normal genital anatomy if not diagnosed at an early stage. Symptoms include vaginal dryness, pruritus, dyspareunia, and pain to touch around the introitus, particularly concentrated at the Skene’s and Bartholin’s duct openings. Genital GVHD may occur alone, but typically is associated with involvement of other mucosal sites [1]. (a) Chronic lichen planus-like GVHD of the genital mucosa is characterized by reticulate leukokeratosis (Wickham striae) overlying erythematous patches or erosions and can lead to complete resorption of the labia minora (arrow), clitoral hood agglutination (arrowhead), and narrowing of the vaginal orifice (double arrowhead). The vagina should always be examined for involvement in all forms of GVHD. (b) Erosive GVHD is characterized by painful erosions and ulcerations favoring the modified mucous membranes of the labia minora, perineum, clitoral prepuce, vestibule, and vaginal mucosa. The resulting vaginal stenosis, synechiae, and labial adhesions often require surgical correction to maintain sexual and urinary function and to prevent hematocolpos [2]. (c) Lichen sclerosus–like GVHD is characterized by waxy, hypopigmented plaques (arrow) and loss of genital structures secondary to scarring. Agglutination of the labia minora (arrowhead) and clitoral hood scarring (double arrowhead) may be seen. (d) Male genital GVHD is not well characterized. Reported presentations include appearances resembling lichen planus (arrow) or lichen sclerosus, phimosis, meatal scarring [3], and Peyronie’s disease [4]. Coronal fusion (arrowhead) may also be seen