• Usually noted in first 2 decades of life but persist throughout life; may remit and exacerbate

• White-to-gray, folded, painless, edematous, and spongy appearance of buccal mucosa (most common), tongue, labial mucosa, and floor of mouth; may have esophageal and genital involvement (Fig. 2-1)

• Variable parakeratosis, benign epithelial hyperplasia with “spongy appearance” caused by cytoplasmic vacuolation (from glycogen) and not true spongiosis; minimal to no inflammation (Fig. 2-2, A and B)

• Perinuclear eosinophilic condensations of keratin and dyskeratotic cells sine qua non for diagnosis (see Fig. 2-2, C); rare cases with epidermolytic hyperkeratosis

• Leukoedema morsicatio mucosae oris exhibit keratinocytic endema but do not exhibit perinuclear keratin condensations.

• Hereditary benign intraepithelial dyskeratosis (see later) has “cell-within-a-cell” structures.

• No treatment is required usually; some cases respond to antibiotic therapy.

• Associated with Haliwa Indians in North Carolina and their descendants (usually on East Coast of the United States); diagnosed in first 2 decades of life

• Oral mucosa with thickened painless, diffuse, folded spongy white plaques similar to white sponge nevus

• Eye lesions present as gelatinous plaques on bulbar conjunctiva in perilimbic location

• Hyperparakeratosis and acanthosis; dyskeratotic “tobacco” cells (because of their brown color seen in Papanicolaou stains) in upper epithelium in a typical cell-within-a-cell appearance (Fig. 2-3)

• White sponge nevus (see earlier) shows perinuclear keratin condensations.

• Darier disease or warty dyskeratoma is acantholytic with dyskeratosis without the cell-within-a-cell appearance.

• No treatment is effective.

• Darier disease characterized by white, painless, keratotic papules (seen in mild disease) or plaques and cobblestoning of the mucosa (seen in more severe disease) in 10% to 50% of patients with skin disease (Fig. 2-4); onset in first and second decade; lesions on palate, gingiva or tongue; skin findings invariably present; up to one third of cases with parotid or submandibular swelling likely because of strictures and obstruction

• Warty dyskeratoma: isolated white, warty papule usually of the palate or gingiva

• Often umbilicated/crateriform hyperkeratosis, elongated, slender rete ridges 3 to 8 cells wide, and suprabasilar acantholysis with villous-like projections of connective tissue papillae rimmed by basal cells; dyskeratotic cells with dark nuclei in the form of slender grains (needle-shaped) or corps ronds (round) may not be prominent; variable chronic inflammation (Fig. 2-5)

• Pemphigus shows acantholytic cells, no dyskeratosis, and positive direct immunofluorescence studies.

• Pyostomatitis vegetans shows suprabasilar clefting, no dyskeratosis, and many eosinophils.

• Darier disease is managed with topical steroids, whereas warty dyskeratoma is excised.

• Fordyce granules: 1 to 3 mm yellowish papules or macules on the posterior buccal mucosa, vermilion of lips, usually bilateral and symmetric, present in 80% of population (Fig. 2-6)

• Sebaceous hyperplasia and adenoma: larger yellowish papules and nodules at same sites as Fordyce granules

• Sebaceous choristoma: usually midline of tongue in area of foramen cecum

• Fordyce granules: mature sebaceous glands open onto the mucosa via duct; sebocytes have central nuclei and vacuolated cytoplasm; hair and Demodex folliculorum have been reported (Fig. 2-7).

• Hyperplasia: at least 15 lobules (this number is somewhat arbitrary); ducts lined by low cuboidal to columnar epithelium (Figs. 2-8 and 2-9).

• Adenoma: proliferation of germinative cells at the periphery of the lobules

• Salivary gland neoplasms with sebaceous cells are encapsulated tumors with only foci of sebaceous differentiation.

• Excision of sebaceous hyperplasia and adenoma is curative.