Anatomic Pathology: Skin Pathology

• Incontinentia pigmenti is a genodermatosis that is transmitted in an X-linked pattern. It affects the skin in four stages, which can overlap in presentation. These four stages include the vesiculobullous stage, the verrucous stage, the hyperpigmented stage, and the hypopigmented or atrophic stage. The first three stages usually appear during the first 6 months of life.

• The lesions of incontinentia pigmenti are usually arranged along Blaschko lines and are found on the torso and extremities.

• The vesiculobullous stage is histologically characterized by eosinophilic spongiosis and occasional dyskeratotic keratinocytes. Eosinophils are also seen in the dermis. The verrucous stage is characterized by epidermal hyperplasia, papillomatosis, hyperkeratosis, and many dyskeratotic keratinocytes. The hyperpigmented stage shows prominent pigment incontinence. In the hypopigmented or atrophic stage, there is epidermal atrophy and decreased melanin in the basal layer, apoptotic bodies in the epidermis or papillary dermis, and absence of the pilosebaceous units and eccrine glands.

• Incontinentia pigmenti also can affect the central nervous system (seizures, mental retardation, spasticity, encephalopathy), teeth (conical or peg teeth, missing teeth, small teeth), and eyes (retinal vascular abnormalities, cataracts, uveitis). The nails and hair (alopecia) also can be affected.

• Incontinentia pigmenti is caused by a mutation in the gene for nuclear factor κB (NF-κB) essential modulator, which prevents tumor necrosis factor-α–induced apoptosis.

• Overall, most cases of incontinentia pigmenti are seen in females because the defect in NF-κB essential modulator is lethal to genetically normal males (XY genetic background). Rare cases have been described in males associated with Klinefelter syndrome (XXY genetic background) or related to somatic mosaicism and a postzygotic NF-κB essential modulator mutation.