The clinical, biochemical, histological, or ultrastructural abnormalities of five related female Rottweiler dogs with a hereditary disorder of cornification are reported. Three of the five dogs also had multiple noncutaneous congenital defects. Cutaneous abnormalities included generalized, hyperkeratotic, variably pigmented plaques, which in one dog were distributed along Blaschko\'s lines. Moderate to severe parakeratosis involving the follicular infundibula and ostia and focal orthokeratosis with variable vacuolation of spinous cells was observed on histopathologic examination of all skin specimens. Supplementation with oral zinc in two dogs and vitamin A alcohol and calcitriol in one dog did not result in clinical or histological improvement of the hyperkeratotic lesions. This disorder of cornification in dogs is similar to human disorders of cornification that follow the lines of Blaschko. Blaschko\'s lines follow a V-shape over the spine, an S-shape on the abdomen, and an axial distribution on the limbs. No related male dogs were affected, suggesting an X-linked dominant mode of inheritance. Many features of this hereditary DOC correspond to the human condition CHILD syndrome.

A 29-year-old woman presented with dark-colored raised lesions on both eyelids since early childhood. Ophthalmological examination revealed pigmented verrucous lesions on her upper and lower eyelids bilaterally. The patient had a history of generalized tonic-clonic seizures. Dermatological examination revealed hyperpigmented verrucous plaques arranged along lines of Blaschko on the neck, trunk, and arms. On the basis of these findings, the diagnosis of epidermal nevus syndrome (ENS) was made. She had surgery for debulking of the lesions. Histological analysis revealed hyperkeratosis with foci of parakeratosis, acanthosis, and papillomatosis, consistent with linear verrucous epidermal nevus. Postoperative residual lesions did not respond to oral acitretin therapy (10 mg/kg/day for 2 months). Systematized ENS can rarely cause linear verrucous nevi on the upper and lower eyelids on both sides. These patients should be investigated for accompanying systemic anomalies and followed for potential malignant transformation of the skin lesions.

Phacomatosis pigmentokeratotica (PPK) is characterized by the co-existence of epidermal nevi and large segmental speckled lentiginous nevi of the papulosa type. PPK, previously explained as \'twin spot\' mosaicism due to the postzygotic crossing-over of two homozygous recessive mutations, has recently been shown to derive from one postzygotic activating RAS mutation. Epidermal nevi, including those in PPK, are known to give rise to neoplasms such as trichoblastoma and basal cell carcinoma. Within speckled lentiginous nevi, Spitz nevi and melanoma have been well documented. We report a case of PPK with a combined melanocytic and adnexal neoplasm presenting where the nevi conjoined. Using next-generation sequencing techniques, we were able to identify the same HRAS G13R mutation within both components of the tumor, and to show the absence of additional mutated modifier genes in a panel of 300 cancer-related genes. Given the genetic findings in this rare tumor-type, we suggest that this case may be used as a model for understanding the development of biphenotypic neoplasia or intratumoral heterogeneity in some cases.