Segmental basaloid follicular hamartomas derive from a post-zygotic SMO p.L412F pathogenic variant and express hair follicle development-related proteins in a pattern that distinguish them from basal cell carcinomas.

Basaloid follicular hamartomas (BFH) are benign small basaloid skin tumors that can present as solitary or multiple lesions. Congenital BFH lesions arranged in a segmental distribution have been described, suggesting they derive from a somatic post-zygotic mutational event. Previously, BFH were described in Happle-Tinschert syndrome, which results from a post-zygotic SMO variant and is characterized by segmental BFH with variable involvement of the teeth, skeleton, and central nervous system. Here, we describe two patients with isolated segmental BFH and no systemic involvement. Paired whole exome sequencing of BFH and normal tissue revealed a pathogenic SMO c.1234 C>T, p.L412F variant restricted to BFH tissue. We characterized the proliferation index and expression of Hedgehog and Wnt/beta-catenin pathway related proteins in segmental BFH compared to sporadic basal cell carcinomas (BCCs) and found that segmental BFH had a lower proliferation index. Although segmental BFH expressed a similar level of Gli-1 compared to BCCs, levels of LEF-1 and SOX-9 expression in BFH were weaker for both and patchier for LEF-1. Our results show that a somatic SMO activating variant causes segmental BFH. Since these patients are prone to developing BCCs, differences in SOX9, LEF1, and Ki-67 expression can help distinguish between these two basaloid lesions.

A mutation in the mucosal keratin K4 is associated with oral white sponge nevus.

White sponge nevus (WSN) is a benign autosomal dominant disorder which affects non-cornifying stratified squamous epithelia (MIM 193900) (ref. 1). Phenotypically it presents as white 'spongy' plaques (oral leukokeratoses), most commonly in the mouth but also reported in the esophagus and anogenital mucosa. Histologically, the plaques show evidence of hyperproliferation, acanthosis and tonofilament aggregation. These types of pathogenic changes are characteristic of many of the epidermal keratin disorders. Keratins are expressed in pairs by epithelial cells in a tissue and cell specific manner. The major differentiation specific keratins of the buccal mucosa, nasal, esophageal and anogenital epithelia are K4 and K13 (ref. 7). The tissue distribution and nature of the lesions in patients affected by WSN suggested that mutations in K4 and/or K13 might be responsible for this disorder. We have now confirmed this hypothesis and report here a three base-pair (bp) deletion in the helix initiation peptide of K4 in affected members from two families with this condition.

Oral leiomyomatous hamartoma of the median maxillary gingiva: a case report and review of the literature.

Oral leiomyomatous hamartoma (OLH) is a rare lesion seen in the oral cavity. It mainly presents on the median maxilla and tongue. In the literature in English, there are only 10 reported cases of OLH of the median maxilla. Most of the cases were found in patients of Japanese and Latin American origin. We report a case of OLH in an 18-month-old boy of Middle Eastern ancestry. The lesion presented as a pedunculated, light pink, soft swelling that was located on the labial gingiva of tooth number 21. Microscopically, it showed proliferative smooth-muscle fascicles dispersed in loose fibrous stroma and multiple small vessels. The lesional cells looked mature and elongated and were deeply eosinophilic spindle cells with basophilic, central "cigar-shaped" nuclei. The diagnosis of OLH was supported by positive immunohistochemical reactivity of smooth-muscle actin and desmin. To our knowledge, this is the first reported case of OLH in a Middle Eastern patient.

Meningothelial proliferations in mature cystic teratoma of the ovary: evidence for the common presence of cranially derived tissues paralleling anterior embryonic plate development. An analysis of 25 consecutive cases.

Mature cystic teratomas (MCTs) of the ovary are typically composed of a cyst lined with neoplastic tumor cells recapitulating ectodermal differentiation including derivatives such as epidermis, dermis, and appendages (sebaceous glands), although mesodermal and endodermal derivatives can also be seen. After the observation of a meningothelial proliferation similar to ectopic meningothelial hamartoma (EMH) in a consult case of MCT and subsequently within dermal tissue in 2 consecutive MCTs, we wanted to assess the frequency of this finding and to consider its possible significance. Twenty-five consecutive cases of ovarian MCT (patient age ranging from 23 to 66 years, mean: 36.3 years; size ranging from 2.5 to 11.5 cm, mean: 6.1 cm) diagnosed in 2008 were retrieved from the archives at Brigham and Women's Hospital. All cases contained tissue that could be localized to the head and neck region including skin with abundant pilosebaceous units (scalp skin), brain, cartilage, bone, teeth, respiratory/sinonasal epithelium, and thyroid tissue. Ten of the 25 cases (40%) contained an EMA-positive meningothelial proliferation akin to EMH, including features such as psammomatous calcifications and pigmented dendritic cells. In all 10 cases, the meningothelial element was immediately adjacent to ectodermally derived skin with pilosebaceous units and glial tissue. This study shows that the presence of meningothelial tissue in MCT of the ovary is quite frequent and its appearance is similar to that of EMH. The similar morphologic appearance of the meningothelial proliferation in MCT to EMH, its localization to the dermal subcutaneous portion of MCT, and its frequent proximity to glial tissue supports the hypothesis that the tissue elements of ovarian MCT are primarily of the head and neck type (eg, scalp skin, brain, upper respiratory/sinonasal, and less commonly thyroid) suggesting that the neoplastic growth of MCT parallels normal anterior embryonic plate development with primarily the formation of the cranial (cephalad) portion of the embryo.