Cutaneous sebaceous tumours and Lynch syndrome: long-term follow-up of 60 patients.

BACKGROUND: Sebaceous neoplasms (SN) may appear sporadically in the general population but may also be part of the Muir-Torre variant of Lynch syndrome (MT-LS). There are few studies in southern Europe on the incidence of MT-LS in the population of patients with SN. AIM: To retrospectively review patients with SN and to analyse their clinical features and the incidence of MT-LS. METHODS: Patients with SN diagnosed between 1995 and 2015 were enrolled in the study. The diagnosis of MT-LS was made according to established clinical criteria and, whenever possible, was confirmed by germline mutation analysis. RESULTS: In 60 patients (32 men, 28 women, mean age 69.22 years), 96 SN were diagnosed: 65 adenomas (67.7%), 16 sebaceomas (16.7%) and 15 carcinomas (15.6%). Of the 60 patients, 50 (83.3%) had a single SN and 10 (16.7%) had multiple lesions. Patients diagnosed with MT-LS (12 patients, 20%) were younger (63.25 years vs. 70.71 years), and had a higher incidence of extrafacial SN (4/12 patients, 33.3%), and were significantly (P < 0.001) more likely to have multiple SNs (8/12, 75%) and keratoacanthomas (KAs) (6/12, 50%). CONCLUSION: Our study confirms that all patients with SN should be investigated, as 20% of our patients were diagnosed with MT-LS. The most specific features of SN associated with MT-LS in our study were the presence of multiple lesions and association with KAs.

Syndromic sebaceous nevus: current findings.

BACKGROUND: Sebaceous nevus is a congenital malformation of the skin that usually occurs on the scalp or face. Syndromic forms do rarely exist with associated cerebral and ocular malformations. The skin lesions are pale at birth and become irregular by puberty. In the adult patient, tumors (usually benign) develop from sebaceous nevus. Their surgical excision during childhood can give a better result in terms of the definitive scar. OBJECTIVES: The aim of this study is to analyze our cases of syndromic sebaceous hamartoma, perform a review of the existing literature, and propose guidelines for the therapeutic plan. METHODS: This is a retrospective study reviewing the cases of syndromic sebaceous nevus treated in the Department of Orthopedic Plastic Pediatric Surgery in Montpellier, France, and the Department of Pediatric Surgery in Lausanne, Switzerland, between 1994 and 2016. RESULTS: The files of six patients with syndromic sebaceous nevus were analyzed. The average age at the first consultation was 4 months. The location was craniofacial in all cases. Cerebral radiological imaging was performed on all patients; two showed abnormal findings. Four patients underwent ophthalmic examination, which all revealed abnormalities. Three patients had other associated malformations. Three patients presented with epilepsy or learning difficulties in the course of follow-up. CONCLUSION: All patients presenting with extensive sebaceous nevus of the craniofacial region should benefit from cerebral imagery and ophthalmic examination since there is a very high probability of associated abnormalities. The developmental problems encountered could not be definitively associated with the skin malformations.

Human papilloma virus is not prevalent in nevus sebaceus.

Nevus sebaceus (NS) is a common congenital cutaneous hamartoma that typically presents on the scalp and face at birth or in early childhood. Occasionally NS can be associated with the Schimmelpenning-Feuerstein-Mims syndrome, which presents with concomitant severe neurologic, skeletal, cardiovascular, ophthalmic, and genitourologic disorders. In a previous study, maternal transmission of the human papillomavirus (HPV) and infection of ectodermal stem cells by HPV was postulated to result in the development of NS. In this study we aimed to determine the incidence of HPV infection in pediatric NS samples to further clarify the potential link between HPV and the pathogenesis of NS. NS tissue samples (N = 16) were analyzed for HPV DNA using type-specific, real-time polymerase chain reaction (PCR) targeting HPV 6, 11, 16, and 18 and conventional PCR with modified general primers designed for broad-range HPV detection. The tissues were also histologically evaluated for evidence of HPV infection. HPV DNA was not detected in any of the NS tissue samples using PCR and HPV-associated histopathologic changes were absent in all 16 NS tissues. HPV infection is an unlikely etiologic cause of NS.

An inflammatory verrucous epidermal nevus concomitant with psoriasis: treatment with adalimumab.

A 42-year-old-man presented with generalized inflammatory linear verrucous epidermal nevus with concomitant psoriasis vulgaris. Because of unresponsiveness of the conventional treatment, we considered treatment with adalimumab. Adalimumab was well tolerated and no side effects were observed. Adalimumab has a limited effect in treating ILVEN lesions. However, it was effective in treating the psoriasis and pruritus related to ILVEN. For these reasons adalimumab can be used in treatment of ILVEN concomitant with psoriasis.

Genetic skin diseases predisposing to basal cell carcinoma.

Basal cell carcinoma (BCC) is the commonest cancer in humans. Predisposing factors reflect common genetic variations and environmental influences in most cases. However, an underlying Mendelian disorder should be suspected in a specific subset of patients, namely those with multiple, early onset lesions. Some specific conditions, including Gorlin, Bazex-Dupré-Christol and Rombo syndromes, and Xeroderma Pigmentosum, show BCC as a prominent feature. In addition, BCC may represent a relatively common, although less specific, finding in many other genodermatoses. These include disorders of DNA replication/repair functions (Bloom, Werner, Rothmund-Thomson and Muir-Torre syndromes), genodermatoses affecting the folliculo-sebaceus unit (Brooke-Spiegler, Schöpf-Schulz-Passarge and Cowden syndromes), immune response (cartilage-hair hypoplasia and epidermodysplasia verruciformis) and melanin biosynthesis (oculocutaneous albinism and Hermansky-Pudlak syndrome), and some epidermal nevus syndromes. Further conditions occasionally associated with BCCs exist, but the significance of the association remains to be proven.

Epidermodysplasia verruciformis-associated and genital-mucosal high-risk human papillomavirus DNA are prevalent in nevus sebaceus of Jadassohn.

BACKGROUND: The hamartoma nevus sebaceus (NS) presents at birth or early childhood as a yellowish plaque characterized histologically by variable acanthosis, papillomatosis, sebaceus hyperplasia, and proliferations of adnexal structures. Clinically apparent human papillomavirus (HPV) infection is also recognized by acanthosis and papillomatosis. OBJECTIVE: We sought to determine the prevalence and physical state of HPV DNA in NS. METHODS: DNA was retrieved from 44 formalin-fixed, paraffin-embedded samples of NS (22 with secondary tumors [eg, trichoblastoma, verruca, syringocystadenoma papilliferum] and two epidermal nevi [EN]). Nested polymerase chain reaction with multiple degenerate consensus and type-specific primers and direct sequencing of polymerase chain reaction products was performed. For selected cases, in situ hybridization using probes specific for HPV 5 and 8 and for high-risk genital-mucosal HPV types was performed. RESULTS: HPV DNA was detected in 82% of NS and both EN, and consisted of genital-mucosal HPV types in 52% (HPV 6, 16, and 33) and a diverse variety of epidermodysplasia verruciformis-associated HPV types in 61%, including well-known epidermodysplasia verruciformis HPV types (5, 8, 15, 20, 22, 24, 36, 37, 38, and 80) and putatively novel epidermodysplasia verruciformis HPV types (DL285, DL287, DL436, and alb-1, -2, -3, -5, -6, -7, -8, -10, -11, -12, and -13). HPV coinfection was frequent, found in 48% (two HPV genotypes in 35% and 3 in 13%). Of NS and EN, 42% had HPV genotypes associated with cancer (ie, HPV 5, 8, 16, 20, 33, and 38); the two most commonly identified HPV types where HPV 16 (39%) and HPV 38 (18%). No differences were detected comparing frequency of HPV DNA detected with respect to age or presence of a secondary tumor. Histologically, all NS and EN showed HPV-associated cytopathic effects (ie, perinuclear halos, altered keratohyaline granules). By in situ hybridization, 64% (18/28) were positive, showing a low-intensity, punctate nuclear signal in epidermal and adnexal keratinocytes, indicating viral integration and low viral genome copy number. LIMITATIONS: Absence of adjacent, uninvolved normal-appearing skin control samples. CONCLUSION: HPV DNA is prevalent in NS, and HPV 16, the most frequently detected genotype, appears to be integrated into the host genome. Whether HPV represents a commensal infection caused by localized cutaneous predisposition, or is an essential factor in the pathogenesis of NS is unknown. The high frequency of oncogenic HPV types implicates maternal transmission of HPV and infection of an ectodermal stem cell leading to an epigenetic mosaic and altered skin development manifested along Blaschko's lines.

Epidermal nevus syndromes.

The term "epidermal nevus syndrome" (ENS) has been used to describe the association of epidermal hamartomas and extra-cutaneous abnormalities. Epidermal nevi follow the lines of Blaschko. The majority of the extra-cutaneous manifestations involve the brain, eye, and skeletal systems. Several subsets with characteristic features have been delineated including the nevus sebaceous syndrome, Proteus syndrome, CHILD syndrome, Becker nevus syndrome, nevus comedonicus syndrome, and phakomatosis pigmentokeratotica. Epidermal nevi have been associated with benign and malignant neoplasms. Advances in molecular biology have revealed that the manifestations of ENS are due to genomic mosaicism. It is likely that the varied clinical manifestations of ENS are due in great part to the functional effects of specific genetic defects. Optimal management of the patient with ENS involves an interdisciplinary approach. Amelioration of the cutaneous features of ENS has been difficult but there have been advances, especially in the use of lasers.