PTCH mutations and deletions in patients with typical nevoid basal cell carcinoma syndrome and in patients with a suspected genetic predisposition to basal cell carcinoma: a French study

The patched (PTCH) mutation rate in nevoid basal cell carcinoma syndrome (NBCCS) reported in various studies ranges from 40 to 80%. However, few studies have investigated the role of PTCH in clinical conditions suggesting an inherited predisposition to basal cell carcinoma (BCC), although it has been suggested that PTCH polymorphisms could predispose to multiple BCC (MBCC). In this study, we therefore performed an exhaustive analysis of PTCH (mutations detection and deletion analysis) in 17 patients with the full complement of criteria for NBCCS (14 sporadic and three familial cases), and in 48 patients suspected of having a genetic predisposition to BCC (MBCC and/or age at diagnosis ⩽40 years and/or familial BCC). Eleven new germline alterations of the PTCH gene were characterised in 12 out of 17 patients harbouring the full complement of criteria for the syndrome (70%). These were frameshift mutations in five patients, nonsense mutations in five patients, a small inframe deletion in one patient, and a large germline deletion in another patient. Only one missense mutation (G774R) was found, and this was in a patient affected with MBCC, but without any other NBCCS criterion. We therefore suggest that patients harbouring the full complement of NBCCS criteria should as a priority be screened for PTCH mutations by sequencing, followed by a deletion analysis if no mutation is detected. In other clinical situations that suggest genetic predisposition to BCC, germline mutations of PTCH are not common

[Lichen planus with linear IgG and C3 deposits at the dermal-epidermal junction (author's transl)]

Report of 4 cases of clinically and histologically typical lichen planus with a linear IgG and C3 deposit at the dermal-epidermal junction in involved (4/4) and healthy (2/2) skin, as detected by direct immunofluorescence. Indirect immunofluorescence was negative (3/3). In these 4 cases, the clinical aspect was different: there were no vesiculo-bullous lesions in case 1; case 2 and 3 were of the partly vesicular type with dermal-epidermal separation only in the involved skin; in case 4, bullae were present on both healthy and lesional skin. This suggests that there might exist a broad spectrum ranging from lichen planus without clinical vesiculo-bullous lesions, but with linear IgG and C3 deposits, to lichen planus associated with clinical, histological and immunological symptoms of bullous pemphigoid

[Melanoma in invisible naevus spilus]

International audienceBACKGROUND: Diagnosis of naevus lesions may be complex where they contain little or no pigmentation. Naevus spilus (or naevus on naevus) is, generally, readily identified by the difference in pigmentation between overlying and underlying naevi and healthy skin. Malignant transformation of naevus spilus is rare. We report two cases of melanoma in which surgical procedures revealed underlying melanocyte lesions, diagnosed at histology but undetectable on clinical examination. PATIENTS AND METHODS: Two patients were operated for melanoma in which surgery, at a site remote from the melanoma, suggested incomplete relapse despite the fact that previous clinical examination had indicated healthy skin. A diagnosis was made of melanoma in invisible naevus spilus. DISCUSSION: Diagnosis of melanoma in invisible naevus spilus may be suspected where several naevi are found together in a specific area. The main problem is the therapeutic stance to be adopted since complete excision of the underlying naevi is difficult in practice. Wood's light examination may be helpful

High frequency of detection of human papillomaviruses associated with epidermodysplasia verruciformis in children with psoriasis.

BACKGROUND: Psoriasis is a T-cell-mediated immunological disease characterized by epidermal proliferation. The nature of the antigen(s) responsible for T-cell activation is still unknown. It has been suggested that the human papillomaviruses (HPVs) associated with epidermodysplasia verruciformis (EV), including the oncogenic HPV5, may contribute to the pathogenesis of psoriasis. OBJECTIVES: To determine whether EV-HPVs may play a role early in the disease, we searched for these viruses in children with psoriasis. The influence of clinical data on EV-HPV infection was investigated. METHODS: We studied scrapings of involved skin from 26 children aged 1.5-13 years with psoriasis. As controls, we analysed scrapings from 28 adults with psoriasis and 15 children with atopic dermatitis, as well as scrapings from normal skin of 28 adults with no known history of HPV infection. We searched for EV-HPV DNA sequences with a nested polymerase chain reaction method using degenerate primers specific for EV-HPVs and primers specific for HPV5 and HPV36, two EV-HPVs frequently detected in adults with psoriasis. RESULTS: Similar high prevalences were observed in children and adults with psoriasis for EV-HPVs (38.5% vs. 35.7%), HPV5 (46.2% vs. 46.4%) and HPV36 (15.4% vs. 25.0%). As in adults, we found several EV-HPV genotypes and HPV5 and HPV36 variants. A novel HPV36 subtype, HPV36b, was identified. Lower prevalences were observed in children with atopic dermatitis and in adults from the general population (6.7-10.1%). No correlation was observed between frequency of detection of HPVs and clinical data. It is noteworthy that HPV5 was identified in an 18-month-old girl and in a boy with psoriasis developing for only 1 week. CONCLUSIONS: The early detection of several EV-HPV genotypes in children further supports the link between psoriasis and EV-HPVs and suggests a putative role for these viruses in the pathogenesis of psoriasis