Cerebral cavernomas (CCMs) are vascular malformations that may be inherited as an autosomal dominant condition for which a gene, CCM1, was mapped to chromosome 7. Poorly defined cutaneous malformations were sometimes described in association with CCMs. During a national survey, 57 French CCM families were studied. Co‐occurrence of CCMs and a distinctive cutaneous vascular malformation was observed in 4 families. Ten individuals belonging to these families showed similar hyperkeratotic cutaneous capillary venous malformations (HCCVMs). In 3 families, the histology showed orthokeratosis and hyperkeratosis as well as dilated capillaries in the dermis extending to the hypodermis and confirmed the diagnosis of HCCVM. Genetic analysis strongly supports linkage of these families to the CCM1 locus on chromosome 7. The HCCVM seems to be a peculiar cutaneous vascular malformation associated with CCMs. These data strongly suggest that HCCVMs and CCMs in these families are due to the same genetic abnormality. Ann Neurol 1999;45:250–254
Dermatofibrosarcoma protuberans (DFSP) is a rare, dermal neoplasm of intermediate malignancy. It is made of spindle-shaped tumor cells in a storiform pattern positive for CD34. Cytogenetically, DFSP cells are characterized by either supernumerary ring chromosomes composed of sequences derived from chromosomes 17 and 22 or more rarely of translocations t(17;22). These chromosomal rearrangements lead to the formation of a specific chimeric gene fusing COL1A1 to PDGFB. So far, the COL1A1-PDGFB fusion gene remains the sole fusion gene identified in DFSP. However, some observations suggest that genes, other than COL1A1 and PDGFB, might be involved in some DFSP cases. We report in this paper a DFSP case presenting as a unique chromosomal abnormality a complex translocation between chromosomes 5 and 8. This is the first report of a DFSP case where the lack of chromosomes 17 and 22 rearrangement and the absence of COL1A1-PDGFB fusion gene have been demonstrated. Using fluorescence in situ hybridization analysis, we showed that the CSPG2 gene at 5q14.3 and the PTK2B gene at 8p21.2 were disrupted by this rearrangement. Although rare, the existence of cases of DFSP negative for the COL1A1-PDGFB fusion has to be taken in consideration when performing molecular diagnosis for a tumor suspected to be a DFSP.
Pseudoepitheliomatous hyperplasia is a benign condition defined by an exuberant proliferation of the epithelium with downward progression into the dermis. It may occur in reaction to several conditions including chronic cutaneous wound. We describe an unusual case of a florid pseudoepitheliomatous hyperplasia mimicking a well-differentiated squamous cell carcinoma, restricted to the red part of a rose tattoo.
IL-20 is involved in the development of skin psoriasis. The molecular mechanisms underlying IL-20 overexpression in psoriatic epidermis remain to be elucidated. We showed that IL-20 was primarily upregulated in psoriatic skin at the post-transcriptional level. The RNA-binding protein HuR relocalized to the cytoplasm of keratinocytes (KCs) of psoriatic patients, suggesting that it stabilizes numerous transcripts, as observed in the human KC cell lines used to assess IL-20 mRNA. We characterized epidermal HuR RNA targets in psoriatic skin using ribonucleoprotein immunoprecipitation analyzed via high-throughput sequencing. Numerous transcripts that are upregulated in psoriasis were targeted by HuR, supporting the participation of HuR in pathogenic processes such as morphological changes, innate and adaptive immune responses, and metabolic inflammatory responses. Finally, we identified the metabolic sensor AMP-activated protein kinase (AMPK) as being responsible for HuR cytoplasmic relocalization because its activity was severely impaired in human psoriatic epidermis, and in vivo drug-mediated AMPK inhibition in mouse epidermis promoted HuR cytoplasmic localization, IL-20 overproduction, acanthosis, and hyperkeratosis. These results provide insights into the molecular links between metabolism and post-transcriptional networks during chronic inflammation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.