Increased Cthrc1 Activates Normal Fibroblasts and Suppresses Keloid Fibroblasts by Inhibiting TGF-ß/Smad Signal Pathway and Modulating YAP Subcellular Location.

Keloid may induce severe impairment of life quality for the patients, although keloid is a cutaneous benign tumor. Collagen triple helix repeat containing protein 1 (Cthrc1) was identified as a novel gene that was originally found in adventitial fibroblasts after arterial injury. To address the role of Cthrc1 in keloid, the expression level of Cthrc1 was assessed in normal skin and keloid tissue, as well as in normal fibroblasts (NFs) and keloid fibroblasts (KFs) by using quantitative PCR, Western blotting and immunohistochemical analysis. The results showed that Cthrc1 was increased in keloid tissue and KFs as compared with normal skin and NFs. Meanwhile, CCK8 and Transwell assays found the cellular proliferation and migration of KFs were increased as compared with NFs. Further, to verify the function of Cthrc1 in NFs and KFs, we increased Cthrc1 expression by transfecting lentivirus (LV) vectors LV-Cthrc1. The cellular proliferation and migration, collagen synthesis and the influence on TGF-ß and YAP signaling were tested. The cellular proliferation and migration were increased in NFs-Cthrc1 as compared with NFs-control. Meanwhile, YAP expression and nuclear-location was increased in NFs-Cthrc1. On the contrary, when Cthrc1 was overexpressed in KFs, the cellular migration was suppressed and YAP expression was reduced and transferred to cytoplasm in KFs-Cthrc1 as compared with KFs-control. But the expression level of collagen I was decreased and pSmad2/3 nucleus transfer was suppressed in both NFs-Cthrc1 and KFs-Cthrc1 by using Western blotting and immunofluorescence. Increased Cthrc1 activated NFs by promoting YAP nucleus translocation, whereas suppressed KFs by inhibiting YAP nucleus translocation. Enhanced Cthrc1 decreased collagen I in both NFs and KFs by inhibiting TGF-ß/Smad pathway. In conclusion, Cthrc1 may play a role in the pathogenesis of keloid by inhibiting collagen synthesis and fibroblasts migration via suppressing TGF-ß/Smad pathway and YAP nucleus translocation.

Generalized multinucleate cell angiohistiocytoma: case report and literature review.

BACKGROUND: Multinucleate cell angiohistiocytoma (MCAH) is an uncommon benign fibrohistiocytic and vascular proliferation, which usually occurs as slow-growing grouped reddish-brown to purple papules and nodules on the distal extremities or face. Patients with generalized MCAH are extremely rare and to our knowledge, there are no more than 11 cases reported previously in the medical literature. OBJECTIVE: To describe the clinical, histopathologic features and immunohistochemical characteristics of all reported cases of generalized MCAH and investigate any potential clinicopathological correlations. METHODS: A systematic review of the literature was done with information collected and organized in a table. A new case report is also described in a 42-year-old female with generalized MCAH. Histopathologic and immunohistochemical features of multiple biopsies were analyzed. RESULTS: Men and women are equally affected. It is crucial to take multiple biopsies preferably from newly formed lesions to reach the correct diagnosis. The divergent results in immunohistochemistry staining for CD68 and estrogen receptor (ER) alpha necessitate further studies to reach a precise etiology and pathogenesis and secure it with certainty. CONCLUSION: Awareness of the clinicopathological hallmarks is important to avoid underdiagnosis of MCAH and the immunohistochemical features may contribute to understanding the pathogenesis of this rare disease.

Mycosis fungoides patient accompanied actinic keratosis, actinic keratosis with squamous cell carcinoma transformation, and porokeratosis after NBUVB therapy - 1st case report and review of the literature.

INTRODUCTION: Mycosis fungoides (MF) is the most common form of primary cutaneous T cell lymphoma. Narrowband ultraviolet B light (NBUVB) is used increasingly in treating MF because of its good toleration and well-established management. CONCERNS: To discuss the risk factors and underlying pathogenic factors in the patients with secondary skin diseases after NBUVB therapy. METHODS: We report in details the first case of a patient with MF accompanied with actinic keratosis (AK), AK with squamous cell carcinoma (SCC) transformation and porokeratosis after NBUVB therapy. Meanwhile, Sequence variants in tumor suppressor p53 gene in the patient's specimens were detected. A literature search of the key word "narrowband ultraviolet B light "and "side effects" was performed on PubMed, 14 cases of this entity were found. A total of 15 patients including our case were reviewed in this study and meaningful conclusion could be drawn. OUTCOMES: The mean age at diagnosis of secondary skin dermatoses after NBUVB therapy was 62.08 years with a male to female ratio of 2:1. The cases were reported more in Europeans than in Asians (2.75:1), and the Fitzpatrick skin type was mainly Ito III (12/15). The mean cumulative number and cumulative dose of UVB treatments were 43.71 and 42, 400 (mJ/cm), respectively. There was a positive relationship between Fitzpatrick skin type and cumulative dose of UVB treatments. Among the secondary skin diseases after NBUVB treatment, 12 were tumors, 2 were non-tumorous dermatoses. Only our patient presented with both. By polymerase chain reaction-single nucleotide polymorphism (PCR-SNP) analysis, C-G mutation of exon 4 of p53 was found in AK and MF specimens in our patient. CONCLUSION: To our knowledge, our case is the first MF patient accompanied with AK, AK with SCC transformation and Porokeratosis after NBUVB treatment. Lower Fitzpatrick skin type may be the risk factor of secondary skin diseases after NBUVB treatment.

Papular acantholytic dyskeratosis of the anogenital and genitocrural area: case series and review of the literature.

BACKGROUND: Papular acantholytic dyskeratosis (PAD) of the anogenital/genitocrural area is described as a rare distinct clinicopathological entity known to dermatopathologists, although its characteristic histopathologic pattern resembles both Hailey-Hailey disease and Darier disease. The objective of this study is to describe the clinical characteristics, histopathologic features and response to treatment of PAD. METHODS: We report in detail six cases of PAD. A literature search of the keyword 'papular acantholytic dyskeratosis' was performed on Google scholar and PubMed, 21 cases of this entity were found. A total of 27 patients including our six cases are reviewed in this study. RESULTS: The mean age at diagnosis was 38.8 years with a male to female ratio of 0.8 : 1. Clinically, papular lesions (55.6%) are the typical manifestation of PAD, and the anogenital area (63%) is the most commonly involved site. Lesions were resistant to topical steroids, subcutaneous interferon and antibiotics while one case showed complete resolution of the lesions after retinoid therapy. Laser therapy showed good results in one case. None of the patients had spontaneous remission. CONCLUSION: Awareness of the clinicopathological hallmarks herein may be important to avoid underdiagnosis of PAD and may contribute to understanding the pathogenesis of this rare disease.