No abstract

Skin tumors are supposed to develop through accumulations of genetic and/or epigenetic events in normal cells of the skin. Among them, we focus on common skin tumors, including benign, seborrheic keratosis, and malignant, squamous cell carcinoma and melanoma. Many important molecules have been detected on the molecular tumorigenesis of each of them to date, and some drugs targeted for their molecules have been already developed. We review updates on the molecular tumorigenesis of these tumors with our current works.

Fibroblast growth factors (FGFs) and their receptors (FGFRs) control a wide range of biological functions; however, their involvement in the pathogenesis of dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) is currently unknown. In this study, we first confirmed the histological diagnosis by detecting fusion COL1A1-PDGFB transcripts in DFSP, and examined the expression of all FGFRs (FGFR1-4), some of their ligands (FGF1, 2, 9), and forkhead box N1 (FOXN1) as a downstream target of FGFR3 in DF and DFSP by immunohistochemical analysis. Although we failed to detect the expression of FGF1 and FGF9 as specific ligands for FGFR3 in DF, overexpression of FGFR3 and FOXN1 was observed in the epidermal regions of DF, suggesting that the epidermal regions of DF were similar to seborrhoeic keratosis both in terms of histological features and the activation of FGFR3/FOXN1. In addition, strong expression of FGF2 and FGFR4 was observed in the tumor lesions of DF. Expression patterns of FGFR3/FOXN1 and FGF2/FGFR4 in DF were in contrast with those of DFSP. The activation of FGFR signaling pathways may be not only relevant to the pathogenesis of DF, but also very useful in the differential diagnosis of DF and DFSP.

Primary cutaneous mucormycosis caused by Mucor irregularis in an immunocompetent patientDear Editor, Mucormycosis, which mainly affects immunocompromised patients, is a rare, life-threatening infection caused by the order Mucorales. Among the six clinical types of mucormycosis, 1 cutaneous mucormycosis is the rarest and is further categorized into two types: (i) the gangrenous type, which only occurs in immunocompromised patients and progresses rapidly, and (ii) the superficial type, which develops in immunocompetent individuals, manifests as erythematous plaques, and progresses slowly. 2 We present a case of superficial cutaneous mucormycosis caused by Mucor irregularis (M. irregularis) involving an immunocompetent patient.A 16-year-oldJapanese boy who was otherwise healthy presented with a 1-year history of a gradually enlarging plaque on his leg. A physical examination demonstrated an erythematous plaque exhibiting slight desquamation on his lower right leg, which he had scraped in a bicycle accident 2 years before (Fig. 1a). A histopathological examination detected a suppurative granuloma containing neutrophils, lymphocytes, and multinucleated giant cells in the dermis (Fig. 1b). Broad, ribbon-like, hyaline, aseptate hyphae were also observed (Fig. 1c). However, fungal hyphae and microvascular thrombosis were not detected in his blood vessels. Skin tissue specimens and skin scales cultured on Sabouraud dextrose agar at 25°C yielded wool-like, light yellow colonies, but no colony growth occurred at 38°C (Fig. 1d). Microscopic examinations of slide cultures detected sporangiophores, which had formed a terminal, globose sporangium. No apophyses were observed (Fig. 1e). These findings were consistent with Mucor fungi, and the isolate was identified as Mucor irregularis based on sequencing of the D1/D2 domain of the large subunit rRNA gene (GenBank accession no. IFM 57177).Before obtaining a diagnosis, we tried itraconazole (100 mg/ day), fluconazole (200 mg/day), and voriconazole (300 mg/day), independently, as empirical therapies, but none of them was effective. However, when we administered high-dose itraconazole (400 mg/day), the patient's plaque gradually regressed. Itraconazole was administered for a total of 9 weeks (Fig. 1f). No recurrence has been observed for 5 years.M. irregularis was originally known as Rhizomucor variabilis, but it was renamed M. irregularis based on its DNA sequence. Cases of mucormycosis due to M. irregularis are rare, and only 14 cases have been reported in the English-language literature.3-5 However, it is worth noting that mucormycosis due to M. irregularis presents with unique clinical features. In contrast to classical mucormycosis, most M. irregularis infections affect immunocompetent patients and do not exhibit angioinvasion, especially in the early stages. Moreover, the majority of M. irregularis infections manifest as the superficial cutaneous type, progress chronically, and persist for several years on exposed sites. It is unknown why M. irregularis infections display the...