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The standard therapies for primary cutaneous anaplastic large cell lymphoma (pcALCL) in an advanced stage remain undefined. A 71-year-old man presented with multiple erythema and nodules. He was diagnosed with lymphomatoid papulosis (LyP) through a skin biopsy from the left postauricular area. All skin lesions achieved complete response by electron beam irradiation. However, nodular lesions appeared in both inner canthi 5 months later. Histopathological evaluation of the lesional biopsy revealed dominant infiltration of CD30-positive large cells. Positron emission tomography/computed tomography revealed fluorodeoxyglucose-positive cervical and inguinal lymph node swelling and right tonsillitis, followed by the diagnosis of pcALCL and TNM classification T3bN3M0. Since the patient had severe chronic obstructive pulmonary disease and recurrent pneumonia, he received low-dose methotrexate (MTX) (15 mg/week) therapy. Low-dose MTX effectively debulked the lymphadenopathies over time without particular adverse effects. Although the standard therapies for pcALCL are not established, low-dose MTX was effective and considered safe for patients with frailty and compromised respiratory function. Further study is warranted on the pathophysiology of pcALCL after the development of LyP and mechanisms of action of low-dose MTX against LyP and pcALCL.

Background Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder mainly caused by heterozygous mutations of PTCH1 . In addition to characteristic clinical features, detection of a mutation in causative genes is reliable for the diagnosis of NBCCS; however, no mutations have been identified in some patients using conventional methods. Objective To improve the method for the molecular diagnosis of NBCCS. Methods We performed targeted exome sequencing (TES) analysis using a multi-gene panel, including PTCH1 , PTCH2 , SUFU , and other sonic hedgehog signaling pathway-related genes, based on next-generation sequencing (NGS) technology in 8 cases in whom possible causative mutations were not detected by previously performed conventional analysis and 2 recent cases of NBCCS. Subsequent analysis of gross deletion within or around PTCH1 detected by TES was performed using chromosomal microarray (CMA). Results Through TES analysis, specific single nucleotide variants or small indels of PTCH1 causing inferred amino acid changes were identified in 2 novel cases and 2 undiagnosed cases, whereas gross deletions within or around PTCH1 , which are validated by CMA, were found in 3 undiagnosed cases. However, no mutations were detected even by TES in 3 cases. Among 3 cases with gross deletions of PTCH1 , deletions containing the entire PTCH1 and additional neighboring genes were detected in 2 cases, one of which exhibited atypical clinical features, such as severe mental retardation, likely associated with genes located within the 4.3Mb deleted region, especially. Conclusion TES-based simultaneous evaluation of sequences and copy number status in all targeted coding exons by NGS is likely to be more useful for the molecular diagnosis of NBCCS than conventional methods. CMA is recommended as a subsequent analysis for validation and detailed mapping of deleted regions, which may explain the atypical clinical features of NBCCS cases.

Cowden syndrome (CS) is an autosomal dominant inherited disorder characterized by macrocephaly and multiple hamartomas. The responsible gene is PTEN (phosphate and tensin homolog detected on chromosome 10), which negatively regulates cell proliferation and survival. We herein present a 46-year-old woman with the typical clinical features of CS. A DNA sequencing analysis of the coding regions and flanking introns of the PTEN gene revealed a novel heterozygous mutation (c.403A > G, p.Ile135Val) in exon 5 that had not been previously reported in CS. J. Med. Invest. 67 : 200-201, February, 2020.

Nivolumab, an anti-programmed death 1 antibody, produces antitumor effects by activating host immunity, which also causes immune-related adverse events (irAEs). The aim of this study was to analyze the association between antitumor effect and irAEs induced by nivolumab in patients with melanoma.Fifteen patients with melanoma who had received nivolumab at Tokushima University Hospital or Ehime University Hospital between January 2015 and December 2016 were enrolled in this study. Patients who had and did not have irAEs during nivolumab treatment were classified into an irAEs-positive group (n = 8) and an irAEs-negative group (n = 7), respectively. We compared the disease control rate (DCR) and overall survival (OS) between the 2 groups. Data on blood cell counts were also analyzed.After a median of 4 cycles of nivolumab treatment, irAEs occurred. The DCRs were 75% and 14% in the irAEs-positive and irAEs-negative groups, respectively (p 0.05). OS in the irAEs-positive group was higher than that in the irAEs-negative group (p 0.05). Multivariable Cox proportional hazards regression analysis revealed that irAE occurrence affected OS with nivolumab treatment. Moreover, the increase in baseline peripheral lymphocyte count at the time of onset of irAEs was significantly greater in the irAEs-positive group than in the irAEs-negative group after 4 cycles of nivolumab treatment (p 0.05).Our study indicated that clinical response with nivolumab treatment improves with irAE occurrence in patients with melanoma. Moreover, the early increase in peripheral lymphocyte count may act as a biomarker for predicting the occurrence of irAEs induced by nivolumab.

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.

Introduction: Appropriate skin care for dry scalp includes treatment for dandruff and itchiness. However, little is known about the appropriate washing methods for subjects with dry scalp. Me- thods: A scalp moisturizing lotion was used for 8 weeks on 30 outpatients at the Tokushima University Hospital who had dry scalp. All subjects were given the same hair shampoo/conditioner and instructions on how to wash their hair. Scalp symptoms were observed before and after the testing period. Indigenous bacteria were collected from the scalp for quantitative assessment. A survey was conducted to assess the quality of life (QOL). Results: All scalp condition items (dryness, scales and desquamation, itchiness, excoriation, and erythema) improved significantly after the testing period; the levels of Malassezia and bacterial colonization also decreased significantly. The QOL evaluation indicated significant improvements in “symptoms”, “emotions”, and “global” measures. A correlation was found between the extent of dryness at the start of the test and the level of Malassezia colonization, as well as QOL scores. Conclusion: Using a scalp moisturizing lo- tion, washing hair with a shampoo and conditioner that cause low irritation levels, and using a hair washing method that avoids irritation led to improvement in scalp condition, QOL, and pa- tient satisfaction.

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.

Auteur(s) : Takeshi ISHIGAMI1, Yoshiaki KUBO1 ykubo@clin.med.tokushima-u.ac.jp, Yoshihiro MATSUDATE1, Shinichi ANSAI1, Seiji ARASE1, Bungo OHYAMA2, Takashi HASHIMOTO2 1 Department of Dermatology, University of Tokushima Institute of Health Biosciences, 3-18-15 Kuramoto-cho, 770-8503 Tokushima-city, Japan 2 Department of Dermatology, Kurume University School of Medicine, Fukuoka, Japan Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease described first by Anhalt et al. in 1990 [1]. [...]