A case of vitiligo that followed the path of a varicose vein in the lower leg.

The Journal of Medical Investigation : JMI


棘刺創部に生じ，限局性リンパ管腫様の臨床像を呈したintralymphatic histiocytosisの1例

Journal of the Japan Organization of Clinical Dermatologists


ヒト乳頭腫ウイルスが検出された肛囲のBowen病・Bowen癌の3例

ヒト乳頭腫ウイルスが検出された肛囲のBowen病・Bowen癌の3例

Japanese Journal of Clinical Dermatology


Podoplanin-positive cells located in the basal layer of Bowen disease include tumor cells with cancer stem cell properties.


Risk of an immediate-type allergy to minocycline hydrochloride ointment

Operative Dentistry, Endodontology and Periodontology


Clinical Guidelines for Diagnosis and Management of Cowden Syndrome/PTEN Hamartoma Tumor Syndrome in Children and Adults-Secondary Publication.

Cowden syndrome (CS)/ hamartoma tumor syndrome (PHTS) is a rare autosomal dominantly inherited condition caused by germline pathogenesis. It is associated with multiple hamartomatous lesions occurring in various organs and tissues, including the gastrointestinal tract, skin, mucous membranes, breast, thyroid, endometrium, and brain. Macrocephaly or multiple characteristic mucocutaneous lesions commonly develop in individuals in their 20s. This syndrome is occasionally diagnosed in childhood due to the occurrence of multiple gastrointestinal polyps, autism spectrum disorders, and intellectual disability. CS/PHTS can be diagnosed taking the opportunity of multigene panel testing in patients with cancer. Appropriate surveillance for early diagnosis of associated cancers is required because patients have a high risk of cancers including breast, thyroid, colorectal, endometrial, and renal cancers. Under these circumstances, there is growing concern regarding the management of CS/PHTS in Japan, but there are no available practice guidelines. To address this situation, the guideline committee, which included specialists from multiple academic societies, was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labour, and Welfare, Japan. The present clinical guidelines explain the principles in the diagnosis and management of CS/PHTS, together with four clinical questions and the corresponding recommendations, incorporating the concept of the Grading of Recommendations Assessment, Development, and Evaluation system. Herein, we present an English version of the guideline, some of which have been updated, to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with CS/PHTS.


JAK阻害薬投与中の関節リウマチ患者に発症し蜂窩織炎様の所見を呈した皮膚クリプトコッカス症の1例


遺残坐骨動脈により生じた足背部難治性皮膚潰瘍の1例

遺残坐骨動脈により生じた足背部難治性皮膚潰瘍の1例


Cancer risk and genotype-phenotype correlation in Japanese patients with Cowden syndrome.

Cowden syndrome (CS) is an autosomal-dominant hereditary disorder caused by a germline PTEN variant and characterized by multiple hamartomas and a high risk of cancers. However, no detailed data on CS in Asian patients nor genotype-phenotype correlation have been reported. We performed the first Japanese nationwide questionnaire survey on CS and obtained questionnaire response data on 49 CS patients. Patients included 26 females (median age 48 years). The incidence of breast, thyroid, endometrium, and colorectal cancer was 32.7%, 12.2%, 19.2% (among females), and 6.1%, respectively. The incidence of any cancers was relatively high among all patients (46.9%, 23/49), and particularly female patients (73.1%, 19/26), compared with previous reports from Western countries. Gastrointestinal (GI) polyps were more frequently found throughout the GI tract compared with previous studies. PTEN variants were detected in 95.6% (22/23) of patients; 12 in the N-terminal region (11 in phosphatase domain) and 10 in the C-terminal (C2 domain) region. The incidence of cancer in the C2 domain group was significantly higher than in the N-terminal region (phosphatase) group. All female patients with C2 domain variant had breast cancer. Our data suggest that Japanese patients with CS, particularly female patients and patients with C2 domain variant may have a high risk of cancers.

International Journal of Clinical Oncology


Bowen disease on the dorsum of the foot associated with human papillomavirus type 16

A 94 years old Japanese female was presented to our hospital with a skin lesion on her left foot. A physical examination found a markedly hyperkeratotic reddish-brown plaque, measuring 3 cm in diameter. A biopsy specimen showed prominent papillomatosis, hyperkeratosis, and atypical keratinocytes throughout the epidermis. Individual cell keratinization, multinucleated keratinocytes, and many keratinocytes with clear cytoplasm were seen. We excised the lesion, and the skin grafting was used for covering the skin defect. We investigated whether human papillomavirus (HPV) was present in the lesion, and HPV 16 DNA was detected using the polymerase chain reaction. Immunohistochemical analysis showed several HPV-positive cells in the upper epidermis. In addition, the tumor cells showed strong and diffuse expression of p16INK4a. Bowen disease (BD) is an intraepidermal squamous cell carcinoma. The precise pathogenesis of BD is unclear, but it involves various factors. HPV infection is one of these factors and is a well-known cause of BD of the genitalia and fingers. It has been shown that some BD lesions occurring at other locations are also associated with HPV. Dysregulation of the Rb/p16INK4a pathway is considered to play an important role in HPV-induced BD, but the precise mechanism remains to be elucidated. J. Med. Invest. 69 : 152-154, February, 2022.


Trends in Investigator-Initiated Clinical Studies at a University Hospital after Enforcement of the 2018 Clinical Trials Act in Japan.

In April 2018, the Clinical Trials Act pertaining to investigator-initiated clinical trials was passed in Japan. The purpose of this study was to investigate activity in investigator-initiated clinical studies before and after enforcement of the new Clinical Trials Act. This was done by analysing the records of the Ethics Committee of Tokushima University Hospital, which reviews studies based on the Japanese government's Ethical Guidelines for Medical and Health Research Involving Human Subjects prior to the Clinical Trials Act, and records of the Certified Review Board established at Tokushima University under the Clinical Trials Act in 2018. The number of new applications to these two review boards during fiscal years 2015-2017 (pre-Act) and fiscal years 2018 and 2019 (post-Act) were used as an indicator of activity in investigator-initiated clinical studies. The number of new applications to the Ethics Committee was 303, 261, 316, 303, and 249 in 2015, 2016, 2017, 2018, and 2019, respectively. The data show that the total number of new interventional studies decreased from 50.3 in average in 2015-2017 (pre-Act) to 42 in 2018 and 40 in 2019 (post-Act), respectively. These results suggest that fewer interventional studies were started following enforcement of the new Clinical Trials Act. To confirm this trend and identify contributing factors, further studies are required. In addition, possible way, such as broader contribution of clinical research coordinators, to promote clinical studies in the new Clinical Trials Act era should be examined.


Sentinel lymph node biopsy for cutaneous malignant melanoma ; clinical significance

徳島大学病院で実施された皮膚悪性黒色腫に対するセンチネルリンパ節生検の臨床的意義について


下腿蜂窩織炎様の臨床像で再発した節外性NK/T細胞リンパ腫の1例

下腿蜂窩織炎様の臨床像で再発した節外性NK/T細胞リンパ腫の1例


ニボルマブ，イピリムマブの併用療法によりVogt-小柳-原田病様ぶどう膜炎を生じた悪性黒色腫の1例


足底に生じ，HPV33型DNAを検出したBowen病の1例

足底に生じ，HPV33型DNAを検出したBowen病の1例

Journal of the Japan Organization of Clinical Dermatologists


腹壁遠心性脂肪萎縮症の1例

腹壁遠心性脂肪萎縮症の1例


A Case of Giant Basal Cell Carcinoma of the Penis with False-positive Metastasis on PET/CT

PET/CTで転移病変として偽陽性を示した陰茎部巨大基底細胞癌の1例


急速に腎障害が進行したクリオグロブリン血症性血管炎

急速に腎障害が進行したクリオグロブリン血症性血管炎


顔面に皮疹を認めなかったBirt-Hogg-Dube症候群の1例

顔面に皮疹を認めなかったBirt-Hogg-Dube症候群の1例

Japanese Journal of Clinical Dermatology


疱疹状天疱瘡を合併した尋常性乾癬の1例

疱疹状天疱瘡を合併した尋常性乾癬の1例


入院中に生じた緑膿菌性毛包炎の母子例

入院中に生じた緑膿菌性毛包炎の母子例


Malignant Melanoma with Hair Repigmentation

毛髪の色素再沈着を伴った悪性黒色腫

症例:79 歳，男性

主訴:頭頂部の痂皮を付着する結節

現病歴:加齢に伴い毛髪は白毛になっていた．約 2 年前から右頭頂部の毛髪が茶褐色調に変化してきたが放置していた．2 カ月前から同部位に痂皮を付着する結節が生じ，徐々に増大傾向のため当科を受診した．

現症:頭頂部右寄りの部位に限局して，毛髪は茶褐色調を呈していた(図 1 a)．同部位には境界不明瞭な不整形の黒褐色斑があり，内部には 11×11 mm の表面に潰瘍を伴う黒色結節を認めた(図 1 b)．

病理組織学的所見:表皮から真皮深層にかけて好塩基性に染まる腫瘍胞巣が密に増殖していた(図 2 a)．腫瘍細胞は核の大小不同や核分裂像を伴っており，一部ではメラニン色素を含んでいた(図 2 b)．腫瘍近傍には，メラニン色素を含む毛包を認めた(図 2 c)．免疫組織化学染色では，腫瘍細胞は S-100，HMB-45(図 2 d)，Melan-A のいずれも陽性であった．Tumor thickness は 5 mm であった．摘出した右耳後部のセンチネルリンパ節に転移は認めなかった．

画像検査所見:PET-CT で転移を疑う所見はなかった．

診断:毛髪の色素再沈着を伴った悪性黒色腫(pT4bN0M0，stage Ⅱc)

治療および経過:2 cm マージンをとり，骨膜上で切除した．断端陰性を確認後に，分層植皮術を行った．現在，術後 2 年以上経過しているが再発や転移を認めていない．


Missense mutation Y449H of the K10 gene in a patient with severe epidermolytic ichthyosis.


Erythema Multiforme Associated with Chemical Burn Due to the Herbicides Alachlor

除草剤アラクロールによる化学熱傷後に生じた多形紅斑の1例


Condyloma acuminatum of the nipple resembling seborrheic keratosis

乳頭に生じ脂漏性角化症様の外観を呈した尖圭コンジローマの1例

A 25-year-old Japanese female presented with a skin lesion on her left nipple. The lesion had been present for three months and was increasing in size. A physical examination revealed a brown hyperkeratotic verrucous nodule on her left nipple. A histological examination of a biopsy specimen showed hyperkeratosis, papillo-matosis, and acanthosis. There were several koilocytes in the upper epidermis. Positive staining for human papillomavirus (HPV) particles by immunohistochemical analysis was seen in several cell nuclei at the upper malpighian layer. Mucous-type HPV DNA was detected in the lesion using the polymerase chain reaction (PCR), and it was identified as HPV type 6 by direct sequencing of the PCR product. We treated the patient by cryotherapy with liquid nitrogen, and the lesion disappeared. Condyloma acuminatum of the nipple is very rare. Interestingly, most reported clinical cases exhibit a seborrheic keratosis-like appearance. Dermatologists should consider condyloma acuminatum in cases in which seborrheic keratosis-like lesions are shown on the nipple.

25歳女．約3か月前より左乳頭部に皮疹が生じ，徐々に大きくなった．左乳頭部に角化傾向の強い暗褐色の疣状結節が，乳頭全体を覆うようにみられた．臨床像からは脂漏性角化症を考えたが，病理組織では，表皮は外方向性に乳頭状に肥厚し，表皮上層には多数のkoilocyteを認めた．抗human papillomavirus(HPV)抗体による免疫染色では，表皮顆粒層近くに陽性細胞を多数認めた．Polymerase chain reaction(PCR)によりHPVの検索を行ったところHPVのDNAが病変部から検出され，遺伝子配列はHPV6型と一致した．以上より，本例を乳頭部に生じた尖圭コンジローマと診断した．液体窒素治療により病変は消褪した．乳頭部に生じた尖圭コンジローマの報告は少ないが，興味深いことにほとんどの症例が，自験例の様に脂漏性角化症様の臨床像を呈している．乳頭に生じた脂漏性角化症様の病変に対しては常に尖圭コンジローマを鑑別に入れるべきである．


CASE REPORTS : Contact Dermatitis Syndrome Due to Betamethasone Valerate

症例 ベタメタゾン吉草酸エステルによる接触皮膚炎症候群の1例


Association Between Immune-Related Adverse Events and Clinical Efficacy in Patients with Melanoma Treated With Nivolumab: A Multicenter Retrospective Study.

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.

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).


A case of cutaneous anaplastic large cell lymphoma with pseudocarcinomatous hyperplasia

偽癌性増殖を伴った皮膚未分化大細胞リンパ腫の1例


オウゴンクジャクヒバによる接触皮膚炎症候群の1例

オウゴンクジャクヒバによる接触皮膚炎症候群の1例


関節症性乾癬に続発した反応性アミロイドーシス

関節症性乾癬に続発した反応性アミロイドーシス


母斑性基底細胞癌症候群の遺伝子診断

母斑性基底細胞癌症候群の遺伝子診断


留置針外套による接触皮膚炎

留置針外套による接触皮膚炎


Target exome sequencing and chromosomal microarray for the molecular diagnosis of nevoid basal cell carcinoma syndrome

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. To improve the method for the molecular diagnosis of NBCCS. 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). 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. 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.


Efficacy and safety of brodalumab in patients with generalized pustular psoriasis and psoriatic erythroderma: results from a 52-week, open-label study.

A T-helper (Th) cell subset Th17 preferentially produces interleukin (IL)-17 and plays a pivotal role in the pathogenesis of psoriasis. However, the pathological roles of IL-17 cascades in generalized pustular psoriasis (GPP) and psoriatic erythroderma (PsE) have not been well established. To evaluate the efficacy and safety of brodalumab, a human immunoglobulin G2 monoclonal antibody against human IL-17-receptor A (IL-17RA), in Japanese patients with GPP and PsE. This was an open-label, multicentre, long-term phase III study in Japanese patients with rare and severe types of psoriasis. Patients received brodalumab 140 mg at day 1 and weeks 1 and 2, and then every 2 weeks until week 52. The primary endpoint was the Clinical Global Impression of Improvement (CGI). Safety evaluations included treatment-emergent adverse events (AEs) and changes in laboratory parameters. A total of 12 patients with GPP and 18 with PsE were enrolled. Ten patients with GPP and 16 with PsE completed the study. At week 52 (last observation carried forward), CGI remission or improvement was achieved in 11 patients with GPP and 18 with PsE. The most commonly reported AE was nasopharyngitis (33 3%). Five serious AEs occurred during the study. However, none was considered treatment-related. Brodalumab significantly improved the symptoms of patients with GPP and PsE throughout the 52 weeks, and demonstrated favourable safety profiles without any new safety signals. Inhibition of IL-17RA-mediated signalling by brodalumab is expected to be a promising new treatment option for patients with GPP and PsE.


ゴム加硫促進剤による接触皮膚炎症候群の1例

ゴム加硫促進剤による接触皮膚炎症候群の1例


ソラフェニブ投与中に生じたケラトアカントーマの1例

ソラフェニブ投与中に生じたケラトアカントーマの1例


Irradiation with narrowband-ultraviolet B suppresses phorbol ester-induced up-regulation of H1 receptor mRNA in HeLa cells

Conclusion These findings suggest that low dose irradiation with 310 nm NB-UVB specifically suppressed the up-regulation of H1R gene expression without inducing apoptosis and that UVB of shorter or longer wavelength than 310 nm NB-UVB had no such effects. Objective To develop a narrowband-ultraviolet B(NB-UVB) phototherapy for allergic rhinitis, this study investigated the effects of irradiation with NB-UVB at wavelength of 310 nm on phorbol-12-myristate-13-acetate (PMA)-induced up-regulation of histamine H1 receptor (H1R) mRNA in HeLa cells. Methods The mRNA levels of H1R in HeLa cells were measured using real-time RT-PCR. Apoptosis were evaluated with DNA fragmentation assay. Results PMA induced a significant increase in H1R mRNA expression in HeLa cells. Irradiation with 305 nm UVB and 310 nm NB-UVB, but not with 315 nm UVB at doses of 200 and 300 mJ/cm(2) significantly suppressed PMA-induced up-regulation of H1R mRNA. At a dose of 200 mJ/cm(2), irradiation with 305 nm UVB, but not with 310 nm NB-UVB, induced apoptosis, although exposure of the cells to both 305 and 310 nm UVB induced apoptosis at a dose of 300 mJ/cm(2) after PMA treatment in HeLa cells. Conversely, irradiation with 315 nm UVB at doses of 200 and 300 mJ/cm(2) did not induce apoptosis.


Interventional Evaluation of Monoammonium Glycyrrhizinate-Glycine/DLMethionine Combination Tablets in Mild Alopecia Areata

Journal of Clinical & Experimental Dermatology Research


ヒアレインミニ点眼液とミドリンP点眼液による接触皮膚炎

ヒアレインミニ点眼液とミドリンP点眼液による接触皮膚炎


A case of pyoderma gangrenosum associated with anterior necrotizing scleritis in a patient with ulcerative colitis.


A case of sarcoidosis diagnosed by granulomatous tattoo reactions

刺青部の肉芽腫病変を契機に診断に至ったサルコイドーシスの1例

Japanese Journal of Clinical Dermatology


Human papillomavirus infection in Bowen disease: Negative p53 expression, not p16(INK4a) overexpression, is correlated with human papillomavirus-associated Bowen disease

Genital Bowen disease (BD) has been linked to the high-risk types of human papillomavirus (HPV) infection. Recently, it has been recognized that HPV also can be associated with extragenital BD. HPV oncoproteins E6 and E7 interfere with the function of p53 and pRb, respectively, leading carcinogenesis. p16(INK4a) overexpression induced by inactivation of pRb is recognized as a surrogate marker for HPV-associated cervical cancer. In this study, we examined the presence of HPV DNA in 142 BD lesions by polymerase chain reaction (PCR), and determined the type of HPV by PCR restriction fragment length polymorphism or direct DNA sequencing. HPV DNA was detected in 66.7% of genital BD and 8.3% of extragenital BD. The types of HPV detected were HPV types 6, 16, 33, 52, 56, 58 and 59. We also investigated the expression of p16(INK4a) , pRb and p53 by immunohistochemistry. Positive expression was detected in 88.6% for p16(INK4a) , 25.2% for pRb, and 63.8% for p53. There was no significant difference in p16(INK4a) and pRb expression between HPV-positive and -negative BD. However, a strong correlation of HPV positivity with p53 negativity was found. A total of 66.7% of HPV-positive BD showed no p53 expression, whereas the corresponding rate was 32.8% of HPV-negative BD. This study demonstrated that HPV can participate in the development of BD, not only in the genital lesion, but also in extragenital lesion. p16(INK) (4a) overexpression is not a marker for HPV infection in BD. Instead, negative p53 expression is correlated with HPV-associated BD.


エキセナチドの皮下注射部位に生じた薬疹の1例

エキセナチドの皮下注射部位に生じた薬疹の1例


Improvement of Scalp Condition and Quality of Life through Proper Skin Care of Dry Scalp

Journal of Cosmetics Dermatological Sciences and Applications


リンパ節転移を伴った mucinous carcinoma of the skin の1例


Case of erythema nodosum associated with granulomatous mastitis probably due to Corynebacterium infection.

Granulomatous mastitis (GM) is a rare chronic inflammatory breast disease that can be mistaken for a variety of inflammatory and neoplastic disorders of the breast. Erythema nodosum (EN) is a common panniculitis, and is often associated with a variety of diseases, yet coexistence of EN and GM is very rare. In this paper, we present a young Japanese woman with EN associated with GM probably due to Corynebacterium infection. Both lesions of EN and GM were successfully treated with oral minocycline and surgical drainage. To the best of our knowledge, this is the first case of EN associated with GM due to Corynebacterium infection in the English-language published work.


A case of methylmalonic academia with acrodermatitis enteropathica-like eruption due to essential amino acids deficiency

症例報告 必須アミノ酸欠乏によると考えられる腸性肢端皮膚炎様皮疹を生じたメチルマロン酸血症の1例


A case of ichthyosiform mycosis fungoides

魚鱗癬様菌状息肉症の1例


Effect of the Biopsy Technique on the Survival Rate of Malignant Melanoma Patients

Cutaneous malignant melanoma has a poor prognosis. The detrimental effect of incisional biopsies on the outcome of malignant melanoma has been debated. The aim of this study was to determine the effect of the presence and type of biopsy on the prognosis of malignant melanoma. The medical records of 109 malignant melanoma patients treated at Tokushima University Hospital from 1983 to 2007 were reviewed. After excluding 28 cases with stage 0 disease or incomplete data, 81 cases were analyzed in detail with respect to patient sex, age, tumor site, clinical stage at diagnosis, presence of ulceration or lymph node metastasis, and prognosis. The five-year survival and five-year disease-free survival rates of patients who underwent incisional or excisional biopsies were compared with those who did not undergo a biopsy. The male-to-female ratio was 1:1.19. The mean age was 61.3 years (range, 19-93 years). The most common site was a lower extremity, and the most common clinical stage was stage II. No significant differences in clinicopathological features, five-year survival rates, and five-year disease-free survival rates were observed among the three groups. The presence and type of biopsy neither affected the metastatic rate nor the prognosis of malignant melanoma. The use of incisional biopsies is not encouraged because tumor thickness cannot be measured accurately. However, they may be helpful for confirming the diagnosis if an excisional biopsy cannot be performed.


Woolly hair nevus associated with digital abnormalities and auditory disturbance.


CASE REPORTS : Two Cases of Contact Dermatitis Due to Hair Dyes

症例 染毛剤による接触皮膚炎の2例


Increased lysophospholipase D activity of autotaxin in sera of patients with atopic dermatitis.


悪性腫瘍を合併した抗155/140kDaタンパク抗体陽性皮膚筋炎の2例

悪性腫瘍を合併した抗155/140kDaタンパク抗体陽性皮膚筋炎の2例


Potential Risk of Metal Allergy Associated with Pierced Earrings Containing Nickel

ニッケル含有ピアスによる金属アレルギー発症の危険性について

Journal of Environmental Dermatology and Cutaneous Allergology

日本皮膚アレルギー・接触皮膚炎学会雑誌


母斑症・遺伝性疾患 高発癌性遺伝性疾患の概要と最近の知見

母斑症・遺伝性疾患 高発癌性遺伝性疾患の概要と最近の知見


Xanthomas Associated with Primary Biliary Cirrhosis

原発性胆汁性肝硬変に合併した黄色腫の1例


A case of livedo vasculopathy successfully treated with dabigatran

ダビガトランが奏効したリベド血管症の1例

Japanese Journal of Clinical Dermatology


A Case of Leg Ulcers due to Juvenile-onset Deep Venous Thrombosis of the Leg Associated with Congenital Stenosis of the Inferior Vena Cava

先天性下大静脈狭窄症による若年発症下肢深部静脈血栓症に伴った下腿潰瘍の1例


Cutaneous Alternariosis on the Face Successfully Treated with a Combination of Terbinafine and Topical Heat Therapy

顔面に生じた皮膚アルテルナリア症-局所温熱療法を併用した1例-


Bowen disease of the palm associated with human papillomavirus 52.

Human papillomavirus (HPV) is a well-known risk factor for many human cancers, especially cervical cancers. Among the nonmelanoma skin cancers, Bowen disease (BD) of the genitalia and fingers has also been shown to be closely associated with the high-risk types of HPV, especially HPV16. We report a case of BD of the palm, which is a very rare location for BD. In addition to its rare location, HPV52, which is classified as a mucous high-risk HPV type, was detected in the lesion by PCR restriction fragment length polymorphism analysis. To our knowledge, this is the first reported case of BD associated with HPV52.


Various Vascular Lesions in a Girl with Bannayan-Riley-Ruvalcaba Syndrome

The Journal of the Japan Pediatric Society


Hypomelanosis of Ito: A Case of Definitive Diagnosis without any Extracutaneous Complication at First Medical Examination and a Case of Presumptive Diagnosis

Hypomelanosis of Ito ―初診時に皮膚外合併症を伴わなかった確定診断例と疑診例―


A novel de novo nonsense mutation in the TRPS1 gene in a Japanese patient with tricho-rhino-phalangeal syndrome type I.


Generalized malignant acanthosis nigricans with "deck-chair sign".


A case of Bowen's disease arising in a region of seborrheic keratosis

脂漏性角化症病巣内に発生したBowen病の1例

A 73-year-old Japanese woman was referred to our hospital because of a left leg skin tumor which was gradually growing. Clinical examination revealed a 14 × 13mm brownish keratotic plaque on her leg. Since an excisional biopsy specimen taken by a local dermatologist suggested squamous cell carcinoma, we performed an excisional biopsy. Histologically, the lesion consisted of proliferating keratinocytes. The periphery of the tumor showed reticulated seborrheic keratosis ; whereas in the center portion of the tumor, tumor cells consisted of atypical keratinocytes in the entire epidermis which was considered to be Bowen's disease. We should keep in mind that although rare, skin cancer, including Bowen's disease, could arise in a lesion of seborrheic keratosis.[Skin Cancer (Japan) 2013 ; 28 : 181-184]

73歳，女性．以前より左下腿外側に淡褐色の結節を自覚していたが，徐々に隆起してきた．地元の皮膚科医院で生検を受け，有棘細胞癌が疑われたため当科に紹介された．左下腿外側に14×13mmの不整形，扁平に隆起する角化性の淡褐色局面を認めた．摘出標本の病理組織では，病変は全体に好塩基性に染まる表皮細胞の増殖より成っていた．腫瘍の辺縁部は，異型性のない表皮細胞の増殖であり，偽角質嚢腫などを認め，脂漏性角化症の像であった．これに対し腫瘍の中央部は極性の乱れた，核の異型性を伴う表皮細胞が表皮全層性に増殖し，異常角化細胞も認めBowen病の所見を呈していた．同部では辺縁に比べKi67が強く発現していた．以上の組織所見から脂漏性角化症内に生じたBowen病と考えた．稀ではあるが良性の脂漏性角化症内にBowen病などの悪性病変を生じる事は，以前より報告されており，念頭に置いておく必要がある．


The involvement of fibroblast growth factor receptor signaling pathways in dermatofibroma and dermatofibrosarcoma protuberans.

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.

The Journal of Medical Investigation : JMI


Drug eruption induced by gonadotropin-releasing hormone analogs accompanying radiation-recall phenomenon.


Two cases of photosensitive drug eruption due to pirfenidone

ピルフェニドンによる光線過敏症の2例

Japanese Journal of Clinical Dermatology


Causal Effect of Earrings for Pierced Ears on Dental Metal Allergy

歯科用金属アレルギーとピアスの関係について

Journal of Environmental Dermatology and Cutaneous Allergology

日本皮膚アレルギー・接触皮膚炎学会雑誌


Squamous cell carcinoma of the scalp associated with human papillomavirus type 16.


A clinicopathological study of primary cutaneous invasive squamous cell carcinoma: relationship between a new clinicopathological classification and program

皮膚原発浸潤性有棘細胞癌(Primary Cutaneous Invasive Squamous Cell Carcinoma)の臨床病理学的検討:臨床病理学的新分類と予後の関係

We performed a clinicopathological analysis of 305 cases of primary cutaneous invasive squamous cell carcinoma (SCC) diagnosed in Tokushima University hospital in the past 25 years. We proposed a new clinicopathological classification of SCC based on epidemiological factors and divided it into nine categories; actinic keratosis type, bowen type, keratoacanthomatous type, cystic type, genital type, cicatricial type, radiodermatitis type, xeroderma pigmentosa type, and miscellaneous type. We examined the clinicopathological characteristics in each category such as favorite locations and prognosis. Among the clinical characteristics of those cases, such as sex ratio and age at the time of the excision, the favorite sites were similar to those in former reports in Japan. The actinic keratosis type is a significant type with little metastasis, but the radiodermatitis type and the genital type showed high metastatic rates. The case that occurred on the face showed little metastasis, but the cases on the lower limbs and genitalia had high metastatic rates. Cases with a tumor thickness of less than 4 mm showed lower metastatic rates than those with a tumor thickness of more than 4 mm. We divided those 25 years into five year segments as investigation periods and examined the numbers of cases, sex ratios, and the frequencies of the actinic keratosis type, the Bowen disease type, and the other types and found that these factors were essentially equal.

1983年から2007年の25年間で，徳島大学病院皮膚科および形成外科で経験した皮膚原発浸潤性有棘細胞癌305例について，特に発症要因を重要視した臨床病理学的新分類法を用いて分類し，日光角化症型，Bowen病型，ケラトアカントーマ型，嚢腫型，外陰部型，瘢痕型，放射線皮膚炎型，色素性乾皮症型，その他，の9型に分類した．各型に関して好発部位や転移の有無/予後の違いなどの臨床病理学的検討を行った．その結果，症例全体の臨床的特徴は，男性に多く発生していること，切除時年齢，発生部位の割合など，本邦における以前の報告とほぼ同様であった．さらに病型では，日光角化症型は転移を起こしにくく，外陰部型・放射性皮膚炎型は転移を起こしやすかった．次に発生部位では顔面に生じたものは転移を起こしにくく，下肢・外陰部に生じたものは転移を起こしやすかった．腫瘍の厚さでは4 mm未満の症例は転移を起こしにくく，4 mm以上の症例は転移を起こしやすかった．調査した25年間を5年毎に区切り，各年代における日光角化症型，Bowen病型，それ以外のタイプの4群の症例数の推移と男女比を調査したが，その構成に大きな変化はなかった．


Relapsing polychondritis associated with psoriasis vulgaris and alopecia areata.


Ichthyosis hystrix, Curth-Macklin type: a new sporadic case with a novel mutation of keratin 1.


Generalized hypopigmented macules after bone-marrow transplantation.


Clinical case reports: Coexistence of low-grade sebaceous carcinoma and basal cell carcinoma in a nevus sebaceous

症例 低悪性度脂腺癌および基底細胞癌を併発した脂腺母斑

A 60-year-old Japanese man visited our outpatient clinic complaining of a black protruding tumor on his left cheek with a 3-year history. The tumor arose in a pre-existing skin-colored plaque that had been noticed since his childhood. We suspected a basal cell carcinoma (BCC) arising in a nevus sebaceus (NS), and excised the lesion including the NS. A histopathological examination of the whole specimen demonstrated the coexistence of a low-grade sebaceous carcinoma (low-grade SC) and BCC in an NS. An NS is classified into three progression stages, and various types of epithelial tumors occur secondarily in the lesion at the third stage, especially when patients are more than 50 years old. Among those secondary malignant tumors, BCC is the most common, and SC is rather rare. We reviewed the literature and summarized 31 cases of malignant sebaceous tumors arising in an NS, focusing on clinical characteristics. Surprisingly, seven cases had other malignant tumors, most of which were BCC as in our case. Only one patient with SC in an NS died from metastasis, and another 30 cases were cured after appropriate treatments. Therefore, we suggest that SC in an NS is curable by careful extirpation, although the prognosis of common SC is rather poor. But seen on the background of this case the concept of `low-grade SC' should be kept in mind.

60歳，男性．幼少時より左耳前部に正常皮膚色局面があった．初診の3年前より病変内に黒色腫瘤が出現し，徐々に増大したため当科を受診した．脂腺母斑から発生した基底細胞癌と考え，脂腺母斑を含めて切除した．摘出標本では，脂腺母斑内の離れた場所に基底細胞癌と低悪性度脂腺癌が独立して認められた．脂腺母斑に続発する悪性腫瘍では基底細胞癌が最も多く，脂腺癌の報告はまれである．脂腺母斑に続発した悪性脂腺腫瘍の症例を検討し，臨床的特徴について若干の考察を加え報告する．


Paraneoplastic pemphigus associated with non-Hodgkin's lymphoma.


Coexistence of giant blue nevus of the scalp with hair loss and alopecia areata.

A 43-year-old Japanese man presented with a 13-year history of a grayish macule measuring 7 cm in diameter with sparse hairs on the vertex. Histopathological examination demonstrated two types of melanocytes, spindle-shaped and ovoid cells, with abundant melanin aggregated around the upper part of the pilosebaceous apparatus. Fibrous, thick collagen bundles were also seen surrounding the upper part of the small hair follicles. There was no infiltration of melanocytes or lymphocytes in the lower dermis or adipose tissue. Based on these findings, a diagnosis of blue nevus, cellular type, was made. Giant cellular blue nevi on the scalp are rare, and 11 cases reported in the published work have shown characteristic features such as hair loss and cranial invasion of nevus cells. It should be noted that melanocytes of giant blue nevi have a high potential to damage other organs such as underlying bone and hair follicles. The patient also showed a typical lesion of alopecia areata on the left temporal which was successfully treated with topical corticosteroid.


Scalp angiosarcoma successfully treated with weekly docetaxel and linac electron beam

電子線照射とWeeklyドセタキセル療法が奏効した頭部血管肉腫の1例


Basal cell carcinoma arising on the palm.


Diltiazem-associated photodistributed hyperpigmentation: report of two Japanese cases and published work review.

Scherschum et al. proposed diltiazem-associated photodistributed hyperpigmentation as a novel type of drug-induced photosensitive lichenoid eruption. The characteristic clinical features were slate-gray reticulated hyperpigmentation on sun-exposed areas, while lichenoid dermatitis with prominent pigmentary incontinence was noted histologically. Although the clinical and histological features were similar to those of lichen planus pigmentosus, the histological features did not show either compact hyperkeratosis or wedge-shaped hypergranulosis, which are typical histological features of lichen planus. We describe two Japanese cases of diltiazem-associated photodistributed hyperpigmentation, who were successfully treated with topical tacrolimus, and review the published work.


嚥下障害を伴った皮膚筋炎に対し免疫グロブリン大量療法(IVIG)が奏効した2例

嚥下障害を伴った皮膚筋炎に対し免疫グロブリン大量療法(IVIG)が奏効した2例


Resin splint as a new conservative treatment for ingrown toenails.

Several conservative as well as surgical methods are used for the treatment of ingrown toenails until date. The conservative methods are either based on nail splinting or on orthonyxia, but no methods employing both principles have been reported thus far. Moreover, surgical methods usually involve postoperative pain, prolonged wound healing and restricted activities of daily living. Therefore, considering the need of a simplified, non-invasive method, in this study, we applied a novel splint to treat patients with ingrown toenails and estimated the clinical efficacy as well as rate of recurrence following treatment. The splint is a plate made of resin that is attached to the lateral edge of the nail using a bandage. We studied 61 patients (19 men and 42 women; mean age 36 years), with an average application duration of 9.3 months and an average follow-up period of 10 months in all patients. All patients experienced pain relief within a week of splint application and a decrease in the degree of nail deformity. Moreover, follow-up revealed a recurrence rate of 8.2%. Therefore, we believe that this new device is an excellent conservative treatment method for patients with ingrown toenails.

The Journal of Medical Investigation : JMI


【肉芽腫症】 右環指の腫脹を契機に診断したサルコイドーシスの1例

【肉芽腫症】 右環指の腫脹を契機に診断したサルコイドーシスの1例


硫酸クロピドグレルによる薬剤性過敏症症候群の1例

硫酸クロピドグレルによる薬剤性過敏症症候群の1例


60年以上続くリンパ浮腫肢に生じた脈管肉腫の1例

60年以上続くリンパ浮腫肢に生じた脈管肉腫の1例


Isaacs症候群を合併し難治であったびまん性筋膜炎の1例

Isaacs症候群を合併し難治であったびまん性筋膜炎の1例


Clinicopathological Study of Drug-induced Hypersensitivity Syndrome (DIHS)


【血管炎・血行障害】 片側の指端壊死で発症した混合性結合組織病続発の抗リン脂質抗体症候群


Prevention of pressure ulcers in home care patients

きず・きずあと(創傷)治療:最近の進歩床ずれの在宅ケア

A large proportion of home care patients are at risk of pressure ulcer. The occurrence rate of pressure ulcer is higher in home care patients than that in the patients of hospitals and welfare facilities. The home care patients need long-term conservative treatment because of the depth of the pressure ulcers.Treatment of the pressure ulcers at home results in increase of caregivers burden. Therefore,prevention and early detection of pressure ulcers are important in home nursing. In early stage of pressure ulcers，``deep tissue injury''should be taken into consideration because of its progressive nature. It is a new concept which presents deep tissue damage remaining superficial skin intact.One of clinical features in this condition is induration in a deep layer.The past decade has seen a huge growth in the application of pressure relieving mattresses,absorbent products for urinary and faecal incontinence, and skin barrier products to prevention of the pressure ulcers. Economical, physical, and psychological burden of nursing at home should be decreased with an accumulation of these information and utilization of the products. Therefore, it is important for caregivers to consult with their care managers and acquire new knowledge and information.


Centrifugal lipodystrophy of the scalp presenting with an arch-form alopecia: a 10-year follow-up observation.

We describe a 10-year follow-up observation of progressive arch-form alopecia caused by centrifugal lipodystrophy (CLD) in a Japanese boy. A 2.5-year-old boy developed a slightly depressed lesion demarcated by a horseshoe-shaped erythematous border on his right neck, which then extended to the scalp. Four years later, arch-form alopecia became apparent in the right temporal region along with an erythematous border. The arch-form alopecia gradually expanded centrifugally, leaving a slight residual depression, but hair regrowth was seen within the area of alopecia. Histological examination of the erythematous border revealed non-specific inflammatory changes in the subcutaneous fat. Magnetic resonance imaging findings revealed a loss of subcutaneous fat inside the lesion. The alopecia continuously extended until he was 12 years old, but, thereafter, expansion ceased and hair regrowth gradually occurred in the arch-form alopecia. A linear non-hairy lesion 5 cm in length still remained when he was 13 years old. CLD might involve the scalp and cause linear, arch-form alopecia.


Real-time in vivo imaging of p16Ink4a reveals cross-talk with p53

Expression of the p16(Ink4a) tumor suppressor gene, a sensor of oncogenic stress, is up-regulated by a variety of potentially oncogenic stimuli in cultured primary cells. However, because p16(Ink4a) expression is also induced by tissue culture stress, physiological mechanisms regulating p16(Ink4a) expression remain unclear. To eliminate any potential problems arising from tissue culture-imposed stress, we used bioluminescence imaging for noninvasive and real-time analysis of p16(Ink4a) expression under various physiological conditions in living mice. In this study, we show that oncogenic insults such as ras activation provoke epigenetic derepression of p16(Ink4a) expression through reduction of DNMT1 (DNA methyl transferase 1) levels as a DNA damage response in vivo. This pathway is accelerated in the absence of p53, indicating that p53 normally holds the p16(Ink4a) response in check. These results unveil a backup tumor suppressor role for p16(Ink4a) in the event of p53 inactivation, expanding our understanding of how p16(Ink4a) expression is regulated in vivo.


Brunsting-Perry type localized bullous pemphigoid, possibly induced by furosemide administration and sun exposure.

A 56-year-old male visited our hospital complaining of irregular-shaped atrophic erythematous plaques with blood crust, erosion, pigmentation, and depigmentation, localized on his forehead, bilateral cheeks, and ear lobes, for over one year. He has been receiving peritoneal dialysis and furosemide administration due to chronic renal failure for four years. Direct immunofluorescence examination exhibited linear depositions of IgG and C3 in the basement membrane zone. Antibodies against the recombinant NC16a-domain of BP180 were negative by enzyme-linked immunosorbent assays (ELISA), though BP230 ELISA was positive. Immunoblotting using extracts of normal human epidermis demonstrated that the patient's serum reacted with BP180 and BP230. IgG class autoantibodies to recombinant proteins of the C-terminal domain of BP180 were also detected by immunoblotting. This case was diagnosed as localized bullous pemphigoid (LBP). Oral administration of prednisolone 10 mg daily was started and furosemide administration was ceased. The eruptions disappeared thereafter with superficial scars. This is the second reported case of Brunsting-Perry type LBP associated with IgG class autoantibodies to the C-terminal domain of BP180. Furthermore, photosensitivity caused by furosemide administration may contribute to the induction and exacerbation of the lesions.


Primary dermal melanoma: A case report and molecular characterization.

Swetter et al. proposed primary dermal melanoma (PDM) as a distinct entity based on an excellent prognosis. The histopathological features of PDM are extremely similar to those of metastatic melanoma or clear cell sarcoma (CCS). We describe a 38-year-old woman with a subcutaneous tumor in her left thigh. Physical and imaging examinations showed no evidence of metastatic melanoma. The lesion showed obvious strong expression of KIT by immunohistochemistry, but no EWS-ATF1 fusion transcript specific for CCS was detected by reverse transcription polymerase chain reaction. In further analyses of KIT expression in other tumors, three of four primary melanomas (75%) and six of 12 metastatic melanomas (50%) were moderately or strongly positive, however, both the primary and metastatic lesions of CCS tested negative. We believe this to be a case of PDM, and emphasize the distinctiveness of PDM.


Pemphigoid nodularis : the importance of ELISA for diagnosis


Malignant acanthosis nigricans with enhanced expression of fibroblast growth factor receptor 3.


Identification of ultraviolet B-sensitive genes in human peripheral blood cells.

Ultraviolet B (UVB) is a serious irritant for the skin and increases a risk for skin cancer. To identify UVB-sensitive genes in peripheral blood, 11 healthy male volunteers were exposed to 0.3 J/cm(2) of narrow-band (NB)-UVB, about half of minimal erythema dose (MED) in Japanese, and gene expression in blood was analyzed at 4 h, 24 h, 4 d and 7 d after the irradiation using microarray carrying oligonucleotide probes for 2,000 stress-responsive genes. RNA prepared before the irradiation was used as a reference control. Microarray analysis identified 21 genes as UVB-responsive genes with a peak at 24 h in 6 subjects, and real-time PCR validated the significant down-regulation of 9 (ABCB10, ATF1, ABCD3, TANK, FAS, SLC30A9, CHUK, CASP1, and ABCE1) out of the 21 genes in 11 subjects. Considering sensitive and characteristic features of 9 marker genes, they may be useful indicators for monitoring systemic response to UVB irradiation.

The Journal of Medical Investigation : JMI


血管拡張性肉芽腫に対する硬化療法の工夫

血管拡張性肉芽腫に対する硬化療法の工夫

9歳，男児左小指指尖部に生じた欠陥拡張性肉芽腫に対してモノエタノールアミンオレイン酸溶液の局所注入が奏功した．この硬化療法は，従来の凍結療法が有用でない場合にも効果的であり，病変部への注入量を0.1ml以下にすることで副作用も起こりにくいと考えられる．血管拡張性肉芽腫に対して有用な保存的治療であると思われた．


Advances in distraction techniques for craniofacial surgery.

Distraction osteogenesis has been applied to the craniofacial skeleton as well as the long bones of the extremities. This technique does not require bone grafting and allows correction of craniofacial deformities with less invasion. Moreover, the distraction procedures can expand the overlying soft tissues simultaneously. We determined the indications of distraction osteogenesis, analyzed the types of devices available, and examined patients treated with distraction for the mandible, midface, and cranium. In all three sites, the devices tended to be the buried type and made of absorbable materials. Administration of some cytokines for shortening the consolidation period may be considered. Among disorders indicated for distraction osteogenesis, there are several syndromic craniosynostoses, which involve mutations in the fibroblast growth factor receptor (FGFR) 2 gene. The FGFR 2 mutation was suggested to clinically accelerate osteogenesis at the distraction site. The usefulness and appropriateness of the distraction protocol must be assessed for each individual disorder. Although distraction osteogenesis in the craniofacial skeleton has advanced technologically, all possible risks must be discussed with the patient and family members when obtaining preoperative informed consent, especially until establishment of fully safe distraction procedures.

The Journal of Medical Investigation : JMI


Malignant Melanoma of Soft Parts (Clear Cell Sarcoma) --- A Case Report

A subcutaneous tumor localized on the sole of the foot of a 25-year-old Japanese man was diagnosed as a malignant melanoma of the soft parts. We performed a wide local excision, elective lymph node dissection, and chemotherapy. Eight years after treatment, the patient is alive without local recurrence or metastasis.


Sclerotherapy of Hemangioma with late involution

Most cutaneous hemangiomas involute spontaneously. However, the lesion existing on the face poses a cosmetic problem during the waiting period for involution. Hemangioma showing late involution was treated by local injection of monoethanolamine oleate solution. The lesion flattened and was excised serially. Sclerotherapy with monoethanolamine oleate can shorten the waiting period for involution and can decrease the risk of psychosocial trauma. Moreover, it provides good preparation for further surgery. Such sclerotherapy is effective in the treatment of hemangioma with late involution.


Escaping G1 Restraints on Neoplasia: Cdk4 Regulation by Ras and NF-κB.


NF-kappaB blockade and oncogenic Ras trigger invasive human epidermal neoplasia.

The nuclear factor NF-kappaB and oncogenic Ras can alter proliferation in epidermis, the most common site of human cancer. These proteins are implicated in epidermal squamous cell carcinoma in mice, however, the potential effects of altering their function are uncertain. Whereas inhibition of NF-kappaB enhances apoptosis in certain tumours, blockade of NF-kappaB predisposes murine skin to squamous cell carcinoma. Because therapeutics inhibiting Ras and NF-kappaB pathways are being developed to treat human cancer, it is essential to assess the effects of altering these regulators. The medical relevance of murine studies is limited, however, by differences between mouse and human skin, and by the greater ease of transforming murine cells. Here we show that in normal human epidermal cells both NF-kappaB and oncogenic Ras trigger cell-cycle arrest. Growth arrest triggered by oncogenic Ras can be bypassed by IkappaBalpha-mediated blockade of NF-kappaB, generating malignant human epidermal tissue resembling squamous cell carcinoma. Human cell tumorigenesis is dependent on laminin 5 and alpha6beta4 integrin. Thus, IkappaBalpha circumvents restraints on growth promotion induced by oncogenic Ras and can act with Ras to induce invasive human tissue neoplasia.


CDK4 coexpresssion with Ras generates malignant human epidermal tumorigenesis.

Ras acts with other proteins to induce neoplasia. By itself, however, strong Ras signaling can suppress proliferation of normal cells. In primary epidermal cells, we found that oncogenic Ras transiently decreases cyclin-dependent kinase (CDK) 4 expression in association with cell cycle arrest in G1 phase. CDK4 co-expression circumvents Ras growth suppression and induces invasive human neoplasia resembling squamous cell carcinoma. Tumorigenesis is dependent on CDK4 kinase function, with cyclin D1 required but not sufficient for this process. In facilitating escape from G1 growth restraints, Ras and CDK4 alter the composition of cyclin D and cyclin E complexes and promote resistance to growth inhibition by INK4 cyclin-dependent kinase inhibitors. These data identify a new role for oncogenic Ras in CDK4 regulation and highlight the functional importance of CDK4 suppression in preventing uncontrolled growth.


Molecular carcinogenesis of squamous cell carcinomas of the skin.

Squamous cell carcinomas (SCCs) of the skin were suggested to develop through a multistep process that involves activation of proto-oncogenes and/or inactivation of tumor suppressor genes in the human skin keratinocytes. Exposure to ultra-violet (UV), especially UV-B, radiation is the most common cause for these genetic abnormalities in cells. We review causation of SCCs and genetic abnormalities in human SCCs with the current work. To elucidate the multistep process, we developed a method for examining the combinatorial function in vivo of plural genes in human keratinocytes. Using high efficiency retroviral transductions, we could express plural genes serially in normal human primary keratinocytes and use these cells to regenerate human skin on SCID mice. A combinatorial transduction of H-RasV12 and cyclin dependent kinase 4 (CDK4) produced human epidermal neoplasia resembling SCC. These findings were consistent with our previous results of mutation analysis in SCCs, one of which had both mutations of H-Ras gene and the INK4a locus. Therefore, it is suggested that a combination of these genetic abnormalities might be crucial to the carcinogenesis at least in a subset of SCCs.


足底に難治性潰瘍を伴ったWerner症候群の3例 --- WRN遺伝子変異の検討


Treatment of Pyogenic Granuloma with a Sclerosing Agent


A novel PTEN mutation in a Japanese patient with Cowden disease.

Cowden disease (CD) is an autosomal dominant syndrome characterized by multiple hamartomatous lesions and an increased risk for malignancies. Recent evidence has indicated that the PTEN gene, encoding a protein tyrosine phosphatase, is the CD susceptibility gene. However, another line of evidence has suggested that CD might be genetically heterogeneous. Clinical features of CD are variable, and there are interfamilial differences in the expression of skin lesions. Therefore, information on PTEN mutations in CD patients should be accumulated to clarify the genotype-phenotype correlation. In the present study, we found heterozygous germline mutations of PTEN in all of three Japanese patients with CD examined, indicating no genetic heterogeneity among our patients. The mutations included two non-sense mutations of R335X and R130X, and a mis-sense mutation of C136R. To the best of our knowledge, the C136R mutation has not previously been reported in CD patients. This novel mutation was located outside the core motif of the phosphatase domain of PTEN protein, where most of the missense mutations previously reported in CD patients were clustered. Mucocutaneous manifestations were far fewer in the patient with this mutation than in the patients with nonsense mutations. Whether the phenotypic difference in mucocutaneous features was due to the different mutations remains unclear.


Lack of somatic mutation in the PTEN gene in squamous cell carcinomas of human skin.

The tumor suppressor gene PTEN is deleted and/or mutated in a variety of tumors and the susceptibility gene for Cowden disease. Loss of heterozygosity of chromosome 10q23, where PTEN resides, in squamous cell carcinomas (SCCs) of human skin and the association of SCC with Cowden disease were reported previously. In the present study, we screened for mutations of PTEN in SCCs by polymerase chain reaction single strand conformation polymorphism analysis to examine whether PTEN is involved in the carcinogenesis of SCC. None of 21 SCCs showed somatic mutations in the coding regions of PTEM. Instead the same allelic variation was detected in two cases without any clinical features of Cowden disease. Our results indicate that inactivation of PTEN does not play an important role in the carcinogenesis of SCC.


Lower eyelid reconstruction with a cheek flap supported by fascia lata.


Lack of mutation in the INK4a locus in basal cell carcinomas.


東洋人のApert症候群患者におけるFibroblastgrowth factor receptor 2遺伝子の変異―2症例の検討―


Mutation of the fibrobrast growth factor receptor2 gene in Japanese patients with Apert syndrome


Mutations of the INK4a locus in squamous cell carcinomas of human skin.

Biochemical and Biophysical Research Communications


単純性血管腫上に生じた基底細胞癌

単純性血管腫上に生じた基底細胞癌


Frequent p53 Accumulation in the Chronically Sun-Exposed Epidermis and Clonal Expansion of p53 Mutant Cells in the Epidermis Adjacent to Basal Cell Carcinoma.

The Journal of Investigative Dermatology


A germline insertion in the tuberous sclerosis (Tsc2) gene gives rise to the Eker rat model of dominantly inherited cancer.

The Eker rat hereditary renal carcinoma (RC) is an excellent example of a mendelian dominant predisposition to a specific cancer in an experimental animal. We have previously established a new conserved linkage group on rat chromosome 10q and human chromosome 16p13.3, and shown that the Eker mutation is tightly linked to the tuberous sclerosis (Tsc2) gene. We now describe a germline mutation in the gene encoding Tsc2 caused by the insertion of an approximately 5 kilobase DNA fragment in the Eker rat, resulting in aberrant RNA expression from the mutant allele. The phenotype of tuberous sclerosis in humans differs from that of the Eker rat, except for the occurrence of renal tumours. The Eker rat may therefore provide insights into species-specific differences in tumourigenesis and/or phenotype-specific mutations.


Allelic loss at the Tuberous Sclerosis (Tsc2) gene locus in spontaneous uterine leiomyosarcomas and pituitary adenomas in the Eker rat model.


Early detection of Knudson's two-hit in preneoplastic renal cells of the Eker rat model by the laser microdissection procedure.


p53 Gene Mutations in Human Skin Cancers and Precancerous Lesions: Comparison with Immunohistochemical Analysis.


Allelic loss at the predisposing gene locus in spontaneous and chemically induced renal cell carcinomas in the Eker rat.


Bilateral leg ulcers secondary to dystrophic calcinosis in a patient with rheumatoid arthritis.

Calcinosis cutis can be classified into four subtypes: dystrophic, metastatic, idiopathic, and iatrogenic. Of these subtypes, dystrophic calcinosis (DC) is the most common, and is most frequently associated with connective tissue disease, particularly dermatomyositis and systemic sclerosis, and less commonly with systemic lupus erythematosus. However, DC associated with rheumatoid arthritis (RA) is extremely rare. In this paper, we present a Japanese woman with RA, who suffered from bilateral leg ulcers secondary to DC. To the best of our knowledge, only two cases of DC associated with RA have been reported to date. Similar to this case, the DC lesions were observed in the extremities, including the buttocks in the other two cases. Although the ulcers on her left leg were gradually epithelialized after one year, they may easily recur due to whitish abnormal underlying tissues, and a large ulcer remains on her right leg. Thus, it is important for physicians to identify DC when encountering non-healing leg ulcers associated with connective tissue diseases. J. Med. Invest. 64: 308-310, August, 2017.

The Journal of Medical Investigation : JMI


後天性リンパ管腫を契機に診断に至ったCowden病の1家系

後天性リンパ管腫を契機に診断に至ったCowden病の1家系


リップクリーム中のミツロウによる接触皮膚炎

リップクリーム中のミツロウによる接触皮膚炎


下口唇に有棘細胞癌を生じた色素性乾皮症バリアント

下口唇に有棘細胞癌を生じた色素性乾皮症バリアント


Multiple Bowen disease lesions with the eyeliner sign in a psoriasis patient after long-term narrow-band ultraviolet B light therapy.

The American Journal of Dermatopathology


A case of childhood granulomatous periorificial dermatitis mimicking lichen nitidus


A case of an insect bite-like reaction in a patient with angioimmunoblastic T-cell lymphoma.


Coexistence of X-linked ichthyosis and Nagashima-type palmoplantar keratosis: A case report.


Case of papular acantholytic dyskeratosis of the genital area successfully treated with topical vitamin D3 ointment


Chemotherapy-induced inflammation of seborrheic keratoses due to pemetrexed treatment


Case of multiple Bowen diseases associated with human papillomavirus type 16 in a patient with atopic dermatitis.


Case of nevoid basal cell carcinoma syndrome with multiple cutaneous keratocysts.


Primary cutaneous mucormycosis caused by Mucor irregularis in an immunocompetent patient


Woolly hair nevus: neonatal alopecia can be an initial manifestation.


Improvement of palmoplantar pustulosis lesions after angioplasty for Leriche syndrome.

Although a wide range of treatments have been used in the treatment of palmoplantar pustulosis (PPP), PPP is still very difficult to treat. We report a patient who had a dramatic reduction in PPP lesions after bypass surgery for Leriche syndrome. We assume that improved blood circulation had a crucial impact in reducing PPP lesions and suggest improving blood circulation could be another treatment option.


A case of lichen planus significantly improved after topical heparinoid treatment


Multiple epidermal cysts in hemodialysis patients


Verrucous skin lesions on the feet in diabetic neuropathy successfully treated with topical maxacalcitol


Verrucous extramammary Pagets disease accompanying human papillomavirus 40-associated condyloma acuminatum: importance of multiple skin biopsies


Multiple pilosebaceous cysts induced by topical steroid therapy


Lack of association between extramammary Pagets disease and human papillomavirus infection