Clinical history analysis of Japanese melanoma cases and characteristics of melanoma with childhood onset.

It remains debatable whether melanoma with a clinical history of early childhood onset truly arises from a nevus. To clarify the clinical and genetic characteristics of melanoma detected at birth or several years afterwards, 249 melanoma cases seen at Shinshu University Hospital between 2006 and 2015 were retrospectively analyzed. Ten (4.0%) cases (median age 39.5 years, range 19-70 years; male/female 2/8; lesion site, 6 extremities, 2 trunk, 1 head, 1 face; cumulative sun damage [CSD] skin, 9 low-CSD, 1 high-CSD; detection at birth 3) had recorded early childhood onset. Median Breslow's tumor thickness in those cases was 6.0 mm (range: 0.4-17.5 mm). The frequency of lesions detected at <20 years of age was significantly higher for low-CSD melanoma (17.5%) than for high-CSD (3.3%) and acral (0.8%) melanoma. Although melanoma with a history of early childhood onset is rare, the characteristics of such cases should be established since most have progressed to an advanced stage at the initial visit.

Prevalence of Psoriatic Arthritis in Nagano Prefecture, Japan, and Efficacy of the Psoriasis Epidemiology Screening Tool: A Real-World Survey.

Pain, stiffness, and swelling are the main joint symptoms of psoriatic arthritis (PsA); however, they are also common symptoms of other joint diseases. Therefore, it is challenging to distinguish PsA from other joint diseases. To evaluate the prevalence of PsA and the frequency of joint symptoms in psoriasis patients, we conducted a prefecture-wide survey using the Psoriasis Epidemiology Screening Tool (PEST), a patient questionnaire for screening PsA to assess joint symptoms. Data were collected from 764 psoriasis patients, all of whom visited hospitals (55.1%) or clinics (44.9%) in Nagano Prefecture, Japan. The proportion of psoriasis patients with PsA was 6.5% (50 of 764); four patients (1.2%) with PsA were treated in clinics, while 46 patients (10.9%) were treated in hospitals. Based on the responses to the PEST, 18.1% of patients with psoriasis had joint symptoms. In contrast, 73.2% of psoriasis patients with joint symptoms did not have PsA. The PEST showed 52% sensitivity and 93.4% specificity for PsA. In addition, fingernail alterations were common in PsA. The proportion of the population with PsA was lower than reported previously in Japan. This may have been due to the enrollment of a large number of patients treated in clinics. Many patients with PsA were treated at hospitals, which likely reflects the tendency of patients with joint symptoms to receive intensive treatment in hospitals. In addition, based on the lower sensitivity of the PEST in this study, further studies are necessary to establish the validity of the PEST.

Skin and soft tissue infections in adolescent chronic myeloid leukemia under dasatinib treatment.

Although skin complications are common adverse events from tyrosine kinase inhibitors (TKIs) for the treatment of chronic myeloid leukemia (CML), no reports have focused on skin and soft tissue infections (SSTIs) associated with TKI use. We herein present five episodes of SSTIs in three CML patients under dasatinib treatment. All patients were adolescents and had been receiving dasatinib for more than 4 years. In contrast, none of 41 adult CML patients experienced SSTIs in a retrospective analysis. Our findings suggest that long-term dasatinib treatment in adolescent patients may be associated with the increased risk of SSTIs.

Dermoscopic diagnostic performance of Japanese dermatologists for skin tumors differs by patient origin: A deep learning convolutional neural network closes the gap.

In the dermoscopic diagnosis of skin tumors, it remains unclear whether a deep neural network (DNN) trained with images from fair-skinned-predominant archives is helpful when applied for patients with darker skin. This study compared the performance of 30 Japanese dermatologists with that of a DNN for the dermoscopic diagnosis of International Skin Imaging Collaboration (ISIC) and Shinshu (Japanese only) datasets to classify malignant melanoma, melanocytic nevus, basal cell carcinoma and benign keratosis on the non-volar skin. The DNN was trained using 12 254 images from the ISIC set and 594 images from the Shinshu set. The sensitivity for malignancy prediction by the dermatologists was significantly higher for the Shinshu set than for the ISIC set (0.853 [95% confidence interval, 0.820-0.885] vs 0.608 [0.553-0.664], P < 0.001). The specificity of the DNN at the dermatologists' mean sensitivity value was 0.962 for the Shinshu set and 1.00 for the ISIC set and significantly higher than that for the human readers (both P < 0.001). The dermoscopic diagnostic performance of dermatologists for skin tumors tended to be less accurate for patients of non-local populations, particularly in relation to the dominant skin type. A DNN may help close this gap in the clinical setting.

Dermoscopy image-based self-learning on computer improves diagnostic performance of medical students compared with classroom-style lecture in ultra-short period.

The educational effectiveness of dermoscopy image-based self-learning on a computer for medical students has not been well examined. To assess the effect of an image-based self-learning session on the dermoscopic diagnostic performance for malignant melanoma (MM), basal cell carcinoma, melanocytic nevus and seborrheic keratosis (SK) on non-acral regions in comparison with a conventional classroom-style lecture, 114 fourth-year medical students (mean age, 23.7 years; male : female, 73:41) were enrolled. The subjects were randomly assigned to either a self-learning to lecture (SL) or lecture to self-learning (LS) group to receive a 15-min image-based self-learning computer session and a 15-min video lecture session in different orders. The user interface of the digital content was the same as that on a website (https://dz-image.casio.jp). Diagnostic performance was determined using the total number of correct answers for the four diseases and by malignancy prediction in examination A (before training), B (after receiving one session) and C (after receiving both sessions). The examinations were all unique and contained five dermoscopic images each of the four diseases. The total number of correct answers and malignancy prediction results for examination B were significantly higher in the SL group than in LS (11.6 and 15.2 vs 10.1 and 13.4, respectively; both P < 0.01), with no remarkable differences for examination C (13.5 and 16.8 vs 13.3 and 16.4, respectively; P = 0.62 and P = 0.21). In subanalyses, the number of correct answers for SK in examination B was significantly higher in the SL group (3.6 vs. 1.8, P < 0.01), while that for MM was significantly lower (2.2 vs 3.0, P < 0.01). Diagnostic performance was comparable between sexes for examination B. In conclusion, computer-assisted dermoscopy image-based self-learning may be a suitable and non-inferior alternative to classroom-style instruction for medical students within an ultra-short training period.

Significance of 5-S-Cysteinyldopa as a Marker for Melanoma.

Melanoma is one of the most lethal and malignant cancers and its incidence is increasing worldwide, and Japan is not an exception. Although there are numerous therapeutic options for melanoma, the prognosis is still poor once it has metastasized. The main concern after removal of a primary melanoma is whether it has metastasized, and early detection of metastatic melanoma would be effective in improving the prognosis of patients. Thus, it is very important to identify reliable methods to detect metastases as early as possible. Although many prognostic biomarkers (mainly for metastases) of melanoma have been reported, there are very few effective for an early diagnosis. Serum and urinary biomarkers for melanoma diagnosis have especially received great interest because of the relative ease of sample collection and handling. Several serum and urinary biomarkers appear to have significant potential both as prognostic indicators and as targets for future therapeutic methods, but still there are no efficient serum and urinary biomarkers for early detection, accurate diagnosis and prognosis, efficient monitoring of the disease and reliable prediction of survival and recurrence. Levels of 5-S-cysteinyldopa (5SCD) in the serum or urine as biomarkers of melanoma have been found to be significantly elevated earlier and to reflect melanoma progression better than physical examinations, laboratory tests and imaging techniques, such as scintigraphy and echography. With recent developments in the treatment of melanoma, studies reporting combinations of 5SCD levels and new applications for the treatment of melanoma are gradually increasing. This review summarizes the usefulness of 5SCD, the most widely used and well-known melanoma marker in the serum and urine, compares 5SCD and other useful markers, and finally its application to other fields.

Japanese Dermatological Association Guidelines: Outlines of guidelines for cutaneous melanoma 2019.

With consideration of the ongoing developments in treatment options for cutaneous melanoma, the Japanese Skin Cancer Society published the first guidelines for cutaneous melanoma in 2007 and later revised them in 2015. Here, we report on an English version of the 2019 Japanese Melanoma Guidelines. In this latest edition, all processes were carried out according to the Grading of Recommendations, Assessment, Development and Evaluation system. A comprehensive published work search, systematic review and determination of recommendations in each clinical question were performed by a multidisciplinary expert panel consisting of dermatologists, a plastic and reconstructive surgeon, and a radiation oncologist. The advent of novel agents, such as immune checkpoint inhibitors and molecular-targeted agents, has drastically changed the nature of treatment for adjuvant and advanced-stage diseases among melanoma patients worldwide. Additionally, recent reports of clinical trials regarding surgical procedures and a better understanding of molecular biology and tumor immunology in clinical types of melanoma have had an impact on clinical practise. Based on these viewpoints, eight relevant clinical questions were raised in this report that aim to help clinicians select the appropriate therapeutic approach.

Classification of 3097 patients from the Japanese melanoma study database using the American joint committee on cancer eighth edition cancer staging system.

BACKGROUND: The American Joint Committee on Cancer (AJCC) 8th Edition Cancer Staging System was implemented in 2018; however, it has not been validated in an Asian melanoma population. OBJECTIVE: The purpose of this study was to validate the new system using a cohort of Japanese melanoma patients. METHODS: The AJCC 7th and 8th Editions were used for TNM classification of patients in a database established by the Japanese Melanoma Study Group. Patient data with sufficient information to be applicable to the AJCC 8th staging were selected. The Kaplan-Meier method was used to estimate disease-specific survival and relapse-free survival. RESULTS: In total, data for 3097 patients were analyzed. The 5-year disease-specific survival according to the 7th and 8th Edition staging system were as follows: IA = 98.5%/97.9%; IB = 95.4%/96.2%; IIA = 94.2%/94.1%; IIB = 84.6%/84.4%; IIC = 72.2%/72.2%; IIIA = 76.2%/87.5%; IIIB = 60.7%/72.6%; IIIC = 42.0%/55.3% and IIID = none/26.0%. The 5-year relapse-free survival according to the 7th and 8th Edition staging was as follows: IA = 94.5%/92.7%; IB = 85.4%/85.3%; IIA = 80.1%/79.4%; IIB = 71.4%/70.6%; IIC = 56.8%/55.7%; IIIA = 56.8%/69.4%; IIIB = 42.6%/56.8%; IIIC = 20.0%/33.3% and IIID = none/6.5%. CONCLUSION: The results show that new staging system could efficiently classify our Japanese melanoma cohort. Although there was no difference in Stage I and II disease between the 7th and 8th Edition systems, we should be careful in managing Stage III disease since the survival curves of the 8th Edition staging were completely different from the 7th Edition. Moreover, our results indicate that adjuvant therapies for Stage IIB and IIC should be developed, since the relapse-free survival for these stages were equivalent to Stage IIIA and IIIB, respectively.

Clinical and histopathological characteristics and survival analysis of 4594 Japanese patients with melanoma.

BACKGROUND: The incidence of melanoma among those of an Asian ethnicity is lower than in Caucasians; few large-scale Asian studies that include follow-up data have been reported. OBJECTIVES: To investigate the clinical characteristics of Japanese patients with melanoma and to evaluate the prognostic factors. METHODS: Detailed patient information was collected from the database of Japanese Melanoma Study Group of the Japanese Skin Cancer Society. The American Joint Committee on Cancer seventh Edition system was used for TNM classification. The Kaplan-Meier method and Cox proportional hazards model were used to estimate the impact of clinical and histological parameters on disease-specific survival in patients with invasive melanoma. RESULTS: In total, 4594 patients were included in this analysis. The most common clinical type was acral lentiginous melanoma (40.4%) followed by superficial spreading melanoma (20.5%), nodular melanoma (10.0%), mucosal melanoma (9.5%), and lentigo maligna melanoma (8.1%). The 5-year disease-specific survival for each stage was as follows: IA = 98.0%, IB = 93.9%, IIA = 94.8%, IIB = 82.4%, IIC = 71.8%, IIIA = 75.0%, IIIB = 61.3%, IIIC = 41.7%, and IV = 17.7%. Although multivariate analysis showed that clinical classifications were not associated with survival across all stages, acral type was an independent poor prognostic factor in stage IIIA. CONCLUSIONS: Our study revealed the characteristics of melanoma in the Japanese population. The 5-year disease-specific survival of each stage showed a similar trend to that of Caucasians. While clinical classification was not associated with survival in any stages, acral type was associated with poor survival in stage IIIA. Our result might indicate the aggressiveness of acral type in certain populations.

Clinical and Histopathologic Characteristics of Melanocytic Lesions on the Volar Skin Without Typical Dermoscopic Patterns.

Importance: It is challenging to differentiate melanoma from melanocytic nevus on the volar skin in the absence of typical dermoscopic patterns. Objective: To identify the frequency and clinical and dermoscopic characteristics of melanocytic lesions on the volar skin not displaying a parallel furrow pattern, lattice-like pattern, fibrillar pattern, or parallel ridge pattern on results of dermoscopy. Design, Setting, and Participants: In this retrospective cohort study, a total of 504 melanocytic lesions on the volar skin were evaluated in the Shinshu University Hospital department of dermatology between January 1, 2000, and December 31, 2012. Dermoscopic images were independently assessed by 3 dermoscopists for the presence of established dermoscopic criteria. Statistical analysis was performed from October 1, 2017, to April 30, 2018. Main Outcomes and Measures: Frequency of dermoscopic criteria and corresponding clinical (patient age and size and location of lesion) and histopathologic features. Results: Of 504 lesions, 110 (21.8%) (melanocytic nevus, 97; melanoma, 8; and equivocal melanocytic lesion, 5) from 108 patients (68 female and 40 male patients; mean age, 40.1 years [range, 1-86 years]) did not show a parallel furrow pattern, lattice-like pattern, fibrillar pattern, or parallel ridge pattern. Among them, the mean patient age was significantly higher for melanoma than for melanocytic nevus (65.3 vs 38.0 years; P < .001), as was mean maximum lesion diameter (11.8 vs 5.7 mm; P < .001). Melanomas and equivocal melanocytic lesions tended to be distributed on weight-bearing areas of the foot sole, such as the heel, while nevi were spread over non-weight-bearing regions. Dermoscopically, 95 melanocytic nevi (97.9%) were symmetrical in 1 or 2 axes while melanomas were not. A total of 91 melanocytic nevi (93.8%) had 1 or 2 colors per lesion, and 4 melanomas (50.0%) had more than 2 colors. Vascular structures were seen in 3 melanocytic nevi (3.1%) and 3 melanomas (37.5%). Blue-white structures were seen in 18 melanocytic nevi (18.6%) and 3 melanomas (37.5%). Dots and globules were seen in 22 melanocytic nevi (22.7%) and 4 melanomas (50.0%). Vascular structures, blue-white structures, and dots and globules were irregularly distributed in the melanomas. Ulcer, hyperkeratosis, and irregular streaks were observed only in melanomas. Conclusions and Relevance: More than one-fifth of melanocytic lesions on the volar skin did not display typical dermoscopic patterns. Asymmetry, numerous colors (≥3), and other melanoma-specific dermoscopic findings were more frequently observed for melanomas. Clinical information, including patient age and lesion size and location, was helpful in differentiating melanoma from melanocytic nevus. Further prospective clinical studies are warranted to clarify the diagnostic accuracy of dermoscopy combined with clinical information.

Serum 5-S-cysteinyldopa behavior in the early phase of nivolumab treatment of 12 melanoma patients.

Along with the expansion of therapeutic options for metastatic melanoma, the development of useful biomarkers is urgently required to predict and monitor treatment response. Serum 5-S-cysteinyldopa (5-S-CD) has been identified as a diagnostic marker of malignant melanoma, but its utility as a biomarker for emerging therapeutic agents remains unknown. We assessed serum 5-S-CD in 12 metastatic melanoma patients (median age, 76 years; six men and six women) who had been treated with nivolumab (Nivo) at Shinshu University Hospital between 2014 and 2016. Serum 5-S-CD and lactate dehydrogenase levels before and at 3-6 weeks of Nivo treatment were obtained and their changes were compared with clinical responses as defined by the Response Evaluation Criteria in Solid Tumors criteria (version 1.1). A decrease of 10 nmol/L or more of serum 5-S-CD was observed only in partial response patients (2/3 cases, 67%), while an increase of 10 nmol/L or more of serum 5-S-CD was witnessed only in progressive disease patients (4/8 cases, 50%). Serum 5-S-CD changes were within ±10 nmol/L in the remaining six patients (partial response, one; stable disease, one; progressive disease, four). The results of the four moderately affected progressive disease patients were suspected to have been influenced by small-sized metastatic lesions, a mixed response that included diminished and enlarged metastatic lesions, prior therapy to Nivo with BRAF inhibitors or radiation, or the development of brain metastasis. Serum 5-S-CD in the early phase of Nivo treatment may be helpful to predict therapeutic response in metastatic melanoma.