Missense mutation of NRAS is associated with malignant progression in neurocutaneous melanosis.

Neurocutaneous melanosis (NCM) is a rare congenital neurocutaneous syndrome characterized by congenital melanocytic nevus of skin and abnormal proliferation of leptomeningeal melanocytes. Early acquisition of post-zygotic somatic mutations has been postulated to underlie the pathogenesis of NCM. The pathogenesis of NCM remains to be fully elucidated, and treatment options have not been established. Here, we report for the first time, multiregional genomic analyses in a 3-year-old autopsied girl with leptomeningeal melanomatosis associated with NCM, in which a ventriculo-peritoneal (VP) shunt was inserted for the treatment of hydrocephalus. The patient expired six months after the onset due to respiratory failure caused by abdominal dissemination via VP shunt. We performed multiregional exome sequencing to identify genomic differences among brain and abdominal tumors, nevus, and normal tissues. A total of 87 somatic mutations were found in 71 genes, with a significantly large number of gene mutations found in the tumor site. The genetic alterations detected in the nevus were only few and not shared with other sites. Three mutations, namely GNAQ R183Q, S1PR3 G89S and NRAS G12V, considered pathogenic, were found, although S1PR3 mutations have not been previously reported in melanocytic tumors. GNAQ and S1PR3 mutations were shared in both tumor and normal sites. Moreover, the mutant allele frequencies of the two mutations were markedly higher in tumor sites than in normal sites, with copy-neutral loss-of-heterozygosity (CN-LOH) occurring in tumor. NRAS mutation was found only in the abdominal tumor and was thought to be responsible for malignant progression in the present case. Multiregional comprehensive genetic analysis may lead to discovering novel driver mutations associated with tumorigenesis and targeted therapy.

Deep dermatophytosis caused by Trichophyton rubrum in an elderly patient with CARD9 deficiency: A case report and literature review.

Deep dermatophytosis is an invasive and sometimes life-threatening fungal infection mainly reported in immunocompromised patients. However, a caspase recruitment domain-containing protein 9 (CARD9) deficiency has recently been reported to cause deep dermatophytosis. Herein, we report the first Japanese case of deep dermatophytosis associated with CARD9 deficiency. An 80-year-old Japanese man with tinea corporis presented with subcutaneous nodules on his left sole. Histopathological findings revealed marked epithelioid cell granulomas with filamentous fungal structures in the deep dermis and subcutis, and the patient was diagnosed with deep dermatophytosis. Despite antifungal therapy, the subcutaneous nodule on his left sole gradually enlarged, his left calcaneal bone was invaded, and the patient finally underwent amputation of his left leg. Genetic analysis revealed a homozygous CARD9 c.586 A > G (p. Lys196Glu) variant, suggesting a CARD9 deficiency. Here, we discuss the clinical features of CARD9 deficiency-associated deep dermatophytosis with a case report and review of the literature.

Diagnostic accuracy of dermoscopy for 934 basal cell carcinomas: A single-center retrospective study.

Although the efficacy of dermoscopic diagnosis of basal cell carcinoma (BCC) has already been established, most studies have been conducted in Western countries. However, there are racial differences in the clinicopathological characteristics of BCC, highlighting the need for a survey among Asians. Herein, we aimed to investigate the diagnostic accuracy of dermoscopy in 934 Japanese patients with BCC and statistically analyze the clinicopathological factors affecting diagnostic accuracy. We analyzed 5093 skin lesions, including 934 BCCs that were diagnosed consecutively from 1998 to 2018. The sensitivity and specificity of dermoscopic diagnosis for BCC were calculated. The sensitivity and specificity of dermoscopic diagnosis were 92.2% and 96.0%, respectively. There were 73 false-negative cases of BCCs that were clinically diagnosed with other diseases. The most common incorrect clinical diagnosis was seborrheic keratosis (n = 18), followed by melanocytic nevus (n = 15). Multiple logistic regression analysis showed that sensitivity was significantly lower in BCCs located on the trunk and extremities, which showed low pigmentation (less than 10% of the lesion surface) and were diagnosed by a resident dermatologist. Experience of 3-6 months of 12 resident dermatologists revealed increased sensitivity. Dermoscopy is a reliable tool for the accurate diagnosis of BCC in Japanese individuals. Care should be taken when diagnosing BCCs of the trunk and extremities, and the less-pigmented subtype because of lower sensitivity. A certain amount of experience is required to improve the skills for dermoscopy.

A case of cutaneous syncytial myoepithelioma with extensive adipocytic metaplasia: Usefulness of EWSR1-PBX3 gene fusion analysis.

Cutaneous syncytial myoepithelioma (CSM) is a recently recognized variant of myoepithelioma characterized by an intradermal syncytial proliferation of spindled, ovoid, and histiocytoid cells. Immunohistochemically, tumor cells usually show strong expression of S-100 protein and epithelial membrane antigen (EMA). Here we report a case of CSM in the thigh of a 51-year-old Japanese woman. Histopathological findings showed a sheet-like growth of ovoid cells and histiocytoid cells with an eosinophilic syncytial cytoplasm, and adipocytic metaplasia was widely observed in the tumor. Immunohistochemical staining revealed a diffuse, strong pattern for EMA, smooth muscle actin (SMA), and HHF35, and variable expression of S-100 protein and p63 in ovoid and histiocytoid cells without significant mitotic figures or pleomorphism. In addition, EWSR1-PBX3 gene fusion, which is characteristic of CSM, was observed in the tumor. Based on these findings, we diagnosed the patient as having CSM. Our case shows that CSM can exhibit extensive adipocytic metaplasia, which could make its histopathological diagnosis challenging.

Case of cutaneous botryomycosis in an 8-year-old immunocompetent boy with a review of the published work.

Botryomycosis is a rare chronic suppurative granulomatous infection caused by several genera of non-filamentous bacteria. The clinical and histopathological findings are similar to those of mycetoma caused by true fungi or aerobic actinomycetes. Botryomycosis is divided into cutaneous and visceral disease, with the cutaneous form being more common. Histopathology shows granules of etiologic bacteria called "sulfur granules". Botryomycosis occurs more commonly among immunocompromised patients, although some cases have also been reported in immunocompetent patients. We report the case of an 8-year-old immunocompetent boy who visited our hospital with a 4-mm diameter subcutaneous tumor with mild tenderness on his right heel for several months. We surgically removed the tumor with an initial diagnosis of epidermal cyst. Histopathology showed sulfur granules surrounded by an eosinophilic matrix, indicating the Splendore-Hoeppli phenomenon. The granules consisted of Gram-positive cocci, leading to a diagnosis of botryomycosis. The patient was successfully treated by excision and oral trimethoprim/sulfamethoxazole (240 mg b.i.d.) for 2 weeks as adjuvant therapy. No recurrence was noted following treatment. The subcutaneous tumor in this case was smaller than the typical in botryomycosis infections. We reviewed the infection duration and tumor size in reported cases of botryomycosis in immunocompetent patients. Small tumor size may suggest that the case is in an early stage; therefore, it is important to remove and investigate these lesions proactively.

CADM1 is a diagnostic marker in early-stage mycosis fungoides: Multicenter study of 58 cases.

BACKGROUND: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. Early-stage MF patches or plaques often resemble inflammatory skin disorders (ISDs), including psoriasis and atopic dermatitis. Cell adhesion molecule 1 gene (CADM1), which was initially identified as a tumor suppressor gene in human non-small cell lung cancer, has been reported as a diagnostic marker for adult T-cell leukemia/lymphoma. OBJECTIVE: We investigated CADM1 expression in MF neoplastic cells, especially during early stages, and evaluated its usefulness as a diagnostic marker for MF. METHODS: We conducted a retrospective study by using immunohistochemical staining and confirmed the expression of CADM1 in MF. In addition, we compared CADM1 messenger RNA expression in microdissected MF samples and ISD samples. RESULTS: In the overall study period, 55 of 58 MF samples (94.8 %) stained positive for CADM1. None of the 50 ISD samples showed positive reactivity (P < .0001). We found CADM1 messenger RNA expression in the intradermal lymphocytes of patients with MF but not in those of patients with an ISD. LIMITATIONS: We did not conduct a validation study for MF cases in other institutions. CONCLUSIONS: CADM1-positive cells can be identified in early stages with fewer infiltrating cells and may be useful as a diagnostic marker for early-stage MF.

A case of pure red cell aplasia during nivolumab therapy for cardiac metastatic melanoma.

Nivolumab is an antibody against programmed cell death 1 and functions as an immune checkpoint inhibitor for various malignancies, including unresectable melanomas. Nivolumab causes several immune-related adverse events, which typically include skin rash, pneumonitis, thyroid dysfunction, hepatitis, and colitis; in rare cases, anemia may be present. There are several reports of autoimmune hemolytic anemia that has developed in response to nivolumab; however, there are few reports of pure red cell aplasia (PRCA). We describe a patient who developed PRCA during nivolumab administration. A 70-year-old Japanese woman received nivolumab for cardiac metastasis from malignant melanoma from an unknown site. Twenty-one months after nivolumab administration (31 courses), treatment was discontinued because she developed severe anemia. Blood test results indicated normocytic, normochromic anemia, and reticulocytopenia, but all other components were normal. Bone marrow aspiration showed increased megakaryocytes and decreased erythroblasts; these findings were consistent with PRCA. Anemia improved without recurrence after treatment with corticosteroids and blood transfusions. The steroid dosage was reduced gradually, and to date, the patient has not experienced recurrence of anemia. The tumor decreased in size and the patient has shown a continued response to treatment with decrease in disease for 3 years. Although it is unclear how nivolumab causes PRCA, hematological toxicities have been reported in patients treated with immunotherapy drugs. PRCA might be an unrecognized immune-mediated adverse event that did not manifest during the clinical trial phase.

Investigating the use of tie-over dressing after skin grafting.

Tie-over bolster dressing after skin grafting can prolong operative time, and cause hematoma and seroma formation because of uneven pressure application. To describe the possibility of discontinuing the use of tie-over dressing, we carried out a retrospective comparative study of patients who underwent skin grafting at an institution between January 2009 and December 2014. We investigated and compared the take rate, healing period, wound infection rate and hematoma formation rate for the tie-over dressing group and the non-tie-over dressing group. Among 266 patients, 148 and 118 patients were included in the tie-over dressing group and non-tie-over dressing group, respectively. There were no significant differences between the take rate, healing period, wound infection rate and hematoma formation rate for the two groups. Multivariate analysis showed that the complete graft take rate was not significantly influenced by tie-over dressing, age, sex, graft site, graft procedure and skin graft diameter. Although the use of tie-over dressing might remain necessary on sites with a free margin, including the eyelids, lips or nostrils, because of the difficulty in using tape fixation, the present study showed that alternative dressing with polyurethane foam is also useful in most cases of skin grafting.