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Promising antitumor activities of nivolumab, a fully humanized IgG4 inhibitor antibody against the programmed death-1 protein, were suggested in previous phase 1 studies. The present phase 2, single-arm study ( JAPIC- CTI #111681) evaluated the antitumor activities of nivolumab and explored its predictive correlates in advanced melanoma patients at 11 sites in Japan. Intravenous nivolumab 2 mg/kg was given repeatedly at 3-week intervals to 35 of 37 patients enrolled from December 2011 to May 2012 until they experienced unacceptable toxicity, disease progression, or complete response. Primary endpoint was objective response rate. Serum levels of immune modulators were assessed at multiple time points. As of 21 October 2014, median response duration, median progression-free survival, and median overall survival were 463 days, 169 days, and 18.0 months, respectively. The overall response rate and 1- and 2-year survival rates were 28.6%, 54.3%, and 42.9%, respectively. Thirteen patients remained alive at the end of the observation period and no deaths were drug related. Grade 3-4 drug-related adverse events were observed in 31.4% of patients. Pretreatment serum interferon-γ, and interleukin-6 and -10 levels were significantly higher in the patients with objective tumor responses than in those with tumor progression. In conclusion, giving repeated i.v. nivolumab had potent and durable antitumor effects and a manageable safety profile in advanced melanoma patients, strongly suggesting the usefulness of nivolumab for advanced melanoma and the usefulness of pretreatment serum cytokine profiles as correlates for predicting treatment efficacy. [ABSTRACT FROM AUTHOR]

Subungual melanomas ( SUM) are rare, and amputation is often required. Non-amputative wide local excision ( WLE) of the nail unit with the periosteum of the distal phalanx, followed by skin graft, has been accepted for in situ or SUM of 0.5 mm or less thickness. However, previous reports have included a limited number of cases, and not all more than 0.5-mm thick SUM exhibit invasion or attachment to the distal phalanx. The aim of the present study was to investigate the local recurrence and prognosis for in situ, minimally invasive and invasive SUM that were treated using WLE. We retrospectively reviewed 50 patients with in situ ( n = 48) or minimally invasive SUM ( n = 2) ( in situ or minimally invasive group) and 12 patients with more than 0.5-mm thick invasive SUM (invasive group) who were treated using WLE. All patients survived the follow-up period (24-207 months), although four patients with in situ SUM experienced local recurrence at the lateral margin and re-excision was required. In the invasive group, no patients experienced local recurrence, although one patient (8.3%) developed nodal metastasis at 86 months and regional lymph node dissection was required. WLE may provide acceptable local control for in situ and intermediate thickness SUM, without compromising the vital prognosis. However, a larger randomized prospective study with long-term follow up is required to evaluate adequately the risks associated with a non-amputative WLE for in situ and invasive SUM. [ABSTRACT FROM AUTHOR]

Subungual melanoma ( SUM) is rare and represents approximately 2-3% and 20% of all cutaneous melanomas in Caucasians and Asians, respectively. Amputation has usually been performed for invasive SUM; however, not all invasive SUMs invade or attach to the distal phalanx. To investigate the possibility of non-amputative surgery for patients with invasive SUM, the distances between the deepest base of the melanoma cells and the bony surface in the surgical specimens of invasive SUM were measured. Thirty surgical specimens of invasive SUM were retrospectively reviewed. The contents of the specimens were as follows: 14 first toes, 10 thumbs, three second fingers, two third fingers, and one fifth finger. Four specimens showed bone invasion, and the tumor was attached to the bone in four specimens. The tumor-to-bone distance exceeded 0.9 mm in all the specimens with thicknesses <4 mm. In the non-ulcerated SUMs (nine specimens), only one SUM specimen showed bone attachment. There was a higher likelihood of bone attachment or invasion when tumor thickness (TT) exceeded 4 mm (Pearson chi-square test, P = 0.009; Fisher exact test, P = 0.004; student t test, 0.033). Univariate and multivariate analysis also revealed that thick TT had a statistically significant affect (odds ratio 1.807 and 1.865, 95% CI 1.11-3.01 and 1.11-3.13, P = 0.023 and 0.018). Non-amputative surgery may be possible for SUM tumors that are of intermediate-thickness. However, there has been little evidence demonstrating survival with non-amputative surgery for invasive SUM. A large, randomized, prospective clinical study is required to address this issue. [ABSTRACT FROM AUTHOR]

Lipomas are common, benign, small-sized, soft-tissue tumors. However, giant lipomas are uncommon and the tumor size can cause pain and nerve compression syndrome. The axilla is an extremely rare location for development of giant lipomas. We report two cases of axillary giant lipoma. A 47-year-old man (case 1) and a 42-year-old woman (case 2) presented with a large mass in the axillary region. Case 2 had tenderness in the shoulder and numbness in the upper arm. Magnetic resonance imaging of each tumor showed a homogenous soft-tissue mass in the axillary region, suggestive of lipoma. In case 2, the tumor extended from the axilla to the supraclavicular region and split and compressed the neurovascular bundle. Each lesion was successfully excised surgically without serious complications and recurrence. In case 2, the tenderness and numbness disappeared. Histologically, each lesion was composed of multilobulated, mature adipose cells, which led to a diagnosis of benign lipoma. Axillary giant lipoma is preferably excised surgically to avoid damage caused by tumor compression to the major vessels or nerves, to offer better local control and to establish a correct final diagnosis. [ABSTRACT FROM AUTHOR]

Mucoepidermoid carcinoma ( MEC) usually originates from the salivary glands. However, there has been no report on mucoepidermoid carcinoma of the columella. In this study, we report the case of a high-grade MEC of the columella that was successfully reconstructed after surgical resection with bilateral nasolabial flaps set up in a sandwich shape and an auricular cartilage graft. A 66-year-old man presented with a nodule on the columella. Histological findings were suggestive of a high-grade mucoepidermoid carcinoma. Wide excision was performed, and the defects of the columella and the nasal floor were reconstructed with bilateral nasolabial flaps set up in a sandwich shape and an auricular cartilage graft. The postoperative cosmetic result was good with excellent tissue texture. The reconstructed columella had an appropriate, not bulky, width as well as satisfactory height and depth. This reconstructive technique is particularly useful for correcting the large defect of the columella with nasal septum and/or nasal floor defects. [ABSTRACT FROM AUTHOR]

The standard technique using lymphoscintigraphy, blue dye and a gamma probe has established a reliable method for sentinel node biopsy for skin cancer. However, the detection rate of cervical sentinel lymph nodes ( SLN) is generally lower than that of inguinal or axillary SLN because of the complexity of lymphatic drainage in the head and neck region and the 'shine-through' phenomenon. Recently, indocyanine green fluorescence imaging has been reported as a new method to detect SLN. We hypothesized that fluorescence navigation with indocyanine green in combination with the standard technique would improve the detection rate of cervical sentinel nodes. We performed cervical sentinel node biopsies using the standard technique in 20 basins of 18 patients (group A) and using fluorescence navigation in combination with the standard technique in 12 basins of 16 patients (group B). The mean number of sentinel nodes was two per basin (range, 1-4) in group A and three per basin (range, 1-5) in group B. The detection rate of sentinel nodes was 83% (29/35) in group A and 95% (36/38) in group B. The false-negative rate was 6% (1/18 patients) in group A and 0% in group B. Fluorescence navigation with indocyanine green may improve the cervical sentinel node detection rate. However, greater collection of data regarding the usefulness of cervical sentinel node biopsy using indocyanine green is necessary. [ABSTRACT FROM AUTHOR]

Non-melanoma skin cancer is the most frequently occurring type of cancer worldwide and is caused by epidermal carcinogenesis and malignant progression that involve dysregulated expression of proto-oncogenes and tumor suppressor genes. The proto-oncogene pituitary tumor-transforming gene 1 ( PTTG1) is a ubiquitously expressed transcription factor that can promote enhanced proliferation of cultured epidermal keratinocytes. To investigate the potential roles of PTTG1 in epidermal carcinogenesis and malignant progression, the expression of PTTG1 was analysed by immunohistochemistry along with Ki67, keratin 10 (K10) and p53 in tissue samples of cutaneous squamous cell carcinomas ( SCC), actinic keratoses ( AK) and Bowen's disease ( BD). Expression levels of PTTG1 were compared among these disease groups to test for correlations with proliferation, differentiation capacity or the existence of mutated tumor suppressor genes in each disease group. In each disease group, the expression levels of PTTG1 correlated positively with those of Ki67, although the differentiation status, measured by K10 expression, did not show any correlation. In contrast, the existence of mutated p53 proteins showed a positive correlation only in the SCC group. Moreover, the expression levels of PTTG1 in SCC did not correlate with known prognostic factors such as TNM staging or tumor thickness. These results suggest that PTTG1 may represent a proliferation marker associated with mutated p53 proteins but is not an informative predictor of poor clinical outcomes in SCC. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type I ( NF1) is associated with typical hypervascular tumors, including neurofibroma, glioma, malignant peripheral nerve sheath tumors ( MPNST) and glomus tumors. Previously, we and other groups reported that neurofibromas showed high-level expression of vascular endothelial growth factor ( VEGF), a potent angiogenic factor involved in neovascularization. However, the molecular mechanism underlying the upregulation of VEGF in neurofibromas remains unclear. In this study, we examined the effects of Nf1 gene silencing on VEGF expression in Schwann cell and non-Schwann cell line and the upstream mTOR- HIF-1α - VEGF pathway in Schwann cell line. The results indicated that Nf1 gene silencing by lentiviral-mediated RNA interference resulted in elevated expression of VEGF, HIF-1α and phosphorylated mTOR at the protein level. The results obtained from Nf1 gene silencing in murine Schwann cell line analogously suggest that NF1 gene haploinsufficiency in human tumor Schwann cells may directly elicit upregulation of VEGF expression without the tumor microenvironment by activation of the mTOR- HIF-1α - VEGF pathway. We also showed that interleukin-6 is upregulated in Nf1 gene knock-down Schwann cells at the protein level. [ABSTRACT FROM AUTHOR]

Loricrin is a major component of the epidermal cornified cell envelope and is expressed only in terminally differentiated keratinocytes. This cell differentiation-specific expression pattern suggests specific regulatory mechanisms for activation of loricrin gene transcription in differentiated keratinocytes. Here, we identified a positive regulatory element in the proximal promoter region of the loricrin gene involved in activation of its expression in differentiated keratinocytes. A database search indicated that this sequence contained a GATA-3 binding motif. Constructs with point mutations in the GATA-3 binding motif showed decreased reporter activity, indicating that GATA-3 positively regulates loricrin gene transcription. Western blotting analysis indicated that GATA-3 is more abundant in differentiated than in undifferentiated keratinocytes. Cotransfection experiments indicated that GATA-3 activates transcription of the loricrin gene in a cooperative manner with c-Fos and Sp1. These findings indicate that GATA-3 contributes to keratinocyte differentiation-specific activation of loricrin gene transcription via interaction with c-Fos and Sp1. [ABSTRACT FROM AUTHOR]

Background Although basal cell carcinoma (BCC) is the most common type of skin cancer, the incidence of metastasis is exceedingly low. Objective Case presentation of a basal cell carcinoma arising on the dorsum of the foot with inguinal and pelvic lymph node metastases. Method Case presentation with literature review. Result On the basis of our review of Japanese literature, the risk factors for BCC metastasis are occurrence on the genitalia, diameter of more than 3 cm, deep invasion of tumor cells into extradermal structures, and infiltrative/morpheic histological type. Conclusion Although metastasis from BCC is extremely rare, the prognosis of metastatic BCC is often poor. Careful follow-up is recommended in cases with high risk factors. [ABSTRACT FROM AUTHOR]

Giant congenital blue nevus (GCBN) is rare and usually occurs on the scalp. Malignant blue nevus (MBN) is also rare and has a poor prognosis. We report a case of MBN arising in a GCBN on the back. There have been three previous reports of MBN associated with GCBN on the trunk; our case had the earliest onset of MBN arising in a GCBN. [ABSTRACT FROM AUTHOR]

Various microscopic classifications of metastatic sentinel lymph nodes (SLN) have been reported along with predictors of additional lymph node positivity and their correlations with the prognosis. The purpose of this study was to re-evaluate these classifications in the Japanese population. We selected the following three classifications, based on the procedural simplicity of the measurements: maximum diameter (maximum diameter of the largest tumor lesion in the SLN; <0.1, 0.1-1.0, >1.0 mm), invasion depth (depth of tumor invasion measured from the capsule in the SLN; SI ≤0.3 mm, SII >0.3 to ≤1.0 mm, SIII >1.0 mm), and microanatomic location (microanatomic location of the tumor deposits within the SLN; 'subcapsular', 'parenchymal', 'combined', 'multifocal', 'extensive'). A retrospective study, using prescribed survey forms, was carried out. Among the 450 patients, including the 149 cases with SLN metastasis, an additional lymph node positivity rate of 0% could be predicted only in patients with a maximum diameter category of less than 0.1 mm. As compared with that in the SLN metastasis-negative cases, however, the prognosis was poorer in cases with SLN metastasis, even those with lesions falling under the maximum diameter category of less than 0.1 mm, invasion depth category of SI (≤0.3 mm) and microanatomic location category of subcapsular. The prognosis is particularly poor for the microanatomic location category of extensive, which should thus be regarded as a macrometastasis. A prospective study with standardized procedures, including pathological evaluation, is needed in order to confirm our conclusion. [ABSTRACT FROM AUTHOR]

Ultraviolet (UV) radiation is one of the most important environmental factors involved in the pathogenesis of premature skin ageing, termed photoageing. The harmful effects of UV in photoageing are associated with the generation of reactive oxygen species, and cellular antioxidants act to prevent the occurrence and reduce the severity of UV-induced photoageing. The transcription factor Nrf2 and its cytoplasmic anchor protein, Keap1, are central regulators of the cellular antioxidant response. Here, we investigated the role of the Nrf2-Keap1 pathway in photoageing using nrf2 gene-deficient (nrf2-/-) mice. Our results indicated that UVB-irradiated nrf2-/- mice showed accelerated photoageing, such as coarse wrinkle formation, loss of skin flexibility, epidermal thickening and deposition of extracellular matrix in the upper dermis. In addition, nrf2-/- mice also showed an increase in cutaneous reactivity for the lipid peroxidation product 4-hydroxy-2-nonenal and a significant decrease in cutaneous glutathione level. These findings indicate that Nrf2 plays the important role in the protection against UVBinduced photoageing. [ABSTRACT FROM AUTHOR]

Background Reconstruction of vulvovaginal defects after tumor excision requires good-quality skin cover because of the cosmetic and functional importance of this region. Although numerous techniques for vulvovaginal reconstruction have been described, an ideal approach has yet to be widely accepted. Methods Seven gluteal-fold flaps advanced in a V-Y fashion were used to cover vulvovaginal defects in five patients who underwent surgical treatment for extramammary Paget's disease or carcinoma of the vulva. Results Each flap survived completely with no complication other than partial dehiscence in one case and temporary postoperative discomfort and pain upon sitting. None of the patients suffered from recurrence of the tumor. Conclusions In our experience, this flap is easily elevated, not bulky, and reliable because it is supplied by the internal pudendal artery and vein perforators without excessive skeletonization of the vascular pedicle, and it has matched local skin quality. In addition, it has minimal donor-site morbidity as the scar is concealed in the gluteal fold. It can cover medium-sized vulvovaginal defects after tumor excision. [ABSTRACT FROM AUTHOR]

Background Tumor lysis syndrome (TLS) is rare in the treatment of solid tumors, but it may occur in myelolymphoproliferative diseases. Methods A 58-year-old man with bulky metastatic melanoma of the liver was treated with transcatheter arterial infusion of cisplatin and embolization therapy. The patient developed classic signs of TLS within 24 h of chemotherapy, including acute renal failure. Results The patient was treated with aggressive hydration, allopurinol, and repeated hemodialysis. He gradually improved and his biochemical markers returned to normal. Conclusion TLS is an uncommon, but potentially life-threatening, complication in melanoma and other solid tumors. It is important for oncologists to recognize this complication and prevent its development if bulky metastatic disease and several pre-existing risk factors, such as multiple and bulky liver metastases, elevated lactate dehydrogenase, and hyperuricemia, are present. [ABSTRACT FROM AUTHOR]

We have demonstrated that dendritic cells (DCs) genetically modified to express tumor-associated antigens (TAAs) with retroviral vectors elicit more potential anti-tumor effect than those loaded with peptides because they can prime antigen-specific CD4+ T cells resulting in production of tumor-specific antibody. In this study, we showed the importance of antigen presentation via a major histocompatibility complex (MHC) class II molecule in cancer immunity against non-membrane bound TAAs such as the melanoma antigen gp100 by using DCs derived from MHC class II-deficient mice (C2KO). DCs were prepared by transduction of gp100 cDNA into haematopoietic progenitor cells obtained from C2KO followed by differentiation with cytokines (C2KO-gp/DCs). When C2KO-gp/DCs were inoculated into immunocompetent mice, the mice scarcely primed the antigen-specific Th1 cells and developed fewer CD8 T cells than did those inoculated with transduced DCs prepared from normal mice. The attenuated anti-tumor effect was also confirmed in a postimmunization setting where, while two of eight control mice eradicated the pre-existing melanoma cell line B16 (25%), no mice inoculated with C2KO-gp/DCs did. These results suggested not only the limitation of current protocols using MHC class I-restricted tumor peptides but also the usefulness of DCs expressing gp100 in vaccine therapy against melanoma. [ABSTRACT FROM AUTHOR]

Previous studies of epidermal-specific gene promoters suggested that a limited set of transcription factors regulate keratinocyte-specific and differentiation-specific gene expression in the epidermis. In the present study, we investigated the functional importance of AP-1- and Sp1-binding elements in the determination of cell type-specific and differentiation-specific gene expression by transient transfection into undifferentiated and differentiated keratinocytes as well as into various non-epidermal cell lines. Synthesized short AP-1- and/or Sp1-binding elements were inserted into a minimal reporter vector, and the artificial promoter containing both AP-1 and Sp1 elements showed high levels of transcriptional activity only when transfected into differentiated keratinocytes. Promoters containing either the AP-1 or the Sp1 motif alone showed little activity in any of the cells examined. We also found that close proximity of the Sp1 and AP-1 sites is essential for transcriptional activity, suggesting that the physical interaction between Sp1 and AP-1 factors is important for functional activity. These results clearly demonstrate that the combination of ubiquitously expressed transcription factors AP-1 and Sp1 confers keratinocyte specificity and differentiation specificity on the gene expression. Our findings also provide a simple model of the mechanisms underlying regulation of cell type-specific and cell differentiation-specific gene expression by ubiquitously expressed transcription factors. [ABSTRACT FROM AUTHOR]

Chloasma (melasma), an acquired hypermelanosis, is often recalcitrant to various treatments and an amenable, as well as safe, pigment-reducing modality is needed. We investigated that the reducing effect of proanthocyanidin, a powerful antioxidant, on chloasma in a one-year open design study. Proanthocyanidin-rich grape seed extract (GSE) was orally administered to 12 Japanese woman candidates with chloasma for 6 months between August 2001 and January 2002 and to 11 of these 12 for 5 months between March and July 2002. Clinical observation, L* value (lightening) and melanin index, and size (length and width) measurements of chloasma were performed throughout the study period. The first 6 months of GSE intake improved or slightly improved chloasma in 10 of the 12 women (83%, p < 0.01) and following 5 months of intake improved or slightly improved chloasma in 6 of the 11 candidates (54%, p < 0.01). L* values also increased after GSE intake (57.8 ± 2.5 at the start vs 59.3 ± 2.3 at 6 months and 58.7 ± 2.5 at the end of study). Melanin-index significantly decreased after 6 months of the intake (0.025 ± 0.005 at the start vs 0.019 ± 0.004 at 6 months) ( p < 0.01), and also decreased at the end of study (0.021 ± 0.005) ( p < 0.05). GSE is effective in reducing the hyperpigmentation of women with chloasma. The beneficial effects of GSE was maximally achieved after 6 months and these was no further improvement after this period. The latter GSE intake for 5 months may prevent chloasma from becoming worse prior to the summer season. GSE is safe and useful for improving chloasma. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Yoshida C, Kojima H, Ishigaki T, Katsura Y, Kaneko S, Suzukawa K, Hasegawa Y, Kawachi Y, Otsuka F, Nagasawa T. Association of pyoderma gangrenosum and sterile osteomyelitis in a patient having myelodysplastic syndrome with der(1;7)(q10;q10). Eur J Haematol 2004: 72: 149–153. © Blackwell Munksgaard 2004. Neutrophilic dermatoses such as Sweet's disease and pyoderma gangrenosum (PG) are occasionally associated with myelodysplastic syndrome (MDS). We present here a 67-yr-old male having PG and sterile osteomyelitis in association with underlying MDS (refractory anemia) and Crohn's disease. To establish the diagnosis of MDS, sternal bone marrow puncture was performed, which showed chromosomal abnormality containing der(1;7)(q10;q10). After the puncture, he suffered from gradually progressive skin ulceration, flare, and bone pain. Magnetic resonance imaging (MRI) of the sternum showed severe inflammation in the sternum and the overlying subcutaneous tissue. All of the cultures obtained from the wound were negative for both bacteria and fungus. Biopsy was performed from the antero-sternal skin lesion, which showed epidermal ulceration with prominent infiltration of neutrophils. He was thus diagnosed as having PG and sterile osteomyelitis, and was treated with prednisolone, which completely resolved the symptoms. We consider that the bone marrow aspiration in the present patient provoked PG and sterile osteomyelitis. As was previously reported by others, certain chromosomal abnormalities in MDS may be related with the development of neutrophilic dermatoses. [ABSTRACT FROM AUTHOR]

Antioxidants such as vitamins C and E have been reported to inhibit the progression of ultraviolet (UV) radiation-induced pigmentation in the skin of hairless mice. However, little is known of the lightening effect of proanthocyanidin, a powerful polyphenolic antioxidant, on UV-induced pigmentation of the skin. We investigated the lightening effect of oral administration of a proanthocyanidin-rich grape seed extract (GSE) using guinea pigs with UV-induced pigmentation. These pigmented guinea pigs were fed diets containing 1% GSE or 1% vitamin C (w/w) for 8 weeks. GSE-feeding had an apparent lightening effect on the guinea pigs’ pigmented skin. Histologic evaluation demonstrated a decrease in the number of 3,4-dihydroxyphenylalanine (DOPA)-positive melanocytes as well as 8-hydroxy-2′-deoxyguanosine (8-OHdG)-positive, Ki-67-positive, proliferating cell nuclear antigen (PCNA)-positive melanin-containing cells in the basal epidermal layer of the UV-irradiated skin in GSE-fed guinea pigs. In contrast, these parameters did not change in the skin of vitamin C-fed or control guinea pigs. GSE inhibited the activity of mushroom tyrosinase and also inhibited melanogenesis without inhibiting the growth of cultured B16 mouse melanoma cells. In conclusion, we demonstrated that oral administration of GSE is effective in lightening the UV-induced pigmentation of guinea pig skin. This effect may be related to the inhibition of melanin synthesis by tyrosinase in melanocytes and the reactive oxygen species (ROS)-related proliferation of melanocytes. [ABSTRACT FROM AUTHOR]

Abstract: We studied the expression of angiogenic factors (vascular endothelial growth factor, basic fibroblast growth factor, platelet-derived growth factor and hepatocyte growth factor) in cutaneous neurofibroma samples from patients with neurofibromatosis-1. Immunohistochemical staining and the reverse transcribed polymerase chain reaction (RT-PCR) method demonstrated that vascular endothelial and basic fibroblast growths factor are highly expressed in neurofibroma cells at both the protein and mRNA level. These data suggest that vascular endothelial and basic fibroblast growth factors may contribute to both the angiogenesis and hypervascularity of neurofibromas. [ABSTRACT FROM AUTHOR]

Disseminated superficial actinic porokeratosis (DSAP), skin lesions of which are known to he induced by ultraviolet (UV) light, does not develop into skin cancer as frequently as other types of porokeratosis (PK). To establish the cellular basis of this characteristic of DSAP, we examined the colony-forming ability of UVC light- or X-ray-irradiated cultured fibroblasts derived from DSAP patients' skin. Sensitivity to the lethal effects of UV light was not significantly different between 3 DSAP and 5 control cell strains. In contrast, DSAP cell strains were significantly hypersensitive to the lethal effects of X-radiation, although the sensitivity was less than that of cell strains from other types of PK patients. The results indicate that the actinic character of DSAP is not reflected in the cellular response to the lethal effects of UV light, but suggest that DSAP shares X-ray sensitivity, which is probably associated with the cancer-prone nature of PK. [ABSTRACT FROM AUTHOR]

Background. The patient with xeroderma pigmentosum provides an appropriate human model for the evaluation of tumor development and progression. Methods. We describe a patient with variant-type xero- derma pigmentosum who developed actinic keratoses, a squamous cell carcinoma, and its metastasis into a lymph node. DNA ploidy was measured and analyzed in cells of these tumors and the patient's sun-exposed as well as sun- shielded skin. Results. The sun-shielded skin showed a normal diploid DNA distribution pattern, while the sun-exposed skin had an increased number of hyperdiploid cells. The actinic keratosis showed further Increased hyperdiploid cells. The squamous cell carcinoma showed a large number of hyperdiploid cells and formed an aneuploid cell fraction. Histographically, the aneuploid cell fraction became more apparent and was revealed to be a major fraction in the metastatic squamous cell carcinoma. Conclusions. The changes in the DNA ploidy pattern well reflect the clinical and histologic characteristics of the respective skin conditions and likely provide the cellular basis for the sequential or stepwise carcinogenic process in the patient's xeroderma pigmentosum skin. Further studies are necessary to determine whether the present results explain the similar carcinogenic process in sun-damaged skin of the nonpredisposed general population. [ABSTRACT FROM AUTHOR]

Despite various studies, there are serious disagreements about the cellular differentiation of papillary eccrine adenoma. in the present study, 2 specimens of papillary eccrine adenoma were analyzed by immunohistochernical techniques, using a panel of monoclonal antibodies against keratins, to elucidate its differentiation. Histopathologically, the tumor was composed of multiple tubular structures lined by two or more layers of epithelial cells. The luminal cells of the tubules were flattened or cuboidal. The former were noted in large dilated tubules. The latter were usually observed in small-to-moderate-sized tubules, and formed intraluminal papillary projections in some tubules. Immunohistochemically, there were two kinds of cuboidal cells in the luminal layers of the tubules. Most of the large dilated tubules and some of the small-to-moderate-sized tubules expressed immunophenotypes similar to those of the eccrine dermal duct. The other tubular structures, including the small tubules resembling those of syringoma, expressed immunophenotypes similar to those of the transitional portions between the dermal ducts and the secretory segments of eccrine glands. From the above comparative studies, papillary eccrine adenoma is considered to differentiate towards the dermal duct and the transitional portions between the dermal ducts and the secretory segments of eccrine glands. [ABSTRACT FROM AUTHOR]

The article describes the case of a 38-year-old man who had an erythematous plaque with a progressive erythematous lesion on the glans penis. The patient was initially treated with topical application of imiquimod for six months which failed to resolve his condition. The tumor was surgically removed and the patient could urinate in standing position after two months following surgery.

Subcutaneous panniculitis-like T-cell lymphoma is an uncommon form of CD8-positive cytotoxic T-cell lymphoma of the skin that predominantly affects the subcutaneous tissue and is extremely rare in early childhood (<3 yrs). Here, we present an early pediatric case with an indolent form of subcutaneous panniculitis-like T-cell lymphoma occurring at 12 months old. The subcutaneous nodules gradually disappeared spontaneously, and the girl showed excellent prognosis with no aggressive treatment. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which focuses on a case study of a 13-year-old boy with multiple angiomatous nodules on the right arm, shoulder, back and chest.

A 33-year-old man (Case 1) developed scaling and erythema on the extensor side of his extremities, head, and back, 3 years before his first visit to our hospital. The lesions spread out to form several plaques and became persistent (Fig. 1a). Serum antistreptolysin O (ASO) was within the normal range and a pharyngeal culture showed normal flora. Histologic findings were compatible with psoriasis vulgaris (Fig. 1b). Topical steroid therapy was effective; however, scaling and erythema persisted. The 8-year-old daughter (Case 2) of Case 1 had suffered severe tonsillitis 2 months prior to the skin eruptions. Numerous rain drop-like scaly papules appeared on her legs and generalized rapidly (Fig. 2a). Her tonsils were swollen and reddish. Streptococcus pyogenes was detected by pharyngeal smear. The ASO value was at a high level. Histologic examination showed slightly elongated rete ridges, focal lack of the granular layer, parakeratosis, mild spongiosis, and exostosis of neutrophils (Fig. 2b). She was diagnosed with acute guttate psoriasis. Administration of oral antimicrobials reduced the ASO value and led to remission of the disease. After 1 month of antimicrobial treatment, the erythematous papules disappeared. The human leukocyte antigen (HLA) typing of the father was HLA-A24, A31, B7, B39, and Cw7, and that of the daughter was HLA-A24, A31, B39, and Cw7. Both possessed HLA-A24, B39, and Cw7. The HLA typing of other family members was also studied. The mother had HLA-A11, A24, B39, B62, Cw4, and Cw7, and her son had HLA-A11, A24, B7, B62, Cw4, and Cw7. The result of HLA typing is shown in Table 1. Lymphocyte stimulating test was performed using heat-killed S. pyogenes which were boiled at 70 °C for 10 min and sonicated. The stimulation index was twofold higher in the daughter than in the father (Fig. 3). [ABSTRACT FROM AUTHOR]

A letter to the editor about the case of a 65-year-old male patient with a history of metastatic angiosarcoma of the spleen associated with disseminated intravascular cuagulation (DIC) that was treated with docetaxel is presented.

We describe a female neonate with large flaccid pustules on her trunk and extremities. Cultures were negative, and a Wright-stained smear of pustule contents showed numerous eosinophils (>90%). The pustules resolved without leaving pigmentation after 2 weeks. We diagnosed this case as sterile transient neonatal pustulosis. [ABSTRACT FROM AUTHOR]

The linear arrangement of discoid lupus erythematosus is uncommon. Here, we report a 6-year-old Japanese girl with linear discoid lupus erythematosus following the lines of Blaschko on her face and neck. Topical tacrolimus treatment improved the eruptions. The present case also indicated the important role of epidermal and dermal cells as well as immune cells in the pathogenesis of cutaneous lupus erythematodes. [ABSTRACT FROM AUTHOR]

We report clinical findings in a 12-year-old girl with long-term recurrent and disseminated multiple eruptions of tinea faciei and tinea corporis, which persisted for 10 years. Mycological examination revealed the dermatophyte Trichophyton tonsurans in both scale samples from the body lesions and in brushing samples from her asymptomatic scalp, suggesting that she was an asymptomatic dermatophyte carrier on the scalp, and autoinoculation of the dermatophyte was responsible for the recurrent and disseminated tinea faciei/corporis. [ABSTRACT FROM AUTHOR]

Neutrophilic dermatoses (ND), with or without accompanying myelodysplastic syndrome (MDS), were examined in terms of nuclear abnormality like pelgeroid anomaly of infiltrating cells into skin lesions. Six ND accompanying MDS showed 1.0 to 13.5% of such anomalous cells among infiltrating cells. In contrast, ND without accompanying myeloproliferative disorders rarely had such anomalous cells. Our findings suggest that pelgeroid-like anomalous cells infiltaring into ND are probably a good marker of underlying MDS. [ABSTRACT FROM AUTHOR]

Kyrle disease, or hyperkeratosis follicularis et parafollicularis in cutem penetrans, is characterized by generalized prurigo-like keratotic papules. Association of this disease with diabetes mellitus, chronic renal failure, or hepatic disorder has been reported. Kyrle disease skin lesions were historically said to be recalcitrant to treatment, although more recently retinoids have been found to be beneficial or have been used successfully. Corticosteroid therapy, either topical or systemic administration, however, has been known to be ineffective in Kyrle disease.

A 32 year old Japanese male has had several synchronized attacks of psoriatic arthritis and hypopyon-iridocyclitis. During exacerbations, he has a leucocytosis with neutrophilia and elevated C-reactive protein. Assessment for adhesiveness, aggregation and deformation of peripheral neutrophils revealed strikingly high 'rheological activity', whereas during periods of remission the activity was only slightly elevated above normal. [ABSTRACT FROM AUTHOR]

Neurofibromas of neurofibromatosis 1 (NF1) are highly vascular. Because the number of PDGF beta receptors in neurofibroma-derived cultured cells (NF-derived cells) has been reported to be increased, we tested whether platelet-derived growth factor BB (PDGF-BB) could induce expression of vascular endothelial growth factor (VEGF) in NF-derived cells. When analysed by reverse transcription-polymerase chain reaction, VEGF mRNA expression was found to be stimulated by PDGF-BB and TGF-beta1. Those growth factors stimulated the secretion of VEGF from NF-derived cells. PDGF-BB furthermore induced the mitogen-activated protein kinase phosphorylation in NF-derived cells from patients with NF1. In conclusion, PDGF-BB stimulated VEGF secretion in NF-derived cells, and this stimulation is probably important in neurofibroma hypervascularization.