Angiosarcoma of the Auricle in a Patient with Xeroderma Pigmentosum Variant.

Xeroderma pigmentosum (XP) is an inherited autosomal recessive disorder characterized by photosensitivity and an increased risk of developing multiple skin neoplasms at sites exposed to the sun. We report a 73-year-old Japanese man with angiosarcoma of the auricle and an XP-variant, which is a very rare condition. In this case, long-term physical stimulation due to auricular deformation after surgery may have been the cause. Angiosarcoma associated with XP has a better prognosis than common angiosarcoma, perhaps because of the smaller tumor size. As XP patients are at high risk of skin neoplasms, they consult dermatologists regularly, and therefore skin tumors are likely to be detected early.

A Case of Cellular Fibrous Histiocytoma on the Right Elbow with Repeated Relapse within a Short Period.

Cellular fibrous histiocytoma, a variant of fibrous histiocytoma, is a designation used for lesions showing increased cellularity with a fascicular growth pattern and frequent extension into the subcutis. Here we describe a case of cellular fibrous histiocytoma showing repeated recurrence in a 36-year-old woman who initially presented with a 2-cm cutaneous tumor on her right elbow. Histopathologically, the first resected specimen demonstrated irregularly arranged collagen fibers mixed with scattered proliferating plump to spindle-shaped fibrohistiocytes. However, examination of the resected specimens obtained after recurrence showed that the cellularity had increased, the spindle-shaped cells showing monomorphic proliferation with a fascicular and storiform growth pattern extending into the subcutis, as well as an increase of Ki-67 positivity. Since the lesion showed repeated relapse within a short period, we performed wide-field resection of the tumor with a 3-cm margin. Currently, 48 months after surgery, there has been no local recurrence or metastasis, but continuous strict follow-up will be necessary.

A Case of Basal Cell Carcinoma with Outer Hair Follicle Sheath Differentiation.

A 70-year-old Japanese man presented at our hospital with an asymptomatic, blackish, irregularly shaped plaque with a gray nodule in the periphery on his left lower leg. The lesion had been present for 10 years and had recently enlarged, associated with bleeding. Histopathologically, the tumor consisted of three distinct parts: The first part showed massive aggregation of basophilic basaloid cells with peripheral palisading and abundant melanin granules, and was diagnosed as solid-type basal cell carcinoma. The second part showed aggregation of clear cells with squamous eddies, and was diagnosed as proliferating trichilemmal tumor. The third part showed reticular aggregation of basaloid cells with infundibular cysts in the papillary dermis, and was diagnosed as infundibulocystic basal cell carcinoma. We diagnosed this tumor as basal cell carcinoma with various forms of hair follicle differentiation, including differentiation into the outer root sheath.

Immunohistochemistry for histone h3 lysine 9 methyltransferase and demethylase proteins in human melanomas.

Methylation and demethylation of histone H3 lysine 9 (H3K9) play a role in the transcriptional regulation of several cancer-related genes and are closely associated with malignant tumor behavior. A novel study has recently demonstrated that SETDB1, a member of the H3K9 methyltransferases, accelerates tumor formation significantly in a zebrafish melanoma model. However, the expression of H3K9 methyltransferases including SETDB1 and demethylases has not been systematically examined in samples of human melanoma. Here, we used immunohistochemistry to examine the expression of the H3K9 methyltransferases, EHMT2 and SETDB1, and a H3K9 demethylase, LSD1, in 67 patients with melanoma. Overexpression of EHMT2, SETDB1, and LSD1 was observed in 14 (21%), 38 (57%), and 53 (79%) of the 67 patients, respectively. A significant relationship was observed between overexpression of EHMT2 or SETDB1 and aggressive tumor behavior such as lymph node metastasis and/or distant metastasis (P < 0.05), whereas no significant relationship was evident for LSD1 immunoreactivity. Univariate log-rank tests demonstrated that patients with melanoma overexpressing EHMT2 had a poorer outcome (P < 0.001), whereas overexpression of SETDB1 or LSD1 had no prognostic impact. These results suggest that overexpression of EHMT2 might be a prognostic marker in patients with melanoma.

Improvement of pustulosis palmaris et plantaris by periodontal infection control in a patient with chronic periodontitis.

BACKGROUND: Pustulosis palmaris et plantaris (PPP) is a chronic, inflammatory, autoimmune-type disease characterized by sterile pustules of skin. The skin inflammation is influenced by several factors such as drugs, sunlight, metabolic and psychogenic factors as well as metal allergy. Here, we report a rare case that intensive periodontal treatment might have contributed to the improvement of skin inflammation. RESULTS: Skin inflammation regressed 1 month after intensive periodontal treatment. Both CD4/CD8 ratio and % of B cells in the blood sample were slightly decreased corresponding to the improvement of periodontal inflammation. CONCLUSIONS: Infection control of periodontal lesions might be one of attractive therapeutic targets in management of PPP.

Nucleus accumbens-associated 1 contributes to cortactin deacetylation and augments the migration of melanoma cells.

We investigated the prognostic significance and post-transcriptional acetylation-modification of cortactin (CTTN) via the nucleus accumbens-associated 1 (NACC1)-histone deacetylase 6 (HDAC6) deacetylation system in primary melanomas and melanoma cell lines. Overexpression of CTTN protein was observed in 56 (73%) of 77 stage I-IV melanomas, and was significantly correlated with tumor thickness, lymph node metastasis, distant metastasis, and disease outcome. The patients whose tumors exhibited CTTN overexpression had a poorer outcome than patients without this feature (P=0.028, log-rank test). NACC1 and CTTN proteins, but not HDAC6, were overexpressed in four melanoma cell lines in comparison with a primary culture of normal human epidermal melanocytes. Knockdown of both NACC1 and HDAC6 markedly downregulated the migration activity of all melanoma cell lines (P<0.05), and induced a gain of CTTN protein acetylation status. Confocal microscopy showed that hyperacetylation of CTTN modulated by depletion of both NACC1 and HDAC6 induced disappearance of CTTN protein at the leading edge of migrating cells, resulting in stabilization of the focal adhesion structure and development of actin stress fibers. These data suggest that the acetylation status of CTTN modulated by the NACC1-HDAC6 deacetylation system induces acceleration of melanoma cell migration activity via an actin-dependent cellular process, possibly contributing to aggressive behavior (invasion/metastasis) of the melanoma cells.

Multiple vascular eccrine spiradenomas: a case report and published work review of multiple eccrine spiradenomas.

Eccrine spiradenoma (ES) usually occurs as a solitary small nodule. It presents rarely as multifocal or multiple localized tumors arranged in a linear, zosteriform or nevoid distribution. We present a rare case of a 55-year-old woman who had a 48-year history of multiple vascular eccrine spiradenomas (VES) localized on the left side of the submandibular region and neck. All five tumors were skin-colored or pinkish-purple, and ranged in size 1.5-2.5 cm. Histologically, each tumor was composed of two characteristic cell types and many dilated vascular spaces were noted in the stroma. Contrast-enhanced computed tomography showed irregularly shaped, enhanced areas at the center of the tumors. A published work search revealed 35 cases of multiple ES, but multiple VES was extremely rare. We summarized the features of previously reported multiple ES and discuss the clinical and histological classification of ES.

Loss of class III beta-tubulin induced by histone deacetylation is associated with chemosensitivity to paclitaxel in malignant melanoma cells.

Overexpression of class III beta-tubulin (TUBB3) is an important mechanism of taxane resistance. Using 7 melanoma cell lines, 2 normal neonatal human epidermal melanocyte (NHEM) cultures, and 49 primary melanomas, we investigated TUBB3 expression, its relationship to chemosensitivity to taxane derivatives, and the epigenetic mechanism controlling TUBB3 gene expression. Normal melanocytes in vitro and in vivo strongly expressed TUBB3 protein. NHEMs exhibited marked chemoresistance to paclitaxel-induced apoptosis. A subset (10 of 49, 20%) of primary malignant melanomas was TUBB3 negative. The incidence of TUBB3-negative melanomas increased with stage of progression. TUBB3 protein expression varied among cell lines; one (HMV-I) of the seven cell lines exhibited an extremely low endogenous level. TUBB3 protein expression correlated well with chemosensitivity to paclitaxel-induced apoptosis (P<0.05). Treatment with a histone deacetylase (HDAC) inhibitor restored TUBB3 expression in HMV-I. Chromatin immunoprecipitation assays revealed that histones H3 and H4 were hypoacetylated at the TUBB3 gene in HMV-I as compared with a TUBB3-overexpressing cell type (HMV-II). Treatment with the HDAC inhibitor induced gain of histone acetylation only in HMV-I. These results suggest that loss of TUBB3 protein may be induced by histone deacetylation in a subset of malignant melanomas, and may be associated with chemosensitivity to taxane.

Vascular lesion in a patient of chronic active Epstein-Barr virus infection with hypersensitivity to mosquito bites: vasculitis induced by mosquito bite with the infiltration of nonneoplastic Epstein-Barr virus-positive cells and subsequent development of natural killer/T-cell lymphoma with angiodestruction.

This report describes a vasculitis and subsequently developing angiodestructive lymphoma in an 11-year-old Japanese-Filipino girl exhibiting mosquito allergy with the background of chronic active Epstein-Barr virus (EBV) infection. She developed necrotic skin ulcer at the site of mosquito bite, and histopathological examination revealed EBV-positive mononuclear cell infiltration throughout the wall of small-sized muscular artery. These EBV-positive lymphoid cells were oligoclonal in Southern blot analysis for EBV terminal repeats. Effectiveness of steroid therapy also supports the nonneoplastic nature. Approximately 1 year later, she developed progressive large skin ulcer without mosquito bites. Microscopically, the angiocentric or angiodestructive pattern of EBV-positive atypical cells supported the diagnosis of extranodal natural killer/T-cell lymphoma. Southern blot analysis revealed the monoclonal neoplastic nature of EBV-positive cells. In contrast to the primary mosquito bite lesion, natural killer/T-cell lymphoma cells exhibited the higher expression of EBV latent membrane protein 1 mRNA and the apparent protein expression detected by immunohistochemistry.

Glucosyldiacylglycerol enhances reciprocal activation of prourokinase and plasminogen.

Reciprocal activation of prourokinase (pro-u-PA) and plasminogen is an important mechanism in the initiation and propagation of local fibrinolytic activity. We found that glucosyldiacylglycerol (GDG) enhanced the reciprocal activation by 1.5- to 2-fold at 0.7-16 microM, accompanying increased conversions of both zymogens to active two-chain forms. The reciprocal activation system consists of (i) plasminogen activation by pro-u-PA to form plasmin, (ii) pro-u-PA activation by the resulting plasmin to form two-chain u-PA (tcu-PA), and (iii) plasminogen activation by the resulting tcu-PA. Whereas GDG minimally affected steps (ii) and (iii) in isolated systems, it markedly enhanced step (i) in the absence of the conversion of pro-u-PA to tcu-PA. GDG significantly increased the intrinsic fluorescence of pro-u-PA (6.7%), but not that of tcu-PA or plasminogen. The large change in intrinsic fluorescence suggests that GDG selectively affects pro-u-PA to alter its conformation, and this mechanism may account for enhancement of its intrinsic plasminogen activator activity.