Nodular Cutaneous Amyloidosis at the Temple Schucht, Kathrin; Schröder, Josef; Siegmund, Heiko ...
Case reports in dermatology,
07/2016, Letnik:
8, Številka:
2
Journal Article
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A 52-year-old woman presented with a large partially yellow and erythematous tumor on her right temple. She reported that it had grown over the last 4 years. Regional lymph nodes were impalpable. A ...punch biopsy showed eosinophilic material in the dermis and subcutis. Immunohistochemistry showed positive staining for kappa and lambda light chains. Electron microscopy showed the typical amyloid fibrils (7–10 nm in diameter). There was no evidence of systemic amyloidosis, paraproteinemia or underlying plasmacytoma. The tumor was completely removed via curettage. At follow-up, the patient presented in good health with no signs of relapse.
A 50-year-old man presented with congenital scaling and hyperkeratosis on his palms, the soles of his feet and the extensor areas of his joints. The flexural areas were unaffected. His maternal ...grandmother, questionably his maternal uncle, his mother, all three brothers, one of his two sisters as well as two nephews and three nieces have or had similar skin changes. A punch biopsy was taken from the left palm. Clinical and histological signs led to the diagnosis of erythrodermia congenitalis ichthyosiformis bullosa of Brocq. We confirmed this genetically and found a heterozygous duplication (c.1752dupT) in the keratin 1 gene (KRT-1). To our knowledge, this is the first case of this skin condition reported in the literature with a heterozygous duplication (c.1752dupT) in KRT-1.
Elevated lactate dehydrogenase A (LDHA) expression is associated with poor outcome in tumor patients. Here we show that LDHA-associated lactic acid accumulation in melanomas inhibits tumor ...surveillance by T and NK cells. In immunocompetent C57BL/6 mice, tumors with reduced lactic acid production (Ldhalow) developed significantly slower than control tumors and showed increased infiltration with IFN-γ-producing T and NK cells. However, in Rag2–/–γc–/– mice, lacking lymphocytes and NK cells, and in Ifng–/– mice, Ldhalow and control cells formed tumors at similar rates. Pathophysiological concentrations of lactic acid prevented upregulation of nuclear factor of activated T cells (NFAT) in T and NK cells, resulting in diminished IFN-γ production. Database analyses revealed negative correlations between LDHA expression and T cell activation markers in human melanoma patients. Our results demonstrate that lactic acid is a potent inhibitor of function and survival of T and NK cells leading to tumor immune escape.
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•Human melanoma metastases exhibit a “Warburg phenotype” with high lactic acid levels•LDHA-associated lactic acid production and acidification lead to immune evasion•Lactic acid and acidification diminish NFAT levels and T and NK cell activation•LDHA expression in melanoma patients correlates with survival and T cell activity
Brand et al. link altered tumor glucose metabolism and immune escape and show that increased lactic acid production by LDHA in cancer cells impairs cytokine production, in particular IFN-γ, in tumor-infiltrating T cells and NK cells, thereby inhibiting tumor immunosurveillance and promoting tumor growth.
The proton-sensing GPCRs (pH-GPCRs) GPR4 (GPR19), TDAG8 (GPR65, T-cell death associated gene 8), OGR1 (GPR68, ovarian cancer GPCR1), and G2A (GPR132, G2 accumulation protein) are involved in sensing ...and transducing changes in extracellular pH (pH
). Extracellular acidification is a central hallmark of solid cancer. pH-GPCR function has been associated with cancer cell proliferation, adhesion, migration and metastasis, as well as with modulation of the immune system. Little is known about the expression levels and role of pH-GPCRs in skin cancer. To better understand the functions of pH-GPCRs in skin cancer in vivo, we examined the expression-profiles of GPR4, TDAG8, OGR1 and G2A in four common skin tumors, i.e. squamous cell carcinoma (SCC), malignant melanoma (MM), compound nevus cell nevi (NCN), basal cell carcinoma (BCC). We performed immunohistochemistry and immunofluorescence staining on paraffin-embedded tissue samples acquired from patients suffering from SCC, MM, NCN or BCC. We show the expression of pH-GPCRs in four common skin cancers. Different expression patterns in the investigated skin cancer types indicate that the different pH-GPCRs may have distinct functions in tumor progression and serve as novel therapeutic targets.
A 59-year-old man with chronic renal failure and diabetes mellitus presented with pruritic crusted lesions which histologically were perforating disorders, showing features of both Kyrle disease and ...acquired perforating collagenosis. The mechanisms of transepidermal elimination and the classification of perforating disorders are briefly discussed. Additionally, we question the concept of perforation, as epidermal damage and exposure of subepidermal substances may artificially present as perforation.
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