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Background The pathogenesis of infantile haemangioma ( IH) is unknown. Several mechanisms have been proposed, including hypoxia, which triggers upregulation and stabilization of hypoxia-inducible factor ( HIF)1α. HIF1α stimulates downstream transcription of target genes that enhance angiogenesis. Aim To identify possible involvement of hypoxia in the pathogenesis of IH, as hypoxia signalling constitutes a potential therapeutic target. Methods IH tissue samples collected during the period 1991-2011 (preserved in paraffin wax) were immunohistochemically analysed for HIF1α and the known HIF1α targets: BCL2/adenovirus E1B kD-interacting protein family member 3 (BNIP3), carbon anhydrase (CA)-IX, glucose transporter (GLUT)-1, phosphorylated protein kinase B ( pAKT), phosphorylated S6 protein ( pS6) and vascular endothelial growth factor (VEGF). Four observers independently assessed the findings. Results Of the 10 IH samples, 2 appeared to be in the growth phase. In all samples, GLUT-1, BNIP3, pAKT and VEGF were positive, CA-IX was weakly positive, and HIF1α was negative. pS6 was positive in 9/10 cases and negative in 1/10. Conclusions Several factors implicated in hypoxia-induced angiogenesis may be involved in IH development. However, the small sample size and retrospective approach of the study preclude definitive conclusions. Prospective studies are needed to conclusively determine which of the factors involved in the (hypoxia) cascade are required for an IH to grow, and could thus be a possible target of drugs for IH treatment. [ABSTRACT FROM AUTHOR]

The article describes the case of a 63-year-old Moroccan woman who developed soft, yellowish papules on the neck. Melanophages and a mild perivascular lymphocytic infiltration in the superficial dermis were identified, and fragmentation of elastic fibers in the reticular dermis and loss of elastic fibers in the papillary dermis were observed. The patient was diagnosed with Pseudoxanthoma elasticum-like papillary dermal elastolysis (PXE-PDE), a rare dermatological disorder.

In another prospective study, the PPV of an OCT diagnosis that was made with high confidence was only 80%, but the BCC prevalence in that study was also lower (58-2%) than in the present study (95-6%). Dear Editor, Clinical examination appears to be very sensitive for diagnosing basal cell carcinoma (BCC) (90%), but the specificity is reported to be low (28-6-48-9%).1,2 Additional use of dermoscopy can increase specificity to 54-3-55-6% compared with clinical examination alone.1,2 With use of optical coherence tomography (OCT), a noninvasive diagnostic method, in addition to clinical and dermoscopic examination, it is possible to further increase the specificity to 76% at a sensitivity of 95%.1,3,4 These results apply to a population of patients with a clinical suspicion of BCC who had an indication for biopsy (e.g. high-risk location or uncertainty about diagnosis). Before surgery, an OCT scan was obtained for study purposes and the OCT diagnosis did not influence the treatment decision. [Extracted from the article]

Under conditions of reduced tissue oxygenation, hypoxia-inducible factor (HIF) controls many processes, including angiogenesis and cellular metabolism, and also influences cell proliferation and survival decisions. HIF is centrally involved in tumour growth in inherited diseases that give rise to renal cell carcinoma (RCC), such as Von Hippel-Lindau syndrome and tuberous sclerosis complex. In this study, we examined whether HIF is involved in tumour formation of RCC in Birt-Hogg-Dubé syndrome. For this, we analysed a Birt-Hogg-Dubé patient-derived renal tumour cell line (UOK257) that is devoid of the Birt-Hogg-Dubé protein (BHD) and observed high levels of HIF activity. Knockdown of BHD expression also caused a threefold activation of HIF, which was not as a consequence of more HIF1α or HIF2α protein. Transcription of HIF target genes VEGF, BNIP3 and CCND1 was also increased. We found nuclear localization of HIF1α and increased expression of VEGF, BNIP3 and GLUT1 in a chromophobe carcinoma from a Birt-Hogg-Dubé patient. Our data also reveal that UOK257 cells have high lactate dehydrogenase, pyruvate kinase and 3-hydroxyacyl-CoA dehydrogenase activity. We observed increased expression of pyruvate dehydrogenase kinase 1 (a HIF gene target), which in turn leads to increased phosphorylation and inhibition of pyruvate dehydrogenase. Together with increased protein levels of GLUT1, our data reveal that UOK257 cells favour glycolytic rather than lipid metabolism (a cancer phenomenon termed the 'Warburg effect'). UOK257 cells also possessed a higher expression level of the L-lactate influx monocarboxylate transporter 1 and consequently utilized L-lactate as a metabolic fuel. As a result of their higher dependency on glycolysis, we were able to selectively inhibit the growth of these UOK257 cells by treatment with 2-deoxyglucose. This work suggests that targeting glycolytic metabolism may be used therapeutically to treat Birt-Hogg-Dubé-associated renal lesions. [ABSTRACT FROM AUTHOR]