Cutaneous sarcoma: a review and practical approach to management.

Sarcomas arising in the skin are rare but potentially fatal. These tumours originate from mesenchymal cells and can be divided between those that arise in soft tissue and those arising from bone. General guidelines exist for the management of soft-tissue sarcomas; however, there are no specific guidelines for cutaneous sarcomas. Current literature was reviewed for management of seven cutaneous sarcomas including atypical fibroxanthoma, pleomorphic dermal sarcoma, dermal and subcutaneous leiomyosarcoma, dermatofibroma sarcoma protuberans, Kaposi sarcoma, cutaneous angiosarcoma and malignant peripheral nerve sheath tumour. All suspected sarcomas should be discussed in a sarcoma multidisciplinary team meeting. This article is not a clinical guideline but should serve as a practical summary of how these tumours present, how they are recognized histologically, and how best to manage and follow-up patients. The aim is to support clinicians and facilitate the best and most evidence-based standard of care available.

Impaired neutrophil extracellular trap formation: a novel defect in the innate immune system of aged individuals.

Neutrophil extracellular traps (NETs) are a recently discovered addition to the defensive armamentarium of neutrophils, assisting in the immune response against rapidly dividing bacteria. Although older adults are more susceptible to such infections, no study has examined whether aging in humans influences NET formation. We report that TNF-α-primed neutrophils generate significantly more NETs than unprimed neutrophils and that lipopolysaccharide (LPS)- and interleukin-8 (IL-8)-induced NET formation exhibits a significant age-related decline. NET formation requires generation of reactive oxygen species (ROS), and this was also reduced in neutrophils from older donors identifying a mechanism for reduced NET formation. Expression of IL-8 receptors (CXCR1 and CXCR2) and the LPS receptor TLR4 was similar on neutrophils from young and old subjects, and neutrophils challenged with phorbol-12-myristate-13-acetate (PMA) showed no age-associated differences in ROS or NET production. Taken together, these data suggest a defect in proximal signalling underlies the age-related decline in NET and ROS generation. TNF-α priming involves signalling through p38 MAP kinase, but activation kinetics were comparable in neutrophils from young and old donors. In a clinical setting, we assessed the capacity of neutrophils from young and older patients with chronic periodontitis to generate NETs in response to PMA and hypochlorous acid (HOCL). Neutrophil extracellular trap generation to HOCL, but not PMA, was lower in older periodontitis patients but not in comparison with age-matched controls. Impaired NET formation is thus a novel defect of innate immunity in older adults but does not appear to contribute to the increased incidence of periodontitis in older adults.