No abstract

Pediatric melanoma is rare but increasing in incidence. Because early diagnosis and treatment improves prognosis, clinicians need to include it as a possible diagnosis when evaluating a pigmented lesion in a pediatric patient. Some risk factors for melanoma include xeroderma pigmentosum, giant congenital melanocytic nevi, dysplastic nevus syndrome, atypical nevi, many acquired melanocytic nevi, family history of melanoma, and immunosuppression. Definitive treatment is with surgical excision. Adjuvant therapies such as chemotherapy, immunotherapy, and radiation therapy can be used in advanced cases.

No abstract

Fas (CD95, APO-1, TNFRSF6) is a TNF receptor superfamily member that directly triggers apoptosis and contributes to the maintenance of lymphocyte homeostasis and prevention of autoimmunity. Although FADD and caspase-8 have been identified as key intracellular mediators of Fas signaling, it is not clear how recruitment of these proteins to the Fas death domain leads to activation of caspase-8 in the receptor signaling complex. We have used high-resolution confocal microscopy and live cell imaging to study the sequelae of early events in Fas signaling. These studies have revealed a new stage of Fas signaling in which receptor ligation leads to the formation of surface receptor oligomers that we term signaling protein oligomerization transduction structures (SPOTS). Formation of SPOTS depends on the presence of an intact Fas death domain and FADD but is independent of caspase activity. Analysis of cells expressing Fas mutations from patients with the autoimmune lymphoproliferative syndrome (ALPS) reveals that formation of SPOTS can be disrupted by distinct mechanisms in ALPS.