Despite remarkable progress in melanoma therapy, the exceptional heterogeneity of the disease has prevented the development of reliable companion biomarkers for the prediction or monitoring of therapy responses. Here, we show that difficulties in detecting blood-based markers, like circulating tumor cells (CTC), might arise from the translation of the mutational heterogeneity of melanoma cells towards their surface marker expression. We provide a unique method, which enables the molecular characterization of clinically relevant CTC subsets, as well as circulating tumor DNA (ctDNA), from a single blood sample. The study demonstrates the benefit of a combined analysis of ctDNA and CTC counts in melanoma patients, revealing that CTC subsets and ctDNA provide synergistic real-time information on the mutational status, RNA and protein expression of melanoma cells in individual patients, in relation to clinical outcome.

Calciphylaxis is a rare and potentially life-threatening disease which occurs most frequently in end-stage renal disease. Here, we describe a 69-year-old male patient who presented to the clinic with extremely painful necrotic ulcers of the right lower extremity. His risk factors included hypertension, diabetes mellitus type II, steatosis hepatis, and chronic hepatitis B. Laboratory studies revealed no signs for uremia, hyperparathyroidism, and normal phosphorus as well as calcium levels. A diagnosis of nonuremic calciphylaxis was made in correlation with clinical and histological features. A novel therapeutic approach combining sodium thiosulfate and iloprost showed remarkable improvement of the wound-associated pain and healing of the ulcers within 3 months. Due to its high mortality rate, an early diagnosis and initiation of treatment are crucial to be beneficial for patient outcomes.