Subject and methodsAt age 48, a female VHL patient presented with pain in her left arm. She was diagnosed with VHL at age 25. Genetic testing of peripheral blood had confirmed a c.500G > A (p.Arg167Gln) VHL gene mutation. Her medical history included surgery for central nervous system hemangioblastomas at age 26, 28, 39 and 45 as well as a retinal hemangioma for which she underwent a coagulation procedure at age 26. Imaging studies suggested a lytic lesion in the left distal ulna (Fig. 1). A biopsy was taken that was suggestive of clear cell chondrosarcoma. Additional immunohistochemical analysis showed strong S-100 staining. Antibodies directed at cytokeratins 8, 18, AE1-3 and also inhibin, which are used for the identification of renal cell carcinoma or hemangioblastoma, were negative. Bone scintigraphy did not reveal any other bone lesions. Surgical resection resulted in complete removal of the tumor. Tumor tissue was frozen after surgery. DNA was isolated and after PCR amplification the VHL gene locus was analyzed by Sanger sequencing [3]. In addition, tumor DNA was subjected to comprehensive genetic and epigenetic analysis using an Ion Ampliseq Cancer Hotspot v2 panel (Thermo Fisher Scientific), Infinium CytoSNP-850 K and Infinium MethylationEPIC-850 K beadchip (Illumina). In parallel, tissue was processed for immunohistochemical analysis using monoclonal antibodies directed at pVHL and the pVHL-suppressed target Cyclin D1 (VHL, Cat.no. 556347, 1:200, BD Biosciences; Cyclin D1(SP4), Cat.no. 241R-15, 1:100, Cell Marque). The patient was informed and gave written permission for this case report.