Mutations of the von Hippel-Lindau (VHL) gene are considered critical for the initiation of clear cell renal cell carcinoma. The VHL protein is involved in regulation of the cell cycle and neo-vascularization. In this study, the association of VHL mutations with tumour cell proliferation, angiogenesis, and clinical outcome was analysed in 113 clear cell renal cell carcinomas. The degree of angiogenesis and tumour cell proliferation was immunohistochemically determined by counting microvessels (microvessel density, anti-CD34 antibody) and cells with proliferating activity (Ki-67 labelling index, MIB-1 antibody). Forty-eight different VHL sequence alterations were found in 38 of 113 patients (34%) by direct sequencing. Nineteen VHL mutations were frameshifts and nonsense mutations, predicted to change the open reading frame of VHL. These 'loss-of-function' mutations correlated with worse prognosis in univariate analysis (p=0.02). Tumour grade, stage, microvessel density, and tumour cell proliferation were not associated with VHL alterations. These findings may indicate that 'loss-of-function' VHL mutations are involved in the progression of a clear cell renal cell carcinoma subset, whereas regulation of angiogenesis and proliferation of renal carcinoma in vivo is apparently not directly influenced by VHL alterations.

We show that detection of GM by EIA does not precede detection of major lesions by pulmonary CT. In the clinical setting, the decision to administer mold-active treatment should based on detection of new pulmonary infiltrates on CT performed early during infection, rather than on results of EIA for detection of GM.

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IntroductionPrimitive neuroectodermal tumors (PNETs) occur predominantly in childhood preferentially in the soft tissues of the lower extremity and the paraspinal region. We present here a rare case of a PNET of the kidney in an adult.Case presentationA tumor adjacent to the right kidney was detected by ultrasound coincidentally at a routine check-up in a 46-year-old woman with irritable bowel syndrome in her medical history. The patient had no clinical signs. Contrast-enhanced computerized tomography scan of the abdomen demonstrated a highly vascularized renal tumor. A retroperitonealectomy with en-bloc resection of the kidney was performed, and histopathological work-up showed a primitive neuroectodermal tumor of the kidney with the characteristic translocation t(11;22)(q24;q12).ConclusionThis tumor entity must be accurately distinguished from other renal neoplasms because of the prognostic and therapeutic impact.