This was also emphasized by Tanimoto and colleagues, who have only observed 36 asymptomatic patients with localized OAML. After an impressive median follow-up of 7 years, PHA-793887 approximately 70% did still not require treatment, while progression was noted in 47% and 6% died due to progressive lymphoma. Taken together, the current retrospective series of 60 patients reflects the excellent prognosis, but also the heterogeneous nature of OAML under ����daily-life���� conditions. There was no significant difference in TTP and response rates between local vs systemic therapy, and also wait and see as well as antibiotics appeared to be sensible options in selected patients. In view of our data, we strongly suggest that a randomized trial of radiation versus systemic therapy in patients requiring therapy is warranted to answer the question of optimal management. In the clinical practice, however, our data suggest that OAML is an idolent disease irrespective of stage and does not require immediate therapy in a large Ionomycin percentage of patients. In the absence of randomized studies, various forms of therapy appeared to be equally effective in our analysis. This suggests that the individual management should be based on minimizing toxicities and also take in to account the respctive center��s experience with various forms of therapy along with patients�� preferences. Study limitations include the small sample size, uncertainty about the presence of LOH and whether the novel variants are germ line or somatic. Given the very low incidence of INHA genetic variants in this substantial set of 37 ACCs, it is very unlikely that INHA mutations play a significant role in ACC formation in man. Although LOH was not studied directly in these samples, the occurrence of heterozygous variants in the ACCs pleads against complete knockout of the gene. Importantly, only homozygous Inha knock-out mice developed adrenocortical tumors pleading against tumorigenic potential of single copy number deletion. Finally, paired sequencing of normal and tumor tissue might reveal whether the previously undescribed variants have a germ line or somatic origin, but this was not available for the current study.