PTEN and Langerhans cell histiocytosis: But we also chose it because, when these experiments were being planned, a case report had appeared which described a major clinical response to an AKT inhibitor in an LCH patient.[46] However, a clinical trial of the inhibitor in LCH patients showed minimal activity[47] and further genetic analysis of a large number of LCH cases showed only rare disruption or alteration of the PTEN/AKT/PIK3C pathway.[4, 5, 48] In fact, very few LCH cases with alterations in MAP kinase pathway genes show genetic alterations affecting other pathways.