In conclusion, our study split the histological marker-null LCC category into two different transcriptomic entities, with POU2F3, FOXI1, and AIM2 genes as differential expression markers that might be probed by immunohistochemistry for the differential diagnosis between Pure-LCC and ADLike-LCC. This evidence concerns the gene POU2F3 and leukoencephalopathy with calcifications and cysts.