Tumor Progression in DICER1-mutated Cystic Nephroma – witnessing the genesis of Anaplastic Sarcoma of the Kidney

We report a 7 month old girl with a multicystic left renal tumor having histological features predominantly of a cystic nephroma (CN), but with microscopic cellular foci which contained atypical mitotic figures and anaplastic nuclei. Immunohistochemistry showed strong TP53 reactivity in the anaplastic region. DICER1 sequencing confirmed two mutations: germ-line mutation c.2450delC, and c.5438A > G somatic within the tumor. Despite an initial consideration of CPDN, the presence of anaplasia ruled that possibility out, as this is not an acceptable feature for that diagnosis. Moreover, the germ-line DICER1 mutation prompted consideration that this case represents a unique 'nascent' anaplastic sarcoma of kidney (ASK), and further IHC work-up demonstrated cytoplasmic, but no nuclear WT-1 reactivity in the cellular foci. The importance of meticulous sampling of cystic lesions is highlighted by this unprecedented case, which lends support to the recent recognition of ASK as a DICER1-associated cancer.

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