title: Tumor progression in DICER1-mutated cystic nephroma-witnessing the genesis of anaplastic sarcoma of the kidney.
abstract: We report a 7-month-old female infant with a multicystic left renal tumor having histologic features predominantly of a cystic nephroma, but with microscopic cellular foci which contained atypical mitotic figures and anaplastic nuclei. Immunohistochemistry showed strong p53 reactivity in the anaplastic region. DICER1 sequencing confirmed 2 mutations: germ line mutation c.2450delC and c.5438A>G somatic within the tumor. Despite an initial consideration of cystic partially differentiated nephroblastoma, 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, and further immunohistochemical workup 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 anaplastic sarcoma of kidney as a DICER1-associated cancer.
authors.affiliation: Department of Medical Genetics, Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC H3T 1E2, Canada.
authors.forename: Mona K
authors.initials: MK
authors.lastname: Wu
authors.affiliation: Histology Laboratory, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland.
authors.forename: Maura B
authors.initials: MB
authors.lastname: Cotter
authors.affiliation: Oncology Department, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland.
authors.forename: Jane
authors.initials: J
authors.lastname: Pears
authors.affiliation: Histology Laboratory, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland.
authors.forename: Michael B
authors.initials: MB
authors.lastname: McDermott
authors.affiliation: Departments of Oncology and Experimental Medicine, McGill University, Montréal, QC H3T 1E2, Canada.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Fabian
authors.affiliation: Department of Medical Genetics, Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC H3T 1E2, Canada; Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, QC H3T 1E2, Canada.
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
authors.affiliation: Histology Laboratory, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland; Trinity College, University of Dublin, Dublin 2, Ireland; The National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland. Electronic address: Maureen.osullivan@tcd.ie.
authors.forename: Maureen J
authors.initials: MJ
authors.lastname: O'Sullivan
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007680:Kidney Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D043244:Ribonuclease III / Q000235:genetics*; D012509:Sarcoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics; D025721:WT1 Proteins / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025721:WT1 Proteins; C583751:WT1 protein, human; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: Anaplastic sarcoma; Cystic nephroma; Germline mutation; Kidney DICER1