Subject(s)
Gene Fusion , Proteins/genetics , Proto-Oncogene Proteins c-ret/genetics , Soft Tissue Neoplasms/genetics , Thigh/pathology , Antigens, CD34/genetics , Antigens, CD34/metabolism , Child, Preschool , Humans , Male , Proteins/metabolism , Proto-Oncogene Proteins c-ret/metabolism , S100 Proteins/genetics , S100 Proteins/metabolism , Soft Tissue Neoplasms/metabolism , Soft Tissue Neoplasms/pathologyABSTRACT
AIMS: Clear cell sarcoma of the kidney (CCSK) is a rare paediatric renal malignant tumour. The majority of CCSKs have internal tandem duplications (ITDs) of the BCOR gene, whereas a minority have the YWHAE-NUTM2 gene fusion. A third 'double-negative' (DN) category comprises CCSKs with neither BCOR ITDs nor YWHAE-NUTM2 fusion. The aim of this study was to characterise 11 histologically diagnosed CCSKs immunohistochemically (with CCND1, BCOR and CCNB3 stains) and genetically. METHODS AND RESULTS: By next-generation sequencing, 10 cases (90.9%) had BCOR exon 15 ITDs, with positive BCOR immunoreactivity being found in four (36%) or eight (72%) cases, depending on the antibody clone. By reverse transcription polymerase chain reaction, none had the YWHAE-NUTM2 fusion. The DN case had a BCOR-CCNB3 fusion and strong nuclear CCNB3 and BCOR immunoreactivity. Quantitative polymerase chain reaction showed markedly elevated BCOR expression in this case, whereas BCOR ITD cases had lower levels of elevated BCOR expression. CONCLUSIONS: The majority of the CCSKs in our cohort had BCOR ITDs, and none had the YWHAE-NUTM2 fusion. We verified the strong, diffuse cyclin D1 (CCND1) immunoreactivity in CCSKs described in recent reports. BCOR immunoreactivity was not consistently positive in all CCSKs with BCOR ITDs, and therefore cannot be used as a diagnostic immunohistochemical stain to identify BCOR ITD cases. The DN case was a BCOR-CCNB3 fusion sarcoma. BCOR-CCNB3 sarcoma is typically a primary bone sarcoma affecting male adolescents, and this is the first report of it presenting in a kidney of a young child as a CCSK. The full spectrum of DN CCSKs awaits more comprehensive characterisation.
Subject(s)
Cyclin B/genetics , Kidney Neoplasms/genetics , Oncogene Proteins, Fusion/genetics , Proto-Oncogene Proteins/genetics , Repressor Proteins/genetics , Sarcoma, Clear Cell/genetics , Child , Child, Preschool , Exons , Female , Humans , MaleABSTRACT
Congenital myeloproliferative disorders and transient leukemic disorders have been described in the perinatal period in infants with trisomy 21 (Down syndrome). We report a novel case of a neonate with trisomy 21 with GATA1-mutated congenital myeloproliferative disorder complicated by placental fetal thrombotic vasculopathy featuring chorionic vessel leukemic thrombi, fetal circulation vascular injuries, and large aggregates of avascular villi. These thrombotic and vasculopathic changes within the placenta are likely a reflection of the hypercoagulable state caused by the myeloproliferative disorder. Placental fetal thrombotic vasculopathy is associated with adverse outcomes for the infant, and should be documented during formal pathological examination of the placenta.
