Clear cell sarcoma of kidney involving a horseshoe kidney and harboring EGFR internal tandem duplication

Abstract

Clear cell sarcoma of kidney (CCSK) is a rare renal malignancy, previously unreported in horseshoe kidney (HSK). B-cell lymphoma 6 corepressor (BCOR) gene internal tandem duplication (ITD) was identified as a recurrent somatic alteration in approximately 85% of CCSKs. This and the YWHAE-NUTM2B/E fusion, the second most common recurrent molecular alteration in CCSK (10%), are considered to be mutually exclusive. However, there is a subset of CCSKs that do not harbor either the BCOR-ITD or YWHAE-NUTM2 translocation and lack known molecular alterations. Herein, we report the first case of CCSK arising in HSK and harboring epidermal growth factor receptor ITD.

Clear cell sarcomas of the kidney are characterised by BCOR gene abnormalities, including exon 15 internal tandem duplications and BCOR–CCNB3 gene fusion

“…Very recently, an epidermal growth factor receptor ( EGFR ) ITD was reported in a DN CCSK originating from a horseshoe kidney. This had diffuse cytoplasmic EGFR immunoreactivity suggesting receptor internalisation, similar to FLT3 ITD in acute myelogenous leukaemia . This report thereby expands the genetic findings in DN CCSK.…”

BCOR‐CCNB3 fusion‐positive clear cell sarcoma of the kidney

“…CCSK is most often seen in children between 2 and 4 years of age with a male predominance . There are two recurrent somatic alterations reported in CCSK: BCOR (encoding the BCL‐6 corepressor) internal tandem duplication (ITD) is seen in approximately 85% of patients with CCSK; the second most common genetic abnormality is YWHAE‐NUTM2B/E gene fusion, which is seen in approximately 12% of patients with CCSK . A minority of patients with CCSK do not have BCOR‐ITD or YWHAE‐NUTM2B/E fusion .…”

“…[1][2][3] There are two recurrent somatic alterations reported in CCSK: BCOR (encoding the BCL-6 corepressor) internal tandem duplication (ITD) is seen in approximately 85% of patients with CCSK; the second most common genetic abnormality is YWHAE-NUTM2B/E gene fusion, which is seen in approximately 12% of patients with CCSK. 2,4,5 A minority of patients with CCSK do not have BCOR-ITD or YWHAE-NUTM2B/E fusion. 5 Other molecular abnormalities have been reported in these patients, including one patient with EGFR (epidermal growth factor receptor) ITD and three patients with BCOR-CCNB3 (where CCNB3 is cyclin B3) fusion joining 5 ′ partner BCOR to the 3 ′ partner CCNB3 (encoding the testis-specific cyclin B3) 3,5,6 that had been originally reported as a recurrent gene fusion in a subset of Ewing-like undifferentiated soft tissue sarcomas.…”

“…2,4,5 A minority of patients with CCSK do not have BCOR-ITD or YWHAE-NUTM2B/E fusion. 5 Other molecular abnormalities have been reported in these patients, including one patient with EGFR (epidermal growth factor receptor) ITD and three patients with BCOR-CCNB3 (where CCNB3 is cyclin B3) fusion joining 5 ′ partner BCOR to the 3 ′ partner CCNB3 (encoding the testis-specific cyclin B3) 3,5,6 that had been originally reported as a recurrent gene fusion in a subset of Ewing-like undifferentiated soft tissue sarcomas. 8 We report two additional patients with BCOR-CCNB3 fusion-positive CCSK who presented with advanced disease and had an excellent response to chemotherapy.…”

Clear Cell Sarcoma of the Kidney

“…16,31 Those cases are histomorphologically, immunophenotypically, and transcriptomically indistinguishable from CCSK with BCOR ITD. 27 Other reported genetic alterations in CCSK include IRX2-TERT gene fusion 32 and EGFR gene amplification, point mutation (T790M), 33 and internal tandem duplication, 34 although it is not clear (apart from the single report of EGFR ITD) whether these alterations are mutually exclusive with the canonical BCOR and YWHAE-NUTM2 mutations.…”