The correct answer is ...
Clear cell sarcoma of the kidney.
Clear cell sarcoma of the kidney (CCSK) is an uncommon neoplasm of young children (<5 years old; M:F::2:1).1 It is an aggressive tumor, often metastatic at presentation (bones are a common site).1 Histology is variable with a myxoid pattern seen in approximately 50% of the cases, and with plump tumor cells that can exhibit indistinct borders.2 By immunohistochemistry, these tumors are frequently positive for BCOR and Cyclin D1.3 The molecular profile is characterized by in-frame internal tandem duplications (ITDs) in BCOR, Xp11.4 (exon 15), in approximately 90% of the cases.4 Rarer abnormalities make up the remaining 10%, such as t(10;17) (q22;p13) YWHAE-NUTM2B/E.1
BCOR (Bcl6 transcriptional corepressor) is an epigenetic regulator through histone modifications, important for germinal center B-cell development, tissue differentiation and chromatin remodeling.4 CCSK is one of the members of the “BCOR Family of Tumors,” which also includes Ewing sarcoma-like sarcomas/small blue round cell tumors with BCOR rearrangements.5 CCSK treatment is based on surgery, radio- and chemotherapy (highly responsive to doxorubicin).2 With treatment, 5-year survival is ~80%; relapses can happen in 15% of cases.1,2
BCOR germline loss-of-function variants are associated with X-linked dominant oculo-facio-cardio-dental (OFCD) syndrome (prenatal lethality in hemizygous males) and X-linked recessive Lenz’s microphthalmia (attenuated variant).6
Wilm’s tumor: triphasic histology (blastema, epithelial, and stromal elements); multiple altered genes have been described including WT1, REST, and TRIM28. Alterations in loci 11p13 and 11p15 are associated with WAGR syndrome and Beckwith-Wiedemann syndrome, respectively.
Malignant rhabdoid tumor of the kidney: rhabdoid tumor cells, INI1 (SMARCB1) loss.
Renal cell carcinoma, clear cell type: typically, not seen in pediatric patients. 3p deletion (including VHL) is often seen.
Alessia Buglioni, M.D.
Fellow, Molecular Genetic Pathology
Kevin Halling, M.D., Ph.D.
Consultant, Laboratory Genetics and Genomics
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science