August 2022 – Laboratory Genetics and Genomics

  • 23-month-old boy
  • Right kidney mass 
  • Nephrectomy (gross): kidney >1kg; 15 cm fleshy, tan, encapsulated mass 
  • See histology (Figures 1 and 2) and molecular changes in BCOR (Figure 3) 
Figure 1: Low-power magnification of the lesion
Figure 2: High-power magnification of the lesion
Figure 3: Molecular findings

What is the diagnosis?

  • Wilms tumor
  • Clear cell sarcoma of the kidney
  • Renal cell carcinoma, clear cell type
  • Malignant rhabdoid tumor of the kidney

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

Incorrect answers:

Wilm’s tumor: triphasic histology (blastema, epithelial, and stromal elements); multiple altered genes have been described including WT1REST, 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. 


  1. Ueno-Yokohata H, Okita H, Nakasato K, et al. Consistent in-frame internal tandem duplications of BCOR characterize clear cell sarcoma of the kidney. Nat Genet. 2015 Aug;47(8):861-3. doi:10.1038/ng.3338
  2. Argani P, Perlman EJ, Breslow NE, et al. Clear cell sarcoma of the kidney: a review of 351 cases from the National Wilms Tumor Study Group Pathology Center. Am J Surg Pathol. 2000 Jan;24(1):4-18. doi:10.1097/00000478-200001000-00002
  3. Wong MK, Ng CCY, Kuick CH, et al. Clear cell sarcomas of the kidney are characterized by BCOR gene abnormalities, including exon 15 internal tandem duplications and BCOR–CCNB3 gene fusion. Histopathology. 2018 Jan;72(2):320-329. doi:10.1111/his.13366
  4. Astolfi A, Fiore M, Melchionda F, Indio V, Bertuccio SN, Pession A. BCOR involvement in cancer. Epigenomics. 2019 May;11(7):835-855. doi:10.2217/epi-2018-0195
  5. Kao YC, Owosho AA, Sung YS, et al. BCOR-CCNB3 fusion positive sarcomas. A clinicopathologic and molecular analysis of 36 cases with comparison to morphologic spectrum and clinical behavior of other round cell sarcomas. Am J Surg Pathol. 2018 May;42(5):604-615. doi:10.1097/PAS.0000000000000965
  6. Ng D, Thakker N, Corcoran CM, et al. Oculofaciocardiodental and Lenz microphthalmia syndromes result from distinct classes of mutations in BCOR. Nat Genet. 2004 Apr;36(4):411-6. doi:10.1038/ng1321
Photo of Alessia Buglioni, M.D.

Alessia Buglioni, M.D.

Fellow, Molecular Genetic Pathology
Mayo Clinic

Kevin Halling, M.D., Ph.D.

Consultant, Laboratory Genetics and Genomics
Mayo Clinic
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

MCL Education

This post was developed by our Education and Technical Publications Team.