Kidney tumor

Childhood tumors

Clear cell sarcoma

Last author update: 1 October 2016
Last staff update: 26 January 2023 (update in progress)

Copyright: 2002-2023,, Inc.

PubMed Search: Clear cell sarcoma [title]

Maxwell Rollins, M.D.
Carla L. Ellis, M.D., M.S.
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Cite this page: Ellis C, Rollins M. Clear cell sarcoma. website. Accessed March 21st, 2023.
Definition / general
  • Clear cell sarcoma of the kidney (CCSK) is composed of uniform, small round cells with a clear appearance and evenly distributed fine chromatin separated by a delicate vascular network (eMedicine)
  • First described in 1978 by three distinct groups: Beckwith and Palmer (Cancer 1978;41:1937), Morgan and Kidd (Cancer 1978;42:1916), and Marsden and coworkers (Cancer 1978;42:1922); it was initially named "bone metastasizing renal tumor of childhood" since it has predilection for skeletal metastasis (J Neonatal Surg 2014;3:35)
  • Most frequently misdiagnosed renal tumor in children, as it is unusual, has varied morphology and there are no specific diagnostic markers (J Neonatal Surg 2014;3:35)
Essential features
  • Typically a male child, half are diagnosed at 2 - 3 years of age
  • Many histological variants exist (see below), but the classic histological appearance is nests or cords of small, plump cells separated by networks of delicate vascular septa
  • Clear cells occur in only 20% of cases, despite its name
  • Immunohistochemistry has limited use: it is usually only positive for vimentin, although Cyclin D1 may be useful (as of 2015, see below)
  • The most important drug treatment is Doxorubicin (Adriamycin®)
  • Recent molecular advances in CCSK tumorigenesis have implicated the BCOR gene (see below)
ICD coding
  • ICD-10: C64.9 - malignant neoplasm of unspecified kidney, except renal pelvis
  • Rare (20 cases per year); 3% - 5% of all pediatric renal tumors
  • Mean age of diagnosis is 36 months (range, 2 months - 14 years), half are diagnosed at 2 - 3 years of age (Am J Surg Pathol 2000;24:4)
  • Rarely diagnosed in adolescents / adults (Am J Surg Pathol 1999;23:1455)
  • 2 / 3 male
Diagrams / tables

AFIP images

Age distribution of 156 cases

Clinical features
  • Bone metastases occur in 17% - 40% of patients with CCSK, vs. <2% in Wilm tumor (J Neonatal Surg 2014;3:35)
  • 5% of patients have metastatic disease at presentation including bone, lung, brain and liver
  • Overall, survival varies with stage (5 year survival is 97% for stage I vs. 50% for stage IV, Am J Surg Pathol 2000;24:4)
Prognostic factors
  • Four important prognostic factors are:
  • Stage IV disease and young age are significant adverse prognostic factors for event free survival (Eur J Cancer 2013;49:3497)
Case reports
  • 28 day old boy with increasing abdominal mass (J Neonatal Surg 2014;3:35.)
  • 8 month old boy with increasing abdominal lump for 3 months (J Cancer Res Ther 2014;10:1104)
  • 19 month old boy with renal mass (University of Pittsburgh case #201)
  • 5 year old boy with jaw swelling, hematuria and abdominal swelling with bilateral renal masses and a 1 year old girl with a 4 month history of gradual abdominal swelling followed by gross hematuria (J Egypt Natl Canc Inst 2015;27:97)
  • 9 year old boy with a cystic structure with calcification on computed tomography (Diagn Pathol 2015;10:108)
  • Treatment
    • Total nephrectomy followed by postoperative chemotherapy and flank radiation therapy (RT) (Eur J Cancer 2013;49:3497)
    • Highly responsive to combination treatment with doxorubicin, vincristine and actinomycin, with doxorubicin the most important (eMedicine)
    • The essential role of doxorubicin in therapy emphasizes the need for pathologists to accurately identify CCSK (Am J Surg Pathol 2000;24:4)
    Gross description
    • Unilateral and unicentric mass with irregular but sharp tumor / kidney interface
    • Large (mean 11 cm); centered in central kidney or medulla
    • Cut surface is homogenous tan / gray or gelatinous and firm with occasional cysts
    Gross images

    Images hosted on other servers:

    Clear cell sarcoma

    Large tan to tannish yellow tumor

    Microscopic (histologic) description
    • Classic pattern: nests or cords of small, plump cells separated by network of delicate vascular septa (also called chicken wire capillaries)
      • This pattern is almost always focally present, but other patterns may be present
    • The 8 variant patterns are myxoid (50%), sclerosing (35%), cellular (26%), epithelioid (trabecular or acinar type) (13%), palisading verocay body (11%), spindle cell (7%), storiform (4%) and anaplastic (2.6%) (Am J Surg Pathol 2000;24:4)
    • Anaplasia is defined as nuclear hyperchromasia, atypical mitoses and giant nuclei (Am J Surg Pathol 2000;24:4)
    • Cells may take on a spindle appearance, particularly near the vascular septae, these cells are termed "septal cells" (Zhou: Uropathology, 1st Edition, 2012)
    • Although the border appears sharp at low power, high power reveals subtle infiltration of the cells into the normal parenchyma at the periphery
    • Nuclei have smooth chromatin and appear washed out, similar to papillary thyroid carcinoma
    • Nucleoli are not prominent; rare mitoses
    • Only 20% have clear cells, and origin of clear cells varies per source: the clear nature of the cells is due to intracytoplasmic vacuoles or an extracellular mucopolysaccharide matrix that imparts a clear cell appearance (Bostwick: Urologic Surgical Pathology, 3rd Edition, 2014, Zhou: Uropathology, 1st Edition, 2012)
    • Vascular invasion common
    Microscopic (histologic) images

    Contributed by Maxwell Rollins, M.D.

    Various images

    AFIP images

    3rd Series, Vol. 11

    Images hosted on other servers:

    Small oval cells

    Clear and spindle cells, fibrovascular septas

    Renal mass

    Renal mass in a 19 month old boy


    Cytology description
    • Cells with moderate pale blue cytoplasm (Cytopathology 2008;19:80), cord cells with few stromal fragments
    • Spindle cell variant has myxoid stromal fragments and septal cells
    • Anaplastic variant has bizarre pleomorphic nuclei, coarse chromatin and atypical mitotic figures (Diagn Cytopathol 2005;33:83)
    Cytology images

    Contributed by Maxwell Rollins, M.D.

    Touch prep

    AFIP images

    Fine needle aspiration

    Positive stains
    Negative stains
    Molecular / cytogenetics description
    • Despite clear cell sarcoma of the kidney (CCSK) being the second most common renal tumor in children, its mechanism has not yet been fully elucidated
    • A 2012 study demonstrated 12% (6 / 50 cases) contain a t(10;17), resulting in YWHAE - NUTM2B/E(FAM22B) fusion, confirming an earlier report (Arch Pathol Lab Med 2007;131:446)
      • The prognostic significance of this translocation is unknown (J Pathol 2012;227:72)
      • The t(10;17) is the same translocation seen in high grade endometrial stromal sarcoma
    • There is a correlation between BCOR gene aberration and CCSK tumorigenesis
      • Internal tandem duplications in the BCOR gene (BCL6 corepressor) were identified in 100% (20 / 20) of CCSK vs 0 of 193 other pediatric renal tumors
        • None of these 20 cases had the YWHAE – NUTM2 fusion (Nat Genet 2015;47:861)
        • In another study, internal tandem duplications in the BCOR gene (BCL6 corepressor) were identified in 85% (23 / 27) of CCSK (Nat Commun 2015;6:8891)
    • Downregulated vascular endothelial growth factor A (VEGFA) and its interacting genes may initiate clear cell sarcoma of the kidney (CCSK) development by interrupting two different pathways, kinase regulation and protein tyrosine kinase metabolism
      • IIn a 2016 gene expression study of 14 CCSK and 3 fetal kidney samples, a total of 2681 differentially expressed genes were identified, of which 2138 genes were downregulated, including VEGFA, and 543 were overexpressed (Oncol Lett 2016;11:953)
    Differential diagnosis
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