Kidney tumor

Childhood tumors

Clear cell sarcoma



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Last staff update: 20 February 2024

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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. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneytumorclearcellsarcoma.html. Accessed March 19th, 2024.
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
Epidemiology
  • 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 Various images Various images Various images Various images Various images

    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

    EGFR+

    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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