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Clear cell sarcoma of kidney: A mimicker of Wilms' tumor

1 Department of Pathology, Sanjay Gandhi Post-Graduate Institute Of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Radiodiagnosis, Sanjay Gandhi Post-Graduate Institute Of Medical Sciences, Lucknow, Uttar Pradesh, India
3 Department of Urology, Sanjay Gandhi Post-Graduate Institute Of Medical Sciences, Lucknow, Uttar Pradesh, India

Date of Submission15-Mar-2021
Date of Decision08-Jun-2021
Date of Acceptance20-Jun-2021
Date of Web Publication02-Jun-2022

Correspondence Address:
Gupta Aviral,
13-A, Sararswati Puram, Raibareli Road, Lucknow - 226 014, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.jcrt_432_21

 > Abstract 

The differential diagnosis for an abdominal mass in a 2-year-old child is broad and includes lesions of renal, hepatic, gastrointestinal, adrenal, and lymphatic origins. Of these, Wilms' tumor and neuroblastoma are the most common tumors, where Wilms' tumor represents about 92% of renal masses in children. Non-Wilms' renal tumors, rhabdoid tumors, and clear cell sarcoma of the kidney (CCSK) are uncommon. CCSK constitutes approximately 3% of all malignant renal tumors in childhood. In this report, we present a child presenting with a huge renal mass consistent with Wilms' tumor on computed tomography and initial biopsy. However, the final pathologic diagnosis after resection revealed CCSK.

Keywords: Clear cell sarcoma of the kidney, pediatric tumors, Wilms' tumor

How to cite this URL:
Aviral G, Sarvesh C M, Sushila J, Ansari M S. Clear cell sarcoma of kidney: A mimicker of Wilms' tumor. J Can Res Ther [Epub ahead of print] [cited 2022 Aug 16]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=346537

 > Introduction Top

Clear cell sarcoma of the kidney (CCSK) is an uncommon renal sarcoma of uncertain histogenesis, occurring in children. CCSK constitutes approximately 3% of all malignant renal tumors in childhood.[1] There is no association with nephroblastoma-related syndromes or nephrogenic rests. It is also known as bone-metastasizing renal tumor of childhood, due to its propensity to undergo bone metastasis.[2]

 > Case Report Top

An asymptomatic 2-year-old girl presented to us with a lump in the right abdomen incidentally detected by parents. Contrast-enhanced computerized tomography (CT) of the abdomen showed a large well-defined heterogeneously enhancing mass in the lower pole of the right kidney measuring 9.6 cm × 8.5 cm and a separate similar looking well-defined mass in the aortocaval region measuring 5.2 cm × 3 cm [Figure 1] and [Figure 2]. Tru-cut biopsy was performed from a renal mass which was reported as stroma predominant triphasic Wilms' tumor [Figure 3]. Subsequently, the patient received seven cycles of neoadjuvant chemotherapy (EE4A regimen); however, there was no radiological resolution of the lesion. Thereafter, the patient underwent open radical nephroureterectomy. Intraoperative findings showed a large encapsulated tumor in the right kidney measuring 12 cm × 10 cm × 10 cm, which was pushing the surrounding organs with no infiltration. Another similar looking well-defined pararenal mass measuring 10 cm × 8 cm × 6 cm was seen in the right aortocaval region along with an enlarged inter-aortocaval lymph node. Right renal mass, right pararenal mass, and inter-aortocaval lymph node were excised [Figure 2]. Histopathology showed a tumor composed of nests and sheets of neoplastic cells traversed by incomplete fine fibrous septa. These neoplastic cells were round displaying minimally pleomorphic nuclei with vesicular nuclei, occasional conspicuous nucleoli, and moderate amount of clear cytoplasm. Large areas of myxoid stroma with spindling of tumor cells were also noted [Figure 4]. Inter-aortocaval lymph node showed tumor metastasis. Tumor cells were positive for vimentin, cyclin D1 (nuclear positivity), and BCL-2 (cytoplasmic positivity with perinuclear accentuation) [Figure 5]. Cytokeratin, CD34, desmin, myogenin, HMB-45, S-100, MIC-2, synaptophysin, and chromogranin were negative. Ki67 index was 4%. Based on histomorphological and immunohistochemical findings, the diagnosis was confirmed as CCSK. At the time of last follow-up, the patient was slated to undergo bone scan for staging of tumor and subsequent chemoradiotherapy in accordance with the National Wilms' Tumor Study (NWTS-5) protocol.
Figure 1: Contrast-enhanced computerized tomography showing a well-defined heterogeneously enhancing tumor involving right kidney and a well-defined similar looking pararenal mass (marked with asterisk) in coronal view (a) and axial view (b)

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Figure 2: Clear cell sarcoma of kidney. Well-defined, homogenous grayish white appearance completely replacing the kidney

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Figure 3: Tru-cut biopsy showing chiefly myxoid area with spindle-shaped cells (a, H and E, ×100). Occasional entrapped normal renal tubules are also seen (b, H and E, ×400). Initial biopsy was misdiagnosed as stroma predominant triphasic Wilms' tumor

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Figure 4: Excision biopsy showing tumor disposed in nests with clear cell morphology (a, H and E, ×400). Myxoid areas with spindling of tumor cells, imperceptibly merging with classical pattern (b, H and E, ×200)

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Figure 5: On immunohistochemistry, tumor cells are vimentin positive (a, IHC, ×200), pan-cytokeratin negative (b, IHC, ×200), cyclin D1 nuclear positive (c, IHC, ×400), and BCL-2 cytoplasmic positive (d, IHC, ×400)

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 > Discussion Top

CCSK is a tumor that is frequently misdiagnosed due to its rarity and lack of specific features. The mean patients' age at diagnosis is 3 years and it shows a 2:1 male-to-female predominance.[2] Clinical features are nonspecific making diagnosis of CCSK difficult. Workup should follow standard algorithms for an abdominal mass in a pediatric age group. CT and ultrasonography do not provide discriminatory findings that would differentiate between CCSK and Wilms' tumor. Evidence of bony metastases should raise the suspicion of CCSK, which may occur in up to 60% of patients with CCSK compared to a 2% incidence of bony metastases in Wilms' tumor.[3]

United Kingdom Children's Cancer Study Group recommend the use of preoperative percutaneous biopsy of suspected Wilms' tumor because they found a high concordance between percutaneous biopsy and final surgical pathology in 94%–99% of cases. Furthermore, the use of pretreatment biopsy has not been associated with any increase in recurrence or complication.[4]

Unfortunately, this patient fell into this small subset of patients whose diagnosis on initial core biopsy was discordant with the final pathologic diagnosis. In retrospect, we concluded that the core biopsy was taken from myxoid area of the tumor and entrapped normal renal tubules prompted the pathologist to diagnose it as stroma predominant triphasic Wilms' tumor. CCSK is a malignant mesenchymal neoplasm characterized by nests or cords of the cells separated by regularly spaced, arborizing fibrovascular septa. Although the majority of CCSK displays “classic” features on histopathology, those with a cellular pattern may resemble pediatric small round blue cell tumors and those with epithelioid (trabecular or pseudo-acinar) patterns may resemble nephroblastoma. CCSK is typically immunoreactive for BCL-2, cyclin D1, and vimentin and uniformly negative for CD34, S-1OO, desmin, and cytokeratin.[2],[5] Immunohistochemistry (IHC) should be used for the confirmation of CCSK.

Approximately 10% of CCSKs have the recurring chromosomal translocation t (10;17)(q22; p13), resulting in YWHAE-FAM22 gene fusion. Consistent in-frame duplications of the BCOR gene distinguish CCSK from other pediatric renal tumors.[2] A subset of CCSK shows hypermethylation, particularly at the site THBS1 CPG, a suspected angiogenic factor. CCSK has recently been shown to harbor internal tandem duplications in the last exon of the BCOR gene in over 90% of cases.[6] However, these genetic mutations appear sporadic with no familial cases of CCSK reported, to date.[7]

Once diagnosis of CCSK is confirmed, treatment includes radical nephrectomy followed by adjuvant chemoradiation. The National Wilms' Tumor Study Group (NWTSG) guidelines call for cyclophosphamide, etoposide, vincristine, and doxorubicin for any stage of CCSK.[8] Doxorubicin has been reported to impart significant improvements in survival, and prolonged chemotherapy regimens may improve relapse-free survival.[9] Although some have withheld adjuvant radiotherapy in children with stage I disease, the addition of radiotherapy (10 Gy) to the tumor bed is standard in protocols for patients of any stage with CCSK.

Despite having unfavorable histology, long-term survival is reasonable. The latest results observed on the NWTS-5 showed that 5-year event-free survival and overall survival of patients receiving treatment according to the NWTSG guidelines were 79% (95% confidence interval [CI]: 71%–88%) and 90% (95% CI: 84–96%) with a median follow-up of 9.7 years after diagnosis.[10]

 > Conclusion Top

CCSK should be considered as a differential diagnosis in a suspected case of Wilms' tumor in a pediatric patient, which should be confirmed by IHC. It is of considerable therapeutic importance that clear cell sarcoma be not only correctly diagnosed but early too.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

Dome JS. Identification and management of high-risk Wilms' tumors. Erasmus University Rotterdam 2019;1:4.  Back to cited text no. 1
WHO Classification of Tumours of the Urinary System and Male Genital Organs. 4th edition (2016), Lyon, France. pp. 54-5.  Back to cited text no. 2
Franco A, Dao TV, Lewis KN, Biddinger PW. A case of clear cell sarcoma of the kidney. J Radiol Case Rep 2011;5:8-12.  Back to cited text no. 3
Mitchell C, Pritchard-Jones K, Shannon R, Hutton C, Stevens S, Machin D, et al. Immediate nephrectomy versus preoperative chemotherapy in the management of non-metastatic Wilms' tumors: Results of a randomized trial (UKW3) by the UK Children's Cancer Study Group. Eur J Cancer 2006;42:2554-62.  Back to cited text no. 4
Uddin N, Minhas K, Abdul-Ghafar J, Ahmed A, Ahmad Z. Expression of cyclin D1 in clear cell sarcoma of kidney. Is it useful in differentiating it from its histological mimics? Diagn Pathol 2019;14:13.  Back to cited text no. 5
Argani P, Pawel B, Szabo S, Reyes-Múgica M, Timmons C, Antonescu CR. Diffuse strong BCOR immunoreactivity is a sensitive and specific marker for clear cell sarcoma of the kidney (CCSK) in pediatric renal neoplasia. Am J Surg Pathol 2018;42:1128-31.  Back to cited text no. 6
Gooskens SL, Furtwangler R, Vujanic GM, Dome JS, Graf N, van den Heuvel-Eibrink MM. Clear cell sarcoma of the kidney: A review. Eur J Cancer 2012;48:2219-26.  Back to cited text no. 7
Ahmed HU, Arya M, Levitt G, Duffy PG, Sebire NJ, Mushtaq I. Part II: Treatment of primary malignant non-Wilms' renal tumours in children. Lancet Oncol 2007;8:842-8.  Back to cited text no. 8
Seibel NL, Li S, Breslow NE, Beckwith JB, Green DM, Haase GM, et al. Effect of duration of treatment on treatment outcome for patients with clear-cell sarcoma of the kidney: A report from the National Wilms' Tumor Study Group. J Clin Oncol 2004;22:468-73.  Back to cited text no. 9
Seibel NL, Chi YY, Perlman EJ, Tian J, Sun J, Anderson JR, et al. Impact of cyclophosphamide and etoposide on outcome of clear cell sarcoma of the kidney treated on the National Wilms Tumor Study-5 (NWTS-5). Pediatr Blood Cancer 2019;66:e27450.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]


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