Kidney tumor
Adult renal cell carcinoma
Sarcomatoid renal cell carcinoma

Author: Daniel Anderson, M.D., MBA
Senior Author: Maria Tretiakova, M.D., Ph.D.
Editor-in-Chief Review: Debra Zynger, M.D.

Revised: 1 October 2018, last major update August 2018

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed Search: Sarcomatoid renal cell carcinoma [title] kidney AND (Humans[Mesh])

Cite this page: Anderson, D. Sarcomatoid renal cell carcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/kidneytumormalignantrccsarcoma.html. Accessed November 17th, 2018.
Definition / general
Essential features
  • Represents RCC loss of epithelial phenotype and gain of mesenchymal characteristics, epithelial-mesenchymal transition, a more aggressive phenotype with increased risk for local spread and high metastatic potential (Cancer 2005;104:1195)
  • May be diffuse or focal; even focal sarcomatoid component is important and associated with a poor prognosis
  • When the background RCC subtype is recognizable, it should be specified under histologic type
  • If no underlying RCC subtype is detected, then tumor with pure sarcomatoid differentiation falls into the category of unclassified RCC and should be distinguished from sarcoma
  • Sarcomatoid morphology is categorized as WHO / ISUP grade 4 (CAP: Protocol for the Examination of Specimens from Patients with Invasive Carcinoma of Renal Tubular Origin [Accessed 29 August 2018])
Terminology
  • Also called spindle cell carcinoma or carcinosarcoma
ICD-10 coding
  • C64: consider laterality designation
Epidemiology
Clinical features
  • 90% symptomatic with pain, gross hematuria, weight loss
  • Presentation with advanced disease and metastasis common
Radiology images

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CT with large renal mass

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PET/CT with widespread disease

Prognostic factors
Case reports
Treatment
  • Nephrectomy
  • Combination chemotherapy regimens such as doxorubicin plus gemcitabine
  • Interferon or interleukin-2 immunotherapy (J Urol 2002;167:65)
Gross description
  • Grayish white mass with infiltrative margins and fleshy to fibrous cut surface; must sample these areas
  • Mean size 9 cm (Am J Surg Pathol 2001;25:275)
  • May have heterogeneous patchy appearance: yellow, hemorrhagic, necrotic
Gross images

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Extensive sarcomatoid component

Sampling sarcomatoid areas



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Clear cell renal cell carcinoma with sarcomatoid differentiation

Microscopic (histologic) description
  • Atypical spindle cells or tumor giant cells with marked nuclear pleomorphism and abnormal mitotic figures
  • May resemble undifferentiated pleomorphic sarcoma or fibrosarcoma with poorly formed fascicles
  • Most commonly seen pattern is undifferentiated spindle cell sarcoma; other patterns include leiomyosarcoma, rhabdomyosarcoma, chondrosarcoma, osteosarcoma, angiosarcoma (Urology 1992;40:381)
  • RCC subtype (ex: clear cell, papillary, etc) present in the majority of cases with generous sampling (mean ~40% of the tumor is sarcomatoid, median ~50%); pure sarcomatoid RCC extremely rare
  • Occurs in 8% clear cell RCC, 3% papillary RCC, 9% chromophobe RCC, 29% collecting duct RCC, 11% unclassified RCC (Am J Surg Pathol 2001;25:275)
  • Sarcomatoid morphology by definition is WHO / ISUP grade 4
  • Wavy or rhabdoid regions that maintain epithelial features should not be considered sarcomatoid (Am J Surg Pathol 2004;28:435)
Microscopic (histologic) images

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Contributed by Daniel Anderson, M.D., MBA

Sarcomatoid spindle cell differentiation

Atypical pleomorphic spindle cells

Atypical pleomorphic spindle cells

Pleomorphic sarcomatoid cells

Atypical spindled and giant cells from a clear cell RCC


Sarcomatoid differentiation in clear cell RCC

Rhabdoid cells are not sarcomatoid



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Sarcomatoid component

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Clear cell RCC

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Osteo / chondrosarcomatous

Positive stains
Negative stains
Electron microscopy description
  • Shows epithelial differentiation, including desmosomal cell junctions with sarcomatoid differentiation such as rhabdomyosarcomatous differentiation (Hum Pathol 2002;33:68)
Electron microscopy images

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Osteoid

Molecular / cytogenetics description
  • Complex set of chromosomal gains and losses, -13q (75%) and -4q (50%)
  • Similar X chromosome inactivation patterns in both sarcomatoid and "parent" tumor suggesting common cell origin (Cancer 2005;104:1195)
  • Significant heterogeneity in the tumor components, suggesting genetic divergence (Mod Pathol 2007;20:303, Proc Natl Acad Sci U S A 2016;113:2170, Clin Cancer Res 2017;23:6686)
  • Sarcomatoid component in comparison to epithelioid component have:
    • Higher mutational burden/hypermutation status
    • More frequent mutations of p53, RELN, SETD2, ARID1A, BAP1 and PTEN, but fewer deletions of clear cell RCC specific genes VHL (3p21-25) and PBRM1 (Clin Cancer Res 2017;23:6686)
    • Loss of heterozygosity on chromosomes 1p, 9, 10, 14, 17p, 18 and 22 (Proc Natl Acad Sci U S A 2016;113:2170)
    • Upregulation of TGFβ signaling
  • FOXO3A induced epithelial to mesenchymal transition of tumor cells by up-regulating Snail
  • Snail protein expression significantly associated with tumor stage, histological grade and presence of sarcomatoid differentiation
  • Epithelial to mesenchymal transition orchestrates the sarcomatoid conversion of clear cell RCC, characterized by E- to N-cadherin switching, dissociation of β-catenin from the membrane and increased expression of Snail and Sparc (Mol Diagn Ther 2016;20:111)
Differential diagnosis
Board review question #1

    A chromophobe renal cell carcinoma is well sampled and an area is seen in the above image. What is the value of documenting the percentage of this component?

  1. Associated with lower stage
  2. The finding has a worse prognosis
  3. The finding has an improved prognosis
  4. There is no prognostic implication
Board review answer #1
B. Worse prognosis. Those with higher percentages of sarcomatoid differentiation in a renal cell carcinoma have a worse prognosis including distant metastases at time of nephrectomy and higher overall mortality than if no sarcomatoid component was identified.
Board review question #2

    A radical nephrectomy specimen is received. Which area is most likely to contain sarcomatoid component of renal cell carcinoma?

  1. The area designated by letter "A".
  2. The area designated by letter "B".
  3. The area designated by letter "C".
Board review answer #2
C. Though there are multiple areas suspicious for sarcomatoid renal cell carcinoma, part C is most suspicious as this shows a more whitish, fleshy cut surface that appears to be different from the surrounding tumor. The yellow background of the tumor is consistent grossly with a clear cell renal cell carcinoma.

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