Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Clinical features | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Electron microscopy description | Electron microscopy images | Molecular / cytogenetics description | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Anderson D, Tretiakova M. Sarcomatoid. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneytumormalignantrccsarcoma.html. Accessed January 15th, 2021.
Definition / general
- Sarcoma-like histology in a renal tumor is not a distinct entity but a pathway of transformation (dedifferentiation) in subtypes of renal cell carcinoma (RCC) (Cancer 2005;104:1195)
- 1 - 5% of RCC have a sarcomatoid component (Am J Surg Pathol 1997;21:1188, Ann Diagn Pathol 2003;7:296)
- Presence of even a focal sarcomatoid component is associated with a worse prognosis (Am J Surg Pathol 2001;25:275)
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 coding
- C64: consider laterality designation
Epidemiology
- Mean age 60 years, 60% men, usually stage 3 or 4
- Aggressive with median survival of 4 - 19 months; 5 year survival 22%, 10 year survival 13% (vs. 79%/76% without sarcomatoid differentiation) (J Urol 2002;167:65) (Oncologist 2012;17:46, Urol Oncol 2015;33:427)
- Metastases to lung and bones are common
Clinical features
- 90% symptomatic with pain, gross hematuria, weight loss
- Presentation with advanced disease and metastasis common
Radiology images
Prognostic factors
- Percentage of sarcomatoid component may be prognostic, currently optional to report percentage:
- ≥ 50% yielded poor prognosis (Am J Surg Pathol 2004;28:435)
- > 40% least likely to be alive at 1 year (Urol Oncol 2015;33:427)
- > 10% had higher risk of death (Urol Oncol 2015;33:427)
Case reports
- 45 year old man patient with rhabdomyosarcomatous sarcomatoid differentiation into the renal sinus and the ureter (BMC Nephrol 2018;19:84)
- 45 year old woman with sarcomatoid chromophobe renal cell carcinoma with squamous differentiation (Arch Pathol Lab Med 2008;132:1672)
- 55 year old man with renal cell carcinoma with spindle cell sarcomatoid component (J Clin Diagn Res 2014;8:FD01)
- 62 year old man with sarcomatoid renal cell carcinoma with wide metastasis (J Kidney Cancer VHL 2018;5:1)
- 71 year old woman with divergent growth pattern (Arch Pathol Lab Med 2005;129:1057)
- 72 year old woman with pleomorphic spindle cells and rapid progression (Urol Case Rep 2017;16:6)
- 78 year old man with papillary renal cell carcinoma with sarcomatoid transformation (Arch Pathol Lab Med 2000;124:1830)
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
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
Contributed by Daniel Anderson, M.D., M.B.A.
Images hosted on other servers:
Positive stains
Negative stains
- High molecular weight keratin 34βE12, S100 (usually) (Arch Pathol Lab Med 1993;117:636)
Electron microscopy description
- Shows epithelial differentiation, including desmosomal cell junctions with sarcomatoid differentiation such as rhabdomyosarcomatous differentiation (Hum Pathol 2002;33:68)
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
- Clear cell carcinoma with early spindle cell change: stroma is not malignant (Hum Pathol 2007;38:1372)
- Primary renal sarcoma: usually leiomyosarcoma; primary renal sarcomas have no epithelial component after careful sampling
- Primary retroperitoneal soft tissue sarcoma: usually liposarcoma; no epithelial component after careful sampling
Board review style question #1
Board review style 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.
Reference: Kidney tumor - Sarcomatoid renal cell carcinoma
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Reference: Kidney tumor - Sarcomatoid renal cell carcinoma
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Board review style question #2
Board review style 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.
Reference: Kidney tumor - Sarcomatoid renal cell carcinoma
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Reference: Kidney tumor - Sarcomatoid renal cell carcinoma
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