Kidney tumor

Adult renal cell carcinoma - rare

Sarcomatoid

Authors: Daniel Anderson, M.D., M.B.A., Maria Tretiakova, M.D., Ph.D.

Editor-in-Chief: Debra L. Zynger, M.D.

Topic Completed: 1 August 2018

Minor changes: 22 November 2021

Copyright: 2003-2021, PathologyOutlines.com, Inc.

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

Page views in 2020: 8,063

Page views in 2021 to date: 7,689

Table of Contents

Cite this page: Anderson D, Tretiakova M. Sarcomatoid. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneytumormalignantrccsarcoma.html. Accessed December 7th, 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

ICD-10: C64 - malignant neoplasm of kidney, except renal pelvis; 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

Images hosted on other servers:

CT with large renal mass

PET / CT with widespread disease

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

Contributed by Daniel Anderson, M.D., M.B.A.

Extensive sarcomatoid component

Sampling sarcomatoid areas

Images hosted on other servers:

Clear cell
RCC 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

Contributed by Daniel Anderson, M.D., M.B.A.

Sarcomatoid spindle cell differentiation

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

Images hosted on other servers:

Clear cell RCC

Positive stains

AE1 / AE3, vimentin (56%), EMA (50%), CAM 5.2 (40%)
Also actin (33%) and LeuM1 (22%) in spindled areas

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

Associated with lower stage
Finding has a worse prognosis
Finding has an improved prognosis
There is no prognostic implication

Board review style answer #1

B. Finding has a 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.

Comment Here

Reference: Sarcomatoid

Board review style question #2

The area designated by letter "A"
The area designated by letter "B"
The area designated by letter "C"

Board review style answer #2

C. The area designated by letter "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.

Comment Here

Reference: Sarcomatoid