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Adult renal cell carcinoma - rare

Sarcomatoid


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

Last staff update: 24 March 2023 (update in progress)

Copyright: 2003-2023, PathologyOutlines.com, Inc.

PubMed Search: Sarcomatoid renal cell carcinoma

Daniel Anderson, M.D., M.B.A.
Maria Tretiakova, M.D., Ph.D.
Page views in 2022: 8,451
Page views in 2023 to date: 2,144
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Diagrams / tables | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2
Cite this page: Anderson D, Tretiakova M. Sarcomatoid. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneytumormalignantrccsarcoma.html. Accessed March 26th, 2023.
Definition / general
Essential features
Terminology
  • Previously called carcinosarcoma of the kidney, sarcomatoid renal cell carcinoma and spindle cell carcinoma (J Pathol Bacteriol 1963;85:139, Cancer 1968;22:556, Jpn J Clin Oncol 1997;27:58)
  • Currently not considered its own variant
  • When the background carcinoma subtype is recognized, the primary histologic diagnosis should be the renal cell carcinoma subtype with sarcomatoid dedifferentiation mentioned in the report (e.g., papillary renal cell carcinoma with sarcomatoid features)
    • Sarcomatoid elements, sarcomatoid dedifferentiation, sarcomatoid differentiation, sarcomatoid features and sarcomatoid component are terms that are used interchangeably
    • If pure sarcomatoid with no recognizable epithelial component upon extensive sampling, it should be considered as an unclassified renal cell carcinoma once primary or metastatic sarcoma is excluded
ICD coding
  • ICD-10: C64.9 - malignant neoplasm of kidney, unspecified laterality
Epidemiology
  • Mean age: 60 years
  • M:F = 1.3:1 - 2:1
  • Usually presents with locally advanced or metastatic disease at presentation (stage III or IV)
  • Aggressive with median survival of 4 to 19 months (J Urol 2002;167:65, Oncologist 2012;17:46, Urol Oncol 2015;33:427.e17)
    • Patients with clear cell RCC (ccRCC) with a sarcomatoid component have a worse prognosis than those without at every stage of disease (World J Urol 2016;34:1429)
    • 5 year disease specific survival for stage I, II, III and IV: 77.7%, 67.8%, 35.4% and 3.5%, respectively (Clin Genitourin Cancer 2019;17:e447)
    • For patients with no evidence of disease following nephrectomy, 77% of patients experienced a recurrence; median time to recurrence is 26.2 months (Urol Oncol 2015;33:166.e21)
  • Metastases in decreasing order of prevalence: lung, bones, lymph nodes, liver and brain
Sites
  • Kidney
Pathophysiology
  • Not clearly understood
  • May arise from common cell of origin epithelial cell, which undergoes epithelial mesenchymal transition
    • Beta catenin translocates to nucleus and acts as transcription factor for Snail, a transcriptional repressor for E-cadherin, loses epithelial phenotype and gains mesenchymal characteristics (upregulation of Snail and cytoplasmic N-cadherin) (J Clin Pathol 2011;64:1088, Cancer Sci 2010;101:293)
Diagrams / tables

Images hosted on other servers:

Signalling pathways involved in EMT reported in sRCC

Clinical features
  • 90% symptomatic with pain, gross hematuria, weight loss, fatigue, fever, nights sweats
  • Presentation with advanced / late stage disease and metastasis is common
Diagnosis
  • Sarcomatoid growth represents a pathway of transformation (dedifferentiation) in subtypes of renal cell carcinoma
    • It is associated with poor prognosis and is therefore important to identify and document its presence and percentage
    • It constitutes ISUP / WHO grade 4 in applicable renal cell carcinomas
  • Extensive sampling should be performed in order to identify the primary renal cell carcinoma subtype and rule out involvement by other carcinomas (urothelial, adrenocortical) and sarcomas
  • Immunohistochemistry may be helpful to subtype the neoplasm based on the histologic findings present in one's case and is generally best done in more well differentiated areas
Radiology description
Radiology images

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MRI

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CT with large renal mass

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PET / CT with widespread disease

Prognostic factors
  • Percentage of sarcomatoid component may be prognostic
  • Higher percentage of sarcomatoid dedifferentiation may confer a worse prognosis; recommended to report percentage by ISUP consensus conference (Am J Surg Pathol 2004;28:435, Am J Surg Pathol 2013;37:1490)
    • 6% increase in risk of death for every 10% increase in the amount of sarcomatoid differentiation
    • 52% more likely to die from RCC if tumors contained ≥ 30% sarcomatoid differentiation (BJU Int 2015;115:405)
    • > 40% least likely to be alive at 1 year (Urol Oncol 2015;33:427.e17)
    • > 10% sarcomatoid component had higher risk of death (Urol Oncol 2015;33:427.e17)
    • In ≥ T3, M0 disease, patients with ≥ 25% sarcomatoid features had ~30% increased overall risk of dying of any cause over those without sarcomatoid features
    • Overall survival was not affected by % sarcomatoid in patients with cM1 disease (Clin Genitourin Cancer 2015;13:225)
  • Older age, higher tumor stage and nephrectomy found to independently affect disease specific survival (Clin Genitourin Cancer 2019;17:e447)
Case reports
Treatment
Gross description
  • Grayish white bulging 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.

Heterogeneous white mass

White mass arising from ccRCC



Images hosted on other servers:

Clear cell
RCC with
sarcomatoid
differentiation

Microscopic (histologic) description
  • Areas of sarcomatoid dedifferentiation may be heterogenous or uniform and may display fibrosarcoma-like, pleomorphic undifferentiated sarcoma (malignant fibrous histiocytoma-like) or unclassified morphology
  • Heterologous differentiation such as chondrosarcoma, osteosarcoma or rhabdomyosarcoma is rare
  • Usually fibrosarcoma-like with haphazard, infiltrative growth without well formed fascicles
  • Atypical, spindle cells or tumor giant cells with marked nuclear pleomorphism
  • Frequent mitosis, abnormal mitotic figures
  • Necrosis common
  • Sarcomatoid pattern is due to dedifferentiation from subtype of RCC
  • Metastases of sarcomatoid RCC can exhibit only sarcomatoid (58%), only carcinoma pattern (38%) or both components; > 30% sarcomatoid pattern in primary tumor frequently associated with metastatic sarcomatoid histology (Cancer 2010;116:616)
  • Sarcomatoid morphology by definition is WHO / ISUP grade 4
  • Rhabdoid regions that maintain epithelial features should not be considered sarcomatoid but reported separately (Am J Surg Pathol 2004;28:435, Am J Surg Pathol 2013;37:1490)
  • Biopsy's ability to detect sarcomatoid differentiation low on primary biopsy is ~7.5% (J Urol 2017;198:530)
  • Presence of any amount of sarcomatoid dedifferentiation sufficient for diagnosis of sarcomatoid differentiation (Am J Surg Pathol 2013;37:1490)
  • ISUP consensus conference addressed definition and issues surrounding sarcomatoid RCC (Am J Surg Pathol 2013;37:1490)
    • 41% of participants felt that a tumor is sarcomatoid if it consists of atypical spindle cells and resembles any form of sarcoma
    • 34% voted that a spindle cell morphology need not be present as long as the tumor is very atypical and resembles any form of sarcoma
    • 22% considered a tumor sarcomatoid if it had a spindle cell pattern
    • 3% considered a tumor to be sarcomatoid if it showed early sarcomatoid change characterized by elongation of epithelial tumor cells
    • Consensus among participants (71%) that a minimum proportion of sarcomatoid tumor was not required to make a diagnosis of sarcomatoid carcinoma
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

Virtual slides

Images hosted on other servers:

sRCC with MFH-like pattern

Direct extension of sRCC into spleen

sRCC with fibrosarcoma-like pattern

sRCC with unclassified
pleomorphic to
rhabdomyosarcoma-
like morphology

sRCC with spindle
cell morphology
(left) and high
grade ccRCC (right)

sRCC with spindle cell morphology

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)
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, CEN Case Rep 2021;10:199)
  • Sarcomatoid component in comparison to epithelioid component have
    • Higher mutational burden / hypermutation status
    • More frequent mutations of p53, RELN, SETD2, ARID1A, BAP1 and PTEN which were associated with decreased survival but fewer deletions of genes VHL (3p21-25) and PBRM1 (Clin Cancer Res 2017;23:6686)
      • Reelin (RELN) inhibits TGFB1 induced cell migration
    • 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
  • In a single patient with autosomal dominant polycystic kidney disease and sarcomatoid RCC, there were mutations in ATM (c.9156G>C), CTNNB1 (c.1187A>T) and NF2 (c.1021C>T); gene upregulation in Wnt, PI3K-mTOR, MAPK and interleukin 6 and downregulation of CDKN2A in the sRCC component (Mol Genet Genomic Med 2022;10:e1853)
  • Some had increased expression of BAP1 (10.5%), ARIDA1A (15.7%) and novel somatic single nucleotide variants in FAT1, FAT2, FAT3, TSG101, LRIF1, RQCD1 and PTK7 (Proc Natl Acad Sci U S A 2016;113:2170)
  • Most frequently mutated genes were TP53 (42.3%), CDKN2A (26.9%) and NF2 (19.2%) (Eur Urol 2016;70:348)
  • NF2 mutations may be associated with sarcomatoid papillary RCCs (CEN Case Rep 2021;10:199)
  • Frequency of Hippo-YAP pathway mutations in sRCCs was significantly higher than in nonsarcomatoid RCCs (Sci Rep 2020;10:701)
  • Increased prevalence of JAK2 amplification with coamplification of PDL1 and PDL2 on 9p24.1 locus; finding correlates with higher PDL1 IHC expression than grade 4 ccRCC (Mod Pathol 2019;32:1344, Cancer 2017;123:4823, Cancer Immunol Res 2015;3:1303, CEN Case Rep 2021;10:199)
  • mRNA expression of POLR2A and RUNX2 increased and miR-378 suppressed in sRCC (Anticancer Res 2022;42:811)
  • 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-cadherin to N-cadherin switching, dissociation of beta catenin from the membrane and increased expression of Snail and Sparc (Mol Diagn Ther 2016;20:111)
Sample pathology report
  • Right kidney, radical nephrectomy:
    • Renal cell carcinoma, unclassified (15 cm), ISUP grade 4 of 4, with sarcomatoid and rhabdoid features (see comment)
    • Unifocal
    • Tumor necrosis: present, 25%
    • Sarcomatoid: present, 60%
    • Tumor extension: tumor extends into the renal sinus and into major veins (renal vein or segmental branches), pelvicalyceal system and extends into the perinephric adipose tissue
    • Margins: carcinoma is present in soft tissue at renal vein margin.
    • Lymphovascular invasion: present, extensive
    • Adrenal gland without significant diagnostic alteration; negative for neoplasm
    • Comment: Immunohistochemistry is performed. The carcinoma cells are positive for AMACR, CD10, RCC, CAIX (focal) and TFE3 (patchy). CK7 and HMB45 are negative. Per report, TFE3 FISH is negative. On H&E stained slides, there are areas of tumor with clear cell features and areas of papillary growth with more oncocytic cytoplasm. CAIX displays staining that is not seen in clear cell renal cell carcinoma. Therefore, the tumor is best categorized as renal cell carcinoma, unclassified, due to the heterogeneity of morphological findings and unclear immunohistochemical pattern.
Differential diagnosis
Board review style question #1
Missing Image


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

  1. It is associated with lower stage
  2. This finding has a worse prognosis
  3. This finding has an improved prognosis
  4. There is no prognostic implication
Board review style answer #1
B. This finding has a worse prognosis. Renal carcinomas with higher percentages of sarcomatoid differentiation have a worse prognosis including distant metastases at time of nephrectomy and higher overall mortality than if no sarcomatoid component was identified. In a recent study, tumor necrosis and sarcomatoid differentiation was associated with increased risk of progression, poor prognosis and decreased overall survival and was proposed as a reproducible component of a 2 tiered chromophobe grading system (Annals of Oncol 2019;30:361).

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Reference: Sarcomatoid renal cell carcinoma
Board review style question #2
Missing Image


    A radical nephrectomy specimen is received and a gross image is shown above. 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 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, which was proven histologically. The yellow background of the tumor is consistent grossly with a clear cell renal cell carcinoma.

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Reference: Sarcomatoid renal cell carcinoma
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