Bladder & urothelial tract
Urothelial carcinoma - invasive
Sarcomatoid variant
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Last author update: 14 May 2021
Last staff update: 16 August 2024
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PubMed Search: Urothelial carcinoma sarcomatoid renal pelvis
See also: Urothelial carcinoma of renal pelvis
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Frozen section description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Brown ML, Tretiakova M. Sarcomatoid variant. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bladdersarcomatoidvariant.html. Accessed December 27th, 2024.
Definition / general
- Variant of urothelial carcinoma; morphologically indistinguishable from sarcoma
- Heterologous elements may be present (Histopathology 2019;74:77)
Essential features
- Biphasic malignant neoplasm with morphologic and immunohistochemical evidence of both epithelial and mesenchymal differentiation
- Rare (0.3 - 0.6% of all urothelial carcinomas) and biologically aggressive variant
- Associated with radiation therapy or cyclophosphamide
- If present, heterologous elements should be mentioned in the report
Terminology
- WHO recommends the term sarcomatoid variant of urothelial carcinoma for these biphasic malignant neoplasms
- Terms carcinosarcoma, metaplastic carcinoma, spindle cell carcinoma and malignant mixed tumor have been used interchangeably but can lead to confusion and are therefore discouraged
ICD coding
- Location based ICD-10 coding:
- Renal pelvis, including pelviureteric junction and renal calyces
- Ureter, including ureteric orifice of bladder
- Bladder
- C67.0 - malignant neoplasm of trigone of bladder
- C67.1 - malignant neoplasm of dome of bladder
- C67.2 - malignant neoplasm of lateral wall of bladder
- C67.3 - malignant neoplasm of anterior wall of bladder
- C67.4 - malignant neoplasm of posterior wall of bladder
- C67.5 - malignant neoplasm of bladder neck
- C67.6 - malignant neoplasm of ureteric orifice
- C67.7 - malignant neoplasm of urachus
- C67.8 - malignant neoplasm of overlapping sites of bladder
- C67.9 - malignant neoplasm of bladder, unspecified
Epidemiology
- Estimated to represent 0.3 - 0.6% of all urothelial carcinomas (Mod Pathol 2009;22:S96, Eur Urol Focus 2020;6:653)
- Seen in up to 2.4% of all high grade urothelial carcinomas in renal pelvis
- Age 45 - 82 years (mean 71.6); M > F (2 - 3:1) (Oncol Lett 2014;8:1208, Pathol Res Pract 1996;192:1218)
- Although rare, sarcomatoid carcinoma is more common than primary sarcoma
Sites
- Kidney pelvis, proximal ureter and bladder
Pathophysiology
- TERT C228T promoter mutations in 35% of sarcomatoid carcinoma (Histopathology 2019;74:77, Eur Urol Focus 2020;6:653)
Etiology
- Probably has a common malignant clonal origin, with epithelial and mesenchymal differentiation (J Pathol 2007;211:420)
- Common final pathway of all forms of bladder tumors, supported by molecular and morphologic evidence (Histopathology 2019;74:77)
- Risk factors include previous exposure to radiotherapy and intravesicular cyclophosphamide (Eur Urol Focus 2020;6:653)
Clinical features
- Gross hematuria, flank pain, an abdominal mass and hydronephrosis
- Similar to those of conventional urothelial tumors
- Reference: ISRN Urol 2014;2014:794563
Diagnosis
- Cystoscopy
- CT scan
- MRI
- Reference: ISRN Urol 2014;2014:794563
Laboratory
- Hematuria
Radiology description
- Thickened bladder wall with or without intraluminal papillary or nodular mass; heterologous elements such as calcification in osteosarcoma may be demonstrated (Radiographics 2006;26:553)
Prognostic factors
- Poor prognosis, as frequently presents at an advanced stage and is associated with a worse overall survival when compared with pure urothelial carcinoma (Eur Urol Focus 2020;6:653)
- Similar to bladder, sarcomatoid urothelial carcinoma of renal pelvis has a worse prognosis on univariate analysis (ISRN Urol 2014;2014:794563, Oncol Lett 2014;8:1208, J Urol 2012;188:398)
- Associated with higher tumor stage, multifocality, tumor necrosis, frequent metastases at presentation; however, insufficient case numbers in kidney to confirm independent negative prognostic impact on multivariate analysis (J Urol 2012;188:398)
- May have heterologous elements, without definite prognostic significance (Mod Pathol 2009;22:S96)
Case reports
- 49 year old man with urothelial carcinoma arising in renal pelvis with exuberant chondrosarcomatous element (Indian J Pathol Microbiol 2014;57:284)
- 63 year old man with squamous cell and sarcomatoid variant urothelial carcinoma (BMC Surg 2021;21:96)
- 68 year old man with sarcomatoid carcinoma arising in renal pelvis (Open J Pathol 2013;3:96)
- 72 year old man with sarcomatoid urothelial carcinoma of the ureter with heterologous elements of chondrosarcoma and osteosarcoma and divergent squamous differentiation (Urol Case Rep 2020;34:101484)
- Sarcomatoid carcinoma of renal pelvis with giant cell tumor-like features (Int J Urol 2005;12:199)
Treatment
- Chemotherapy resistant (Eur Urol Focus 2020;6:653)
- No standard treatment due to rarity (Cancer Cell Int 2020;20:550)
Gross description
- Gray fleshy cut surface with infiltrative margins similar to sarcoma in appearance
Gross images
Contributed by Nicole K. Andeen, M.D. and Maria Tretiakova, M.D., Ph.D.
Mass involving hilum
Frozen section description
- Not typically diagnosed on frozen section
Microscopic (histologic) description
- Most common component is undifferentiated high grade spindle cell sarcoma (Histopathology 2019;74:77)
- Sarcomatoid areas admixed with conventional high grade urothelial carcinoma
- Spindle cell component may account for 10% to > 60% of tumor
- Epithelial component has urothelial differentiation or less commonly squamous or glandular differentiation
- Highly variable and can mimic nonepithelial neoplasms (J Biol Chem 2019;294:1579)
- Most common heterologous element is osteosarcoma, followed by chondrosarcoma, rhabdomyosarcoma, leiomyosarcoma, liposarcoma and angiosarcoma (Histopathology 2019;74:77)
Microscopic (histologic) images
Contributed by Megan L. Brown, M.D., Nicole K. Andeen, M.D., Maria Tretiakova, M.D., Ph.D. and Kenneth A. Iczkowski, M.D.
High grade spindled to epithelioid cells
Elongated spindled cells
Classic urothelial carcinoma
Neoplasm with admixed carcinomatous and sarcomatous elements
Osteosarcomatoid differentiation
GATA3 and CK7
Positive stains
- Spindle cell component: vimentin (100%), EMA (100%), SMA (73%), AE1 / AE3 (70%), OSCAR cytokeratin (68%), p63 (50%), GATA3 and CK7 (Am J Surg Pathol 2009;33:99, Pathol Res Pract 1996;192:1218)
- PAX8 variable (Histopathology 2019;74:77)
Negative stains
- ALK1 (Am J Surg Pathol 2009;33:99)
- Desmin, calponin, h-caldesmon, myogenin (Histopathology 2019;74:77)
- CK5/6 (27% positive), 34βE12 (25% positive)
Molecular / cytogenetics description
- Overexpression of markers representative of epithelial - mesenchymal transition, including vimentin, FOXC2, SNAIL and ZEB1 (Histopathology 2019;74:77)
- TERT C228T promoter mutations in 35% of sarcomatoid carcinoma (Histopathology 2019;74:77, Eur Urol Focus 2020;6:653)
- Studies in urinary bladder showed:
- Similar patterns of allelic losses (J Pathol 2007;211:420)
- Similar TP53 point mutations between the carcinomatous and sarcomatous elements (Mod Pathol 2009;22:113)
- This suggests a common clonal origin with divergent differentiation (J Pathol 2007;211:420)
Sample pathology report
- Bladder, transurethral resection:
- High grade urothelial carcinoma with sarcomatoid differentiation (80%) (see comment)
- Comment: Invasive of muscularis propria (T2)
- Angiolymphatic invasion absent
- Muscularis propria present, involved by tumor
Differential diagnosis
- Inflammatory myofibroblastic tumor (IMT):
- IMT does not have associated malignant epithelial component
- Immunohistochemically, IMT expresses pankeratins but is usually negative for high molecular weight cytokeratins 34βE12 and CK5/6 and should express ALK (Histopathology 2009;55:491)
- Primary or metastatic sarcoma
- Sarcomatoid renal cell carcinoma:
- Identification and classification of associated in situ or invasive epithelial component is necessary; may require additional sampling and immunostaining
- Urothelial carcinoma with pseudosarcomatous stroma:
- Characterized by myxoid stroma, blood vessels and atypical cells
- Unlike sarcomatoid urothelial carcinoma, the stromal component lacks an expansile growth pattern, mitoses or expression of epithelial markers (Arch Pathol Lab Med 2007;131:1244, Mod Pathol 2009;22:S96)
Additional references
Board review style question #1
A 65 year old presented with bladder wall thickening on ultrasound. Transurethral resection of bladder tumor is performed and shows a lesion with features on H&E as seen in the image shown above. Which of the following is likely in the patient’s medical history?
- Asbestos exposure
- Family history of prostate adenocarcinoma
- High nitrate consumption in their diet
- Intravesical cyclophosphamide
- Woodworking hobby
Board review style answer #1
D. Intravesical cyclophosphamide has been associated with the development of sarcomatoid variant of urothelial carcinoma (Eur Urol Focus 2020;6:653)
Comment Here
Reference: Sarcomatoid variant
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Reference: Sarcomatoid variant
Board review style question #2
What is the most commonly identified heterologous element identified in association with the pictured lesion?
- Chondrosarcoma
- Leiomyosarcoma
- Liposarcoma
- Osteosarcoma
- Rhabdomyosarcoma
Board review style answer #2
D. Osteosarcoma is the most commonly identified heterologous element in the sarcomatoid variant of urothelial carcinoma (Histopathology 2019;74:77)
Comment Here
Reference: Sarcomatoid variant
Comment Here
Reference: Sarcomatoid variant
