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Undifferentiated small round cell sarcoma of bone and soft tissue

Undifferentiated pleomorphic sarcoma


Yelena Piazza, M.D.
Hatem Kaseb, M.D., Ph.D., M.P.H.

Last author update: 29 February 2024
Last staff update: 29 February 2024

Copyright: 2003-2024, PathologyOutlines.com, Inc.

PubMed search: Undifferentiated pleomorphic sarcoma

Yelena Piazza, M.D.
Hatem Kaseb, M.D., Ph.D., M.P.H.
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Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | 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 #2
Cite this page: Piazza Y, Kaseb H. Undifferentiated pleomorphic sarcoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/boneMFH.html. Accessed April 20th, 2024.
Definition / general
  • Undifferentiated pleomorphic sarcoma (UPS) is a pleomorphic malignant neoplasm of bone lacking a distinct line of differentiation
Essential features
  • Distinct clinicopathologic entity in the WHO Soft Tissue and Bone Tumours classification (5th edition)
  • Mesenchymal tumor of bone
  • Pleomorphic spindle shaped and epithelioid cells in a storiform or fascicular growth pattern
  • No osteoid or cartilage matrix production
  • No identifiable line of differentiation; diagnosis of exclusion
  • Diagnosis requires correlation with clinical, radiological and pathologic findings
Terminology
  • Malignant fibrous histiocytoma of bone, pleomorphic fibrosarcoma of bone
    • This terminology is currently not recommended
ICD coding
  • ICD-O: 8802/3 - pleomorphic cell sarcoma
  • ICD-11: 2B54 & XH0947 - unclassified pleomorphic sarcoma, primary site & malignant fibrous histiocytoma
Epidemiology
Sites
  • Usually unicentric (Cancer 1997;79:482)
  • Long tubular bones, particularly around the knee (Cancer 1997;79:482)
  • Femur is most commonly involved, followed by tibia and humerus
  • Among the bones of the trunk, pelvic bones are most commonly affected
Pathophysiology
  • Shows many diverse genetic alterations and chromosomal structural aberrations
  • Chromosomal losses of 8p, 9p, 10, 13q and 18q and gains of 4q, 5p, 6p, 7p, 8q, 12p, 14q, 17q, 19p, 20q, 22q and X have been reported
  • Loss of heterozygosity in multiple genes has been reported, including
  • Mutations in TP53 (~30%) or chromatin remodeling genes (~40%) including ATRX, DOT1L and H3F3A are most frequent (J Pathol 2019;247:166)
Etiology
  • Largely unclear and unknown
  • First described in 1972 by Frieda Feldman and David Norman (Radiology 1972;104:497)
  • Most cases are de novo (primary) (Semin Diagn Pathol 2021;38:163, Cancer 1997;79:482)
  • Secondary (nearly 30% of cases)
    • Some cases arise from preexisting bone disease
      • Bone infarct, Paget disease
    • Prior irradiation in the field of the affected bone
    • Rare cases were associated with metallic prosthesis or hardware
    • Some cases associated with hereditary diaphyseal medullary stenosis (Hardcastle syndrome)
Clinical features
Diagnosis
  • Diagnosis requires correlation with clinical, radiological and pathologic findings
  • Pathologic findings
    • Pleomorphic spindle shaped and epithelioid cells in a storiform or fascicular growth pattern
    • No osteoid or cartilage matrix production
    • No identifiable line of differentiation; diagnosis of exclusion
Radiology description
  • Radiological features are nonspecific but the majority of cases demonstrate an aggressive osteolytic neoplasm with ill defined margins, cortical destruction, an associated soft tissue mass and pathologic fracture (Skeletal Radiol 2021;50:1491)
  • On magnetic resonance imaging (MRI), the tumor is heterogeneous on T1 and T2 weighted images (Semin Diagn Pathol 2021;38:163)
  • Tumors are usually centered in the metadiaphyseal region of long bones and occasionally extend into the epiphysis
Radiology images

Contributed by AFIP and Mark R. Wick, M.D.
Radiograph of tibial tumor

Radiograph of tibial tumor

Primary, distal femur

Primary, distal femur

Prognostic factors
  • Depends on staging
  • Overall, 5 year and 10 year survival rates of 38.3% and 30.5%, respectively (J Surg Oncol 2020;121:1097)
  • Localized disease tends to have a favorable prognosis
  • Secondary undifferentiated pleomorphic sarcoma and metastatic disease are associated with a poorer prognosis
Case reports
Treatment
  • Radical surgery with adjuvant chemotherapy
  • Radiotherapy for unresectable tumors
Gross description
  • Tumor is usually centered in the medullary cavity (Semin Diagn Pathol 2021;38:163)
  • Tumor grows with a permeative pattern, encasing preexisting bony trabecula (Semin Diagn Pathol 2021;38:163)
  • Variable color (white-gray, tan-yellow and tan-brown)
  • Typically shows cortical bone destruction and soft tissue mass
  • Areas of necrosis and hemorrhage
Gross images

Contributed by Mark R. Wick, M.D.
Primary

Primary

Microscopic (histologic) description
  • Usually hypercellular and composed of spindle shaped, epithelioid or polygonal cells with marked pleomorphism arranged in a haphazard, storiform and fascicular growth pattern
  • Background could be hyalinized with some inflammatory cells
  • No osteoid or cartilaginous matrix
  • Usually atypical mitotic figures and necrosis is present
  • Considered a grade 3 sarcoma and is distinguished from grade 2 adult type fibrosarcoma by the significantly greater degree of atypia and architectural arrangement (Semin Diagn Pathol 2021;38:163)
Microscopic (histologic) images

Contributed by Hatem Kaseb, M.D., Ph.D., M.P.H., Mark R. Wick, M.D. and AFIP
Significant pleomorphism   Significant pleomorphism

Significant pleomorphism

Significant pleomorphism   Significant pleomorphism

Significant pleomorphism


Significant pleomorphism

Significant pleomorphism

Fascicles of fibroblasts

Fascicles of fibroblasts

Irregular deposits of noncalcified collagen

Noncalcified collagen

Negative stains
Sample pathology report
  • Bone, right distal femur, radical resection (status postneoadjuvant chemotherapy):
    • Residual undifferentiated pleomorphic sarcoma of bone (see synoptic report)
    • Synoptic report
      • Tumor size: 11.3 x 8.0 x 8.0 cm
      • Tumor location: right distal femur
      • Percent treatment response: ~80% (~20% residual viable tumor)
      • Discontinuous tumor foci: not identified
      • Lymphovascular invasion: not identified
      • Surgical margins: negative for tumor
      • Lymph nodes: 1 benign lymph node (0/1)
      • Additional findings: biopsy site
      • Stage (AJCC, 8th edition): ypT2 ypN0
Differential diagnosis
  • High grade sarcomas:
    • Osteosarcoma:
      • Typically shows osteoid matrix and positive SATB2
    • Leiomyosarcoma:
      • Some areas could show fascicles of spindled cells
      • SMA positivity with an additional myogenic marker
    • Rhabdomyosarcoma:
      • Shows distinct morphological features of types, such as alveolar or embryonal
      • Typically positive for desmin, myogenin and MyoD1
    • Synovial sarcoma:
      • Morphology consistent with monophasisc or biphasic could be helpful for differentiation
      • Harbors t(X;18)(p11;q11) SYT::SSX fusion
  • Metastatic sarcomatoid carcinoma:
    • Typically has a different clinical presentation
    • Usually partially / diffusely CK positive
  • Metastatic carcinoma:
    • Typically has a different clinical presentation
    • Usually positive for CK7 or CK20 or both, depending on the primary tumor site
  • Metastatic melanoma:
    • Typically has a different clinical presentation
    • On morphology, pigment seen in the cytoplasm or cells with prominent eosinophilic nucleoli could be helpful for differentiation
    • Usually positive for S100, SOX10, MelanA or HMB45
  • Dedifferentiated chondrosarcoma:
    • Usually shows IDH1 or IDH2 mutations (Hum Pathol 2017:65:239)
    • Usually shows a well differentiated cartilaginous component
    • Shows some distinct clinical, radiologic and pathologic features
  • Fibrous dysplasia:
    • Caused by mutations in GNAS gene
Board review style question #1


Which of the following stains is usually positive in undifferentiated pleomorphic sarcoma of bone?

  1. CD31
  2. Desmin
  3. Myogenin
  4. SATB2
  5. Vimentin
Board review style answer #1
E. Vimentin. The only stain that is usually positive in undifferentiated pleomorphic sarcoma of bone is vimentin. Answers A - D are incorrect because CD31, desmin, myogenin and SATB2 are usually negative or show focal positivity in this tumor.

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Reference: Undifferentiated pleomorphic sarcoma
Board review style question #2
Which of the following risk factors has been associated with undifferentiated pleomorphic sarcoma of bone?

  1. Diaphyseal medullary stenosis
  2. Ethnic origin
  3. Increased alcohol consumption
  4. Nonmetallic prosthesis or hardware
  5. Smoking
Board review style answer #2
A. Diaphyseal medullary stenosis. Diaphyseal medullary stenosis has been shown to be associated with undifferentiated pleomorphic sarcoma of bone. Answers B - E are incorrect because all of these other risk factors have not been shown to be associated with undifferentiated pleomorphic sarcoma of bone.

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Reference: Undifferentiated pleomorphic sarcoma
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