Bone & joints

Undifferentiated / poorly differentiated small round / spindle cell tumor

BCOR::CCNB3 sarcoma


Editorial Board Member: Farres Obeidin, M.D.
Deputy Editor-in-Chief: Borislav A. Alexiev, M.D.
Kemal Kösemehmetoğlu, M.D.

Last author update: 1 June 2022
Last staff update: 1 June 2022

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PubMed Search: BCOR::CCNB3 sarcoma

Kemal Kösemehmetoğlu, M.D.
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Cite this page: Kösemehmetoğlu K. BCOR::CCNB3 sarcoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/boneBCORCCNB3.html. Accessed July 6th, 2022.
Definition / general
  • Undifferentiated round cell sarcoma characterized by BCOR::CCNB3 rearrangement (previously Ewing-like sarcoma)
Essential features
  • Predominantly arises from the bones of children and young adult males
  • Sheets or fascicles of round and spindle cells forming whorls and hemangiopericytic patterns, usually within a myxoid background
  • Nuclear CCNB3 and BCOR positivity as well as TLE1 and SATB2 coexpression
  • Molecular diagnosis is highly recommended: BCOR::CCNB3
  • Similar treatment and comparable prognosis with Ewing sarcoma
Terminology
  • BCOR::CCNB3 positive sarcoma
  • Undifferentiated round cell sarcoma with BCOR::CCNB3 fusion
Epidemiology
  • Children and young adult males (mean age is 15; M:F = 3.1) (Am J Surg Pathol 2018;42:604, Nat Genet 2012;44:461, Rekhi B et al. (in press) Spectrum of Histopathological, Immunohistochemical, Molecular and Radiological Features in Seven Cases of BCOR::CCNB3-Positive Sarcomas with Literature Review. Ann Diagn Pathol)
  • Accounts for 4% of undifferentiated round cell sarcomas (Surg Pathol Clin 2017;10:587)
Sites
Pathophysiology
  • Both CCNB3 itself and BCOR::CCNB3 as a full fusion transcript seem to play a role in oncogenesis and phenotype (Nat Genet 2012;44:461)
Etiology
  • Unknown
Clinical features
  • Mainly metastasizes to the lung
Diagnosis
  • Core needle biopsy
  • Confirmatory demonstration of BCOR::CCNB3 fusion by FISH, PCR or massive parallel sequencing (MPS)
  • Reference: Rekhi B et al. (in press) Spectrum of Histopathological, Immunohistochemical, Molecular and Radiological Features in Seven Cases of BCOR::CCNB3-Positive Sarcomas with Literature Review. Ann Diagn Pathol
Radiology description
  • Permeative lytic / sclerotic tumor invariably associated with cortical thickening in the metadiaphyseal region of long bones
  • Wide zone of transition with periosteal reaction
  • MRI: iso or hypointense on T1 and heterogeneously hyperintense on T2 with postcontrast enhancement
  • PET CT: mean SUVmax = 6.3 (range: 5.7 - 6.9)
  • Reference: Skeletal Radiol 2021;50:521
Radiology images

Contributed by F. Bilge Ergen, M.D.

Plain Xray features

MRI of BCOR::CCNB3 sarcoma

Prognostic factors
Case reports
Treatment
Gross description
  • 5 - 15 cm (median of 10 cm)
  • Well circumscribed, gray-cream colored, soft and fleshy, solid, homogeneous mass with necrotic foci
  • Metadiaphysis of long bones with soft tissue involvement
  • Reference: Rekhi B et al. (in press) Spectrum of Histopathological, Immunohistochemical, Molecular and Radiological Features in Seven Cases of BCOR::CCNB3-Positive Sarcomas with Literature Review. Ann Diagn Pathol
Gross images

Contributed by Kemal Kösemehmetoğlu, M.D.

BCOR::CCNB3 sarcoma of radius

Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Kemal Kösemehmetoğlu, M.D.

Typical morphology of BCOR::CCNB3 sarcoma

High power cytological morphology

Various cellularity

Hemangiopericytic pattern


Whorling pattern

Subtle osteoid formation

Epithelioid balls and nests

Telangiectatic areas

CCNB3 expression

CD99


BCOR

SATB2

TLE1

Focal EMA expression

Diffuse cyclin D1 expression

Cytology description
Cytology images

Contributed by Kemal Kösemehmetoğlu, M.D.

Cytological features of BCOR::CCNB3

Molecular / cytogenetics description
  • Accounts for 60% of BCOR gene alterations (BCOR internal tandem duplication [ITD]); other partner genes are MAML3 and ZC3H7B
  • Paracentric inversion on chromosome X resulting in recurrent gene fusion of BCOR (encoding BCL6 interacting corepressor) on Xp11.4 and CCNB3 (cyclin B3) on Xp11.22
  • Gene profiling and single nucleotide polymorphism (SNP) analyses resulted in a distinct cluster from small round cell sarcomas, including Ewing sarcoma (Nat Genet 2012;44:461)
Molecular / cytogenetics images

Contributed by Kemal Kösemehmetoğlu, M.D.

Reverse transcription PCR for BCOR::CCNB3

Videos

BCOR::CCNB3 sarcoma of the proximal tibia

Sample pathology report
  • Proximal metadiaphyseal region of the right tibia, incisional biopsy:
    • BCOR::CCNB3 sarcoma (see comment)
    • Comment: Undifferentiated round and spindle neoplastic cells showed dot-like CD99 staining as well as TLE1 and SATB2 coexpression. BCOR and CCNB3 were diffusely positive. Breakapart FISH was negative for EWSR1 or SYT rearrangements. On reverse transcription PCR, BCOR::CCNB3 fusion product / band was observed at 140 bp.
Differential diagnosis
Additional references
Board review style question #1


Biopsy from a lytic mass located at the proximal part of the right tibia of a 15 year old boy is represented in the above figures. Immunohistochemically, tumor cells showed a dot-like CD99 expression as well as TLE1 and SATB2 coexpression. Desmin and AE1 / AE3 were negative. What is the expected molecular alteration of this tumor?

  1. BCOR::CCNB3
  2. CIC-DUX4
  3. EWSR1-FLI1
  4. EWSR1-NFATC2
  5. SYT-SSX
Board review style answer #1
A. BCOR::CCNB3

Comment Here

Reference: BCOR::CCNB3 fusion
Board review style question #2
Which following the clinicopathological settings is the most suitable for BCOR::CCNB3 sarcoma?

  1. CD99 and SATB2 positive bone producing sarcoma with prominent pleomorphism in the right distal femur
  2. Large and deep soft tissue mass in the lower leg of an elderly man
  3. Lytic bone tumor composed of small round to spindle cells with an abrupt transition in a 17 year old boy
  4. Lytic mass in the proximal humerus of a 65 year old woman
  5. NKX2.2 positive small round cell tumor in the vertebra of a 15 year old boy
Board review style answer #2
C. Lytic bone tumor composed of small round to spindle cells with an abrupt transition in a 17 year old boy

Comment Here

Reference: BCOR::CCNB3 fusion
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