Bone & joints
Undifferentiated small round cell sarcoma of bone and soft tissue
BCOR::CCNB3 sarcoma
Author: Kemal Kösemehmetoğlu, M.D.
Editorial Board Member: Farres Obeidin, M.D.
Deputy Editor-in-Chief: Borislav A. Alexiev, M.D.
Last author update: 1 June 2022
Last staff update: 8 February 2023
Copyright: 2022, PathologyOutlines.com, Inc.
PubMed Search: BCOR::CCNB3 sarcoma
Table of Contents
Definition / general | Essential features | Terminology | 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 | Cytology description | Cytology images | Positive stains | Negative stains | Molecular / cytogenetics description | Molecular / cytogenetics images | Videos | 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: Kösemehmetoğlu K. BCOR::CCNB3 sarcoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/boneBCORCCNB3.html. Accessed November 30th, 2024.
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, Int J Surg Pathol 2023 Jan 2 [Epub ahead of print])
- Accounts for 4% of undifferentiated round cell sarcomas (Surg Pathol Clin 2017;10:587)
Sites
- Bone > soft tissues > viscera (e.g., kidney) (Am J Surg Pathol 2018;42:604, Nat Genet 2012;44:461)
- Mostly long bones > pelvis > vertebral column
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: Int J Surg Pathol 2023 Jan 2 [Epub ahead of print]
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
- Prognosis is comparable to Ewing sarcoma and less aggressive than CIC-DUX4 sarcoma
- 5 year overall survival is 75%; disease free survival is 70% (Pediatr Blood Cancer 2014;61:2191, Am J Surg Pathol 2018;42:604)
Case reports
- 1 year old boy with refractory pediatric BCOR::CCNB3 sarcoma with complete response to palbociclib (JCO Precis Oncol 2020;4:PO.19.00258)
- 11 and 12 year old boys with primary renal sarcomas with BCOR::CCNB3 fusion (Am J Surg Pathol 2017;41:1702)
- 18 year old man with a primary renal sarcoma (Int J Surg Pathol 2021;29:194)
Treatment
- Similar to Ewing sarcoma
- Neoadjuvant chemotherapy with Ewing regimen followed by surgery or radiation for local control (Pediatr Blood Cancer 2014;61:2191)
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: Int J Surg Pathol 2023 Jan 2 [Epub ahead of print]
Gross images
Contributed by Kemal Kösemehmetoğlu, M.D.
BCOR::CCNB3 sarcoma of radius
Microscopic (histologic) description
- Round or spindle cells arranged in sheets or fascicles
- Angulated and hyperchromatic nuclei with fine chromatin and inconspicuous nucleoli
- Wide range of mitosis (5 - 60/10 high power fields, median of 30) (Pediatr Blood Cancer 2014;61:2191)
- Small foci of necrosis (50 - 90%)
- Significant variation in cellularity and morphological patterns, usually with an abrupt transition:
- Small clusters of epithelioid cells (Virchows Arch 2017;470:373)
- Nests and cords of tumor cells
- Myxoid background (50%) (Am J Surg Pathol 2018;42:604)
- Collagenous stroma (36%) (Am J Surg Pathol 2018;42:604)
- Hemangiopericytic pattern
- Whorling pattern
- Hemorrhagic / telangiectatic areas
- References: Am J Surg Pathol 2017;41:1713, Am J Surg Pathol 2014;38:1307, Am J Surg Pathol 2018;42:604, Nat Genet 2012;44:461, Pediatr Blood Cancer 2014;61:2191, Indian J Med Res 2019;150:557, Virchows Arch 2017;470:373, Mod Pathol 2015;28:575
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
- Round, spindle and rhabdoid-like cells
- Double cell population similar to Ewing sarcoma (larger, lighter cells and smaller, darker cells)
- Small clusters with thin and delicate vascular cores (in contrast to thicker vascular cores in Ewing sarcoma and synovial sarcoma)
- References: Cytopathology 2021;32:771, Am J Clin Pathol 2020;153:315
Cytology images
Contributed by Kemal Kösemehmetoğlu, M.D.
Cytological features of BCOR::CCNB3
Positive stains
- CCNB3 (~100%; nuclear) (Nat Genet 2012;44:461, Am J Surg Pathol 2017;41:1713, Indian J Med Res 2019;150:557)
- BCOR (~100%; nuclear) (Virchows Arch 2017;470:373, Am J Surg Pathol 2017;41:1713)
- CD99 (60 - 80%; dot-like: 50%; cytoplasmic: 25%; membranous: 16%) (Nat Genet 2012;44:461, Pediatr Blood Cancer 2014;61:2191, Indian J Med Res 2019;150:557)
- SATB2 (80 - 90%) (Am J Surg Pathol 2018;42:604)
- TLE1 (60 - 80%) (Am J Surg Pathol 2017;41:1713)
- Cyclin D1 (90 - 100%) (Am J Surg Pathol 2017;41:1713, Am J Surg Pathol 2018;42:604)
- BCL2 (80 - 100%) (Am J Surg Pathol 2017;41:1713, Am J Surg Pathol 2014;38:1307)
- CD56 (80%) (Am J Surg Pathol 2017;41:1713)
Negative stains
- SMA, desmin, myogenin, MyoD1
- S100, SOX10
- NKX2.2 (0 - 30%)
- WT1
- CD34
- Pankeratin (AE1 / AE3), CAM5.2
- EMA (positive up to 30%) (Am J Surg Pathol 2017;41:1713, Histopathology 2016;69:792)
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
- Mainly other small round cell tumors
- Ewing sarcoma:
- CIC-DUX4 sarcoma:
- Median age is higher
- Soft tissue > bone
- Sheets separated with septi
- Prominent nucleoli
- WT1+, ETV4+
- CIC-DUX4 fusion
- Small cell osteosarcoma:
- CD99-
- Small cell osteosarcoma can also be positive for CD99, so positive staining with this marker is not helpful (J Bone Oncol 2020;24:100305)
- Osteoid production may be seen in both
- Lacks specific gene fusion
- CD99-
- Synovial sarcoma:
- Rare in bone
- Both synovial sarcoma and BCOR::CCNB3 sarcomas are TLE1+
- EMA can be focally positive in BCOR::CCNB3 sarcoma but pankeratin is negative
- SS18-SSX fusion specific antibody and SSX C terminus positive
- SYT-SSX fusion
- Rhabdomyosarcoma:
- Sclerosing epithelioid fibrosarcoma / low grade fibromyxoid tumor:
- Rare in bone
- Cords of small to epithelioid cells in collagenous background
- MUC4+
- EWSR1-CREBL1/2 fusion
- Malignant peripheral nerve sheath tumor:
- Neuroblastoma (metastasis):
- CD99-
- PHOX12B+, synaptophysin+
- Lacks BCOR alteration
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?
- BCOR::CCNB3
- CIC-DUX4
- EWSR1-FLI1
- EWSR1-NFATC2
- SYT-SSX
Board review style answer #1
Board review style question #2
Which following the clinicopathological settings is the most suitable for BCOR::CCNB3 sarcoma?
- CD99 and SATB2 positive bone producing sarcoma with prominent pleomorphism in the right distal femur
- Large and deep soft tissue mass in the lower leg of an elderly man
- Lytic bone tumor composed of small round to spindle cells with an abrupt transition in a 17 year old boy
- Lytic mass in the proximal humerus of a 65 year old woman
- 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
Comment Here
Reference: BCOR::CCNB3 fusion
