Soft tissue
Uncertain differentiation
CIC-DUX4 fusion tumor


Topic Completed: 15 September 2020

Minor changes: 15 September 2020

Copyright: 2020, PathologyOutlines.com, Inc.

PubMed Search: Bone CIC-DUX4 fusion tumor

Borislav A. Alexiev, M.D.
Lawrence J. Jennings, M.D., Ph.D.
Page views in 2020 to date: 1,200
Cite this page: Alexiev B, Jennings L. CIC-DUX4 fusion tumor. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/boneCICDUX4.html. Accessed November 25th, 2020.
Definition / general
Essential features
Terminology
  • Undifferentiated round cell sarcoma with CIC-DUX4 fusion
ICD coding
  • ICD-O: 8803/3 - Small cell sarcoma
Epidemiology
Sites
Etiology
  • CIC-DUX4 fusion oncoprotein potentiates the transcriptional activity of CIC and activates the expression ETV1/4/5, which is a member of the E26 transformation specific (ETS) family of transcription factors (Sci Rep 2020;10:684)
  • MYC amplification in majority of cases (Mod Pathol 2015;28:57)
Clinical features
Diagnosis
Radiology description
  • Large heterogeneous appearing hypermetabolic mass on PET / CT
Radiology images

Contributed by Borislav Alexiev, M.D.

PET / CT

Prognostic factors
Case reports
Treatment
Gross description
Gross images

Contributed by Borislav Alexiev, M.D.

Soft tissue mass

Frozen section description
  • Diagnosis of CIC-DUX4 sarcoma on a small tissue fragment without molecular studies would be challenging
Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Borislav Alexiev, M.D.

Chest wall mass

Small round cell morphology

Solid growth pattern

Spindle cell morphology

Mitoses

Myxoid stroma


CD99 expression

WT1 expression

MYC expression

Cytology description
  • Hypercellular smears, with tumor cells arranged in large groups and singly dispersed
  • Individual cells with high nuclear to cytoplasmic ratio, eccentric round to ovoid nuclei, irregular nuclear contours and small nucleoli (Diagn Cytopathol 2018;46:958)
  • Cytoplasmic vacuoles (Cancer Cytopathol 2016;124:350)
  • Mitotic figures
  • Necrosis
  • Myxoid stromal component
Electron microscopy description
  • Heterogeneity: in cell density, from tightly packed to loosely unconnected areas (Ultrastruct Pathol 2020;44:237)
  • Polygonal to pleomorphic cells with small processes
  • Round, oval, polygonal or elongated nuclei
  • Abundant glycogen in the cytoplasm and rare cell adhesions
  • No neuroendocrine granules present
Molecular / cytogenetics description
Molecular / cytogenetics images

Contributed by Lawrence J. Jennings, M.D., Ph.D.

Real time RT-PCR

Sample pathology report
  • Chest wall mass, excision:
    • CIC-DUX4 associated undifferentiated small round cell sarcoma (see comment)
    • Comment: There is a subcutaneous solid nodular proliferation of small to medium sized round / ovoid and spindle cells with scant amount of amphophilic or lightly eosinophilic cytoplasm. The cells contain medium sized round to oval vesicular nuclei with small nucleoli. High mitotic activity (21 mitoses/10 high power fields) and areas of necrosis are present. Patchy myxoid or edematous stromal changes are seen.
    • Immunohistochemically the cells have strong expression of CD99, WT1 (N terminal) and MYC while are negative for pankeratin AE1 / AE3, EMA, myogenin, S100 and SOX10. INI1 is preserved. The tumor is positive for CIC-DUX4 fusion transcript.
    • This constellation of morphological, immunohistochemical and molecular features strongly supports the diagnosis of CIC-DUX4 associated undifferentiated small round cell sarcoma. It is a sarcoma associated with an aggressive clinical course, with an inferior overall survival compared to Ewing sarcoma.
Differential diagnosis
Board review style question #1
Which of the following is true about CIC-DUX4 rearranged sarcoma?

  1. High metastatic rate, brain most common
  2. Diagnosis always requires clinicopathological and radiological correlation
  3. Prognosis is poor
  4. Tumor is always negative for ERG
  5. Tumor is characterized by cords of epithelioid cells distributed in a desmoplastic stroma
Board review answer #1
C. Prognosis is poor

Reference: CIC-DUX4 fusion tumor

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Board review style question #2

A 65 year old man presented with a left thigh mass. Hematoxylin eosin stains demonstrated proliferation of small to medium sized round / ovoid cells with medium sized round to oval vesicular nuclei and clear or pale eosinophilic cytoplasm. Increased mitotic activity, geographic necrosis and patchy myxoid stromal change were seen. Immunohistochemical stains for CD99, WT1 and DUX4 were positive in tumor cells while all of the following were negative: pankeratin AE1 / AE3, S100, SOX10, myogenin, NY-ESO-1, NKX2.2 and CCNB3. INI1 was retained. Which of the following is most likely the correct diagnosis?

  1. Synovial sarcoma, poorly differentiated
  2. Extraskeletal Ewing sarcoma
  3. Epithelioid sarcoma
  4. BCOR-CCNB3 (Ewing-like) sarcoma
  5. CIC-DUX4 associated undifferentiated round cell sarcoma
Board review answer #2
E. CIC-DUX4 associated undifferentiated round cell sarcoma

Reference: CIC-DUX4 fusion tumor

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