Stains & CD markers
DUX4

Editorial Board Members: Borislav A. Alexiev, M.D., Jose G. Mantilla, M.D.
Bradford Siegele, M.D., J.D.

Topic Completed: 26 May 2021

Minor changes: 16 June 2021

Copyright: 2021, PathologyOutlines.com, Inc.

PubMed Search: DUX4 [title] pathology

Bradford Siegele, M.D., J.D.
Page views in 2021 to date: 241
Cite this page: Siegele B. DUX4. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsDUX4.html. Accessed October 23rd, 2021.
Definition / general
  • Double homeobox 4 transcription factor, encoded by retrogene material within D4Z4 polymorphic macrosatellite repeat sequence
  • Involved in normal development in fetal skeletal muscle
  • Expression in differentiated tissues is normally suppressed through epigenetic mechanisms
Essential features
  • Nuclear marker with limited expression in normal tissues (fetal skeletal muscle, mature testis)
  • Variable expression in skeletal muscle of patients with facioscapulohumeral dystrophy 1 (FSHD1)
  • Diffuse, strong expression in CIC-DUX4 fusion tumors with both t(4;19) and t(10;19) translocations
Clinical features
  • Decreased epigenetic repression of the D4Z4 macrosatellite array and resulting expression of DUX4 is hypothesized to be primarily responsible for facioscapulohumeral dystrophy 1 (FSHD1) pathophysiology
  • Translocations overexpressing the DUX4 double homeodomain cause B cell leukemia (Cell Rep 2018;25:2955)
Interpretation
  • Nuclear stain
Uses by pathologists
  • Differentiate CIC-DUX4 fusion tumors from many other small round blue cell tumors in pediatric, adolescent and young adult population (Am J Surg Pathol 2017;41:423)
Microscopic (histologic) images

Contributed by Bradford Siegele, M.D., J.D.
<i>CIC-DUX4</i> fusion tumor (H&E)

CIC-DUX4 fusion tumor (H&E)

<i>CIC-DUX4</i> fusion tumor (H&E)

CIC-DUX4 fusion tumor (DUX4)

<i>CIC-DUX4</i> fusion tumor (H&E)

CIC-DUX4 fusion tumor (H&E)

<i>CIC-DUX4</i> fusion tumor (H&E)

CIC-DUX4 fusion tumor (DUX4)


Ewing sarcoma (DUX4)

Ewing sarcoma (DUX4)

Malignant rhabdoid tumor

Malignant rhabdoid tumor (DUX4)

Embryonal rhabdomyosarcoma

Embryonal
rhabdomyosarcoma
(DUX4)

Alveolar rhabdomyosarcoma

Alveolar
rhabdomyosarcoma
(DUX4)

Positive staining - normal
Positive staining - disease
Negative staining
Sample pathology report
  • Soft tissue, flank, excision:
    • Round cell tumor with CIC rearrangement and DUX4 expression by immunohistochemistry (see comment)
    • Comment: This case was sent for fluorescence in situ hybridization for rearrangement of the CIC gene, which was detected. This finding, in combination with strong, diffuse nuclear expression of the DUX4 protein by immunohistochemistry, is consistent with a CIC-DUX4 fusion tumor.
Board review style question #1

A CIC-DUX4 fusion tumor and DUX4 IHC images are shown. Which immunohistochemical profile is commonly seen in CIC-DUX4 fusion tumor?

  1. DUX4+ (cytoplasmic), CD99+ (diffuse), AE1 / AE3-, desmin-, WT1-
  2. DUX4+ (cytoplasmic), CD99+ (patchy), AE1 / AE3-, desmin+ (patchy), WT1-
  3. DUX4+ (cytoplasmic), CD99+ (patchy), AE1 / AE3+ (patchy), desmin-, WT1-
  4. DUX4+ (nuclear), CD99+ (diffuse), AE1 / AE3+ (patchy), desmin-, WT1+
  5. DUX4+ (nuclear), CD99+ (patchy), AE1 / AE3-, desmin-, WT1+
Board review style answer #1
E. DUX4+ (nuclear), CD99+ (patchy), AE1 / AE3-, desmin-, WT1+

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Reference: DUX4
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