Stains & molecular markers
SALL4


Topic Completed: 16 April 2020

Minor changes: 16 April 2020

Copyright: 2002-2020, PathologyOutlines.com, Inc.

PubMed Search: SALL4[TI] pathology free full text[sb]

Derek Hoerres, M.D.
Sara Wobker, M.D., M.P.H.
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Cite this page: Hoerres D, Wobker S. SALL4. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainssall4.html. Accessed June 4th, 2020.
Definition / general
  • One of four members of the SALL (spalt-like, sal-like) family of transcription factors
  • Involved in the maintenance of embryonic stem cell pluripotency and self renewal
  • Novel oncogene important in the initiation and progression of cancers
Essential features
  • Malignant germ cell tumor marker (Am J Surg Pathol 2009;33:1065, Am J Surg Pathol 2014;38:e50)
  • Marker of stem cell-like dedifferentiation in many non germ cell cancers
  • Differentiates rhabdoid tumor from epithelioid sarcoma
  • Poor prognosis in hepatocellular carcinoma, other solid tumors
Terminology
  • Spalt-like transcription factor 4
  • Sal-like protein 4
Pathophysiology
  • Master regulator of embryonic stem cell pluripotency
  • Zinc finger transcriptional factor at 20q13.2
  • In mice, essential for neural tube closure, anogenital tract formation, and limb and heart development; loss of SALL4 expression causes differentiation along trophectoderm lineage (Development 2006;133:3005, Nat Cell Biol 2006;8:1114)
  • In cancers, interacts with many oncogenic partners as a transcriptional regulator including PTEN/AKT and Wnt/B-catenin pathways, DNMT, OCT 3/4, SOX2, MYC, others (Gene 2016;584:111)
  • Impacts cancer cell proliferation, invasion, and chemoresistance (Cancer Lett 2015;357:55)
Clinical features
  • SALL4 related disorders: Okihiro / Duane radial ray syndrome, acro-renal-ocular syndrome, thalidomide embryopathy (J Med Genet 2003;40:473)
Interpretation
Uses by pathologists
Prognostic factors
Microscopic (histologic) images

Contributed by Derek Hoerres, M.D.
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Yolk sac tumor

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Yolk sac tumor, SALL4

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Seminoma

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Seminoma, SALL4

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Metastatic germ cell tumor

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Metastatic germ cell tumor, SALL4

Positive staining - normal
Positive staining - disease
Negative staining
Board review style question #1

    SALL4 immunohistochemistry is most likely to be positive in which of the following tumor types?

  1. Clear cell carcinoma
  2. Epithelioid carcinoma
  3. Granulosa cell tumors
  4. Yolk sac tumor
Board review answer #1
D. Yolk sac tumor. SALL4 is expressed in most germ cell tumors (except some trophoblastic tumors) and nearly 100% sensitive for gonadal and extragonadal yolk sac tumors. The other answers are typically negative for SALL4, which can be used to differentiate from histologically similar diagnoses which are SALL4 positive.

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