Stains & CD markers
Microphthalmia associated transcription factor (MITF)


Topic Completed: 20 September 2021

Minor changes: 20 September 2021

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PubMed Search: Microphthalmia associated transcription factor [title]

Thomas H. Long, M.D.
Ata Moshiri, M.D., M.P.H.
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Cite this page: Long TH, Moshiri A. Microphthalmia associated transcription factor (MITF). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsmitf.html. Accessed October 24th, 2021.
Definition / general
  • Microphthalmia associated transcription factor (MITF), also known as melanocyte inducing transcription factor (GeneCards), is a regulator of gene expression essential for melanocyte survival, development and proliferation; it also has relevance in melanoma biology and nonmelanocyte cellular functions (Genes Dev 2019;33:983)
  • MITF labels most melanocytic proliferations but is not specific for them
Essential features
  • Transcription factor expressed in melanocytes and a variety of other cell types
  • Essential for the survival, development and function of melanocytes
  • Nuclear stain, positive in most melanocytic proliferations, with the notable exception of desmoplastic melanoma
  • Positive in perivascular epithelioid cell neoplasms
  • Nonspecific, with pitfalls including certain soft tissue tumors as well as reactive cells in excision scars
Terminology
  • Homolog of mouse microphthalmia
  • MI
  • Melanocyte inducing transcription factor (renamed by HUGO Gene Nomenclature Committee in 2017) (HGNC: Symbol Report for MITF [Accessed 8 April 2021])
  • Microphthalmia associated transcription factor (original gene name)
  • Class E basic helix - loop - helix protein 32 (BHLHe32)
  • Waardenburg syndrome, type 2A (WS2, WS2A)
  • CMM8
  • COMMAD
Pathophysiology
  • Encodes a transcription factor of the basic domain helix - loop - helix leucine zipper (bHLH-LZ) class that binds DNA as dimers
  • Located on chromosome 3p14.1
  • A member of the MiT subfamily of factors that also includes TFEB, TFE3 and TFEC, with which it can form heterodimers (Genes Dev 1994;8:2770)
  • Required for the proper development of several cell lineages, including osteoclasts, melanocytes, retinal pigment epithelial cells, mast cells and natural killer cells (Bone 2004;34:689)
  • Hundreds of downstream targets involved in lineage specific functions (i.e. tyrosinase in melanocytes, TRAP in osteoclasts) and a diverse range of additional nonlineage specific functions, including regulation of proliferation, DNA damage repair, metabolism, lysosome biogenesis and autophagy (Genes Dev 2019;33:983)
  • Regulates function of pancreatic beta cells and may play a role in glucose homeostasis (Diabetes 2013;62:2834)
Clinical features
Interpretation
  • Nuclear stain
Uses by pathologists
Prognostic factors
  • Loss of expression in melanomas is associated with decreased survival and increased risk of occult lymph node metastasis (Melanoma Res 2015;25:496)
Microscopic (histologic) images

Contributed by Ata Moshiri, M.D., M.P.H.
Neurocristic hamartoma

Neurocristic hamartoma

Neurocristic hamartoma MelanA

Neurocristic hamartoma MelanA

Neurocristic hamartoma SOX10

Neurocristic hamartoma SOX10

Neurocristic hamartoma MITF scanning Neurocristic hamartoma MITF scanning Neurocristic hamartoma MITF scanning

Neurocristic hamartoma MITF scanning


Neurocristic hamartoma CD34

Neurocristic hamartoma CD34

Desmoplastic melanoma H&E Desmoplastic melanoma H&E

Desmoplastic melanoma H&E

Desmoplastic melanoma S100

Desmoplastic melanoma S100

Desmoplastic melanoma MITF

Desmoplastic melanoma MITF

Desmoplastic melanoma P16

Desmoplastic melanoma P16


Epithelioid angiomyolipoma H&E

Epithelioid angiomyolipoma H&E

Epithelioid angiomyolipoma MITF

Epithelioid angiomyolipoma MITF

Positive staining - normal
Positive staining - disease
Negative staining
Sample pathology report
  • Skin, left chest, punch biopsy:
    • Mastocytosis (see comment)
    • Comment: The dermal mononuclear proliferation stains positively with tryptase, CD117, and MITF, compatible with mast cell lineage.
Board review style question #1
Which of the following is the best situation to use the MITF immunohistochemical stain?

  1. Margin assessment in an excision of a biopsy proven desmoplastic melanoma
  2. To differentiate melanocytes from epithelioid histiocytes and multinucleated giant cells
  3. To support a diagnosis of Xp11 translocated renal cell carcinoma with TFE3 gene fusion
  4. Use in addition to smooth muscle actin and HMB45 to support a diagnosis of angiomyolipoma
  5. Use as a marker for poorly differentiated melanoma in a pleomorphic spindle cell neoplasm of the skin
Board review style answer #1
D. MITF, in combination with HMB45 and SMA would support an angiomyolipoma, which is a type of perivascular endothelial cell tumor (PEComa). Answer A is incorrect because desmoplastic melanomas are usually negative for MITF. Answer B is incorrect because histiocytes, particularly multinucleated giant cells, can be positive for MITF. Answer C is incorrect because although TFE3 is a transcription factor related to MITF and these tumors are referred to as MiT family translocation renal cell carcinomas, most are negative for MITF by immunohistochemistry. Answer E is incorrect because MITF is nonspecific for the differential diagnosis of melanoma and can be positive in pleomorphic spindle cell lesions of the skin, including undifferentiated pleomorphic sarcoma, atypical fibroxanthoma and sarcomatoid carcinoma.

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