High prevalence of MiTF staining in undifferentiated pleomorphic sarcoma: caution in the use of melanocytic markers in sarcoma
Corresponding Author
Bonnie Choy
Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA
Address for correspondence: Bonnie Choy, The University of Chicago, 5841 S. Maryland Ave, MC 6101, Chicago, IL 60637, USA. e-mail: [email protected]Search for more papers by this authorElizabeth Hyjek
Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA
Search for more papers by this authorAnthony G Montag
Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA
Search for more papers by this authorPeter Pytel
Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA
Search for more papers by this authorRex Haydon
Department of Orthopedic Surgery, The University of Chicago Medicine, Chicago, IL, USA
Search for more papers by this authorHue H Luu
Department of Orthopedic Surgery, The University of Chicago Medicine, Chicago, IL, USA
Search for more papers by this authorChao J Zhen
Division of Genomic and Molecular Pathology, Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA
Search for more papers by this authorBradley C Long
Division of Genomic and Molecular Pathology, Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA
Search for more papers by this authorSabah Kadri
Division of Genomic and Molecular Pathology, Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA
Center for Research Informatics, The University of Chicago, Chicago, IL, USA
Search for more papers by this authorJeremy P Segal
Division of Genomic and Molecular Pathology, Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA
Search for more papers by this authorLarissa V Furtado
Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA
Search for more papers by this authorNicole A Cipriani
Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA
Search for more papers by this authorCorresponding Author
Bonnie Choy
Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA
Address for correspondence: Bonnie Choy, The University of Chicago, 5841 S. Maryland Ave, MC 6101, Chicago, IL 60637, USA. e-mail: [email protected]Search for more papers by this authorElizabeth Hyjek
Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA
Search for more papers by this authorAnthony G Montag
Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA
Search for more papers by this authorPeter Pytel
Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA
Search for more papers by this authorRex Haydon
Department of Orthopedic Surgery, The University of Chicago Medicine, Chicago, IL, USA
Search for more papers by this authorHue H Luu
Department of Orthopedic Surgery, The University of Chicago Medicine, Chicago, IL, USA
Search for more papers by this authorChao J Zhen
Division of Genomic and Molecular Pathology, Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA
Search for more papers by this authorBradley C Long
Division of Genomic and Molecular Pathology, Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA
Search for more papers by this authorSabah Kadri
Division of Genomic and Molecular Pathology, Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA
Center for Research Informatics, The University of Chicago, Chicago, IL, USA
Search for more papers by this authorJeremy P Segal
Division of Genomic and Molecular Pathology, Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA
Search for more papers by this authorLarissa V Furtado
Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA
Search for more papers by this authorNicole A Cipriani
Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA
Search for more papers by this authorAbstract
Aims
The diagnosis of undifferentiated pleomorphic sarcoma (UPS) may be challenging, as other lesions with undifferentiated spindle cell morphology must be excluded, including melanoma. Microphthalmia-associated transcription factor (MiTF) stains naevi and epithelioid melanomas, as well as some mesenchymal neoplasms. The aim of this study was to evaluate the prevalence of MiTF and melanocytic markers in UPS and a subset of atypical fibroxanthoma (AFX).
Methods and results
MiTF, SOX10, Melan-A, HMB45 and S100 immunostaining was performed on resection specimens from 19 UPSs and five AFXs. Next-generation sequencing of 50 genes was performed in UPSs to exclude dedifferentiated melanoma. In 17 of 19 UPSs (89%), tumour cells showed nuclear positivity for MiTF that was not eliminated by casein block. Three showed focal nuclear staining for HMB45, which was eliminated by casein block. One showed focal nuclear vacuole staining for S100 with red but not brown chromogen. None expressed SOX10 or Melan-A. Mutational analysis of 15 UPSs with adequate DNA showed no mutations within hotspot regions of BRAF, KIT, or NRAS. Four of five AFXs (80%) stained with MiTF; other markers were negative.
Conclusion
There is a high prevalence of nuclear MiTF expression in UPSs (89%) and AFXs (80%). Rare UPSs showed non-specific nuclear HMB45 or S100 staining. These findings argue against using MiTF in isolation to differentiate between UPS or AFX and melanoma, and caution in interpreting focal staining for a single additional melanocytic marker. Casein block may eliminate non-specific staining. MiTF should be used to support a diagnosis of melanoma only if multiple melanocytic markers are positive.
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