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Molecular alterations in malignant blue nevi and related blue lesions

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Abstract

Malignant blue nevi (MBN) are extremely rare dermal melanocytic tumors that arise in association with atypical cellular blue nevi (ACBN), cellular blue nevi (CBN), common blue nevi (BN), or de novo. The frequency of BRAF, NRAS, and KIT mutations in malignant melanoma varies according to histological subtype and localization. These mutations are rarely observed in blue nevi, which have recently been shown to carry activating mutations in GNAQ/GNA11 genes. Only few small molecular studies of MBN have been published. The aim of the present study was to analyze in MBN and related blue lesions such as ACBN, CBN, and BN the prevalence of BRAF, NRAS, KIT, GNAQ, and GNA11 gene mutations and their association with clinicopathological features. We included in our study 12 MBN, 6 ACBN, 29 CBN, and 35 common BN diagnosed between 1996 and 2014. Sanger sequencing method was used for mutation analysis. Overall, GNAQ exon 5 mutation was the most frequent alteration (46 %), in 2 of 12 (17 %) MBN, 1 of 6 (17 %) ACBN, 22 of 29 (76 %) CBN, and 13 of 35 (37 %) common BN. BRAF V600E and GNA11 exon 5 mutations were respectively detected in 3 of 12 (25 %) and in 2 of 12 (17 %) MBN while none in ACBN, CBN, and common BN. None of the cases harbored NRAS exon 2/3, KIT exon 9/11/13/17/18, or GNAQ/GNA11 exon 4 mutations. GNAQ gene exon 5 mutations are rare in MBN and ACBN but frequent in CBN and common BN. Remarkably, BRAF V600E and GNA11 exon 5 mutations were only detected in MBN, whereas none were found in ACBN, CBN, or common BN. Our data contribute new elements to the limited data on molecular alterations in MBN.

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Acknowledgments

This study was approved by the medical ethics committee of Gulhane Military Medical Academy, Haydarpasa Training Hospital (Approval No. 2014-42/24/27.03.2014), and was conducted in accordance with the Helsinki Declaration Principles.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, Gulhane Military Medical Academy, Haydarpasa Training Hospital, Istanbul, Turkey

    Ismail Yilmaz, Gizem Narli, Zafer Kucukodaci & Dilaver Demirel

  2. Department of Pathology, Erzurum Military Hospital, Erzurum, Turkey

    Mehmet Gamsizkan

  3. Istanbul Faculty of Medicine, Department of Pathology, Istanbul University, Istanbul, Turkey

    Sule Ozturk Sari & Nesimi Buyukbabani

  4. Faculty of Medicine, Department of Pathology, Ege University, Izmir, Turkey

    Banu Yaman & Taner Akalin

  5. Cerrahpasa Faculty of Medicine, Department of Pathology, Istanbul University, Istanbul, Turkey

    Cuyan Demirkesen

  6. Faculty of Medicine, Department of Pathology, Ankara University, Ankara, Turkey

    Aylin Heper

  7. Department of Pathology, Izmir Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey

    Aylin Orgen Calli

  8. Department of Pathology, Corlu Military Hospital, Corlu, Tekirdag, Turkey

    Ufuk Berber

  9. Faculty of Medicine, Department of Pathology, Gulhane Military Medical Academy, Ankara, Turkey

    Murat Demiriz

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  1. Ismail Yilmaz
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  2. Mehmet Gamsizkan
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  14. Nesimi Buyukbabani
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Correspondence to Ismail Yilmaz.

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Yilmaz, I., Gamsizkan, M., Sari, S.O. et al. Molecular alterations in malignant blue nevi and related blue lesions. Virchows Arch 467, 723–732 (2015). https://doi.org/10.1007/s00428-015-1851-3

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  • DOI: https://doi.org/10.1007/s00428-015-1851-3

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