TY - JOUR
T1 - Genomic Assessment of Blitz Nevi Suggests Classification as a Subset of Blue Nevus Rather Than Spitz Nevus
T2 - Clinical, Histopathologic, and Molecular Analysis of 18 Cases
AU - Isales, Maria C.
AU - Haugh, Alexandra M.
AU - Bubley, Jeffrey
AU - Verzì, Anna E.
AU - Zhang, Bin
AU - Kudalkar, Emily
AU - Lee, Christina Y.
AU - Yazdan, Pedram
AU - Guitart, Joan
AU - Gerami, Pedram
N1 - Funding Information:
From the Departments of *Pathology, and †Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL; and ‡Robert H. Lurie Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL. Supported by the IDP Foundation. P. Gerami has served as a consultant for Castle Biosciences, Inc, DermTech, Inc, and Myriad Genomics and has received honoraria for this. The remaining authors declare no conflicts of interest. Reprints: Pedram Gerami, MD, Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 (e-mail: pgerami@nmff.org). Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
Publisher Copyright:
© 2018 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - Blitz nevi/tumors are a distinct subset of melanocytic neoplasia which show mixed morphologic features of Spitz and blue nevus. Genomically, most blue nevi have GNAQ or GNA11 mutations while most Spitzoid neoplasms have either an HRAS mutation or translocations involving MET, ROS, BRAF, ALK1, NTRK1, and RET. The criteria used for the assessment of malignancy in blue and Spitzoid lesions are different, and these lesions have different prognostic markers. In this study, we assess the clinical, morphological, and genomic changes in 18 cases of Blitz nevi/tumors to better characterize this subset of neoplasms and determine their optimal genomic classification. Most lesions occurred on the extremities followed by the head and neck region typical of blue nevi. Histology showed most cases having a prominent plexiform growth pattern with cells aggregating around the adnexal structures and neurovascular bundles also typical of blue nevi. Using next generation sequencing, we detected the presence of somatic mutations in GNAQ or GNA11 in 4 of 7 cases (57%) of Blitz nevi with sufficient DNA available for sequencing. Normal skin samples in these 4 cases were sequenced to confirm that the GNAQ or GNA11 mutations were somatic mutations. All 4 cases were negative for immunohistochemical assessment for wild-type BRAF, RET, ALK, and NTRK1 and mutational analysis of HRAS was also negative in all cases. Hence, our study suggests that Blitz nevi/tumors are a distinct subset which genomically are best classified as a subset of blue nevi.
AB - Blitz nevi/tumors are a distinct subset of melanocytic neoplasia which show mixed morphologic features of Spitz and blue nevus. Genomically, most blue nevi have GNAQ or GNA11 mutations while most Spitzoid neoplasms have either an HRAS mutation or translocations involving MET, ROS, BRAF, ALK1, NTRK1, and RET. The criteria used for the assessment of malignancy in blue and Spitzoid lesions are different, and these lesions have different prognostic markers. In this study, we assess the clinical, morphological, and genomic changes in 18 cases of Blitz nevi/tumors to better characterize this subset of neoplasms and determine their optimal genomic classification. Most lesions occurred on the extremities followed by the head and neck region typical of blue nevi. Histology showed most cases having a prominent plexiform growth pattern with cells aggregating around the adnexal structures and neurovascular bundles also typical of blue nevi. Using next generation sequencing, we detected the presence of somatic mutations in GNAQ or GNA11 in 4 of 7 cases (57%) of Blitz nevi with sufficient DNA available for sequencing. Normal skin samples in these 4 cases were sequenced to confirm that the GNAQ or GNA11 mutations were somatic mutations. All 4 cases were negative for immunohistochemical assessment for wild-type BRAF, RET, ALK, and NTRK1 and mutational analysis of HRAS was also negative in all cases. Hence, our study suggests that Blitz nevi/tumors are a distinct subset which genomically are best classified as a subset of blue nevi.
KW - Blitz nevus
KW - GNA11
KW - GNAQ
KW - Spitz nevus
KW - blue nevus
KW - epithelioid blue nevus
KW - sequencing
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UR - http://www.scopus.com/inward/citedby.url?scp=85048361994&partnerID=8YFLogxK
U2 - 10.1097/DAD.0000000000000918
DO - 10.1097/DAD.0000000000000918
M3 - Article
C2 - 28475519
AN - SCOPUS:85048361994
VL - 40
SP - 118
EP - 124
JO - American Journal of Dermatopathology
JF - American Journal of Dermatopathology
SN - 0193-1091
IS - 2
ER -