Improving classification of melanocytic nevi: Association of BRAF V600E expression with distinct histomorphologic features

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: A subset of melanomas carrying a B-Raf proto-oncogene, serine/threonine kinase gene (BRAF) V600E mutation, which is the most common targetable mutation in melanoma, arise in association with a melanocytic nevus that is also harboring a BRAF V600E mutation. The detailed histomorphologic characteristics of nevi positive for BRAF V600E have not been systematically documented. Objective: To identify histomorphologic features correlating with BRAF V600E status in nevi. Methods: We retrospectively identified melanocytic nevi from our laboratory reporting system. We performed a histomorphologic analysis and analysis of BRAF V600E expression by immunohistochemistry. Results: Thirteen nevi (14.8%) were negative and 76 (86.4%) were positive for BRAF V600E. The nevi positive for BRAF V600E were predominantly dermal (predominantly dermal growth in 55.3% of nevi positive for BRAF V600E and 15.4% of nevi negative for BRAF V600E [P =.01]) and showed a congenital growth pattern (congenital growth pattern in 51.3% of nevi positive for BRAF V600E and 15.4% of nevi negative for BRAF V600E [P =.02]). Compared with nevi negative for BRAF V600E, those that were positive for BRAF V600E often exhibited predominantly nested intraepidermal melanocytes, larger junctional nests, abrupt lateral circumscription, and larger cell size. Architectural disorder and inflammatory infiltrates were seen more often in nevi negative for BRAF V600E. BRAF sequencing of a subset of nevi confirmed the immunohistochemical results. Limitations: Limitations include the study's retrospective design and the small sample size of nevi negative for BRAF V600E. Conclusions: BRAF V600E is associated with distinct histomorphologic features in nevi. These features may contribute to improving the accuracy of classification and diagnosis of melanocytic neoplasms.

Original languageEnglish (US)
Pages (from-to)221-229
Number of pages9
JournalJournal of the American Academy of Dermatology
Volume79
Issue number2
DOIs
StatePublished - Aug 1 2018

Fingerprint

Pigmented Nevus
Nevus
Mutation
Melanoma
Growth
Skin
Proto-Oncogenes
Protein-Serine-Threonine Kinases
Melanocytes
Cell Size
Sample Size

Keywords

  • BRAF
  • dermatopathology
  • gene
  • histomorphology
  • immunohistochemistry
  • melanocytic nevus
  • melanoma
  • mutation

ASJC Scopus subject areas

  • Dermatology

Cite this

@article{f7d16dbe587d4befb98f00575a619f23,
title = "Improving classification of melanocytic nevi: Association of BRAF V600E expression with distinct histomorphologic features",
abstract = "Background: A subset of melanomas carrying a B-Raf proto-oncogene, serine/threonine kinase gene (BRAF) V600E mutation, which is the most common targetable mutation in melanoma, arise in association with a melanocytic nevus that is also harboring a BRAF V600E mutation. The detailed histomorphologic characteristics of nevi positive for BRAF V600E have not been systematically documented. Objective: To identify histomorphologic features correlating with BRAF V600E status in nevi. Methods: We retrospectively identified melanocytic nevi from our laboratory reporting system. We performed a histomorphologic analysis and analysis of BRAF V600E expression by immunohistochemistry. Results: Thirteen nevi (14.8{\%}) were negative and 76 (86.4{\%}) were positive for BRAF V600E. The nevi positive for BRAF V600E were predominantly dermal (predominantly dermal growth in 55.3{\%} of nevi positive for BRAF V600E and 15.4{\%} of nevi negative for BRAF V600E [P =.01]) and showed a congenital growth pattern (congenital growth pattern in 51.3{\%} of nevi positive for BRAF V600E and 15.4{\%} of nevi negative for BRAF V600E [P =.02]). Compared with nevi negative for BRAF V600E, those that were positive for BRAF V600E often exhibited predominantly nested intraepidermal melanocytes, larger junctional nests, abrupt lateral circumscription, and larger cell size. Architectural disorder and inflammatory infiltrates were seen more often in nevi negative for BRAF V600E. BRAF sequencing of a subset of nevi confirmed the immunohistochemical results. Limitations: Limitations include the study's retrospective design and the small sample size of nevi negative for BRAF V600E. Conclusions: BRAF V600E is associated with distinct histomorphologic features in nevi. These features may contribute to improving the accuracy of classification and diagnosis of melanocytic neoplasms.",
keywords = "BRAF, dermatopathology, gene, histomorphology, immunohistochemistry, melanocytic nevus, melanoma, mutation",
author = "Kiuru, {Maija Ht} and Danielle Tartar and Lihong Qi and Danyang Chen and Lan Yu and Thomas Konia and Mcpherson, {John Douglas} and Murphy, {William J} and Fung, {Maxwell A}",
year = "2018",
month = "8",
day = "1",
doi = "10.1016/j.jaad.2018.03.052",
language = "English (US)",
volume = "79",
pages = "221--229",
journal = "Journal of the American Academy of Dermatology",
issn = "0190-9622",
publisher = "Mosby Inc.",
number = "2",

}

TY - JOUR

T1 - Improving classification of melanocytic nevi

T2 - Association of BRAF V600E expression with distinct histomorphologic features

AU - Kiuru, Maija Ht

AU - Tartar, Danielle

AU - Qi, Lihong

AU - Chen, Danyang

AU - Yu, Lan

AU - Konia, Thomas

AU - Mcpherson, John Douglas

AU - Murphy, William J

AU - Fung, Maxwell A

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Background: A subset of melanomas carrying a B-Raf proto-oncogene, serine/threonine kinase gene (BRAF) V600E mutation, which is the most common targetable mutation in melanoma, arise in association with a melanocytic nevus that is also harboring a BRAF V600E mutation. The detailed histomorphologic characteristics of nevi positive for BRAF V600E have not been systematically documented. Objective: To identify histomorphologic features correlating with BRAF V600E status in nevi. Methods: We retrospectively identified melanocytic nevi from our laboratory reporting system. We performed a histomorphologic analysis and analysis of BRAF V600E expression by immunohistochemistry. Results: Thirteen nevi (14.8%) were negative and 76 (86.4%) were positive for BRAF V600E. The nevi positive for BRAF V600E were predominantly dermal (predominantly dermal growth in 55.3% of nevi positive for BRAF V600E and 15.4% of nevi negative for BRAF V600E [P =.01]) and showed a congenital growth pattern (congenital growth pattern in 51.3% of nevi positive for BRAF V600E and 15.4% of nevi negative for BRAF V600E [P =.02]). Compared with nevi negative for BRAF V600E, those that were positive for BRAF V600E often exhibited predominantly nested intraepidermal melanocytes, larger junctional nests, abrupt lateral circumscription, and larger cell size. Architectural disorder and inflammatory infiltrates were seen more often in nevi negative for BRAF V600E. BRAF sequencing of a subset of nevi confirmed the immunohistochemical results. Limitations: Limitations include the study's retrospective design and the small sample size of nevi negative for BRAF V600E. Conclusions: BRAF V600E is associated with distinct histomorphologic features in nevi. These features may contribute to improving the accuracy of classification and diagnosis of melanocytic neoplasms.

AB - Background: A subset of melanomas carrying a B-Raf proto-oncogene, serine/threonine kinase gene (BRAF) V600E mutation, which is the most common targetable mutation in melanoma, arise in association with a melanocytic nevus that is also harboring a BRAF V600E mutation. The detailed histomorphologic characteristics of nevi positive for BRAF V600E have not been systematically documented. Objective: To identify histomorphologic features correlating with BRAF V600E status in nevi. Methods: We retrospectively identified melanocytic nevi from our laboratory reporting system. We performed a histomorphologic analysis and analysis of BRAF V600E expression by immunohistochemistry. Results: Thirteen nevi (14.8%) were negative and 76 (86.4%) were positive for BRAF V600E. The nevi positive for BRAF V600E were predominantly dermal (predominantly dermal growth in 55.3% of nevi positive for BRAF V600E and 15.4% of nevi negative for BRAF V600E [P =.01]) and showed a congenital growth pattern (congenital growth pattern in 51.3% of nevi positive for BRAF V600E and 15.4% of nevi negative for BRAF V600E [P =.02]). Compared with nevi negative for BRAF V600E, those that were positive for BRAF V600E often exhibited predominantly nested intraepidermal melanocytes, larger junctional nests, abrupt lateral circumscription, and larger cell size. Architectural disorder and inflammatory infiltrates were seen more often in nevi negative for BRAF V600E. BRAF sequencing of a subset of nevi confirmed the immunohistochemical results. Limitations: Limitations include the study's retrospective design and the small sample size of nevi negative for BRAF V600E. Conclusions: BRAF V600E is associated with distinct histomorphologic features in nevi. These features may contribute to improving the accuracy of classification and diagnosis of melanocytic neoplasms.

KW - BRAF

KW - dermatopathology

KW - gene

KW - histomorphology

KW - immunohistochemistry

KW - melanocytic nevus

KW - melanoma

KW - mutation

UR - http://www.scopus.com/inward/record.url?scp=85049808544&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049808544&partnerID=8YFLogxK

U2 - 10.1016/j.jaad.2018.03.052

DO - 10.1016/j.jaad.2018.03.052

M3 - Article

C2 - 29653212

AN - SCOPUS:85049808544

VL - 79

SP - 221

EP - 229

JO - Journal of the American Academy of Dermatology

JF - Journal of the American Academy of Dermatology

SN - 0190-9622

IS - 2

ER -