Impact of Next-generation Sequencing on Interobserver Agreement and Diagnosis of Spitzoid Neoplasms

Sarah Benton, Jeffrey Zhao, Bin Zhang, Armita Bahrami, Raymond L. Barnhill, Klaus Busam, Lorenzo Cerroni, Martin G. Cook, Arnaud de la Fouchardière, David E. Elder, Iva Johansson, Gilles Landman, Alexander Lazar, Philip LeBoit, Lori Lowe, Daniela Massi, Lyn M. Duncan, Jane Messina, Daniela Mihic-Probst, Martin C. MihmMichael W. Piepkorn, Birgitta Schmidt, Richard A. Scolyer, Christopher R. Shea, Michael T. Tetzlaff, Victor A. Tron, Xiaowei Xu, Iwei Yeh, Sook Jung Yun, Artur Zembowicz, Pedram Gerami

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Atypical Spitzoid melanocytic tumors are diagnostically challenging. Many studies have suggested various genomic markers to improve classification and prognostication. We aimed to assess whether next-generation sequencing studies using the Tempus xO assay assessing mutations in 1711 cancer-related genes and performing whole transcriptome mRNA sequencing for structural alterations could improve diagnostic agreement and accuracy in assessing neoplasms with Spitzoid histologic features. Twenty expert pathologists were asked to review 70 consultation level cases with Spitzoid features, once with limited clinical information and again with additional genomic information. There was an improvement in overall agreement with additional genomic information. Most significantly, there was increase in agreement of the diagnosis of conventional melanoma from moderate (κ=0.470, SE=0.0105) to substantial (κ=0.645, SE=0.0143) as measured by an average Cohen κ. Clinical follow-up was available in all 70 cases which substantiated that the improved agreement was clinically significant. Among 3 patients with distant metastatic disease, there was a highly significant increase in diagnostic recognition of the cases as conventional melanoma with genomics (P<0.005). In one case, none of 20 pathologists recognized a tumor with BRAF and TERT promoter mutations associated with fatal outcome as a conventional melanoma when only limited clinical information was provided, whereas 60% of pathologists correctly diagnosed this case when genomic information was also available. There was also a significant improvement in agreement of which lesions should be classified in the Spitz category/WHO Pathway from an average Cohen κ of 0.360 (SE=0.00921) to 0.607 (SE=0.0232) with genomics.

Original languageEnglish (US)
Pages (from-to)1597-1605
Number of pages9
JournalThe American journal of surgical pathology
Volume45
Issue number12
DOIs
StatePublished - Dec 1 2021

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Fingerprint

Dive into the research topics of 'Impact of Next-generation Sequencing on Interobserver Agreement and Diagnosis of Spitzoid Neoplasms'. Together they form a unique fingerprint.

Cite this