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. 2024 May 1;48(5):538-545.
doi: 10.1097/PAS.0000000000002194. Epub 2024 Mar 25.

BRAF Mutated and Morphologically Spitzoid Tumors, a Subgroup of Melanocytic Neoplasms Difficult to Distinguish From True Spitz Neoplasms

Pedram Gerami  1 , Alice Chen  1 , Natasha Sharma  1 , Pragi Patel  1 , Michael Hagstrom  1 , Pranav Kancherla  1 , Tara Geraminejad  1 , Shantel Olivares  1 , Asok Biswas  2 , Marcus Bosenberg  3 , Klaus J Busam  4 , Arnaud de La Fouchardière  5 , Lyn M Duncan  6 , David E Elder  7 , Jennifer Ko  8 , Gilles Landman  9 , Alexander J Lazar  10 , Lori Lowe  11 , Daniela Massi  12 , Daniela Mihic-Probst  13 , Douglas C Parker  14 , Richard A Scolyer  15   16   17 , Christopher R Shea  18 , Artur Zembowicz  19 , Sook Jung Yun  20 , Willeke A M Blokx  21 , Raymond L Barnhill  22
Affiliations

BRAF Mutated and Morphologically Spitzoid Tumors, a Subgroup of Melanocytic Neoplasms Difficult to Distinguish From True Spitz Neoplasms

Pedram Gerami et al. Am J Surg Pathol. .

Abstract

Drivers of Spitz neoplasms include activating point mutations in HRAS and Spitz-associated genomic fusions. It has become evident that some BRAF -mutated melanocytic neoplasms can morphologically mimic Spitz tumors (STs). These have been termed BRAF mutated and morphologically spitzoid (BAMS). In this study, 17 experts from the International Melanoma Pathology Study Group assessed 54 cases which included 40 BAMS and 14 true STs. The participants reviewed the cases blinded to the genomic data and selected among several diagnostic options, including BAMS, ST, melanoma, and other. A total of 38% of all diagnostic selections in the BAMS cases were for BAMS, whereas 32% were for ST. In 22 of the BAMS cases, the favored diagnosis was BAMS, whereas in 17 of the BAMS cases, the favored diagnosis was ST. Among the 20 cases in the total group of 54 with the highest number of votes for ST, half were BAMS. Of BAMS, 75% had a number of votes for ST that was within the SD of votes for ST seen among true ST cases. There was poor interobserver agreement for the precise diagnosis of the BAMS (kappa = 0.16) but good agreement that these cases were not melanoma (kappa = 0.7). BAMS nevi/tumors can closely mimic Spitz neoplasms. Expert melanoma pathologists in this study favored a diagnosis of ST in nearly half of the BAMS cases. There are BAMS cases that even experts cannot morphologically distinguish from true Spitz neoplasms.

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Conflict of interest statement

Conflicts of Interest and Source of Funding: P.G. has served as a consultant for Castle Biosciences and has received royalties for textbooks from Elsevier. For the remaining authors, none were declared.

References

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