Pathologic Characteristics of Spitz Melanoma With MAP3K8 Fusion or Truncation in a Pediatric Cohort.

Pathologic Characteristics of Spitz Melanoma With MAP3K8 Fusion or Truncation in a Pediatric Cohort.

Publication date: Sep 06, 2019

Spitz melanoma is a rare variant of melanoma defined by distinct clinical, histologic, and genetic features and affecting patients of all ages. Half of these tumors are driven by fusion of kinase genes including ALK, NTRK1/3, ROS1, RET, MET, or BRAF. We recently reported recurrent fusion or truncation of the potentially targetable serine-threonine kinase gene MAP3K8 in 33% of Spitz melanomas. Here we describe the histologic features of these MAP3K8-rearranged tumors (16 pediatric Spitz melanomas; 1 atypical Spitz tumor), using hematoxylin-eosin slides, p16 immunohistochemistry, and CDKN2A fluorescence in situ hybridization. The lesions consisted of a compound melanocytic proliferation, ranging in thickness from 1.5 to 13.4 mm (median, 3.1 mm), with 8 having a predominant dermal and 3 having a predominant junctional component. The predominant cell type was epithelioid (94%). The epithelioid melanocytes were generally monomorphic and amelanotic, arranged in expansile epithelial aggregates, confluent hypercellular nests, or enlarged syncytial nodules in the dermis. Ulceration was present in 9 of 17 tumors (53%) and deep mitotic figures were seen in 15 of 17 tumors (88%). Complete loss of p16 expression and homozygous CDKN2A deletion were observed in 82% and 70% of tumors, respectively. Recognition of MAP3K8-altered Spitz melanoma may thus be facilitated by these morphologic features, most notably presence of cohesive cellular nodules in the dermis and an epithelioid-cell phenotype.

Newman, S., Pappo, A., Raimondi, S., Zhang, J., Barnhill, R., and Bahrami, A. Pathologic Characteristics of Spitz Melanoma With MAP3K8 Fusion or Truncation in a Pediatric Cohort. 24060. 2019 Am J Surg Pathol.

Concepts Keywords
ALK Spitz melanomas
BRAF Ages Half tumors
CDKN2A Rare variant melanoma
Dermis Pediatric Spitz melanomas
Eosin Present tumors
Epithelial Atypical Spitz tumor
Epithelioid Branches of biology
Fluorescence Rare diseases
Genetic Neoplasms
Hematoxylin Spitz nevus
Histologic Melanoma
Homozygous Epithelioid
Hybridization CDKN2A
Immunohistochemistry Health
Kinase ROS1
Melanocytes P16
Melanoma Hybridization
Melanomas
Mitotic
Monomorphic
Morphologic
Nodules
NTRK1
Pediatric
Phenotype
RET
Serine
Spitz
Syncytial
Threonine
Truncation
Tumor
Ulceration

Semantics

Type Source Name
gene UNIPROT CDKN2A
drug DRUGBANK L-Threonine
drug DRUGBANK Serine
gene UNIPROT BRAF
gene UNIPROT MET
gene UNIPROT SLTM
drug DRUGBANK Methionine
gene UNIPROT RET
gene UNIPROT ROS1
gene UNIPROT NTRK1
gene UNIPROT ALK
disease MESH tumors
gene UNIPROT MAP3K8
pathway BSID Melanoma
disease DOID Melanoma
disease MESH Melanoma

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