Spitz tumor with RAF1 fusion: A report of 3 cases

Michele Donati; Daniel Nosek; Shantel Olivares; Julie Lemahieu; Siebe Loontiens; Boulos Mansour; Pedram Gerami; Dmitry V. Kazakov

doi:10.1016/j.anndiagpath.2023.152215

Spitz tumor with RAF1 fusion: A report of 3 cases

Michele Donati^*, Daniel Nosek, Shantel Olivares, Julie Lemahieu, Siebe Loontiens, Boulos Mansour, Pedram Gerami, Dmitry V. Kazakov

^*Corresponding author for this work

Dermatology

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Spitz tumors are melanocytic neoplasms morphologically characterized by spindled and/or epithelioid cells and specific stromal and epidermal changes associated with mutually exclusive fusion kinases involving ALK, ROS1, NTRK1, NTRK2, NTRK3, MET and RET, BRAF and MAP3K8 genes or, less commonly, HRAS mutation. RAF1 fusions have been recently detected in cutaneous melanocytic neoplasms, including conventional melanoma, congenital nevus and BAP-1 inactivated tumors. We report herewith three Spitz neoplasms with a RAF1 fusion, including a previously reported CTDSPL::RAF1 fusion and two novel PPAP2B::RAF1 and ATP2B4::RAF1 fusions. Two cases were classified as Spitz nevus, while the remaining neoplasm was classified as Spitz melanoma at the time of the diagnosis, given 9p21 homozygous deletion and positive sentinel lymph node biopsy. We suggest that RAF1 fused melanocytic neoplasms can represent a novel subgroup of Spitz tumors, with a RAF1 fusion representing an oncogenic driver.

Original language	English (US)
Article number	152215
Journal	Annals of Diagnostic Pathology
Volume	67
DOIs	https://doi.org/10.1016/j.anndiagpath.2023.152215
State	Published - Dec 2023

Funding

Supported by the IDP Foundation . P.G. has served as a consultant for Castle Biosciences and has received an honorarium for this; he has also received royalties for textbooks from Elsevier. For the remaining authors none were declared.

Keywords

RAF1 fusion
Spitz tumor
Unusual melanocytic neoplasms
spitzoid morphology

ASJC Scopus subject areas

Pathology and Forensic Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.anndiagpath.2023.152215

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title = "Spitz tumor with RAF1 fusion: A report of 3 cases",

abstract = "Spitz tumors are melanocytic neoplasms morphologically characterized by spindled and/or epithelioid cells and specific stromal and epidermal changes associated with mutually exclusive fusion kinases involving ALK, ROS1, NTRK1, NTRK2, NTRK3, MET and RET, BRAF and MAP3K8 genes or, less commonly, HRAS mutation. RAF1 fusions have been recently detected in cutaneous melanocytic neoplasms, including conventional melanoma, congenital nevus and BAP-1 inactivated tumors. We report herewith three Spitz neoplasms with a RAF1 fusion, including a previously reported CTDSPL::RAF1 fusion and two novel PPAP2B::RAF1 and ATP2B4::RAF1 fusions. Two cases were classified as Spitz nevus, while the remaining neoplasm was classified as Spitz melanoma at the time of the diagnosis, given 9p21 homozygous deletion and positive sentinel lymph node biopsy. We suggest that RAF1 fused melanocytic neoplasms can represent a novel subgroup of Spitz tumors, with a RAF1 fusion representing an oncogenic driver.",

keywords = "RAF1 fusion, Spitz tumor, Unusual melanocytic neoplasms, spitzoid morphology",

author = "Michele Donati and Daniel Nosek and Shantel Olivares and Julie Lemahieu and Siebe Loontiens and Boulos Mansour and Pedram Gerami and Kazakov, {Dmitry V.}",

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year = "2023",

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doi = "10.1016/j.anndiagpath.2023.152215",

language = "English (US)",

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T2 - A report of 3 cases

AU - Donati, Michele

AU - Nosek, Daniel

AU - Olivares, Shantel

AU - Lemahieu, Julie

AU - Loontiens, Siebe

AU - Mansour, Boulos

AU - Gerami, Pedram

AU - Kazakov, Dmitry V.

PY - 2023/12

Y1 - 2023/12

N2 - Spitz tumors are melanocytic neoplasms morphologically characterized by spindled and/or epithelioid cells and specific stromal and epidermal changes associated with mutually exclusive fusion kinases involving ALK, ROS1, NTRK1, NTRK2, NTRK3, MET and RET, BRAF and MAP3K8 genes or, less commonly, HRAS mutation. RAF1 fusions have been recently detected in cutaneous melanocytic neoplasms, including conventional melanoma, congenital nevus and BAP-1 inactivated tumors. We report herewith three Spitz neoplasms with a RAF1 fusion, including a previously reported CTDSPL::RAF1 fusion and two novel PPAP2B::RAF1 and ATP2B4::RAF1 fusions. Two cases were classified as Spitz nevus, while the remaining neoplasm was classified as Spitz melanoma at the time of the diagnosis, given 9p21 homozygous deletion and positive sentinel lymph node biopsy. We suggest that RAF1 fused melanocytic neoplasms can represent a novel subgroup of Spitz tumors, with a RAF1 fusion representing an oncogenic driver.

AB - Spitz tumors are melanocytic neoplasms morphologically characterized by spindled and/or epithelioid cells and specific stromal and epidermal changes associated with mutually exclusive fusion kinases involving ALK, ROS1, NTRK1, NTRK2, NTRK3, MET and RET, BRAF and MAP3K8 genes or, less commonly, HRAS mutation. RAF1 fusions have been recently detected in cutaneous melanocytic neoplasms, including conventional melanoma, congenital nevus and BAP-1 inactivated tumors. We report herewith three Spitz neoplasms with a RAF1 fusion, including a previously reported CTDSPL::RAF1 fusion and two novel PPAP2B::RAF1 and ATP2B4::RAF1 fusions. Two cases were classified as Spitz nevus, while the remaining neoplasm was classified as Spitz melanoma at the time of the diagnosis, given 9p21 homozygous deletion and positive sentinel lymph node biopsy. We suggest that RAF1 fused melanocytic neoplasms can represent a novel subgroup of Spitz tumors, with a RAF1 fusion representing an oncogenic driver.

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KW - spitzoid morphology

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Spitz tumor with RAF1 fusion: A report of 3 cases

Abstract

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Keywords

ASJC Scopus subject areas

UN SDGs

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