Clinical, Morphologic, and Molecular Findings in MET Fusion Spitz Neoplasms

Area of Science:

• Dermatopathology
• Oncology
• Molecular Pathology

Background:

• Spitz neoplasms are rare melanocytic tumors requiring accurate diagnosis.
• MET fusions are infrequent drivers in Spitz neoplasms, with limited existing literature.
• Understanding these specific subtypes aids clinical management.

Purpose of the Study:

• To characterize the clinical, morphologic, and molecular features of Spitz neoplasms with MET fusions.
• To compare these features with a control cohort of Spitz neoplasms.
• To evaluate the clinical course and outcomes of patients with MET fusion-positive Spitz neoplasms.

Main Methods:

• Retrospective analysis of 10 Spitz neoplasms with MET fusions.
• Morphologic assessment including cytology and growth patterns.
• Molecular analysis for MET fusion status, copy number variations, and other mutations.
• Comparison with 81 control Spitz neoplasms.

Main Results:

• Nine of ten cases were classified as atypical Spitz tumors.
• Three distinct morphologic patterns were identified, with spindle cell cytology and plexiform dermal growth being more common in MET fusion cases.
• ZKSCAN1 was the most frequent fusion partner (4/10); copy number gains of the fusion gene occurred in 61% of cases.
• No TERT promoter mutations or CDKN2A homozygous deletions were observed.

Conclusions:

• Spitz neoplasms with MET fusions exhibit characteristic morphologic features, including spindle cell cytology and plexiform growth.
• These tumors demonstrated favorable clinical outcomes with no recurrences post-reexcision.
• Characterization of MET fusion Spitz neoplasms improves diagnostic accuracy and informs management strategies.