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Toward a Molecular-Genetic Classification of Spitzoid Neoplasms
Michael T Tetzlaff1, Alexandre Reuben2, Steven D Billings3
1Section of Dermatopathology, Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 85, Houston, TX, USA; Department of Translational and Molecular Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 85, Houston, TX, USA.
Molecular genetics advances Spitzoid lesion classification. Distinctive genetic alterations, including HRAS mutations and kinase fusions, now aid in categorizing Spitz nevi, atypical Spitz tumors, and Spitzoid melanomas.
Area of Science:
- Dermatopathology
- Molecular Genetics
- Oncology
Background:
- Spitzoid neoplasms encompass a spectrum from benign Spitz nevi to malignant Spitzoid melanomas.
- Accurate classification is crucial for patient management and prognosis.
- Traditional histopathologic assessment can be challenging for differentiating these lesions.
Purpose of the Study:
- To outline the current molecular-genetic alterations that define Spitzoid neoplasms.
- To demonstrate how these alterations can be utilized for improved classification.
- To highlight the diagnostic utility of molecular findings in Spitzoid lesions.
Main Methods:
- Review of histopathologic and molecular genetic data from Spitzoid neoplasms.
- Utilizing fluorescence in situ hybridization (FISH) for chromosomal alterations (e.g., 11p amplification, 6q23 loss, 9p21 deletion).
- Analysis of specific gene mutations (e.g., HRAS, BRAFV600E, TERT promoter) and oncogenic kinase fusions (e.g., ROS1, ALK, NTRK1/3, MET, BRAF, RET).
Main Results:
- Spitzoid lesions can be categorized into six distinct molecular-genetic groups.
- Group 1: 11p amplification and/or HRAS mutations.
- Group 2: Isolated loss of 6q23 by FISH.
- Group 3: Homozygous deletion of 9p21 by FISH.
- Group 4: BAP1 loss and BRAFV600E mutation.
- Group 5: Translocations involving oncogenic kinase drivers (ROS1, ALK, NTRK1/3, MET, BRAF, RET).
- Group 6: TERT promoter mutations.
Conclusions:
- Molecular-genetic profiling provides a robust framework for classifying Spitzoid neoplasms.
- Distinctive molecular alterations correlate with specific clinicopathologic entities within the Spitzoid spectrum.
- Integration of molecular data enhances diagnostic accuracy and aids in distinguishing benign from malignant Spitzoid lesions.
