Table 3.
Genomic Characteristics of Spitz Tumors.
| Type (Mutation or Translocation) | Fusion Partners | Histopathological Features | Clinical Features | Incidence | |
|---|---|---|---|---|---|
| HRAS | Mutation | N/A | Low cellularity, desmoplasia, infiltrating base (97, 98) | Pleiotropic (97) | 5-22% (30, 99, 100) |
| BRAF | Translocation | NRF1, SOX6 (65), EMLR4, BAIAP2L1 (101) | Epithelioid morphology, high-grade nuclear atypia (102) | Favors extremities, non-metastatic (102) | 5% (65, 100, 102) |
| ROS1 | Translocation | TPM3, PPFIBP1, MYH9, CAPRINI1, MYO5A (104) | Epithelioid and spindle cells homogeneously (104) | Pink/red papules in various locations (104) | 7-19% (100, 104) |
| NTRK1 | Translocation | LMNA, TP53 (105) | Superficial, evenly distributed pigmentation (106) | Favors extremities, may be amelanotic, even sex distribution, median age 26y (100) | 8-19% (13, 100, 106) |
| ALK | Translocation | NPM1, TPR, CLIP1, GTF3C2 (107) | Fascicular growth pattern, infiltrating base, and fibrillar cytoplasm (107) | Favors extremities, may be amelanotic or vascular, more common in females, median age 12y (106, 107) | 8-26% (13, 100, 106, 108) |
| MET | Translocation | TRIM4, ZKSCAN1, DCTN1 (13, 105) | Fusiform or epithelioid morphology, amphophilic cytoplasm, melanocyte nests (105) | Epidermal hyperplasia, good treatment outcomes (105) | 0.5-1% (100, 105) |
| RET | Translocation | GOLGA5, KIF5B (105) | Not well described | Driver of lung cancer formation, can be treated with crizotinib, cabozantinib, and vandetanib (13) | 2-3% (13, 100, 109) |
| MAP3K8 | Both | SVIL, DIP2C, UBL3, STX7, SPECC1, CUBN, PRKACB (16) | Epithelioid morphology, high grade cytological atypia, multinucleated giant cells, p16 loss, junctional nests, desmoplasia (16, 23, 107) | Ulceration, dome-shaped, median age: 18, tendency for lymph node involvement (16, 17, 23) | 8-33% (23, 28, 110) |
N/A, Not Applicable.