Table 1.
Clinicopathologic and genetic features of melanocytic tumors with NTRK3 fusion
| Case | Age (years), Sex | Location | Clinical description | Thickness (mm)* | Diameter (mm)* | Diagnosis (category) | Clinical Follow-up | Studies performed | Copy number aberrations | NTRK3 fusion partner gene |
|---|---|---|---|---|---|---|---|---|---|---|
| 1# | 2, F | Shin | 7×6 mm pink nodule, possible Spitz nevus or juvenile xanthogranuloma or mastocytoma | >1.5 | 6.0 | Spitz nevus | NA | aCGH, RNA-Seq | Gain of 12p (distal to ETV6) loss of distal 15q (distal to NTRK3) | ETV6 |
| 2# | 10, M | Cheek | pilomatricoma? | 4.2 | 4.7 | Spitz nevus | NA | aCGH, RNA-Seq | Small loss near NTRK3, no broad/arm-level losses or gains | MYH9 |
| 3 | 45, F | Nose | basal cell carcinoma | >1.4 | 3.6 | Spitz nevus | NA | aCGH | Gain of 15q between MYO5A and NTRK3 | MYO5A |
| 4 | 2, M | Cheek | Growing pink papule, Spitz nevus, juvenile xanthogranuloma, pyogenic granuloma, wart | >3.7 | 7.3 | Spitz melanocytoma (atypical Spitz tumor) | NA | aCGH | Gains of 12p (proximal to ETV6), gain of 15q (proximal to NTRK3) loss of 15q (distal to NTRK3) | ETV6 |
| 5 | 5, F | Cheek | Atypical nevus, concern for malignancy | 2.6 | 6.7 | Spitz melanocytoma (atypical Spitz tumor) | NA | aCGH | Gain of 5q, loss of distal 13q, gain of 15q between MYO5A and NTRK3 with alternating copy number state in gained segment suggestive of chromothripsis | MYO5A |
| 6# | 6, F | Cheek | Spitz nevus, keratotic nevus, verruca vulgaris | 2.6 | 2.5 | Spitz melanocytoma (atypical Spitz tumor) | SLNB with deposit in 1/2 nodes. Completion lymphadenectomy with 0/33 nodes involved. No recurrence (6 years) | aCGH, RNA-Seq | Loss of 15q (distal to NTRK3), loss of portions of proximal 7q, loss of proximal 12q, loss of distal 18q | ETV6 |
| 7# | 7, M | Cheek | Not available | 1.5 | 4.4 | Spitz melanocytoma (atypical Spitz tumor) | NA | aCGH, RNA-Seq | Loss of distal 15q (distal to NTRK3), small deletion on 12p involving 3’ end of ETV6 and deletion of proximal 12q, loss of most of 8p | ETV6 |
| 8 | 10, F | Dorsal wrist | Cyst, pilomatricoma? | 5.5 | 5.7 | Spitz melanocytoma (atypical Spitz tumor) | NA | aCGH | Gain of proximal 15q proximal to NTRK3 with high copy gain involving 5’ end of MYO5A and 3’ end of NTRK3, gain of distal 17q | MYO5A |
| 9# | 10, F | Earlobe | Nevus with central pyogenic granuloma | >1.2 | 2.9 | Spitz melanocytoma (atypical Spitz tumor) | Complete excision, no recurrence (4.5 years) | aCGH, RNA-Seq | Small gain on 15q involving 5’ end of NTRK3, gain of distal 12p (distal to ETV6), gain of most of 2 (but not distal 2p) | ETV6 |
| 10# | 16, F | Scalp | New nevus? | 1.5 | 8.8 | Spitz melanocytoma (atypical Spitz tumor) | Complete excision, no recurrence (3 years) | aCGH, RNA-Seq | Multiple losses on 15q with loss of 5’ end of NTRK3 and deep deletion of 3’ end of MYO5A alternating copy number states on 15 suggestive of chromothripsis | MYO5A |
| 11 | 19, F | Ear | Not available | >3 | 4.0 | Spitz melanocytoma (atypical Spitz tumor) | NA | aCGH | Gain of 12p (distal to ETV6), gain of 15q (proximal to NTRK3) | ETV6 |
| 12 | 21, M | Shoulder | Atypical nevus, basal cell carcinoma, amelanotic melanoma | 0.7 | 2.8 | Spitz melanocytoma (atypical Spitz tumor) | complete excision, no recurrence (7.5 years) | aCGH | Gain of 15q between MYO5A and NTRK3, loss of distal 4p, loss of portion of 10q (containing PTEN), loss of distal 11q, | MYO5A |
| 13 | 36, M | Shoulder | 9×7 mm variegated deeply pigmented papule | 0.7 | 7.3 | Spitz melanocytoma (atypical Spitz tumor) | NA | aCGH | Gain of 15q between MYO5A and NTRK3 | MYO5A |
| 14 | 32, F | Lateral foot | 8 mm papule | 3.7 | 6.7 | Spitz melanocytoma (atypical Spitz tumor) | NA | RNA-Seq | NA | MYO5A |
| 15 | 38, M | Back | 15 mm polypoid nodule | 5.7 | 12.6 | Spitz melanocytoma (atypical Spitz tumor) | NA | aCGH, RNA-Seq | Gain of 15q between MYO5A and NTRK3 | MYO5A |
| 16# | 41, F | Trunk | Hemangioma, dysplastic nevus | ≥1 | 6.7 | Spitz melanocytoma (atypical Spitz tumor) | NA | aCGH, RNA-Seq | Focal deletions of 15q involving 3’ end of MYO5A, 5’ end of NTRK3 | MYO5A |
| 17 | 47, F | Back | 6×3 mm brown exophytic lesion | 1.1 | 3.7 | Spitz melanocytoma (atypical Spitz tumor) | NA | RNA-Seq | NA | MYO5A |
| 18# | 72, F | Forehead | Nevus present for 30 years without change | 0.9 | 7.6 | Spitz melanocytoma (atypical Spitz tumor) | Complete excision, no recurrence (3 years) | aCGH, RNA-Seq | Loss of 15q proximal to MYO5A and distal to NTRK3 | MYO5A |
| 19 | 1, M | Cheek | 3 mm papule, juvenile xanthogranuloma or Spitz nevus | >1.6 | 4.5 | Melanoma | NA | aCGH | Gain of 15q (proximal to NTRK3), loss of distal 15q with alternating copy number states suggestive of chromothripsis, gain of 12p (distal to ETV6). loss of 8p, loss of distal 20p, loss of proximal 21q | ETV6 |
| 20 | 29, M | Elbow | Cyst, subcutaneous nodule | >5 | 11.0 | Melanoma | NA | aCGH | Gains and losses of 15q with gain of 5’ end of MYO5A and loss of 5’ end of NTRK3 and alternating copy number states suggestive of chromothripisis, gain of distal 2q, small loss and gain on 4p, loss of 8p, losses of 9p with deep deletion of CDKN2A, | MYO5A |
| 21 | 44, F | Shoulder | 15×10 mm nodule | 8.2 | 10.3 | Melanoma | NA | aCGH, RNA-Seq | Gain of 15q (distal to MYO5A) with additional gain if the 3’ end of NTRK3, loss of distal 1p, 2q, 7p, and 9q | MYO5A |
| 22 | 74, M | Forearm | Not available | 4 | 7.5 | Melanoma | NA | aCGH | Gain of 15q (proximal to NTRK3), gain of 22q (distal to MYH9) | MYH9 |
*
maximum value measured in histopathologic sections of the tumor,
#
cases included in our earlier report on NTRK3-rearranged Spitz tumors14
Abbreviations: aCGH: array-based comparative genomic hybridization; RNA-Seq transcriptome sequencing.