Table 3 Summary of patients with atypical melanocytic tumors and adverse clinical outcomes.
Patient no | Sex | Age, y | Site | Breslow index (mm) | Histological type | Cytology | IHC | Molecular findings | Molecular technique usefulness and impact (i score) | Histological category | Follow-up, year | Clinical reexcision, largest diameter | Sentinel node | Clinical outcome |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | F | 62 | Thorax | 2.2 | SRT | Dense nests of spindle cells | p16+ | No 9p21 deletion, no 4-color melanoma FISH abnormality | Not helpful: histologically certain melanoma diagnosis (i = 0) | Spitzoid melanoma (A+) | 12 | Yes, 20 mm | Yes, positive | pT3aN1aM0, in remission to date |
2 | M | 44 | Knee | 5.3 | SRT | Nests of epithelioid cells and spindle cells, desmoplastic stroma | p16– | Heterozygous 9p21 deletion, no BRAF mutation, NRAS p.Q61X mutation | Not helpful: histologically certain melanoma diagnosis (i = 0) | Spitzoid melanoma (A+) | 9 | Yes | Yes, negative | LN metastases and in-transit melanoma metastasis on the same leg, 8 years after initial diagnosis |
3 | M | 49 | Loins | 1.6 | SRT | Moderate cellular proliferation of spindle cells | p16– clonal | Heterozygous 9p21 deletion | Heterozygosity did not aid in the diagnosis (i = 0) | Unclear: Spitzoid melanoma or atypical Spitz tumor (DA+) | 8 | No | No | Tumor-attributed death |
4 | F | 36 | Cheek | NC | SRT | Bundles of spindle cells | p16+, BRAFV600E– | Heterozygous 9p21 deletion | Heterozygosity did not aid in the diagnosis (i = 0) | Atypical Spitz nevus (DA–) | 7 | No | No | Died, but superficial spreading melanoma on the temple (BRAFV600E+) 4 y earlier, considered cause of death |
5 | F | 38 | Foot | 1.8 | SRT | Nests of spindle cells | p16– | Homozygous 9p21 deletion, 4-color melanoma FISH with MYB deletion, NRAS p.Q61K mutation | Switch from DA– to DA+ category (i = 2) | Unclear: Spitzoid melanoma or atypical Spitz tumor (DA+) | 6 | Unknown | No | Pulmonary & subcutaneous metastases, treated with immunotherapy |
6 | H | 24 | Trunk | 2.1 | SRT | Clonal proliferation of spitzoid cells | p16– clonal | Heterozygous 9p21 deletion, 4-color melanoma FISH harbors RREB1 gain, MYB deletion, RREB1/CYP6 | 9p21 did not help, 4-color melanoma FISH confirmed the malignancy (i = 0) | Spitzoid melanoma (A+) | 6 | Yes, 20 mm | No | Regional LN recurrence 1-year post-diagnosis, died while on immunotherapy |
7 | H | 4 | Leg | 3.3 | SRT | Nests of epithelioid cells in a desmoplastic stroma, with some zones of spindle cells | p16–, ALK+ spindle cells | Homozygous 9p21 deletion | 9p21 was helpful, but the ALK+ profile prevented malignancy affirmation (i = 1) | Unclear: Spitzoid melanoma or atypical Spitz tumor (DA+) | 4 | Yes, 10 mm | No | Regional LN metastases relasped 2 years later |
8 | H | 30 | Trunk | 5 | SRT | Area of common naevi with a central spitzoid clone | p16– clonal, ALK+ | No 9p21 deletion, no 4-color melanoma FISH abnormality. CGH: heterozygous deletion of 9p22.3–9p13.2, 10 loss, loss of: 11q14.1-qter, 14q11.2q24.2, 16p12.3p11.2, complex 19p recombinations | Neither FISH technique helped, but CGH was useful (i = 0) | Composite spitzoid nevus (DA–) but CGH abnormalities favor malignancy | 3 | Yes, 5 mm | No | Synchronous discovery of multiple LN, hepatic, pulmonary & pleural metastases; died on immunotherapy and targeted therapy |
9 | F | 27 | Leg | 2.6 | SRT | Nests of spindle cells | p16– | No 9p21 deletion, 4-color melanoma FISH harbors CCND1 and RREB1+ | 9p21 did not help, unlike 4-color melanoma FISH (i = 0) | Unclear: Spitzoid melanoma or atypical Spitz tumor (DA+) | 13 | Yes | Yes, positive | Remission after sentinel-node positive and lymph-node dissection negative |
10 | F | 11 | Leg | 2.4 | SRT | Nests of epithelioid cells | p16– | Heterozygous 9p21 deletion | Finding heterozygous 9p21 did not help; histologically certain melanoma (i = 0) | Spitzoid melanoma (A+) | 5 | Yes, 20 mm | No | Regional LN invasion 3 months post-diagnosis; after immunotherapy, now in clinical remission |
11 | F | 17 | Back | 3 | OMT: BAP | Nests of epithelioid cells with adjacent common nevus | p16–, BAP1 loss in epithelioid cells, BRAFV600E+ | Homozygous 9p21 deletion, BRAF p.V600E/E2/D mutation; CGH: chromosomes 3, 9, 7q & 10 lost | 9p21 did not help (i = 0) | Invasive melanoma developing on BAP1-inactivated melanocytoma (A+) | a | Yes, 20 mm | Yes, positive (micro-metastasis in 1/3 LNs) | LN and leg muscle invasion 2 years later; died on targeted therapy & immunotherapy |
12 | F | 31 | Shoulder | 2.2 | ATNT | Dense proliferation of monotonous epithelioid cells | p16–, β-cat, BAP1+ | Heterozygous 9p21 deletion | 9p21 heterozygosity did not aid in the diagnosis (i = 0) | Uncertain nevoid melanoma (DA+) | 4 | Yes, 20 mm | No | Regional LN-metastasis relapse followed by LN dissection in September 2022; currently on immunotherapy |
13 | H | 56 | Arm | 1.6 | ATNT | Ulcerated dense compound lesion of nevoid cells | p16– | Heterozygous 9p21 deletion, 4-color melanoma FISH harbors RREB1 gain and MYB deletion | 4-color melanoma FISH confirmed the malignancy (i = 0) | Nevoid melanoma (A+) | 5 | Yes, 10 mm | No | Surgical excision of a single transit nodule followed by 6 months of adjuvant immunotherapy, stopped because of poor tolerance |
14 | F | 24 | Side | 2.7 | ATNT | Nevoid cells | p16–, BRAFV600E– | Homozygous 9p21 deletion, 4-color melanoma FISH harbors RREB1 gain and MYB deletion | Both FISH were consistent with the histological diagnosis (i = 1) | Nevoid melanoma (A+) | 10 | Yes, 20 mm | Yes, positive | Sentinel-node positive, LN dissection negative and in transit metastases around the scar |
15 | F | 25 | Arm | 1.3 | ATNT | Nevoid cells | p16– | Heterozygous 9p21 deletion, 4-color melanoma FISH harbors RREB1 gain; NRAS mutation | 9p21 did not help, but 4-color melanoma FISH did (i = 0) | Metastatic nevoid melanoma (A+) | 6 | Unknown | No | Ovarian metastasis of the arm melanoma; clinical remission after immunotherapy |
16 | F | 48 | Leg | 3 | ATNT | Dense nevoid cell proliferation simulating a nevus | p16–, BAP1+, BRAFV600E+, B-cat–, PRAME–, ALK– | Homozygous 9p21 deletion | 9p21 led to category switch from DA+ to A+ diagnosis (i = 2) | Nevoid melanoma (A+) | 2 | Yes, 20 mm | Yes, positive | Sentinel-node positive, LN dissection negative; currently on immunotherapy |
17 | F | 31 | Arm | 1.5 | ATNT | Compound dense nevoid cell proliferation | p16– clonal | No 9p21 deletion, MYB deletion in 4-color melanoma FISH | FISH 9p21 did not aid in the diagnosis (i = 0) | MELTUMP (DA–) | 3 | No | No | Local relapse after initial excision; subsequent re-excision, currently in remission |
