Table 1.
Clinical and genetic details of 12 patients with congenital melanocytic naevus (CMN) and melanoma seen in our department
| Patient number | Sex | Age at diagnosis (years) | Outcome | Screening MRI CNS under 1 year | Primary melanoma site | CMN classification, including recent consensus classification where available3 | Tissue for genetic investigations | Tissue NRAS hotspot genotype (codons 12, 13, 61) | Tissue whole‐genome large (> 1 MB) copy‐number changes |
|---|---|---|---|---|---|---|---|---|---|
| 1 | Male | Not known | Death, age 7·1 years | Normal | Not known | Multiple CMN, largest > 60 cm PAS. Consensus classification: G2 | Not done | Not done | |
| 2 | Male | ~2 | Death, age 2·3 years | Not done | CNS, solid tumour in cerebellum | Multiple CMN, no other details available | Not done | ||
| 3 | Female | 9·7 | Death, age 10·2 years | Normal | CNS, solid tumour in cerebellum, plus diffuse leptomeningeal melanoma, VP shunt, died of spinal cord compression, possible liver metastasis at post mortem | Multiple CMN, largest > 60 cm PAS, bathing trunk, 100–200 naevi in total. Consensus classification: G2, S3, Trunk, C1, R1, N0, H1 | Cerebellar melanoma | c.181C>A; p.Q61K | Multiple large gains and losses of whole and parts of chromosomes |
| 4 | Male | 15·5 | Alive 11 months after diagnosis | Normal | Cutaneous, within largest CMN on the back of the scalp and neck, metastatic to local lymph node at time of diagnosis | Multiple CMN, largest 10–20 cm scalp and neck, 10–20 naevi in total. Consensus classification: M2, S1, Neck, C0, R1, N1, H1 | Cutaneous melanoma | Wild‐type | This sample tested by FISH: gains 6p25, 11q13 |
| 5 | Male | 1·5 | Death, age 2·3 years | Complex congenital neurological disease | CNS, diffuse leptomeningeal melanoma, VP shunt | Multiple CMN, largest PAS > 60 cm, bathing trunk, total naevi 100–200, coexistent X‐linked ichthyosis. Consensus classification: G2, S3, Trunk, C0, R1, N0, H2 | Leptomeningeal melanoma | c.181C>A; p.Q61K | Single large duplication of part of 6p |
| 6 | Male | 0·2 | Death, age 3·6 years | Not done | Not known | Multiple CMN, largest PAS > 60 cm. Consensus classification: G2 | Not done | Not done | |
| 7 | Male | Not known | Death, age 2·5 years | Intraparenchymal melanosis only | CNS, diffuse leptomeningeal melanoma, metastasis to peritoneum via VP shunt | Multiple CMN, largest PAS > 60 cm, bathing trunk, 20–50 naevi in total. Consensus classification: G2, S2, Trunk, C2, R2, N2, H1 | CMN | c.182A>G; p.Q61R | Not done |
| 8 | Male | 4·0 | Death, age 4·6 years | Complex congenital neurological disease | CNS, diffuse leptomeningeal melanoma, VP shunt | Multiple CMN, largest neck and upper back, cape, PAS 20–40 cm, 100–200 naevi in total. Consensus classification: L1, S3, Trunk, C0, R0, N0, H1 | Leptomeningeal melanoma | c.181C>A; p.Q61K | Multiple large gains and losses of parts of chromosomes |
| 9 | Female | 1·8 | Death, age 2·2 years | Complex congenital neurological disease | CNS, diffuse leptomeningeal melanoma, with infiltration of the underlying parenchyma, VP shunt, died of spinal cord compression, no known metastasis | Multiple small CMN, no truly clearly larger naevus although technically one medium CMN, > 400 naevi in total. Consensus classification: S3, C1, R0, N0, H1 | Leptomeningeal melanoma | c.181C>A; p.Q61K | Multiple large copy‐number abnormalities |
| 10 | Male | Not known | Death, age 2·4 years | Normal | Lymph node groin, locally recurrent despite excision, local metastasis | Multiple CMN, largest PAS > 60 cm, bathing trunk, naevus spilus type (difficult to see and quantify small naevi in this type). Consensus classification: G2, Trunk, C2, R1, N0, H1 | Not done | Not done | |
| 11 | Female | 0·2 | Death, age 0·9 years | Complex congenital neurological disease | CNS, diffuse leptomeningeal melanoma, VP shunt, died of spinal cord compression, no known metastasis | Multiple CMN, largest PAS > 60 cm, on back, 20–50 naevi in total. Consensus classification: G2, S2 | Leptomeningeal melanoma | c.181C>A; p.Q61K | Not done |
| 12 | Female | 6·5 | Death, age 7·1 years | Normal | Cutaneous, within largest CMN, at the site of postnatal resection of a benign congenital nodule, metastatic to local lymph node at time of diagnosis | Multiple CMN, largest on scalp, PAS 10–20 cm, 50–100 naevi in total. Consensus classification: M2, S3, C0, R0, N1, H1 | Cutaneous melanoma | c.181C>A; p.Q61K | Gain 1q, 2q, LOH 1p, 5q, 9p, 9q, 11q, 12q, 14q, 17p, 20p |
Genotypes of NRAS and BRAF hotspots and copy‐number changes from tissue biopsies of primary central nervous system (CNS) and cutaneous melanoma are provided where available and consent was given. All patients were wild‐type for hotspots in BRAF. For further details of copy‐number changes in the CNS tumours, see Kinsler et al.39 MRI, magnetic resonance imaging; PAS, projected adult size; VP, ventriculoperitoneal.