Ungual Melanoma
Nail (ungual or subungual) melanoma, SUM, is a primary malignancy arising from melanocytes in the basal layer of the nail matrix that have undergone malignant transformation. Although it accounts for only about 1–3% of melanomas in people of European descent, the figure rises to 10–30% in Asian, African and other darker-skinned populations.
Histologically, 75–90% of subungual melanomas are acral lentiginous melanoma (ALM). Unlike melanoma of ordinary skin, ALM is not linked to UV radiation. It is closely associated with complex genetic changes (KIT, CCND1 and CDK4 alterations, while BRAF V600E mutations are uncommon) and with repeated microtrauma to the fingertips and toes.
- Histopathology:
- In situ subungual melanoma: Atypical melanocytes with large, hyperchromatic nuclei line up along the basal layer of the matrix and show pagetoid spread into the upper epidermis, but the basement membrane is still intact.
- Invasive subungual melanoma: Nests of malignant epithelioid or spindle cells break through the basement membrane and invade deeply into the nail bed dermis, subungual connective tissue, periosteum and distal phalanx.
- Breslow thickness: The distance from the granular layer of the matrix epithelium to the deepest tumor cell. This is the single most important prognostic measure for survival.
- Immunohistochemistry (IHC):
- Tumor cells stain strongly for S100, SOX10 (the most specific melanocytic marker), Melan-A/MART-1, HMB-45 and PNL2.
- The Ki-67/MIB-1 proliferation index is markedly raised (> 15–30%), and p16 protein expression is lost.
SUM is very often diagnosed late (an average delay of 1–3 years), so 5-year survival for advanced invasive tumors is only about 15–50%. The main reason is that it is easily mistaken for a subungual hematoma, benign melanonychia or onychomycosis. In addition, about 20–30% of cases are amelanotic melanomas, which appear as a fleshy pink-red growth that closely resembles a pyogenic granuloma.
Clinical Features, the ABCDEF Rule and Digital Onychoscopy Signs
The ABCDEF Clinical Rule for Subungual Melanoma
- A (Age and ancestry): Peak incidence is between ages 50 and 70; it is more common in people of Asian descent or with darker skin.
- B (Band): A brown-black longitudinal band wider than 3 mm with irregular borders and a triangular shape (broader at the matrix and narrowing toward the free edge).
- C (Change): The band darkens quickly or widens noticeably, or the nail plate becomes deformed, lifts or splits (onycholysis/dystrophy).
- D (Digit): The thumb (pollex) and big toe (hallux) account for more than 75% of cases.
- E (Extension): Pigment spreading onto the proximal nail fold (eponychium) or lateral folds, known as a true Hutchinson’s sign.
- F (Family or personal history): A personal or family history of melanoma.
Digital Onychoscopy (Nail Dermoscopy) Signs
- Loss of parallelism: The longitudinal pigmented lines vary in width and spacing, with alternating darker and lighter segments.
- Multiple colors (polychromasia): Three or four colors in the same lesion (light brown, dark brown, jet black, gray-green or pinkish red).
- Triangular pattern: The band is clearly wider at the base of the nail than at the tip, reflecting ongoing tumor growth in the matrix.
Telling Nail Melanoma Apart from Other Pigmented Nail Lesions
| Subungual Melanoma (SUM) | Benign Longitudinal Melanonychia (BLM) | Subungual Hematoma |
|---|---|---|
| Malignant acral lentiginous melanoma | Melanocyte activation / matrix nevus | Bleeding into the tissue after trauma |
| Hutchinson’s sign POSITIVE (+) (specific) | Negative (–) (or pseudo-Hutchinson) | Hutchinson’s sign negative (–) |
| Irregular, multicolored, triangular lines | Parallel lines with EVEN spacing | Round reddish globules |
| Rapid widening, destroys the nail plate | Stable for many years | Moves out gradually as the nail grows |
| SOX10 (+), S100 (+), HMB45 (+) | S100 (+), Ki-67 (< 1%) | Negative |
Diagnosis, Matrix Biopsy and Surgical Treatment at Haute-Derma
At Haute-Derma, patients with a high-risk pigmented nail band are managed under our multidisciplinary diagnostic and surgical protocol for nail melanoma (Haute-Derma SUM Protocol):
Standard Nail Matrix Biopsy (the Gold Standard)
- Principle: The specimen must include the full depth from the matrix epithelium down to the periosteum. Shave biopsies and laser ablation are NOT acceptable, because they make it impossible to measure Breslow thickness.
- Lateral longitudinal biopsy: Used for lesions in the lateral third of the nail plate.
- Excisional matrix biopsy: The entire matrix area producing the band is removed when the band is wider than 3–5 mm.
Staging and Sentinel Lymph Node Biopsy (SLNB)
- Breslow < 0.8 mm (in situ or very thin invasion): Digit-sparing wide local excision (WLE) of the entire nail unit down to the periosteum, followed by a full-thickness skin graft.
- Breslow 0.8 mm or more, or ulceration: Sentinel lymph node biopsy (SLNB) of the same-side axillary or inguinal nodes is added to detect microscopic spread.
Definitive Surgery and Functional Recovery
- Amputation: When the tumor has invaded deep into the dermis and periosteum, the surgeon performs an amputation at the distal interphalangeal (DIP) joint or the metacarpophalangeal joint.
- Function-sparing surgery: For very early (in situ) tumors, the entire nail apparatus is excised while the distal phalanx is preserved, and the defect is covered with a rotation flap or skin graft.
Systemic Adjuvant Therapy
- For nodal (stage III) or distant (stage IV) metastases: anti-PD-1 immune checkpoint inhibitors (pembrolizumab/nivolumab), or targeted therapy (imatinib) when a KIT mutation is present.
