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Melanoma variantSpitzoid spectrumICD-10 C43.x

Spitzoid melanoma

Spitzoid melanoma · Spitzoid-pattern melanoma · malignant Spitz tumour

Spitzoid melanoma is a melanoma variant with histological resemblance to a Spitz naevus — epithelioid / spindle cell melanocytes, eosinophilic cytoplasm, Kamino bodies — but with malignant biological behaviour. It occupies the malignant end of the Spitzoid spectrum (Spitz naevus → atypical Spitz tumour → Spitzoid melanoma). Modern classification (WHO 2023) emphasises specific molecular drivers — HRAS, ALK, ROS1, NTRK1/3, BRAF, MET, RET, MAP3K8 fusions / rearrangements — with prognostic and emerging therapeutic implications. Diagnosis is a specialist dermatopathology challenge; FISH / CGH / next-generation sequencing increasingly required.

CurrentLast reviewed 16 May 2026

Spitzoid spectrum

  • Spitz naevus (benign): typical in children / young adults; symmetric; HRAS or BAP1-inactivated variants; benign behaviour.
  • Atypical Spitz tumour (AST): indeterminate biological potential; intermediate atypia; see separate monograph.
  • Spitzoid melanoma: malignant; can metastasise; full melanoma staging.
  • Histological appearance overlaps; molecular profile and clinical context inform diagnosis.

Molecular drivers

  • HRAS mutation / amplification — typically benign Spitz; rarely malignant.
  • Kinase fusions: ALK, ROS1, NTRK1, NTRK3, RET, BRAF, MET, MAP3K8 — characterise Spitzoid neoplasms across the benign-to-malignant spectrum.
  • BAP1 loss: BAP1-inactivated melanocytic tumours (BIMT) — Spitz-like; may indicate germline BAP1-TPDS.
  • CDKN2A loss + chromosomal instability — supports malignancy.
  • TERT promoter mutation — strongly associated with malignant behaviour.
  • WHO 2023 classifies Spitzoid neoplasms by these molecular drivers.

Clinical features

  • Pink, red or pigmented dome-shaped nodule or papule.
  • Often rapid growth.
  • Sites: face, trunk, extremities (especially lower limb).
  • Any age but disproportionately in children, adolescents, young adults — distinguishing from common SSM.
  • Symptoms: bleeding, ulceration, change in size or colour.
  • Often amelanotic — see amelanotic melanoma.

Pathology

Spitzoid melanoma shares some Spitz features (epithelioid / spindle cells, eosinophilic cytoplasm) but exhibits malignant features:

  • Asymmetry, lack of maturation, mitoses at base, atypical mitoses.
  • Marked nuclear pleomorphism, prominent nucleoli.
  • Necrosis.
  • Deep dermal invasion.
  • Lymphovascular / perineural invasion.
  • Loss of p16; loss of Rb; HMB-45 retention in deep dermis.
  • IHC: BAP1 (loss in BIMT subset), p16, Ki-67 (high), PRAME (positive supports melanoma).
  • Ancillary molecular:
    • FISH for 6p25 (RREB1), 6q23 (MYB), 11q13 (CCND1), 9p21 (CDKN2A).
    • CGH / next-generation sequencing for kinase fusions and TERT promoter.

Staging

  • Same AJCC 8 staging as conventional melanoma — Breslow, ulceration, mitotic rate, SLNB criteria.
  • Spitzoid melanoma often has higher Breslow thickness at diagnosis due to nodular growth pattern.
  • SLNB discussion per NICE NG14: consider for Breslow 0.8–1.0 mm with ulceration, lymphovascular invasion or mitotic index ≥2, and for Breslow >1.0 mm after discussion.
  • Note: SLN positivity in atypical Spitz tumours may not carry the same prognosis as conventional melanoma — multidisciplinary discussion essential.

Management

  • WLE per NICE NG14 margins by Breslow.
  • SLNB per standard criteria.
  • Adjuvant therapy: per stage and molecular profile.
  • Targeted therapy (advanced disease):
    • Kinase-fusion melanomas → emerging targeted options: TRK inhibitors (larotrectinib, entrectinib) for NTRK fusions; crizotinib / lorlatinib for ALK / ROS1; selpercatinib for RET; tropomyosin pathway inhibitors.
    • Targetable BRAF in Spitz neoplasms is characteristically a BRAF fusion (amenable to MEK-directed strategies), not the V600E point mutation — so V600E-directed BRAF/MEK therapy applies only to the uncommon genuinely V600-mutant spitzoid melanoma.
    • ICI per stage (combination ICI for high-risk).
  • Multidisciplinary management: dermatology, dermatopathology, plastics, oncology, molecular pathology.
  • Specialist sarcoma / paediatric MDT input if young patient.
  • Follow-up per NICE NG14 stage-based protocol.

References

  1. WHO Classification of Tumours Editorial Board. Skin Tumours, WHO Classification of Tumours, 5th ed., vol. 12. Lyon: IARC; 2025.
  2. Bastian BC. The molecular pathology of melanoma: an integrated taxonomy of melanocytic neoplasia. Annu Rev Pathol. 2014;9:239-271.
  3. Yeh I et al. NTRK3 kinase fusions in Spitz tumours. J Pathol. 2016;240:282-290.
  4. Wiesner T et al. Kinase fusions are frequent in Spitz tumours and Spitzoid melanomas. Nat Commun. 2014;5:3116.
  5. Lezcano C et al. PRAME expression in melanocytic tumors. Am J Surg Pathol. 2018;42:1456-1465.
  6. Drilon A et al. Larotrectinib in TRK fusion-positive cancers. N Engl J Med. 2018;378:731-739.

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