Melanocytic immunohistochemistry panel
Melanoma IHC panel; melanocyte markers; S100 / SOX10 / Melan-A / HMB-45 / MITF
The core melanocytic immunohistochemistry panel — S100, SOX10, Melan-A / MART-1, HMB-45 and MITF — supports diagnosis of melanocytic lesions where H&E features are ambiguous, evaluates margin involvement at the lesion edge, and detects micrometastases in sentinel lymph nodes. No single marker is both sensitive and specific in all contexts; the panel approach reflects the trade-offs in coverage. SOX10 has emerged as the most reliable single marker in modern UK practice — highly sensitive, nuclear staining easy to interpret, and works well on desmoplastic melanoma where Melan-A and HMB-45 may be negative. Modern adjuncts include PRAME for ambiguous melanocytic lesions and CK20 for the Merkel-cell differential.
S100 protein
- Nuclear and cytoplasmic staining; calcium-binding protein expressed by neural-crest derivatives.
- Highest sensitivity for melanocytic differentiation (~ 95–100% in classical melanoma, including desmoplastic melanoma).
- Low specificity — also positive in nerve-sheath tumours (schwannoma, neurofibroma), Langerhans cells, chondrocytes, adipocytes, some myoepithelial cells.
- Workhorse marker but interpret with morphology and second-line markers.
SOX10
- Transcription factor; nuclear staining (easier to interpret than cytoplasmic markers).
- Highly sensitive for melanocytic lineage (~ 100% of conventional melanoma; ~ 95% of desmoplastic melanoma — more sensitive than HMB-45 or Melan-A in desmoplastic disease).
- Specificity superior to S100 for melanocytic differentiation; less staining in cartilage / adipose.
- Cross-reacts with myoepithelial cells (breast, salivary), schwannian elements, GIST.
- SOX10 has become the preferred first-line marker in UK melanocytic IHC in many centres.
Melan-A / MART-1
- Melanocyte-specific antigen; cytoplasmic staining.
- High sensitivity in classical melanoma (~ 95%); good for distinguishing melanoma from other epithelial / non-melanocytic tumours.
- Poor sensitivity in desmoplastic melanoma (~ 30–60%) and spindle-cell melanoma — use SOX10 instead in these contexts.
- Cross-reacts with adrenal-cortex cells, sex-cord stromal tumours of the ovary, sometimes Langerhans cells.
- Common use — confirming melanocytic differentiation, marking sentinel lymph-node micrometastases.
HMB-45 (gp100 / Pmel17)
- Cytoplasmic staining of premelanosome glycoprotein.
- Sensitivity 70–90% in conventional melanoma; lower in desmoplastic and metastatic melanoma.
- Distinctive pattern — strong in deep dermal nests of melanoma (loss of "maturation" — naevi mature with depth and lose HMB-45; melanoma retains).
- "Naevus matrix" pattern of HMB-45 — patchy / dermal-deep staining favours melanoma; smooth diminution with depth favours benign naevus.
- Useful for melanoma-vs-naevus distinction at the dermal component; less useful alone for lineage determination.
MITF (Microphthalmia-associated Transcription Factor)
- Nuclear staining; melanocyte master transcription factor.
- Sensitivity ~ 90% in melanoma; less reliable in desmoplastic variant.
- Cross-reacts with macrophages, mast cells, some smooth-muscle tumours.
- Useful adjunct when other markers equivocal.
- Diagnostic distinction between melanoma and clear-cell sarcoma — both express MITF, requires molecular (EWSR1 rearrangement in clear-cell sarcoma).
Clinical context-specific use
- Sentinel lymph node — S100 + Melan-A + HMB-45 (or SOX10 + Melan-A) panel for micrometastasis detection; deposit size matters for AJCC 8 N category.
- Lentigo maligna margins — Melan-A or SOX10 helps highlight scattered atypical junctional melanocytes; SOX10 preferred in chronically sun-damaged skin where Melan-A may stain pigmented keratinocytes.
- Desmoplastic melanoma — SOX10 first-line (most sensitive); S100 second; Melan-A and HMB-45 often negative.
- Spitzoid lesions — PRAME is the most useful adjunct (diffuse staining supports melanoma); see PRAME monograph.
- Distinguishing from MCC — CK20 paranuclear-dot pattern in MCC; CK20-negative melanoma.
- Margin assessment — Melan-A may over-call by staining "pseudomelanocytes" (pigmented keratinocytes) in sun-damaged skin; SOX10 less subject to this confounder.
References
- Plaza JA et al. Melanocytic markers in the diagnosis of melanocytic lesions. Am J Dermatopathol; 2017.
- Mohamed A et al. SOX10 expression in melanocytic lesions — review. J Cutan Pathol; 2013.
- Royal College of Pathologists. Dataset for histopathological reporting of primary cutaneous malignant melanoma and regional lymph nodes. G125. London: RCPath; February 2019.
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