Table 2

Immunohistochemical features of spindle cell melanocytic lesions

IHC stain	Description	Staining in spindle cell/desmoplastic melanomas	Staining in other spindle cell melanocytic lesions	Other lesions in the diagnosis of a spindle cell melanocytic lesion that may stain positively
S100	Acidic calcium-binding protein homodimer or heterodimer formed of three subunits (αα, αβ, ββ); shows cytoplasmic and nuclear staining	Very high sensitivity (98.7%); moderate specificity	Highly sensitive for all melanocytic lesions	Neural lesions (neuroma, neurofibroma, schwannoma, classic neurothekeoma, MPNST) Langerhans cell histiocytosis/sarcoma Langerhans cell or S100+ dendritic component in other lesions (AFX, DF, scar, LMS) Interdigitating dendritic cell sarcoma Some epithelial lesions (eg, myoepithelial, adnexal lesions)
Melan-A/Mart-1	Protein component of the premelanosomal membrane Shows cytoplasmic staining	Low sensitivity (21.6%);very high specificity	Stratified pattern of staining with increased expression in junctional zone and superficial dermis Diffuse positivity in blue naevi, and occasionally in Spitz naevi	PEComa and related tumours Clear cell sarcoma Adrenocortical tumours Non-melanocytic tumours with melanin production
HMB-45	Premelanosomal glycoprotein gp100 Shows cytoplasmic staining	Low sensitivity (17.6%); very high specificity	Stratified pattern of staining with increased expression in junctional zone and superficial dermis Diffuse positivity in blue naevi, and occasionally in Spitz naevi	PEComa and related tumours Clear cell sarcoma Non-melanocytic tumours with melanin production
Tyrosinase	Melanosomal enzyme required for melanin synthesis Shows cytoplasmic staining	Low sensitivity (26.4%); very high specificity	Stratified pattern of staining with increased expression in junctional zone and superficial dermis Diffuse positivity in blue naevi, and occasionally in Spitz naevi	PEComa and related tumours Clear cell sarcoma Non-melanocytic tumours with melanin production
MiTF	Transcription factor expressed by melanocytes and critical for melanocyte development and expression of tyrosinase Shows nuclear staining	Low sensitivity (15.5%); moderate–high specificity	Sensitive stain for most melanocytic tumours May have slightly higher sensitivity for desmoplastic melanoma than other melanocytic specific markers	PEComa and related tumours Clear cell sarcoma Non-melanocytic tumours with melanin production Cellular neurothekeomas and rare expression in other neural lesions (NF, schwannoma) May be expressed by DF, AFX, smooth muscle neoplasms, and rare carcinomas
Other IHC stains that typically show positive staining in melanomas but which lack validated utility in the routine evaluation of melanocytic lesions	Vimentin – highly sensitive but completely non-specific especially in spindled forms NKI/C3 – another high-sensitivity but low-specificity antibody (lower sensitivity in desmoplastic melanoma) p75 – only low–moderate sensitivity and specificity for melanoma but has been advocated as a potentially useful marker in the diagnosis of desmoplastic melanoma CD117 (c-kit) – growth factor receptor crucial for melanocyte migration and development expressed in many melanocytic lesions including melanoma and Spitz naevi MIB-1/Ki67 – increased proliferative fraction (ie, > 10%) suggests a malignant process (although overlap exists, an unequivocally increased proliferative fraction (ie, > 20%), particularly when there is no decrease with depth of the lesion, strongly suggests melanoma) Cyclin D1 – another proliferation marker that may show increased expression in melanomas (and Spitz naevi) compared with other benign melanocytic lesions WT-1 – expression may suggest melanoma over benign melanocytic proliferations (other than Spitz naevi); expressed in desmoplastic melanoma Nestin – a stem cell marker of neural crest-derived cells that may be preserved in a proportion/majority of melanomas
Other IHC stains that may show misleading positive staining in rare cases of melanoma	CD34 (also reported positivity in blue naevi and related lesions) Cytokeratins, epithelial membrane antigen Desmin CD68 CD10 CD56 CD57

AFX, atypical fibroxanthoma; DF, dermatofibroma, IHC, immunohistochemistry; LMS, leiomyosarcoma; MiTF, microphthalmia transcription factor; MPNST, malignant peripheral nerve sheath tumour; NF, neurofibroma; PEComa, perivascular epithelioid cell tumour.