Table 3 Primary malignant non-melanocytic mimics of intradermal melanoma
LesionClinical featuresHistologyImmunohistochemistry
DFSPYoung to middle-aged adultsSpindle-shaped cells in storiform pattern(+) Vimentin (spindled)
TrunkPigmented cells (Bednar tumour)(+) CD34 (spindled)
Low mitotic rate(+) CD 10 (focal)
Minimal cytological atypia(+) Focal S-100 (pigmented)
(+) Apolipoprotein D
(−) HMB-45
(−) Mart1/MelanA
(−) MiTF
Atypical fibroxanthoma (pleomorphic undifferentiated sarcoma of skin)Male predominanceWell-circumscribed lesion(+) Vimentin
Head and neckHaphazard arrangement(+) CD68
Pleomorphic, spindled and epithelioid cells(+) Lysozyme
Numerous mitoses including atypical(+) α-1 Antichymotrypsin
Multinucleated giant cells(+) Focal factor XIIIa
(+) MSA or SMA
(+) CD10 (diffuse)
(−) S-100
(−) Keratin
(−) Desmin
(−) Mart1/MelanA
(−) MiTF
Malignant PNSTButtocks and thighsFasciculated pattern of hyperchromatic spindle cells(+) Focal S100 (subset)
Rare in other skin locations(+) NSE
(+) Leu 7
(+) Myelin
(+) p53
(+) HMGA2
(−) Neurofilament
(−) HMB-45
(−) Mart1/Melan A
(−) MiTF
Cutaneous leiomyosarcomaAdults in their 60sFascicules of spindle-shaped cells with eccentric vacuole(+) Desmin
Male predominancePleomorphism(+) Caldesmon
Hair-bearing skin of lower extremitiesNuclear atypia(+) Vimentin
Mitoses(+) SMA
(+) MSA
(+) S-100 (rare subset)
(−) Mart1/Melan A
(−) HMB-45
(−) MiTF
Epithelioid angiosarcomaElderlyLarge epithelioid tumour cells(+) CD31
May bleed spontaneouslyHobnail pattern(+) CD34
Scalp and neckIrregular nuclei(+) Focal SMA
Mitoses, including atypical ones(+) Factor VIII-RA
Vascular channels(+) S-100 (rare subset)
Extravasated red blood cells(+) LMWCK (Cam5.2)
(+) Pankeratin (AE1/AE3)
(+) Cytokeratin 7
(−) HMB-45
(−) Mart 1/Melan A
(−) MiTF
Epithelioid sarcomaYoung adultPolygonal tumour cells in nodular aggregates with spindle cells in periphery(+) Cytokeratin
MalePleomorphism(+) Vimentin
Distal extremitiesOccasional mitoses(+) EMA
Central necrosis(+) CD34 (subset)
(−) S-100
(−) HMB-45
(−) Mart1/Melan A
(−) MiTF
Spindle cell squamous cell carcinomaElderly menSpindled pleomorphic tumour cells(+) 34βE12
Sun-exposed skinNo keratinisation(+) AE1/AE3
Head and neckMay show desmosomal junctions(+) Cytokeratin 5/6
Upper extremities(+) P63 (nuclear)
Upper back and chest(−) S-100
(−) HMB-45
(−) Mart1/MelanA
(−) MiTF
Cutaneous malignant granular cell tumourRarely seen in childrenNecrosis(+) S-100
Larger than their benign counterpartsSpindling(+) Calretinin
Vesicular nuclei with large nucleoli(+) Inhibin
Increased mitotic activity >2/10 HPF(−) HMB-45
High N/C ratio(−) Mart1/MelanA
Pleomorphism(−) MiTF
Cutaneous lymphoproliferative disorders and other haematological malignanciesCan affect any ageLarge pleomorphic mononuclear cells(+) LCA (CD45)
Depending on type of lymphoma:
B cell markers
T cell markers
Blast markers
Myeloma markers (CD138)
(−) S-100
(−) HMB-45
(−) Mart1/MelanA
Merkel cell carcinomaHead and neck and extremities of older adultsSmall monomorphic basophilic cells with round to oval shaped nuclei and scanty cytoplasm(+) CK20 and LMWCK typical dot-like paranuclear or cytoplasmic staining
Solitary rapidly growing hard noduleNuclei have finely granular dispersed chromatin and small inconspicuous nucleoli(+) Variably for CD56, CD57, EMA, chromogranin and synaptophysin
Tumour cells mainly occupy the dermis, but pagetoid spread of the tumour cells into the epidermis can be seen(−) S-100
(−) HMB-45
(−) Vimentin
(−) Mart 1/Melan A
(−) MiTF
Malignant PEComaDepends on type and site of PEComaClear or eosinophilic spindle-epithelioid cells(+) HMB-45
Fascicular, nested, sheet-like patterns(+) Mart1/MelanA
Perivascular accentuation(+) MiTF
Multinucleated giant cells(+) S-100 in 18%
>8 cm in size, >1 mitotic figure/50 HPFs, necrosis(+) SMA, MSA
(+) Desmin
(+) Cyclin D1
(+) Vimentin
(+) Pan-cytokeratin
Follicular dendritic cell sarcomaMostly affect adultsSpindle to ovoid cells arranged in storiform or fascicular pattern(+) CD21
Intranodal or extranodal painless massOval nuclei, distinct nucleoli, delicate nuclear membrane(+) CD35
Indistinct cell border(+) CD23
Fibrillary cytoplasm(+) Desmoplakin
(+) EMA
(+) Vimentin
(+) S-100 in 35%
(+) CD68 in 11%
(+) Clusterin
(+) Fascin
(+) Podoplanin
(−) HMB-45
(−) Mart1/MelanA
(−) MiTF
(−) Cytokeratin
(−) CD30
(−) CD3
(−) CD79a
(−) CD34
(−) CD1a
Anaplastic/pleomorphic Kaposi sarcomaHIV settingSpindle to epithelioid cells arranged in solid sheets and fascicles(+) CD34
Pleomorphic nuclei with prominent nucleoli(+) D2-40
Atypical mitoses(+) CD31 (patchy)
Extravasated red blood cells(+) HHV-8 latency-associated nuclear antigen-1
(+) VEGFR-3
(+) Podoplanin
(−) S-100
(−) HMB-45
(−) Mart1/MelanA
(−) MiTF
Plexiform fibrohistiocytic tumour of the skinYoung patientsPlexiform pattern(+) CD68
Female predominanceSpindled and histiocytoid cells(+) SMA
Trunk, extremity, faceOsteoclast-type giant cells(+) PGP 9.5
Cellular pleomorphism, mitotic activity, vascular invasion (may sometimes look like non-necrotising granulomas)(+) S-100A6
(+) MiTF
(+) CD57
(−) HMB-45
(−) Mart1/MelanA
Monomorphic spindle synovial sarcomaAdolescents, young adultsSpindle and epithelioid cells(+) EMA, HMWCK, LMWCK
Lower extremitiesHigh nuclear/cytoplasmic ratio(+) Type IV collagen, CD57, rarely S-100
Variable mitotic rate(+) CD99, CD56, neurofilaments
(−) Chromogranin, synaptophysin
(−) HMB-45, Mart1/MelanA, MiTF
Post-radiation sarcomas including rhabdomyosarcomasPost-radiotherapySpindle cells(+) Vimentin, other mesenchymal markers S-100 could be positive
Cellular atypia(−) HMB-45, Mart1/MelanA
High mitotic rate

  • DFSP, dermatofibrosarcoma protuberans; EMA, epithelial membrane antigen; HMB, human melanoma black; HMWCK, high molecular weight cytokeratin; LMWCK, low molecular weight cytokeratin; MiTF, microphthalmia transcription factor; MSA, muscle specific actin; NSE, neuron-specific enolase; PEComa, perivesicular epithelioid cell tumour; PGP, P glycoprotein; PNST, peripheral nerve sheath tumour; SMA, smooth muscle actin; VEGFR, vascular endothelial growth factor receptor.