Table 4 Histopathological and immunohistochemical features of intraepidermal primary cutaneous malignant tumours mimicking melanoma
Intraepidermal mimicHistopathological featuresImmunohistochemical features
Bowen disease
  • Full-thickness keratinocyte dysplasia with acanthosis, parakeratosis and frequent mitotic figures above the basal cell layer

  • Widely scattered atypical pale keratinocytes in all layers of the epidermis in Pagetoid BD separated from each other by normal keratinocytes

  • Sharply demarcated nests of atypical cells within the epidermis in the nested variant of BD

  • HMWCK (+) P63 (+) (nuclear stain)

  • Negative for melanocytic markers (S-100, Mart 1/Melan A, HMB 45)

Mammary and extramammary Paget disease
  • Large cells with abundant pale or eosinophilic cytoplasm containing large vesicular nuclei. The cells are scattered throughout all layers of the epidermis, but the nesting pattern is usually seen above the basal cell layer

  • Melanin pigment can be seen in some cases

  • Mucin stains such as colloidal iron can be of great help. PAS diastase is also positive

  • LMWCK (+), CEA (+), EMA (+), GCDFP-15 (+), CK7 (+)

  • Negative for melanocytic markers (S-100, Mart 1/Melan A, HMB 45)

Mycosis fungoides/Pagetoid reticulosis
  • Infiltration of the epidermis by large irregular lymphoid cells with a moderate amount of lightly eosinophilic cytoplasm and large cerebriform nuclei

  • Cells arrange in single units or nests and are mainly seen in the lower layers of the epidermis (epidermotropism)

  • In mycosis fungoides Pautrier microabscesses can be seen

  • Dermal infiltrate of mature and reactive lymphocytes, histiocytes and few plasma cells

  • CD3 (+), CD5(±), mainly CD4 (+), less likely CD8 (+), or CD4/CD8 double-negative

  • Rare variant of mycosis fungoides shows CD56 positivity

  • Usually negative for CD7 and melanocytic markers* (S-100, HMB 45, Mart 1/Melan A)

Merkel cell carcinoma
  • Small monomorphic basophilic cells with round to oval shaped nuclei and scanty cytoplasm

  • Nuclei have finely granular dispersed chromatin and small inconspicuous nucleoli

  • Tumour cells mainly occupy the dermis, but Pagetoid spread of the tumour cells into the epidermis can be seen

  • CK20 (+) and LMWCK (+) typical dot-like paranuclear or cytoplasmic staining, variably positive for CD56, CD57, EMA, chromogranin and synaptophysin

  • S-100 (−), HMB 45 (−), Mart 1/Melan A (−)

Sebaceous carcinoma with Pagetoid spread
  • Tumour composed of basaloid appearing cells with varying degree of sebaceous differentiation

  • Intraepidermal Pagetoid spread of tumour cells can be seen

  • Cells are vacuolated with scalloped, mulberry-like pattern nuclei. Mitotic figures are frequent

  • AE1/AE3 cytokeratin (+), LMWCK (+), EMA (+), androgen receptor protein (+), CK14 (+), P63 focally (+)

  • S-100 (−), HMB 45 (−), Mart 1/Melan A (−)

Malignant granular cell tumour†
  • Nuclear atypia (prominent nucleoli), nuclear pleomorphism

  • >2 mitoses/10 HPF

  • Increased nuclear/cytoplasmic ratio

  • Necrosis, spindling

  • S100 (+), CD68 (+), inhibin (+), calretinin (+)

  • Negative for other melanocytic markers (HMB 45, Mart 1/Melan A)

Porocarcinoma in situ
  • Nests of atypical polygonal cells that are sharply separated from the adjacent epidermis

  • Cytonuclear atypia, hyperchromatic nuclei and prominent nucleoli

  • Cells may contain melanin

  • Adjacent benign poroid component can be present within occasional tubules

  • S-100 occasionally (+), pancytokeratin (+), CK7 focally (+)

  • HMB 45 (−), Mart 1/Melan A(−)

Pigmented superficial basal cell carcinoma
  • Basaloid cells with atypical nuclei, scant cytoplasm and peripheral palisading of the cells

  • Melanocytes scattered through the tumour nests and melanophages within the stroma

  • HMWCK (+), CK14(+), BerEP4 (+), focally (+) for CK7 and LMWCK

  • Negative for melanocytic markers (S-100, HMB 45, Mart 1/Melan A)

  • *Other melanocytic markers such as cytoplasmic tyrosinase or nuclear microphthalmia transcription factor can be used in some cases if necessary.

  • †Very rare tumour.