Table 1 †"AEIOU” - mnemonic reminder of the major clinical information related to MCC; *MCC - Merkel’s cell carcinoma; ⋆MCCPyV - Merkel’s cell carcinoma-associated polyomavirus, #IHC - Immunohistochemistry

Clinical information

A†: Asymptomatic nodule

E†: fast Expansion

I†: Immunosupression state

O†: Older than 50 years

U†: Ultraviolet exposure

Caucasian

Polyomavirus infection

Head and neck, extremities and trunk

History of neoplasia

Size of lesion before biopsy

Clinical or imaging evidence of lymph node involvement

Histopathology

Small-blue round-cell tumors with ‘salt and pepper’ chromatin pattern

High mitotic rate

Large cells or small cells

Nodular, trabecular or infiltrative pattern

IHC#

CK20 + (90% sensitivity, membranous and/or paranuclear dot-like staining pattern)

Neuroendocrine marker + (chromogranin, synaptophysin, NSE, neurofilament, CD56)

TTF-1 - (rule out small cell lung carcinoma)

CD45 - (rule out lymphoma)

S100 - (rule out melanoma)

Melan A - (rule out melanoma)

CK20 - (complement with desmin/ myogenin to rule out alveolar rhabdomyosarcoma; complement with SATB2 and NF to look for lymph node metastasis)

Ultraviolet-induced MCC* (high tumor mutational burden subtype)

Ultraviolet radiation exposure

TP53 and RB1 mutations

Absence of the MCCPyV⋆ genome

IHC#: p53 +, p63 + and Rb -

Virus-positive MCC* (low tumor mutational burden subtype)

Presence of the MCCPyV⋆ genome

Absence of genetic mutations

IHC#: Rb+, p53 - and p63 -