History and exam

Key diagnostic factors

common

presence of risk factors

Risk factors that may be elicited by the history include chronic ultraviolet (UV) exposure, immunosuppression, advancing age, fair skin type, and male sex.​​[2][30][31][32][33][34]​​​[35]​​​[36][37][38]​​​​​​​​​

firm, non-tender, red or pink-to-violaceous or skin-coloured papule or subcutaneous nodule

The primary cutaneous MCC tumour usually presents as a solitary, firm, erythematous or pink-to-violaceous or skin-coloured papule or subcutaneous nodule, typically on sun-exposed skin.[7][19]

MCC lesions most frequently develop on the sun-exposed areas of head and neck (29% to 44%) and the extremities (37% to 45%). Less than 10% of MCCs occur on partially sun-protected areas (trunk, thighs, and hair-bearing scalp) or highly sun-protected areas (buttocks). Extra-cutaneous sites (e.g., vulva, vagina, oral mucosa, parotid gland, nasal cavity) are very rarely involved.

MCC lesions are typically asymptomatic and not tender to the touch.[7] One study of 195 patients with pathologically confirmed MCC found that 88% of tumours were asymptomatic.[2]

[Figure caption and citation for the preceding image starts]: A primary MCC tumour in an 87-year-old man who presented with a large, fast-growing, red, eroded nodule on the right templeFrom the collection of Dr Kelly Harms and Dr Alison Lee, University of Michigan; used with patient consent [Citation ends].com.bmj.content.model.Caption@19fd9aa3[Figure caption and citation for the preceding image starts]: MCC on the left lower lip of a 68-year-old man. The asymptomatic tumour is an ill-defined reddish-pink, scaly plaque blurring the lower vermillion of the lipFrom the collection of Dr Kelly Harms and Dr Alison Lee, University of Michigan; used with patient consent [Citation ends].com.bmj.content.model.Caption@1993785d[Figure caption and citation for the preceding image starts]: A 2 cm red, nodular MCC with varied vessel patterns on the right upper arm of an 80-year-old manFrom the collection of Dr Kelly Harms and Dr Alison Lee, University of Michigan; used with patient consent [Citation ends].com.bmj.content.model.Caption@52756864

For further clinical images of MCC, see Diagnosis approach.

rapidly growing lesion

The primary MCC tumour typically grows rapidly over the first 3 months.[2]

Other diagnostic factors

common

enlarged lymph nodes

Regional lymph node metastases present as enlarged lymph nodes or masses in the draining nodal lymph node basin.

Rarely, MCC can present with clinically detectable disease in a lymph node without a primary tumour (unknown primary MCC).​[35][46][47]

uncommon

ulceration or bleeding cutaneous lesion

Ulceration and bleeding are infrequent at first presentation of MCC but might occur at advanced stages.[7][19]

small papules or nodules surrounding a primary lesion

Cutaneous satellite or in-transit metastases present as smaller papules or nodules surrounding the primary tumour.

Risk factors

strong

cumulative ultraviolet (UV) exposure

UV-mediated DNA damage is a significant risk factor for MCC.

MCC is strongly associated with lower latitudes and high UV radiation indexes.[13] The primary tumour typically occurs on sun-exposed skin.​[2][7]

MCC tumours that do not harbour integration of Merkel cell polyomavirus (MCPyV) demonstrate a high burden of UV-signature mutations, and UV-mediated DNA damage is considered a pathogenic mechanism of MCC tumorigenesis.[22][23]

immunosuppression

MCC is strongly associated with immunosuppression, with an estimated 6% to 12% of all patients with MCC being immunosuppressed.[7][19]

There is a greater than 34-fold increased risk of MCC in patients with chronic lymphocytic leukaemia (CLL).[15][17]​​​​ Patients with solid organ transplantation have a 23% increased risk of MCC.​[16][27]​​​​ Other immunosuppression mechanisms, such as human immunodeficiency virus (HIV) infection and use of immunosuppressive medications, have also been associated with a higher risk of developing MCC.[7][28]​​​​​

The European Society for Medical Oncology (ESMO) guideline states that 10% of patients with MCC are organ transplant recipients, or have either a haematological malignancy or HIV infection.[19]

advancing age

The median age of MCC diagnosis is 77 years.[6][7][10]​​​ Incidence rates increase sharply with age, and the highest incidence is reported in those aged over 85 years.​[4][5][7]

male sex

There is a higher incidence in men than in women.[7] Studies have reported that 61% to 66% of cases are in men.​[1][4]​​[5][9][10]

white skin

MCC is predominantly seen in white patients and is very rare in people of colour.[7] There is an 8-fold increased incidence in white individuals compared with non-Hispanic black people.[11]

Merkel cell polyomavirus (MCPyV) infection with oncogenic transformation

Oncogenic transformation by MCPyV is a key risk factor for MCC.[29] MCPyV is a ubiquitous virus, with seroprevalence in the adult population of 60% to 80%.[20] Oncogenic transformation by MCPyV is a rare event and requires viral integration into the host genome, resulting in inactivation of a viral replication protein. MCPyV is associated with up to 70% to 80% of MCC tumours in North America and Europe, with lower associations in Australia, where a higher proportion of cases are associated with UV exposure.[7][12][14]

Use of this content is subject to our disclaimer