4: Merkel Cell Carcinoma

This rare but important neuroendocrine small round blue cell carcinoma of the skin is often treated with radiotherapy.


Merkel cell carcinoma is a rare skin neoplasm (incidence 0.25 per 100,000 compared with 160 per 100,000 for squamous cell carcinoma of the skin). It is rare in blacks and usually occurs in older people (mean age 70). 50% of cases arise on the face and 40% on the limbs.

Aetiology and Pathogenesis

Chronic sun exposure is thought to be a primary causative factor due to the localisation of the tumour to the face and limbs. It is also more common in immunosuppressed patients. There is evidence that infection with Merkel Cell Polyomavirus may be causally linked as the virus genome is expressed in a significant portion of patients with Merkel Cell tumours.

Natural History

The tumour arises in the dermis and usually extends deeply; the overlying skin is rarely ulcerated as in BCC/SCC/melanoma.

Clinical Presentation

Patients present with a rapidly growing but otherwise asymptomatic mass, often on the face or limbs. The lesion is rarely ulcerated.

Tumour/Normal Tissue Features


The lesion predominately exists in the dermis and the overlying epidermis is typically intact.


The tumour is a small round blue cell tumour. Cells are arranged in nests or sheets within the epidermis.


Immunohistochemistry is positive for cytokeratin 20 and neuroendocrine markers (synpatophysin, chromogranin, neuron specific enolase). It can be differentiated from metastatic small cell lung cancer by the presence of CK20 + and TTF1 -ve. It can be differentiated from peripheral neuroectodermal tumour/extraosseous Ewing sarcoma by the absence of CD99 staining.

Staging / Classification

Staging is via the 7th edition of the TNM system. Previously Merkel Cell Carcinoma was staged in a group with other non-melanoma skin tumours.

T Stage

T stage is now Merkel Cell Carcinoma specific:

  • T1: < 2 cm size
  • T2: 2-5 cm size
  • T3: > 5 cm size
  • T4: Invasion of adjacent structures

N Stage

N stage is unique for emphasis of clinical or pathological nodal staging:

  • cN0: Clinically node negative
  • pN0: Pathologically node negative
  • N1a: Micrometastases
  • N1b: Macrometastases
  • N2: In transit metastases

M Stage

M Stage is similar to melanoma:

  • M1a: Distant nodal, skin or subcutaeneous metastases
  • M1b: Lung metastases
  • M1c: Other visceral metastases

Final Stage

Stage T N M
IA T1 pN0 M0
IB T1 cN0 M0
IIA T2-3 pN0 M0
IIB T2-3 cN0 M0
IIC T4 N0 M0
IIIA Tany N1a M0
IIIB Tany cN1 / pN1b-2 M0
IV Tany Nany M1