60 y.o. Female. Tumour on the right upper arm. Non-melanoma skin cancer?

CASE 27

Rare

Aggressive

No consensus on management

Keratin 20 Synapsin

CD 56 Ki67

British Association of Dermatology July 2007

British Association of Dermatology July 2007

CK20: cytokeratin 20CK7: cytokeratin 7NSE: neurone-specific enolaseNFP: neurofilament proteinS100: S100 proteinLCA: leucocyte common antigenCD99: cluster-of-differentiation antigen 99TTF1: thyroid transcription factor 1+: positive stain –: negative stain

Tumour CK20 CK7 NSE NFP S100 LCA CD99 TTF1

Merkel-cell carcinoma + - + + - - Rare -

Small-cell carcinoma of lung - + + +/- - - Rare +

Lymphoma - - - - - + - -

Peripheral primitive neuro-ectodermal tumour

- - + Rare - - + -

Small-cell melanoma - - + - - - - -

Immunolabelling Profiles

Cytokeratin 20

Immunohistochemistry

Merkel Cell Carcinoma

• Rare highly malignant neuroendocrine skin tumour

• USA - 0.23 / 100 000

•Male predominance

•Average age at presentation – 69y

Merkel Cell Carcinoma

Associations

• UV light– most commonly seen on the head and neck

region and the lower leg

• Immunosuppression– Post organ transplant (0.13 / 1000 patient yrs)– HIV– Haematological malignancies

Associations

• Clinical diagnosis is difficult

• Red / violaceous nodule

• May resemble an SCC / BCC or amelanotic melanoma

Clinical Diagnosis

Prognostic markers

• Advanced stage at presentation

• Immunosupression

Poor Prognostic Markers

Good Prognostic Markers

• CD+ Lymphocyte invasion of the tumour

• Prescence of Polyomavirus

MCVMCV

MCPyVMCPyV

Clonally Clonally integrated in 80% integrated in 80% of MCCof MCC

Retrospective Analysis of MCC over 10years

14 cases identified

SSMDT

Barts Health NHS Trust

Results: Demographics

9 female, 5 male

Mean age of presentation: 73years (range 54 to 87years)

21% presented with metastatic disease

25%

17%50%

8%

Buttock

Head

Upper limbs

Lower Limbs

Results: TreatmentINTERVENTION Frequency

WLE with 1-3cm margins ALL

Adjunctive Radiotherapy Majority

(57%)

Sentinel Lymph Node Biopsy Few (14%)

Adjunctive Chemotherapy•Enrolled onto MCC-1 Trial

1

Polyomavirus

• 10/14 tested

• 80% had positive polyomavirus

• Positive virus did not correlate with outcome

Results: Survival Rates

• All patients who presented with metastases died within a year (3/14)

• Of the remaining 11/14 patients, 1 died within a year

• Other comorbidities

• 10/14 patients are still alive to date • Date range from 2005- 2012

British Association of Dermatology July 2007

Radiotherapy induced skin cancers

• BCC - 3.6%

• SCC - 0.003%

• Angiosarcoma

• Fibrosarcoma

• Melanoma

• Merkel cell carcinoma

Guidelines

Germany France USA UK

WLE margin 3cm 2-3cm Not specified

Radiotherapy to surgical bed

Yes Yes Yes

SLND Yes Yes Not obligatory

Adjunct Chemotherapy

No No Yes- enrol in Clinical trials

Chemotherapy in Metastases

Yes Yes Yes

Follow-up 5-years 5years Minimum 3years

Suggestions for UK pathway• Histopathological criteria and Staging

• J Diaz- Perez et al. “Merkel cell carcinoma: a clinicopathological study of 11 cases.” JEADV, 2005

• WLE with 2-3cm or Mohs • S. J. Miller, M. Alam, J. Andersen, et al., “Merkel cell carcinoma,”

Journal of the National Comprehensive Cancer Network, vol. 7, no. 3, pp. 322–332, 2009.

• Adjunctive Radiotherapy• L. Mortier, X. Mirabel, C. Fournier, F. Piette, and E. Lartigau,

“Radiotherapy alone for primary Merkel cell carcinoma,” Archives of Dermatology, vol. 139, pp. 1587–1590, 2003

• Sentinel lymph node biopsy• L. K. E. Rodrigues, S. P. L. Leong, M. Kashani-Sabet, and J. H. Wong,

“Early experience with sentinel lymph node mapping for Merkel cell carcinoma,” Journal of the American Academy of Dermatology, vol. 45, no. 2, pp. 303–308, 2001.

• ?Role of Adjunctive chemotherapy