MCC is thought to be derived from Merkel cells, which are touch-sensitivity-associated cells located in the dermo-epidermal junction of the skin. In the eyelid, these cells are mainly found near the lashes, associated with touch receptors [7]. The origin of the cells has been unclear until recently, since they exhibit neuroendocrine and epidermal properties. However, a recent study suggests the development of Merkel cells from epidermal stem cells rather than neural crest progenitors [9]. Interestingly, MCC is located almost exclusively in the dermis and subcutis, although Merkel cells are epithelial cells. This might suggest the cellular origin of this tumour being in dermal progenitor cells rather than in the cell itself [10].

Recent research suggests a DNA virus named Merkel cell polyomavirus (MCV) to be a causative factor for the development of MCC. Integration of a part of the viral genome has been found in 80 % of MCC [11].

MCC is found mainly in whites on UV-exposed skin and incidence is higher in Australia. Moreover, patients receiving PUVA therapy (psoralen + UVA) for psoriasis have been found to present with a higher incidence of MCC [12]. MCC incidence is also higher, and age of onset is lower in immunocompromised individuals following organ transplants, HIV infection or haematolymphoid diseases [13]. Complete regression of metastatic Merkel cell carcinoma has been described [14]. MCC is a dermal tumour and might not be directly related to UV skin damage, but rather to UV-induced downregulation of immune responses [15].

Merkel cell carcinoma presents commonly as red or violaceous firm, painless nodule that can grow rapidly within weeks to months (Fig. 48.1). The surface is often smooth and shiny and ulceration is uncommon [15]. Necrosis can occur in very fast-growing tumours. If the eyelid is involved, the margin is predisposed for the development of these tumours corresponding to the distribution of Merkel cells in the lid in the outer root layer of the cilia [16]. Growth is usually as a nodule, inducing a variable amount of cilia loss and exhibiting telangiectasia. Satellite lesions can occur.

Macroscopic differential diagnoses include chalazion, basal cell carcinoma, sebaceous gland carcinoma, cavernous haemagioma, pyogenic granuloma and metastasis [17, 18].

Histopathology shows a solid, sometimes septate tumour in the dermis with uniform, small, monomorphous cells with basophilic cytoplasm and large, round, clear nuclei with prominent nucleoli. Many mitoses can be seen throughout. The tumour is characteristically separated from the overlying epidermis by a free zone of uninvolved dermis [10]. Sometimes there are pseudorosettes and signs of high cell turnover such as necrosis and apoptosis. Lymphocytic and plasmacellular infiltrates commonly surround the lesion [18] (Fig. 48.2).

Microscopic differential diagnoses are mainly lymphoma, metastasis of small cell (neuroendocrine) carcinoma of the lung and amelanotic melanoma. As discussed above, the tumour cells exhibit epithelial and neuroendocrine histologic properties, which are represented in the positive immunohistochemical (IHC) staining which is usually positive for low-molecular-weight cytokeratin (cytokeratin 20), neuroendocrine markers (neuron-specific enolase, synaptophysin) and neurofilament protein. Differentiation from amelanotic melanoma is with S100 and HMB-45 stains and from metastatic small cell carcinoma is with thyroid transcription factor-1 for which MCC is usually negative [3]. Differentiation from cutaneous non-Hodgkin lymphoma can be made through the positive staining for cytokeratin and negative CD45 staining [19].

Staging and grouping of MCCs in general are done according to the ninth edition of the American Joint Committee on Cancer (AJCC) on the basis of Lemos et al. [20] wherein the eyelid is not included. Eyelid carcinomas are staged by the system designed by AJCC [21].

Tumours are grouped by their Tumour-node-metastasis (TNM) status into groups that define the treatment or enrolment into clinical studies as in cutaneous melanoma.

The staging of MCC in the eyelid and general skin differs to a significant extent because the proximity of the eyelid skin to other crucial structures (muscle, tarsal plate) renders it special treatment, and smaller tumours have greater impact on prognosis.

Although SLNB is generally recommended for skin MCCs, the use of it in eyelid Merkel cell carcinomas is still under debate. Histopathological evaluation of the lymph nodes (via SLNB or elective lymph node resection such as neck dissection or parotid gland dissection in case of eyelid tumours) has been shown to significantly improve prognostic accuracy in MCC [20] and that around one third of patients undergoing only clinical nodal evaluation are understaged because occult microscopic nodal involvement is overlooked [22]. Currently, some authors recommend SLNB for Merkel cell carcinoma of any size, mainly for prognostic purposes [23, 24]. Distant metastases of MCCs have been found in node-negative patients, so that treatment of occult nodal disease might not necessarily mean a better prognosis in eyelid MCC.

Because of the rare occurrence, there is no consensus statement as to the preoperative metastatic workup of patients with MCC. In general, careful clinical examination and palpation of the regional lymph nodes (i.e. preauricular and parotid, cervical and submandibular) are recommended and as per clinical judgement ultrasonography of the lymph node basins and CT or MRI of the chest and abdomen. CT of the chest may be required to rule out neuroendocrine small cell carcinoma of the lung as differential diagnosis might be difficult even with IHC. Abdominal sonography and chest X-ray may be performed, although with limited sensitivity and specificity as discussed in the chapter for cutaneous melanoma. SLNB as stated above is currently controversial. PET/CT can accurately detect Merkel cell carcinoma and might be an adjunct in preoperative assessment [25]. It is to be noted that in large prospective studies of MCC, 27–31 % of patients presented with nodal disease [1, 20]; hence primary nodal involvement has to be taken into account when evaluating this aggressive tumour.

There are no serum markers specific for MCC as of now.