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Merkel cell carcinoma: a rare cutaneous neoplasm.

Giuseppe Fotia MD, Roberto Barni MD, Eleonora Pallucca MD, residents.
School of General and Emergency Surgery.
University of Siena.   Italy.

May 2001.     Review Article.

Merkel cell carcinoma is a rare, malignant tumor of the skin characterized by significant incidence of local recurrence (30% to 45%), early involvement of the locoregional lymph nodes (40% to 70%) and distant metastases (30% to 50%) (17).
Due to its aggressiveness and benign clinical appearance, the prognosis of this neoplasm is poor (17). Reported overall 5-year survival rates range from 30% to 64% (11, 28).
Toker published the first complete description of this neoplasm in 1972, originally describing it as "trabecular carcinoma" (25). Nearly 1000 cases are reported in the English-language literature since the initial description (16).
This tumor is also known as cutaneous small cell undifferentiated carcinoma. At the present, the tumour is classified as a neuroendocrine malignancy (APUDoma) of the skin, generally occurring in elderly patients (12, 15).

Macroscopically the primary tumor arises as a small, non-ulcerated, painless, bluish red, intradermal nodular mass often located in sun-exposed areas of the skin (17).
The commonest sites of presentation are the head and the neck and it is slightly more common in females (1, 19). In rare cases (nearly 3%) the Merkel cell carcinoma presented as a metastatic disease of unknown primary, usually in lymph nodes (16).
This cancer arises in the dermis and subcutaneous tissues from Merkel's cells located in the basal layer of the epidermis and expresses neuroendocrine markers such as neuron-specific enolase, chromogranin, synaptopysin and neurofilament proteins (21).
The most frequent sites of metastasis are distant lymph nodes, distant skin, lung, central nervous system and bone (16).

The histologic diagnosis can be difficult, because with the conventional light microscopy Merkel cell carcinoma can be misdiagnosed as any other poorly differentiated small cell neoplasm (17). The electron microscopy showing a triad of characteristic features (high mitotic index, apoptosis and vescicular nuclei with small nucleoli) and the immunohistochemical staining (neuron-specific enolase and cytokeratin) play an important role in the early diagnosis (3, 9, 22, 26).

The most common staging system is that described by Yiengpruksawan et al., stage I disease for isolated local lesion, stage II disease is characterized by metastatic spread to regional lymph nodes and stage III has evidence of distant metastatic disease at the time of initial presentation (27). Recently a new modified staging system was performed: stage Ia (primary disease only, size < 2cm), stage Ib (primary disease only, size > 2cm), stage II (regional nodal disease), stage III (beyond regional nodes and/or distant disease) (24).

The management of Merkel cell carcinoma is still a challenging problem; the rarity of this tumor and the lack of data concerning its true incidence and long-term responsiveness to therapies make it difficult to determine an "ideal" treatment. Merkel cell carcinoma should be treated aggressively with wide excision of the primary lesion (2-3 cm margins), and prophylactic lymphadenectomy followed by irradiation to the primary site (8, 20). The Mohs micrographic surgery tecnique is resulted to be comparable, or even better, than wide excision for the control of primary skin disease (6, 10, 14).
If lymph nodes involvement is detected, then irradiation to the lymph nodal region must be performed (4).
Chemotherapy is reserved for systemic disease, though the success of this treatment is limited and no chemotherapy protocol has been shown to improve survival (18, 20). Chemotherapeutic regimens most often used for the treatment of Merkel cell carcinoma are similar to those performed for the small cell carcinoma of the lung ( 7, 23, 27).
Radiotherapy alone can be used as palliative treatment with good control of primary and lymph node metastases (5).

The lymph nodal involvement is correlated with the 5-year survival (survival rates for nodal versus no-nodal involvement were 48% and 88% respectively) (27), but it was not associated with overall survival (2, 14). For this reason, some Authors suggest the use of sentinel lymph node biopsy to select those patients who need lymphadenectomy for regional control of disease. (13)

The local recurrence rate is frequentely correlated to the progression of the disease (17).
Tumor location on the trunk usually have a worse prognosis than those on the head and neck (14).
Although systemic involvement indicates a poor prognosis and regression of Merkel cell carcinoma is exceedingly rare, almost 10 cases of spontaneous regression are present in literature (6).


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