In 1875 Fredrich Sigmund Merkel described cells of the snouts of pigs he believed to have receptor function. A carcinoma of the skin with similar cells was first documented by Toker in 1972 as Trabecular carcinoma ₁ . This rare and very aggressive malignant primary tumor has since been termed Merkel cell carcinoma (MCC). Possible etiologic factors include 1) ultraviolet (UV) radiation as MCC tends to appear on sun-exposed skin, and a regional incidence correlation has been found with UVB ₂,₃ ; and 2) declining immune function with an association with immunosuppressive therapy, viral human immunodeficiency, and 76% occurring in those over 65 ₄,₅ .

Agelli and Clegg reported on the epidemiology of MCC based upon a prospective study from 1973 to 1999 of the Surveillance, Epidemiology, and End Results Program (SEER). The age-adjusted incidence rates (per 100,000 person-years) were 0.34 in males and 0.17 in females and cases were much more common in whites (94%) and in elders over age 65 (76%) ₄ . Further, SEER data demonstrated an increasing incidence of 0.15 cases per 100,000 person-years in 1986 to 0.44 in 2001 with the incidence in males tripling ₆ . This represented an age-adjusted increase of 8% per year compared to a 3% year increase for melanoma ₆ .

The tumor most often appears on sun-exposed areas of the head and neck (50%) but can also appear on the extremities (40%). Grossly it appears as a painless firm, rapidly growing, shiny, erythematous to blue, solitary nodule usually less than 2 cm in diameter ₇ . It can spread by dermal invasion producing satellite lesions ₈ and in a series of 1024 MCC patients local lymph node spread occurred in 55% and metastasis to distant lymph nodes (60%), distant skin (30%), lung (23%), central nervous system (18%), and bone (15%) ₂ .

MCC appears microscopically as small, basophilic tumor cells with scant cytoplasm and round to oval, hyperchromatic, evenly dispersed nuclei.

Mitotic rate is high, apoptotic bodies may be present and nucleoli may be absent or few in number. The cells are found in the dermis and may extend into the subcutaneous fat ₉ . Immunohistochemical stains are needed to differentiate MCC from other skin tumors including small cell carcinoma of the lung, lymphoma, carcinoid, neuroblastoma, retinoblastoma, Ewing's sarcoma, and rhabdomyosarcoma ₁₀

Many staging systems have been used for MCC. Recently, however, a four tier system for staging of MCC has been developed as tumor size over 2 cm is an independent predictor of survival (table 1) ₁₁ .

Figure 1

Table 1: Four tier staging system for MCC with size of primary over 2 cm indicating stage II disease

Seventy percent of patients present with stage I or II disease, 25% at stage III and 5% present with distant metastases (stage IV) ₂,₁₂,₁₃

Surgical wide local excision (WLE) at the primary site with 2-3 cm margins is well accepted as initial treatment with the goal of tumor free margins. A chest X-ray is appropriate at initial diagnosis to rule out small cell lung cancer as the primary tumor. Some recommend CT or MRI to find metastasis, however, a high false-positive rate may provoke unnecessary procedures ₁₄ .

Sentinel lymph node biopsy (SLNB) is considered standard of care for patients with clinically localized disease. Some 20% of SLN may be positive for MCC using CK-20 immunostaining ₇,₁₅ .

Radiation treatment to the site of the primary lesion does not improve survival with lesions < 2 cm and tumor free WLE margins ₂,₁₂,₁₆ . For larger lesions or if tumor-free margins cannot be obtained local-regional radiation treatment is indicated ₇ .

Chemotherapy for metastatic MCC has produced response but patients usually die within weeks to months thus its use is unclear ₁₇ .

Forty to 45% of cases have recurrence ₂,₁₂ . Disease prognosis is best defined by lymph node involvement. The strongest factor associated with survival is stage with five year survival rates of 81%, 67%, 52% for stages I, II, and III, respectively reported ₇ Stage IV has a poor prognosis with a reported 11% two year survival rate ₁₂ and survival as low as six months ₁₈ . A retrospective study of 1665 cases from the SEER registry to 2002 demonstrated an improvement in the overall median survival from 45 months to 63 months associated with the use of adjuvant radiation therapy. Factors associated with an improved prognosis include size < 2 cm, female gender and local radiation treatment ₁₉ .

As of 2007 fifteen complete spontaneous remissions (CSR) (complete clinical disappearance of the tumor) of MCC have been reported in the literature ₁₆,₂₀,₂₁ Apoptosis and T-cell immune response involvement has been suggested as the mechanism ₂₂ . This represents the sixteenth case of CSR, in an 86 year-old male with tumor-free survival of over nine years.