MADRID – The discovery of a new virus that appears to play a causative role in most cases of Merkel cell carcinoma has brought a new sense of optimism regarding this most aggressive of all cutaneous neoplasms.
"The discovery of the Merkel cell polyomavirus could be a major breakthrough. It could hopefully lead to new, more successful treatments," Dr. Ingrid Wolf said at the 13th World Congress on Cancers of the Skin.
Among the therapeutic possibilities opened up by the discovery of the new Merkel cell polyomavirus, known as MCPyV for short, are a preventive vaccine, interferon therapy, and serologic screening of individuals at increased risk for Merkel cell carcinoma to identify those infected by MCPyV and thus in need of close surveillance, added Dr. Wolf, a dermatologist at the University of Graz (Austria).
She provided an encouraging case report involving a patient with multiple nodular lesions on the arm. The largest lesion was excised, while the rest were treated with daily injections of interferon-beta for 5 weeks with no adjuvant radiation or chemotherapy. The lesions have regressed, and the patient has since gone 8 years without relapse or recurrence. The discovery of MCPyV provides a mechanistic basis for this success story.
MCPyV was discovered by the same team of investigators that found a new oncogenic herpesvirus that is the cause of Kaposi’s sarcoma, both HIV-related and non-HIV-related (N. Engl. J. Med. 2005;332:1,181-5).
The researchers surmised that MCPyV is far more likely to play an etiologic role in Merkel cell carcinoma than to be a bystander based on their demonstration that the virus is clonally integrated in the tumor genome (Science 2008;319:1,096-100). This observation suggests MCPyV is involved in clonal expansion of the tumor.
The group’s findings have subsequently been confirmed and expanded upon in other laboratories. It is now apparent that MCPyV is present in 70%-80% of Merkel cell carcinomas.
This trend is consistent with two broad population trends: the graying of society, and the steadily increasing population of immunosuppressed individuals. The risk of Merkel cell carcinoma has been estimated to be increased 8-fold in HIV-positive patients, 10-fold in organ transplant recipients, and at least 20-fold in patients living with chronic lymphocytic leukemia. The other major risk factor for Merkel cell carcinoma is age greater than 60. The most common site is the head and neck, reflecting the tumor’s predilection for UV-damaged skin. Sixty-two percent of patients in the SEER analysis were men. Nearly 97% of cases occurred in Caucasians.
MCPyV, like other polyomaviruses, is a small double-helix DNA virus. Infection by the virus is widespread: Serum antibodies are present in 80% of individuals over age 50 and 50% of those less than 15 years old.
The virus appears to be involved in the pathogenesis of other malignancies apart from Merkel cell carcinoma. It has been reported to be present in 6% of Kaposi’s sarcoma specimens and two-thirds of basal cell carcinomas. The basal cell carcinomas linked to MCPyV tend to have more necrosis and less palisading, according to Dr. Fernandez-Figueras of the Autonomous University of Barcelona.
The overall 5-year mortality of Merkel cell carcinoma is 33%. Tumor stage at diagnosis is the chief determinant of prognosis. The 5-year survival rate ranges from 79% for patients with tumors 2 cm or less and no lymph node involvement to 26%-42% with regional nodal involvement to 10%-18% for stage IV disease marked by distant metastasis.
Merkel cell carcinoma is a rapidly growing small cell neuroendocrine tumor of the skin. The Merkel cells present in the tumor are thought to originate from epidermal cells in the basal layer or adnexa, or perhaps from a primitive cutaneous epithelial precursor, Dr. Fernandez-Figueras observed.
It’s important to note that the biologic behavior of Merkel cell carcinoma is the same regardless of whether or not a tumor is associated with MCPyV, she stressed.