Merkel cell carcinoma on the rise

The incidence of MCC is on the rise and it has the highest mortality of any skin cancer. A basic understanding of the risk factors, clinical features and therapeutic options for MCC can assist the clinician in managing this menacing cancer.

MCC's disturbing statistics

MCC incidence is increasing, having tripled since 1986. Fatality rates for MCC are high (one in three) compared to melanoma (one in five), squamous cell carcinoma (one in 50) or basal cell carcinoma (less than one in 10,000). There are approximately 1,000 cases of MCC a year in the United States.

Management options

Dr. Nghiem says that management of MCC is often not optimal.

Underuse of important treatment modalities like sentinel lymph node biopsy (SLNB) and radiation therapy or overuse of therapies including over-aggressive surgery/amputation, scans (CT/MR/PET) and chemotherapy may all be potential reasons for poor patient outcomes.

Risk factors include age (over 65), being Caucasian with prolonged sun exposure, immune suppression, psoralen and long-wave ultraviolet radiation (PUVA) and exposure to arsenic. Similar to solid organ transplant recipients, HIV-positive patients show a 4.5 times to seven times higher MCC incidence, with a higher death rate of 68 percent, versus 26 percent in patients with normal immune systems.

Presentation patterns

Merkel cell carcinoma has a nonspecific clinical presentation, unfortunately leading to diagnostic delays in virtually all cases.

Common nonspecific presenting features are a papule/nodule that is red to purple, nontender, with rapid growth in the prior one month to three months, usually on a sun-exposed area. Common presumptive diagnoses include cyst/acneform lesion, lipoma, dermatofibroma, non-melanoma skin cancer and lymphoma.

Diagnostic particulars

Merkel cells are mechanoreceptors within the basal epidermis.

There are three histologic patterns for MCC (all with similar prognoses). The most common type is the intermediate type (differential diagnoses are small blue cell tumors/melanoma/lymphoma), followed by the small cell type (differential diagnosis is small cell lung carcinoma) and the trabecular type (differential diagnosis is metastatic carcinoid).

Dr. Nghiem says, "In immunohistochemistry examination, the peri-nuclear dot pattern of cytokeratin is pathognomonic. Prior to these specific markers, many MCC cases were misdiagnosed as lymphoma or metastatic small cell lung cancer. If the immunohistochemistry is done properly, the diagnosis is definite."

He says he believes that sentinel lymph node biopsy should be performed routinely in MCC. He reports that among 31 patients without palpable lymph nodes, 10 (32 percent) had a positive SLNB, and that SLNB-positive patients benefited from adjuvant nodal therapy.

For detecting nodal disease, SLNB sensitivity is much greater than CT scan sensitivity, which missed about 90 percent of these metastases. Dr. Nghiem says that there is no need for CT scans if the primary tumor is small and if the SLNB is negative. Scans are useful for SLNB–positive patients to rule out distant metastasis.

Treatment

Dr. Nghiem says that in most cases, SLNB and surgical excision with negative margins should be carried out.

Radiation treatment should be administered to the primary site and should be considered as a treatment modality to the lymph node basin if the patient has a positive SLN, a large primary tumor or is immunosuppressed.